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https://w.atwiki.jp/boare/pages/119.html
Release Note Release Date 14 Jun, 2009 Notes Cadencii requires ".NET Framework Runtime(version 2.0 or later)". Installer of this rumtime is available from the link below. .NET Framework Runtime Download .NET Framework 3.5 SP1 Cadencii can be launched with the latest version of mono. This enable you to use Cadencii with many platforms supported by mono. (Note Several functions using VOCALOID2 VSTi are not available in this case.) Mono is available from the link mono download Download Cadencii version 2.1.0 (603KB) CadenciiSDK version 2.0 (455KB) How to get source codes Source code is available on SourceForege.JP. Please follow the instruction below for checking out the SourceForge.JP s SVN repository. svn checkout -r 255 http //svn.sourceforge.jp/svnroot/cadencii/branches/2.0 ./ These svn command is for checiking out "THIS" version of Cadencii. In order to get the latest source codes, please remove "-r" option.
https://w.atwiki.jp/goldkai1/pages/180.html
Unimplemented contents A few maps and cutscenes Equipment and magic are on the respective pages, and enemies are on the X and youtube, so I don't have to write about them. Character ShopCheery John's WorkdmapMaps of Farnas and other places. Sandrigal Oasis Maps of New Heinrogue Castle and other places. Maps of Sage's Tower Gate and other places Map DataDigging Camp Rune Malna Mell Nautilus Port City Keb Village Conton Ruins Farnas Warrior/Mage Temples Rob Dam Warrior Shrine Mekua Port Io Port Yuuro Port Mystery Port Sandrigal Oasis Mystery CutsceneDOUKUTU HEKIGA MADOU MEGAMI SENSHI SIP WATER Character There are a few NPCs that were never used, most of them are different colors of the characters that are implemented. Shop Cheery John's Originally sold items other than milk, more of a scripting error than unimplemented. Workdmap Maps of Farnas and other places. There was a road going right, maybe to Sandrigal Oasis? Sandrigal Oasis Why was it left unimplemented? Maps of New Heinrogue Castle and other places. I thought there was a direct line to map of the Sage's Road? Maps of Sage's Tower Gate and other places Of course, there's on this side of the map. Map Data Digging Camp Bar？ Not that there's anything in particular. Rune Malna Station？ Inside the large building on the left side of Map4. Is there a mistake in setting the entrance because there are NPCs? Mell Bar？ I thought just flipped bar of the New Heinrogue...? Nautilus Port City Mystery Map There was supposed to be a quest? Keb Village Where Yuuta was Version with open door to basement. Basement Where it was supposed to be used when the pattern was to save Yuuta's family. Conton Ruins Remnants of the unimplemented quest There's this line that comes in DISC 1, it looks like this one was to be the Keb Village. Farnas 2nd floor of inn So-so, it's well made. Warrior/Mage Temples Mysterious object It looks like the connection was where the Guard are - here - Warrior Shrine. Rob Dam Mystery Map1 It leads here from the Dam, you can faintly see the road. Mystery Map2 Map1 - here - at the waterfall, maybe you wanted to express the water flowed... Before the altar When DISC1, they say this, i didn't get a key in DISC2 either. Warrior Shrine Before Entrance When DISC1, they say this. Mekua Port Mystery Map Mystery. Io Port Entrance Usually stays closed. Yuuro Port Entrance Usually stays opened. Mystery Port Wharf Baroa is there, and when talk to him, he'll change where going.There are three destinations New Heinrogue Castle, Old Heinrogue Castle, and Mekua Port.But they won't ride me to Mekua unless complete the statue. Sandrigal Oasis Panoramic view It's a sophisticated pun on the words "Everything that happens twice will surely happen a third time." (nido aru koto ha sando aru) and Sandrigal (sandorua) Indoor All the data for this Oasis is not set up. Indoor I think the frame-like objects in the live-action picture are the four audition winners at the time, as has been said. Indoor The Indoor rest Indoor is Indoor nothing 室内 special. Mystery Mystery I don't know anything about this. Cutscene DOUKUTU Looks like the Sacred Beast Shrine? HEKIGA The location is a mystery, and these gods don't appear in the game. MADOU It's not a place worth showing in a cutscene. MEGAMI It's not a place worth (omit) SENSHI It's not a (omit) SIP The same sound effects as in the Rob Dam's cutscene are played.Maybe they were talking about this happening while traveling by ship, and then an emergency evacuation from there to the Kuuba Port.Then it's not hard to see why the ship is sinking at the far end of Kuuba Port. WATER Camera angles are needlessly elaborate.
https://w.atwiki.jp/2dogs_demo/pages/3.html
更新：2012/07/04 18 50 02 Visitors 合計： - |今日： - |昨日： - This page URL http //www34.atwiki.jp/2dogs_demo/pages/3.html A protest demonstration against Fuji TV. About Two Loyal Tsunami Dogs. Please participate！ update June 4 Fuji TV reported false information "both dogs were rescued." We demand to correct Fuji-TV s false information about Two Loyal Tsunami Dogs of Arahama. The date (Sunday) July 15 2012 1 00 pm get together 1 30 pm start 3 30 pm finish Before demonstration, we will have a meeting, for 10 to 30 minutes. There will be a small party after the demonstration. (you are welcome to join us. share the expenses.) free-for-all. The meeting‐place in Odaiba Tokyo(Tokyo Teleport Station) No postponement for rain. The promoter mii(tottorimiyagi) The purpose On March 17 2011, after the tsunami, Fuji TV reported false information "both dogs were rescued." But in fact, white english setter was not rescued, still missing. We request Fuji TV to broadcast this information "The white setter is still missing. Even now, Two Dog s Owner has been looking for white setter." The owner of the dogs has been searching for his pets after the tsunami, the owner found the brown tan dog. The owner frantically looked for white English setter named Lee chan, but sadly, she was still nowhere to be found. Fuji TV(Japan), CNN, NPR, TYT, CBS, ABC(America), UK telegraph, ITN(England), Apple Daily(Hong Kong), more, major media reported “Two loyal tsunami dogs were rescued. Happy ending!” in March 2011, but in fact white English setter has been missing. Major media still have NOT corrected their wrong reports. Major media reported a wrong information around the world http //www18.atwiki.jp/2dogs/pages/34.html Major media reported false information, but Global Animal had been reporting the truth about two loyal tsunami dogs since March 2011. Thank you Global Animal!! http //www18.atwiki.jp/2dogs/pages/1.html Mr. Yamashina who is Fuji TV reporter met the dog s owner in July 2011. And Mr. Yamashina already know that Lee-chan(white English setter) has been missing. But even now, Fuji TV never correct their wrong report, and they have not contacted the dog s owner since summer 2011. 当日配るチラシ 今日から印刷開始します！家のプリンターでですが。 リーちゃん捜索チラシ→ http //www34.atwiki.jp/2dogs_demo/pages/2.html PET SOSさんの被災ペット愛護団体応援プロジェクトチラシ → http //petsos.nekonikoban.org/ouen.html A4で印刷して、ティッシュと一緒に渡そうかと予定しています。 tottorimiyagi @ Ustream.TV http //www.ustream.tv/user/tottorimiyagi Contact to the promoter twodogs_tottorimiyagi_mii3328@yahoo.co.jp You can contact me(the promoter) on twitter. Feel free to ask me if you have any questions. Twitter @tottorimiyagi http //twtr.jp/user/tottorimiyagi If you cannot join "A protest demonstration against Fuji TV About Two Loyal Tsunami Dogs." but, want to do anything. Please call/fax/e-mail/mail to Fuji TV that “We request Fuji TV to broadcast this information "The white setter is still missing. Even now, Two Dog s Owner has been looking for white setter(Lee-chan)."” Fuji Television English Website. https //wwws.fujitv.co.jp/safe/en/fip_archive_form_new.html Fuji TV Super News(FNN Fuji News Network) FAX：03-5500-0222 ■Wanted Lee chan http //www18.atwiki.jp/2dogs/pages/35.html ■Translation English Japanese two loyal tsunami dogs in Arahama, Sendai-city. http //www18.atwiki.jp/2dogs/pages/1.html
https://w.atwiki.jp/boare/pages/149.html
Release Note Release Date 27 Sep., 2009 Notes Cadencii requires ".NET Framework Runtime(version 2.0 or later)". Installer of this rumtime is available from the link below. .NET Framework Runtime Download .NET Framework 3.5 SP1 Cadencii can be launched with the latest version of mono. This enable you to use Cadencii with many platforms supported by mono. (Note Several functions using VOCALOID2 VSTi are not available in this case.) Mono is available from the link mono download Download Cadencii version 2.3.5 (641KB) How to get source codes Source code is available on SourceForege.JP. Please follow the instruction below for checking out the SourceForge.JP s SVN repository. svn checkout -r 491 http //svn.sourceforge.jp/svnroot/cadencii/branches/2.3 ./ These svn command is for checiking out "THIS" version of Cadencii. In order to get the latest source codes, please remove "-r" option.
https://w.atwiki.jp/boare/pages/153.html
Release Note Release Date 27 Sep., 2009 Notes Cadencii requires ".NET Framework Runtime(version 2.0 or later)". Installer of this rumtime is available from the link below. .NET Framework Runtime Download .NET Framework 3.5 SP1 Cadencii can be launched with the latest version of mono. This enable you to use Cadencii with many platforms supported by mono. (Note Several functions using VOCALOID2 VSTi are not available in this case.) Mono is available from the link mono download Download Cadencii version 3.0.2 (1015KB) How to get source codes Source code is available on SourceForege.JP. Please follow the instruction below for checking out the SourceForge.JP s SVN repository. svn checkout -r 496 http //svn.sourceforge.jp/svnroot/cadencii/branches/3.0 ./ These svn command is for checiking out "THIS" version of Cadencii. In order to get the latest source codes, please remove "-r" option.
https://w.atwiki.jp/hypnosis-eng/pages/97.html
Top D.C. Hammond Handbook of Hypnotic Suggestions and Metaphors contents Handbook of Hypnotic Suggestions and Metaphors 目次 Foreword by Harold B. Crasilneck vii 序文 （[+]をクリックで展開、[-]をクリックで畳込み） +1. Introduction 序論 1. Introduction 序論 The Underlying Therapeutic Philosophy Integrative Hypnotherapy セラピーの基底：統合的な催眠療法 The American Society of Clinical Hypnosis アメリカ臨床催眠学会 Training Opportunities トレーニングの機会 Eligibility for ASCH Membership アメリカ臨床催眠学会の会員資格 Acknowledgments 賛辞 +2. Formulating Hypnotic and Posthypnotic Suggestions 催眠暗示と後催眠暗示の構成 2. Formulating Hypnotic and Posthypnotic Suggestions 催眠暗示と後催眠暗示の構成 Principles of Hypnotic Suggestion 催眠暗示の原則 Types of Hypnotic Suggestions 催眠暗示のタイプ The Phrasing of Suggestions 暗示のコトバはどのようなものか The Process of Suggestions in Facilitating Phenomena 暗示のプロセス：反応を強めるために +3. Hypnosis in Pain Management 痛みと催眠 3. Hypnosis in Pain Management 痛みと催眠 INTRODUCTION Techniques of Hypnotic Pain Management / Joseph Barber Alteringthe Quality of Discomfort Example of Leg Pain / M. Erik Wright Transformation of Pain / WiIliam L. Golden, E. Thomas Dowd, and FredFriedberg Erickson s Suggestions for Pain Control / Milton H.Erickson General Principles for Alleviating Persistent Pain / ErnestL. ROSSaIn d David B. Cheek Religious Imagery of UniversalHealing for Ego-Strengthening and Pain / M. Erik Wright The"Sympathetic Ear" Technique with Chronic Pain / Barry S. Fogel Reactivation of Pain-Free Memories An Example of Intensifying andRelieving Pain / M. Erik Wright Chronic Pain Syndrome / RichardB. Carver Hypnotically Elicited Mystical States in Treating Physicaland Emotional Pain / Paul Sacerdote Active Control Strategy forGroup Hypnotherapy with Chronic Pain / Timothy C. Toomey and ShirleySanders Pain Strategies by Hypnotizability Level / David Spiegel andHerbert Spiegel Reinterpreting Pain as Protection / Charles B.Mutter Splinting Technique for Pain Control / Charles B.Mutter Erickson s Interspersal Technique for Pain TheSetting Sun Pain Metaphor / Alexander A. Levitan Mexican Food Metaphor of the Body Adapting to Pain / D. Corydon Harnrnond Metaphor of Callous Formation / D. Corydon Harnmond Suggestions for Patients with Chronic Pain / Lillian E. Fredericks Pain Reduction / Beata Jencks "Body Lights Approach toAmeliorating Pain and Inflammation (Arthritis) / Ernest L. Rossi andDavid B. Cheek Suggestions with Postherpetic Neuralgia ("Shingles")/ Diane Roberts Stoler Suggestions to Reduce Pain FollowingHemorrhoidectomies / Ernest W. Werbel Suggestions for PainControl / Don E. Gibbons Hypnosis for Migraine / Lillian E.Fredericks Suggestions with Migraine / J.A.D, Anderson,M. A. Busker, and R. Dalton Diminution Rather Than Eliminationof Headache / Irving I. Secter Suggestion for Symptom Substitution/ Gary R. Elkins The Progressive Anesthesia Induction-DeepeningTechnique / D. Corydon Harnmond +4. Hypnoanesthesia and Preparation for Surgery 外科手術のための催眠麻酔 4. Hypnoanesthesia and Preparation for Surgery 外科手術のための催眠麻酔 INTRODUCTION Preparation for Surgery / Lillian E. Fredericks Suggestions forAnesthesia and Surgery / Bertha P. Rodger Hypnosis and theAnesthetist / John B. Corley Summary Steps for PreoperativeHypnosis to Facilitate Healing / Ernest L. Rossi and David B.Cheek Ericksonian Approaches in Anesthesiology / Bertha P.Rodger Examples of Preoperative Suggestions / JosephBarber Preparation for Surgery / Sandra M. Sylvester Temperature Suggestion Following Chest/Abdominal Surgery / D. CorydonHarnrnond Suggestions for Insertion of Needles or ShortProcedures / Esther E. Bartlett Switching Off the Senses / BerthaP. Rodger Rapid Induction Analgesia / Joseph Barber Surgical and Obstetrical Analgesia / Ernest L. Rossi and David B.Cheek Techniques for Surgery / William S. Kroger +5. Ego-Strengthening Enhancing Esteem，Self-Efficacy，an Confidence 自我強化：自尊感情、自己効力感、自信を高める 5. Ego-Strengthening Enhancing Esteem, Self-Efficacy, an Confidence 自我強化：自尊感情、自己効力感、自信を高める INTRODUCTION Ego-Strengthening / Moshe S. Torem An Example of PositiveSuggestions for Well-Being / Sheryl C. Wilson and Theodore X.Barber Positive Suggestions for Effective Living / T. X.Barber Suggestions for Raising Self-Esteem / T. X. Barber Barnett s Yes-Set Method of Ego-Strengthening / Edgar A. Barnett Ego-Enhancement A Five-Step Approach / Harry E. Stanton Suggestions for Modifying Perfectionism / D. Corydon Hammond Suggestions Derived from Rational-Emotive Therapy / Harry E.Stanton Suggestions for Raising Self-Esteem / Helen H.Watkins Suggestions to Facilitate Problem Solving / Don E.Gibbons The Serenity Place / D. Corydon Harnrnond Ego-Strengthening Suggestions / Richard B. Carver TheInevitability of Change / Robert C. Mashman Change Is Necessaryfor Comfort / Robert C. Mashman An Abstract Technique forEgo-Strengthening / B. J. Gorman Learning to Feed Yourself AnExample of Age Regression to Experiences of Mastery / D. CorydonHammond Ego Building /Joan Murray-Jobsis The UglyDuckling Metaphor / Roy L. Rummel The Prominent TreeMetaphor / Alcid M. Pelletier The Seasons of the Year AMetaphor of Growth / Lawrence R. Gindhart ConfidenceBuilding / H. E. Stanton Increasing Determination TheSnowball / H. E. Stanton Suggestions for Emotional Enrichment /Don E. Gibbons Stein s Clenched Fist Technique / D. CorydonHammond Suggestions for Ego-Strengthening / JohnHartland Suggestions for Self-Reinforcement / Don E.Gibbons Visualization of the Idealized Ego-Image / Maurice H.McDowell Cycle of Progress / Douglas M. Gregg A BriefEgo-Strengthening Suggestion / William T. Reardon AFuture-Oriented Suggestion / P. Oystragh +6．Anxiety，Phobias and Dental Disorders 不安、恐怖症、歯牙障害 6．Anxiety, Phobias, and Dental Disorders 不安、恐怖症、歯牙障害 INTRODUCTION Hypnosis with Anxiety Progressive Relaxation Induction or Deepening Technique / D. CorydonHammond Hypnotic Treatment Techniques with Anxiety / DavidSpiegel and Herbert Spiegel The Private Refuge / SeligFinkelstein Imagery Scenes Facilitating Relaxation / H. E.Stanton Island of Serenity / Edwin L. Stickney Deep,Meditative Trance The Approach of Ainslie Meares, M.D. Methods of Relaxed Breathing / Beata Jencks The Autogenic RagDoll / Beata Jencks Hypnotic Suggestion/Metaphor to BeginReframing / Steven Gurgevich Rational-Emotive Suggestions AboutAnxiety / Albert Ellis Stress Reduction Trance A NaturalisticEricksonian Approach / Eleanor S. Field The Closed DrawerMetaphor / Brian M. Alman He Who Hesitates Is Lost AMetaphor for Decision-Making / Michael D. Yapko De-FusingPanic / Marlene E. Hunter Hypnosis with Phobias Paradigm for Flying Phobia / David Spiegel and Herbert Spiegel AReframing Approach for Flight Phobia / Peter A. Bakal, M.D. Hypnosis with Phobic Reactions / Don E. Gibbons Suggestions forSimple and Social Phobias / Michael A. Haberman Example ofTreating Phobic Anxiety with Individually Prepared Tapes / M. Erik Wright180 Treatment of Lack of Confidence and Stage Fright / David Waxman180 Overcoming Anxiety over Public Speaking / Don E. Gibbons Suggestions in Dental Hypnosis Suggestions with TMJ and Bruxism / Harold P. Golan Suggestions with TMJ / Ellis J. Neiburger Erickson s suggestions withBruxism / Milton H. Erickson TMJ and Tension Heachaches / DovGlazer Suggestions to Promote Dental Flossing / Maureen A. Kelly,Harlo R. McKinty, and Richard Carr Gagging / Harold P.Golan Imagery with Hypersensitive Gag Reflex / J. Henry Clarkeand Stephen J. Persichetti Denture Problems and Gagging /Donald R. Beebe Suggestion with Gagging / Irving I.Secter Gagging Suggestion / William T. Heron Control ofSalivation / Zrving I. Sector Dental Phobias and Fears / Louis L.Dubin Illustrative Suggestions with Tooth Extraction / SeligFinkelstein Dental Hypnosis / Victor Rausch Suggestionsfor Operative Hypnodontics / William S. Kroger The Let s PretendGame / Lawrence M. Staples Erickson s Approach with Bruxism inChildren / Milton H. Erickson Use of Fantasy or Hallucination forTongue Thrusting / Zrving l. Secter Suggestions with TongueThrusting / Donald J. Rosinski +7. Hypnosis with Cancer Patients がん患者と催眠 7. Hypnosis with Cancer Patients がん患者と催眠 INTRODUCTION Clinical Issues in Controlling Chemotherapy Side Effects / William H.Redd, Patricia H. Rosenberger s and Cobie S. Hendler Suggestionsand Metaphors for Nausea / Alexander A. Levitan Suggestions forChemotherapy Patients / Alexander A. Levitan Suggestions andMetaphors for Support and Ego-Strengthening in Cancer Patients / Billie S.Strauss General Suggestions for Self-Healing / JoanMurray-Jobsis Hypnotic Suggestions with Cancer / JeffreyAuerbach Hypnotic Suggestions with Cancer Patients / Harold B.Crasilneck and James A. Hall Imagery to Enhance the Control ofthe Physiological and Psycho1 ogical "Side Effects" of Cancer Therapy /Simon W. Rosenberg Breast Cancer Radiation Treatment andRecovery / Diane Roberts Stoler Hypnosis as an Adjunct toChemotherapy in Cancer / Sidney Rosen Hypnotic DeathRehearsal / Alexander A. Levitan +8. Hypnosis with Medical Disorders 身体疾患と催眠 8. Hypnosis with Medical Disorders 身体疾患と催眠 INTRODUCTION Hypnosis with Dermatologic Disorders Treatment of Pruritus / Michael J. Scott Erickson s ReframingSuggestion with Pruritus / Milton H. Erickson Suggestions forItching / Beata Jencks Hypnotic Technique for Treating Warts /Harold B. Crasilneck and James A. Hall Suggestions for Warts[Modeled after Hartland] / Don E. Gibbons Suggestions forVaginal Warts / Diane Roberts StoIer Suggestions with CondylomaAcuminatum (Genital Warts) / Dabney M. Ewin Suggestions forimmunodeficient Children with Warts / M, F. Tasini and Thomas P.Hackett Evoking Helpful Past Experiences and Medical Treatments Example with Skin Rash / M. Erik Wright Suggestions withPruritus / William S. Kroger and William D. Fezler ReducingDermatologic Irritation / D. Corydon Hammond Hypnosis with Burns and Emergencies Suggestions with Burn Patients / Harold B. Crasilneck and James A. Hall228 Emergency Hypnosis for the Burned Patient / Dabney M.Ewin Hypnosis in Painful Burns / R. John Wakeman and Jerold Z.Kaplan Ideomotor Healing of Burn Injuries / Ernest L. Rossi andDavid B. Cheek Direct Suggestions in Emergencies with theCritically Ill / Ernest L. Rossi and David B. Cheek Suggestionsfor Use of Spontaneous Trances in Emergency Situations / M. ErikWright Painless Wound Injection Through Use of a Two-fingerConfusion Technique / Steven F. Bierman Hypnosis for Healing, Psychosomatic Conditions and AutoimmuneDiseases General Approach to Physical Symptoms Caused by Stress / Carol P.Herbert Symphony Metaphor / Marlene E. Hunter Healing Imagery / Marlene E. Hunter Suggestions withAutoimmune Disease / Jeffrey Auerbach Prolonged Hypnosis inPsychosomatic Medicine / Kazuya Kuriyama Further Suggestionsfor Facilitating Prolonged Hypnosis / Stanislav Kratochvil VascularControl Through Hypnosis / Emil G. Bishay and Chingmuh Lee Suggestion for Control of Bleeding / Milton H. Erickson Suggestions for Control of Upper Gastrointestinal Hemorrhage / Emil G.Bishay, Grant Stevens, and Chingmuh Lee Blood PerfusionProtocol / Lawrence Earle Moore Hypnosis with Neurological and Ophthalmological Conditions Teaching the Other Side of the Brain / Marlene E. Hunter Once Learned, Can Be Relearned / Marlene E. Hunter Hypnosiswith Blepharospasm / Joseph K. Murphy and A. Kenneth Fuller Hypnotherapy for Lagophthalmos / Jean Holroyd and EzraMaguen Suggestions for Involuntary Muscle Jerking / Valerie T.Stein Hypnosis with Bell s Palsy / Simon W. Chiasson Hypnosis with Sleep Disorders Suggestions with Sleep Disturbance / Richard B. Carver Suggestions with Sleep Disorders / Doris Gruenewald Visualizationfor Treating Insomnia / H. E. Stanton Hypnosis Techniques withInsomnia / David Spiegel and Herbert Spiegel Suggestions forInsomnia / Milton H. Erickson Snoring A Disease of theListener / Daniel A. Zelling Miscellaneous Medical Applications Hypnotic Techniques and Suggestions for Medical-Physical Complaints /Beata Jencks Paradoxical Self-Hypnotic Assignment for Chronic Urinary Retention or "Bashful Bladder" / Gerald J. Mozdzierz Hypnosis in Postoperative Urinary Retention / Simon W. Chiasson Hypnotic Paradigm-Substitution with Hypochondriasis / Thomas Deiker and D. Kenneth Counts Suggestions with Asthma / Don E.Gibbons Suggestions for Prevention of Seasonal Allergies / HansA. Abraham Erickson s Metaphor with Tinnitus / Milton H.Erickson Procedure with Difficulty Swallowing Pills / Irving I.Secter Suggestion for Alleviating Hiccups / Gerald J.Mozdzierz +9. Hypnosis in Obstetrics and Gynecology 産婦人科と催眠 9. Hypnosis in Obstetrics and Gynecology 産婦人科と催眠 INTRODUCTION Obstetrical Hypnosis Childbirth Training Group Hypnosis Training in Obstetrics / Simon W. Chiasson Outline of Hypnotic Suggestions in Obstetrics / Bertha P. Rodger Suggestions for a Comfortable Delivery / Joseph Barber TheHypnoreflexogenous Technique in Obstetrics / A. Kenneth Fuller Childbirth Suggestions / Larry Goldmann Management ofAntenatal Hypnotic Training / David Waxman Erickson sChildbirth Suggestions / Milton H. Erickson An EricksonianApproach to Childbirth / Noelle M. Poncelet Childbirth Script /Diane Roberts Stoler Preparation for Obstetrical Labor / WilliamS. Kroger Suggestions with Untrained Patients in Labor / NicholasL. Rock, T. E. Shipley, and C. Campbell Premature Labor, Miscarriage and Abortion Hypnotic Relaxation Technique for Premature Labor / HaimOmer Use of Immediate Interventions to Uncover EmotionalFactors in Pre-Abortion Conditions / David B. Cheek Treating theTrauma of Prospective Abortion / Helen H. Watkins Hyperemesis Gravidarum and Miscellaneous GynecologicDisorders Hypnotic Intervention with Hyperemesis Gravidarum / Ralph V.August Control Of Hyperemesis / Larry Goldmann Suggestions for Hyperemesis / William T. Heron ProgressiveAnesthesia Technique for Hyperemesis Gravidarum / D. Corydon Hammond Suggestions for Hyperemesis / Harold B. Crasilneck and James A. Hall Suggestions for Hyperemesis Gravidarum / David Waxman Suggestions with Psychogenic Amenorrhea / William S. Kroger Suggestions with Leukorrhea / F. H. Leckie +10. Hypnosis with Emotional and Psychiatric Disorders 感情障害、精神障害と催眠 10. Hypnosis with Emotional and Psychiatric Disorders 感情障害、精神障害と催眠 INTRODUCTION Suggestive Techniques with Emotional Disorders Hypnotherapeutic Technique for the Reduction of Guilt The Door ofForgiveness / Helen H. Watkins Dumping the "Rubbish" /H. E. Stanton The Red Balloon Technique / D. CorydonHammond Edelstien s Fusion of Extremes Technique / D. CorydoHammond Scenes for Facilitating Self-understanding / H. E.Stanton Meeting an Inner Adviser / David E. Bresler Responsibility to a Fault A Metaphor for Overresponsibility / Michael D.Yapko Different Parts A Metaphor / Michael D. Yapko Enhancing Affective Experience and Its Expression / Daniel P. Brown andErika Fromm Hypnosis with Severely Disturbed Patients Can Hypnosis Help Psychosis? / James R. Hodge Renurturing Forming Positive Sense of Identity and Bonding / JoanMurray-Jobsis Suggestions for Creative Self-Mothering / JoanMurray-Jobsis Hypnotherapeutic Techniques with AffectiveInstability / Louis N. Gruber Hypnotic Suggestions to DeterSuicide / James R. Hodge Hypnosis with Bipolar AffectiveDisorders / A. David Feinstein and R. Michael Morgan Hypnosis with Post-Traumatic Stress Disorder and MultiplePersonality Disorder Emergency Room Suggestions for Physically or Sexually AssaultedPatients / Carol P. Herbert Hypnotic Suggestions with RapeVictims / Bruce Walter Ebert Saying Goodbye to the Abused Child An Approach for Use with Victims of Child Abuse and Trauma / Ronald A.Havens Reframing Dreams in PTSD / Charles B. Mutter Suggestions and Metaphors for Post-Traumatic Stress Disorder and PainControl (in Spanish) / Marlene D. de Rios and Joyce K. Friedman A Fusion Ritual in Treating Multiple Personality / Richard P. Kluft Another Fusion Ritual / Richard P. Kluft Containing Dysphoria inMPD / Richard P. Kluft Modified Ego-Strengthening for MPD /Moshe S. Torem Corporate Headquarters of the Mind / Donald A.Price Metaphors with Multiple Personality and Trauma Patients /D. Corydon Hammond A Projective Ideomotor ScreeningProcedure to Assist in Early Identification of Ritualistic Abuse Victims /D. Corydon Hammond +11. Hypnosis with Sexual Dysfunction and Relationship Problems 性機能不全、対人関係の問題と催眠 11. Hypnosis with Sexual Dysfunction and Relationship Problems 性機能不全、対人関係の問題と催眠 INTRODUCTION Hypnotherapy and Sexual Dysfunction The Master Control Room Technique / D. Corydon Hammond Illustrative Suggestions in Sex Therapy / Bernie Zilbergeld Hypnotherapy with Psychogenic Impotence / Harold B. Crasilneck Suggestions for Spectatoring and Sensate Focus / D. Corydon Hamrnond358 Suggestions for Facilitating Sexual Fantasy / D. Corydon Hammond360 Changes in Preference Metaphor / D. Corydon Hammond Metaphors for Going Out to Dinner and Back Scratching / D. CorydonHammond Organ Transplant Metaphor / D. CorydonHammond The Pee Shyness Metaphor for Sexual Dysfunction /D. Corydon Hammond Metaphoric Suggestions and Word Playsfor Facilitating Lubrication / D. Corydon Harnmond Suggestionfor Ejaculatory Inhibition or Orgasmic Dysfunction / D. CorydonHarnmond Suggestion for Erection or Lubrication / D. CorydonHammond Suggestions for Impotence and Anorgasmia / LeoAlexander Suggestions for Induced Erotic Dreams / D. CorydonHammond Suggestions with Sexual Dysfunctions / Don E.Gibbons Suggestions for Premature Ejaculation / Milton H.Erickson Hypnotic Suggestions for Interpersonal Relationships Hypnotic Ego-Assertive Retraining / David Waxman "Fruits Vegetables" A Simple Metaphor for Understanding People Better / GeraldJ. Mozdzierz Suggestions to Increase Interpersonal Effectiveness /Don E. Gibbons Suggestions for Difficulties in InterpersonalSituations / Kermit E. Parker, Jr. The Symbolic Imagery LetterWriting Technique / Mark S. Carich The Jazz Band Metaphor forFamily Interaction / Philip Barker Golden Retriever Metaphor /D. Corydon Hamrnond The Pygmalion Metaphor / D. Corydon -Hamrnond +12.Hypnosis with Obesity and Eating Disorders 肥満、摂食障害と催眠 12.Hypnosis with Obesity and Eating Disorders 肥満、摂食障害と催眠 INTRODUCTION Hypnosis with Obesity Examples of Suggestions for Weight Reduction / Sheryl C. Wilson andTheodore X. Barber Hypnotic Suggestions for Weight Control /T. X. Barber Hypnotic Strategies for Managing Cravings /D. Corydon Hammond Weight Control / David Spiegel andHerbert Spiegel Suggestions for Patients with Obesity Problems /Joan Murray-Jobsis Computer Metaphor for Obesity / Richard B.Garver Suggestions for Decreasing Food Intake / Harold B.Crasilneck and James A. Hall Historic Landmark Technique forTreating Obesity / William C. Wester Hypnosis in WeightControl / Herbert Mann Weight Control Suggestions / Harry E.Stanton Miscellaneous Suggestions for Weight Control / William S.Kroger and William D. Fezfer Further Suggestions for Managementof Obesity / William S. Kroger Erickson s Suggestions withObesity / Milton H. Erickson Negative Accentuation Vivifying theNegative During Trance / M. Erik Wright Aversive Metaphor forChocolate Eaters / Marvin Stock Symbolic Imagery The Dial BoxShrinking Technique / Mark S. Carich The Attic of the Past /Eleanor S. Field Treatment of Eating Disorders Suggestions to Modify Body Attitude / Eric J. Van Denburg and RichardM. Kurtz Altering Body Image / Hans A. Abraham Suggestions for Increasing Food Intake / Harold B. Crasilneck and JamesA. Hall Suggestions for Presenting Symptoms in AnorexiaNervosa / Meir Gross Metaphors for Bulimia and Anorexia /Michael D. Yapko +13. Smoking，Addictions and Habit Disorders 喫煙、依存症、習癖 13. Smoking, Addictions, and Habit Disorders 喫煙、依存症、習癖 INTRODUCTION Hypnosis with Smoking and Addictions Smoking Suggestions / Joseph Barber Hypnotic Suggestions forSmoking Cessation / T. X. Barber Hypnosis and Smoking A FiveSession Approach / Helen H. Watkins Smoking Control / DavidSpiegel and Herbert Spiegel Suggestions for Smoking Cessation /Harold B. Crasilneck and James A. Hall Smoking Cessation /Richard B. Garver Suggestions Regarding Smoking / StevenGurgevich Suggestions to Modify Smoking Behavior / Harry E.Stanton Suggestions Applicable for Smoking, Obesity and OtherAddictive Behaviors / Doris Gruenewald Suggestions for RationalSelf-Talk for Smoking and Other Addictions / D. CorydonHammond Suggestions for Smoking Cessation / William C.Wester, Aversive Metaphor for Smoking / MarvinStock General Strategies for Overcoming Pleasure-ProducingHabits / M. Erik Wright Illustrative Suggestions with Smokers /Paul Sacerdote A Posthypnotic Suggestion and Cue with Smokers /Brian M. Alman Hypnosis with Habit Disorders Hypnosis with Nailbiting / Harold B. Crasilneck and James A.Hall Erickson s Suggestions for Nailbiting / Milton H.Erickson Suggestions for Nailbiting / David Waxman Suggestions for Nailbiting / Don E. Gibbons Suggestions withTrichotillomania / Marianne Barabasz Suggestions for ScalpSensitivity with Trichotillomania / T. J. Galski +14. Concentration，Academic Performance and Athletic Performance 集中、学力、身体能力 14. Concentration，Academic Performance，and Athletic Performance 集中、学力、身体能力 INTRODUCTION Enhancing Academic Performance Suggestions for Enhancing Academic Performance /Don E.Gibbons The Memory Bank / Douglas M. Gregg Academic Study Suggestions / Stanley Krippner ConcentrationSuggestions / William T. Reardon Suggestion for Concentration /Brian M. Alman Suggestions and Success Imagery for StudyProblems / Jeannie Porter Suggestions for Studying, Concentrationand Text Anxiety / Richard B. Garver Erickson s Suggestions forFacilitating Speed of Learning / Milton H. Erickson Alert TranceSuggestions for Concentration and Reading / E. R. Getting AlertSelf-Hypnosis Technique to Improve Reading Comprehension / David M.Wark Advanced Comprehension Suggestions for an Alert Trance /David M. Wark Improving Reading Speed by Hypnosis / RaymondW. Klauber German s Ego-Strengthening Technique Adapted forReading / G. Gerald Koe Suggestions for Foreign LanguageStudy / Don E. Gibbons Suggestions for Mathematics or StatisticsPerformance / Robert M. Anderson Examination Panic / MiltonH. Erickson Suggestions for Concentration, Studying and, Overcoming Test Anxiety / Alcid M. Pelletier Suggestions forExamination Phobia / David Waxman Suggestions for Aesthetic Refinement Suggestions for Artistic Expression / Don E. Gibbons Suggestionsfor Aesthetic Appreciation and Enjoyment / Don E. Gibbons Suggestions to Enhance Musical Performance / Don E. Gibbons Suggestions to Enhance Writing Ability / Don E. Gibbons Enhancing Sports and Athletic Performance ISuggestions Used to Enhance Sport Performance / Keith P.Henschen Sports Performance Enhancement / Richard B.Garver Metaphor for Athletics/Sports Competition / Richard R.Wooton Metaphor for Facilitating Cooperation and Teamwork inAthletics / Richard R. Wooton rn Suggestions for Concentration /Brian M. Alman A Cognitive-Hypnotic Approach to AthleticPerformance with Weight Lifters / W. Lee Howard and James P.Reardon Suggestions for Sports Performance / Don E.Gibbons Endurance Suggestions with Distance Runners / J. ArthurJackson, Gregory C. Gass, and E. M. Camp +15. Hypnotic Suggestions with Children 子供と催眠暗示 15. Hypnotic Suggestions with Children 子供と催眠暗示 INTRODUCTION Helping Parents See Specific Advantages in Child Hypnotherapy / G. GailGardner Hypnosis with Children / Daniel P. Kohen Hypnosis with Pain Hypnotic Procedure for Pain Relief / Valerie J. Wall Techniquesof Hypnoanalgesia / Karen Olness and G. Gail Gardner PediatricWound Injection Using a Visual Distraction Technique / Steven F.Bierman Examples of Suggestions for Use in PediatricEmergencies / Daniel P. Kohen Hypnosis with Enuresis A Hypnotherapeutic Approach to Enuresis / Daniel P. Kohen Imagery with Bedwetting / H. E. Stanton Induction and OceanMetaphor for Bedwetting / Valerie J. Wall Suggestions withEnuresis / Franz Baumann Erickson s Suggestions with Enuresis /Milton H. Erickson Enchanted Cottage Suggestions for Enuresis /Don E. Gibbons Suggestions for Thumbsucking Erickson s Suggestions for Thumbsucking / Milton H. Erickson Suggestions with a Four-Year-Old Thumbsucker / Lawrence M. Staples Miscellaneous Pediatric Problems Metaphor for a Boy with Behavioral Problems / Norma P. Barretta andPhilip F. Barretta Hypnosis in the Treatment of TouretteSyndrome / David N. Zahm A New Hypnobehavioral Method forthe Treatment of Children with Tourette s Disorder / Martin H. Young andRobert J. Montana Technique with Asthmatic Children / HaroldB. Crasilneck and James A. Hall Suggestions with Dyslexia /Harold B. Crasilneck and James A. Hall Hypnotic Suggestions withStuttering / Harold B. Crasilneck and James A. Hall PersonalizedFairy Tales for Treating Childhood Insomnia / Elaine S. Levine Suggestions with School Phobia / David Waxman A ScienceFiction-Based Imagery Technique / Gary R. Elkins and Bryan D.Carter +16．Time Reorientation Age Regression，Age Progression and Time Distortion 時間の流れを変える：年齢退行、年齢進行、時間歪曲 16．Time Reorientation Age Regression，Age Progression，and Time Distortion 時間の流れを変える：年齢退行、年齢進行、時間歪曲 INTRODUCTION Age Regression and Abreaction Ideomotor Identification Followed by Partial Regression / D. CorydonHammond Imagery Methods of Facilitating Age Regression /H. E. Stanton Improving the Quality of the Age Regression /Daniel P. Brown and Erika Fromm Suggestions to FacilitateRevivification / Eric Greenleaf Erickson s Confusional Method forRevivification / Milton H. Erickson Watkins Affect or SomaticBridge / John G. Watkins Facilitating a Full Abreaction /D. Corydon Hammond An Abreactive Technique / Richard P.Kluft A Vigorous Abreaction Technique / Richard P.Kluft The Fractionated Abreaction Technique / Richard P.Kluft The Slow Leak Technique / Richard P. Kluft Watkin s Silent Abreaction Technique / Helen H. Watkins Erickson s Age Regression Techniques / Milton H. Erickson Gradual Dissociated Release of Affect Technique / D. CorydonHammond Sickness Immunity Metaphors / D. CorydonHammond Metaphor of an Injury, Scab, and Healing /D. Corydon Hammond Example of An Analytical Procedure forRefraining / E. A. Barnett Desensitization An Example of Rapidand Repetitive Memory Evocation / M. Erik Wright ForensicHypnosis Guidelines The "Federal Model" / Richard B. Carver Age Progression Erickson s Time Projection Technique / D. Corydon Hammond Age Progression to Work Through Resistance / Richard B. Carver Suggestions Following Age Progression with Public Speaking / Don E.Gibbons Imagery of the End Result / Errol R. Korn and George J.Pratt Mental Rehearsal The Protective Shield / Errol R. Kornand George. Pratt Mental Rehearsal of Presentation and SalesSkills / Errol R. Korn and George J. Pratt Suggestions forGoal-Imagery / Alcid M. Pelletier End-Result Goal Imagery forSales Productivity / Don E. Gibbons Erickson s Self-suggestionTechnique / D. Corydon Harnmond Time Distortion Training Training Patients to Experience Time Distortion / Linn F. Cooper andMilton H. Erickson Summary of Suggested Steps in TimeDistortion Training / D. Corydon Hammond
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autoclaving avatar avatars axil axillary azide babushka babushkas baccalaureate baccalaureates backchat backslide backslides backslid backslidden backsliding bacteriophage bacteriophages bacteriophagy bailment bakelite ballcock banneret bannerets barbican barbicans barite baryte basmati beachhead beachheads bebop benison benisons benthic berberis bergamot betake betakes betook betaken bilayer binnacle binnacles bint bints biofeedback biogeography biogeographical biogeographic biogeographically biota bipedal bipedally biped bivouack bivouacks blackcap blackfly blackflies blain blains blinder blinders blinker blinkers blotto blowsy blowsier blowsiest blowsiness blowzy blowzier blowziest blowziness bluegrass bock bodkin bodkins bola bolas bolases bollocking bollockings bolthole boltholes bonbon bonbons boogy boogey boogied boogeyed boogying borage borax boreal bosh bract bradycardia breadfruit bren brindle briny brioche britches broadcloth brobdingnagian bromeliad bromeliads bronchodilator bronchodilators brougham brougham buckwheat bullhorn bullhorns bunion bunions burnout burnouts buttermilk butyric cabbalist cabbalistic cabbalism cabbalah kabbalist kabbalistic kabbalism kabbalah caber cabochon caboodle cabotage cadenza cadenzas calvados camshaft camshafts cancerian cancerians canis cannonade cannonades cannonaded cannonading canoodle canoodles canoodled canoodling capercaillie capercaillies captious captiously captiousness capuchin caravanserai caravanserais caravanseries carborundum cardiomyopathy cardiomyopathies cardiomyopathic cardiopulmonary caries carpal carrack carracks carrel carrels caseworker caseworkers casuarina catafalque catafalques catecholamine cathar cathars catharism catharist cathari caulk caulks caulked caulking calk cava cay cays celeriac celeste celestes centile centiles cep ceps cerberus cerberean cerebellum cerulean chai chambray chamfer chamfered chamfering chamomile camomile chancer chancers chapati chapatis chapatti chapattis chapman chapmen charleston chert chi chinoiserie chinook chinooks chipper chlorate chorea chowder chowders chromate chromatin chromatography chromatographic chromatographically cineraria clamour clamours clamoured clamouring clavichord clavichords claymore claymores clitoridectomy clitoridectomies cloaca cloacae cloacal clomp clomps clomped clomping cochineal cockade cockades cockaded codeine codswallop coed coeds coelenterate coelenterates cogitate cogitates cogitated cogitating cogitation cogwheel coir colleen colleens colobus colophon colophons coloratura columbine commensal commingle commingles commingled commingling compote compotes conciliar conciliarly confute confutes confuted confuting confuter conjunct conjunctive conjunctivitis conjunctiva conspecific conspecifics conspectus contraindication contraindications controvert controverts controverted controverting controvertible incontrovertible conventicle conventicles copolymer copolymeric corky corkier corkiest corkiness corm corms cornmeal coronal coronel cortisol cottar cotter cowrie cowry creatine creationist creationism crimplene crinoid critter critters crossbreed crossbred crossbreeding crouton croutons cuirass cuirassed cunnilingus cunnilinctus cupidity curare curari curie curies curmudgeon curmudgeons curmudgeonly curmudgeonliness curtilage cuss cusses cussed cussing cussedness cyclotron cyclotrons cytotoxic cytotoxicity czar czars czarist tzar tzars tzarist tsar tsars tsarist dandle dandles dandled dandling darwinian darwinism darwinists davit davits deadbeat deadbeats deadhead deadheads debouch debouches debouched debouching decile deciles declivity declivities dendrochronology dendrochronological dendrochronologically dendrochronologist denitrification denitrificatier denitrify denitrifies denitrifying denitrified denitrifier denitrifiers dermatological dermis dermal descender descenders descry descries descried descrying despond desponds desponded desponding dextrose diagenesis diagenetic diagenetically diatonic diatonically dieldrin dimethyl dingbat dingbats dingo dingoes diploid diss disses dissed dissing dissentient dissentients dixie dizygotic dizygous dodder dodders doddered doddering doddery dodderer dodderers doge dogleg doglegs doily doilies doyley doylies doyly doylies dolerite doleritic dolorous dolorously dolorousness dolour dolor donee donees doodlebug doodlebugs doorjamb doorjambs dosimetry dosimetric dosimetry downsize downsize downsized downsizing downtime downturn downturns dramaturge dramaturgic dramaturgical dramaturgically drawdown drawdowns dreamtime dromedary dromedaries dungeness dunnock dunnocks earmark earmarks earmarked earmarking eclair eclairs econometrics econometrically econometrician econometrist ectoplasm ectoplasmic edema edematous oedema oedematous efflorescence efflorescent elastin elastomer elastomeric eldritch electroconvulsion electroconvulsive elephantiasis elephantiases elute elutes eluted eluting elution embrocation embrocations emmy emmys emote emotes emoted emoting encephalomyelitis encephalomyelitic endocarditis endocarditic endometrium endometrial endoplasm endoplasmic endotracheal endotracheally ensuite entablature entranced entrancing entrancement epicurean epicureanism epicure epigenetic epigenetically epigenesis epiphenomenon epiphenomena eprom equinox equinoctial erysipelas erythema erythematous escargot escargots escrow espalier espaliers ethidium eukaryote eukaryotic eucaryote eventide excursus excursuses exigent exigently exigence exoskeleton exoskeletal expectorate expectorates expectorated expectorating expectoration expurgate expurgates expurgating expurgated unexpurgated extracorporeal extracorporeally faience fain fairing fantail fantails faucet faucets faux felucca feluccas ferrite fervid fervidly fervidness fescue feta fibrillate fibrillates fibrillated fibrillating fibrillation fibrin fibrinous fibula fibulas fibulae fibular fie filo fillo phyllo firmware flagellate flagellates flagellated flagellating flagellant flagellants flagellantism flammable flammability flatbed flatbeds flatfish flintlock flintlocks flitter flitters flittered flittering fluorine fluorocarbon fluorocarbons flyleaf flyleaves folate folie fontanelle fontanel foursquare foxhound foxhounds franglais franked franking franker freeboard freebooter freebooters freebooting freeload freeloads freeloaded freeloading freeloader freeloaders fricative fritillary fructose fudging fudged fundus fundi furze gabardine gamelan gamey gamy gamier gmiest gammy ganja gar gars garrot garroting garroted garrotte garrotting garrotted gatecrasher gatecrashers gaucherie gaucheries geld gelds gelded gelding gelignite geomorphology geomorphologist germinal germinally gestate gestates gestated gestating gestation gigot gigots gillie gillies gingivitis glissando glissandi globetrotter globetrotters glockenspiel glockenspiels glucagon glug glugs glugged glugging glutamic glutaraldehyde gneiss gneissic gneissic gneissoid gneissose goby gobies godawful godwit godwits goldeneye goldeneyes goldfinch goldfinches golem gonadotrophin gonadotrophins gooly goolies gosling goslings grampus grampuses grandsire grandsires granuloma graticule gratin greenback greenbacks greensward gridlock gridlocked groundsel grout grouts grouted grouting grubs grubbed grubbing grubber grubbers guanine guardhouse guardhouses gudgeon gunk gyp gyps gypped gypping gypsophila gypsophilia gyre gyral gyro gyros haematite hame hames hammy hammier hammiest hamminess hammily harebrained haricot haricots hasidic hassidic hasidism hausa heartwood hedera helipad helipads helot helotry helpmeet helpmeets helpmate helpmates hemolytic haemolytic hemolysis haemolysis heterozygous heterozygously heterozygote hexameter hillbilly hillbillies histocompatibility histocompatible hoar hoary hoarier hoariest hobnail hobnails hobnailed hobnailing hod hods hodder hodders hogwash homophobe homophobes homophobia honcho honchos honeybee honeybees hopscotch hortatory hourglass hourglasses housebreak housebreaks housebroke housebreaking housebroken howl howls howled howling huckleberry huckleberries hummus humus hommos humous hummous hydrocephalus hydrocephaly hydrochloride hydrographic hydrography hydrographer hydrophilic hydrophilicity hydroplane hydroplanes hydrosphere hydrospheric hyperbaric hyperbarically hypercholesterolaemia hypercholesterolaemic hypercholesterolemia hypercholesterolemic hyperthermia hypoallergenic hypocaust hypothyroidism ichor ides ileostomy ilex illocutionary imago immolate immolates immolated immolating immolation immunocompromised immunosuppressed immunosuppression infanticide ingenue inhume inhumes inhumed inhuming inhumation inning innings integument interleukin interpellate interpellates interpellated interpellating interpellation intracranial intracranially intramural intrauterine invigilate invigilates invigilated invigilating invigilator invigilators ionosphere ionospheric ionospherically iridium irredentist irredentism isotherm isothermic isotropic isotropically anisotropic anisotropically jacaranda jacuzzi jacuzzis jejune jejunely jejuneness jigger jiggers jiggered jiggering jockey jockeys jockeyed jockeying jockstrap jockstraps jounce jounces jounceed jouncing kaffir kaffirs afir kafirs keratin keratinous ceratin ketone kiloton kilotons knee knees kneed kneeing knurled knurly kohl kumquat cumquat kumquats cumquats laager laagers laban lacewing lacewings lama lamas lamarckian lamarckianism lamarckism lamella lamellae landlubber landlubbers languorous languorously larkspur larkspurs lavage lea leas lector lectors lederhosen legume leguminous lei leninism leninist levantine levant levee levees leviticus libran libra lightheaded lightheadedness lighthearted lightheartedness limn limns limned limning limner limners linebacker linebackers lisle lithology lithological lithological lockjaw lodestar loadstar loess login luge luger lumpenproletariat lumpenproletarian lymphadenopathy lysine macaroon macaroons machiavellian machiavellianism macrobiotic macrobiotically macrobiotics macromolecule macromolecular macroscopic macroscopically magnetite maharaja mahout mahouts maladroit maladroitly maladroitness malapropism malapropisms mammogram mammograms mammography mammographic mana mandala mandalic mandrake manichean manicheanism manicheism manichaean manichaeism manichaeanism mantilla mantilla maraca maracas marquise marquises maser masers mattock mattocks maxilla maxillas maxillae maxillary mazurka mazourka mazurkas mazourkas medlar medulla medullary meerkat megabit megabits megaton megatons meiosis meiotic meiotically menage meniscus menisci menthol mentholated merino merinos merrymaking mesolithic meson mesons mesonic mesothelioma mesotheliomas mesotheliomata messuage metastasis metastastases metastatic metastatically methacrylate methacrylic methionine metier metiers microcode microcoding microcosm microcosmic microcosmiclly micrometre micrometer micrometres micrometers microprobe microprobes micturate micturates micturated micturating micturition miliary millibar millibars milt minestrone mint mints minted minting minuteman minutemen misericord mocha moggy moggie moggies mojave moloch monicker moniker monickers monikers monistic monist monism monomeric monotype monozygotic moquette moquettes morphogenesis morphogenetic mortician morticians motocross motown muckle muckles mujahedin mulatto mulattos mulattoes murine muscadet mutagenic mutagenesis myalgia myalgic myelin myelinic myoglobin myxomatosis naan naphthalene narwhal narwhale neap necromancy necromancer necromantic necromantically necropsy necropsies needlepoint nematocyst nematocyst neodymium neoplasm neoplastic nephritis nephropathic nephropathy nephropathies nereid netherworld neurobiology neurobiological neurobiologist newton newtons niacin nicotine nicotinic nix nixes nixed nixing noisette noisettes nonce nosegay nosegays nougat nuclide nuclidic numerate numeracy numerology numerological numerologist numinous numinousness nyssa oast oblation ocelot ocelots oculist oculists offchance olivine olivin olivinitic omnivore omnivorous onside ontogeny ontogenetic ontogenesis oolite oolitic openwork openworked operculum operculums opercula optoelectronic optoelectronics optometrist optometrists optometry oracy oriole orioles osier osiers ostensive ostensively otherworld otherworldly otitis outage outages outsource outsources outsourceed outsourcing ouzo ovipositor ovipositors paleography paleographer palaeography palaeographer palindrome palindromic palindromist palindromists palliasse palliasses pallium palmtop palmtops palpitate palpitates palpitated palpitating palpitation palpitations pangolin pangolins panopticon panopticons paralinguistic paralinguistics paralinguistically paralympic paralympics paralympian paranormal paranormally paranormality paraquat parboil parboils parboiled parboiling pardoner pardoners parenteral parenterally parricide parricidal parthian paschal passerine passiflora pastis patella patellas patellae patellar paternoster paternoster pathophysiology pathophysiological paviour pavior pedalo pedalos pederast pederastic pederasty peduncle peduncles peduncle peduncular peepshow peepshows penology penological penologist penologists pentagram pentagrams pentameter pentateuch pentathlon peon peons peones persimmon persimmons petrography petrographic petrographic petrographically petrographer phalarope phalaropes phantasmagoria phantasmagoric phenomenology phenomenologies phenomenologist philadelphus philtre philtres phlogiston phlox phloxes phosphorous phosphorus phosphoric photocell photocells physiography physiographic physiographical physiographer piagetian pianissimo picador picadors pieta pietas piffle piffles piffled piffling pigeonhole pigeonholes pigeonholed pigeonholing pikestaff pilsner pilsener pilsners pilseners pimento pimentos pimpernel pimpernels pinkie pinkies pintail pintails pinto pintos pintoes pipistrelle pipistrelles pipsqueak pipsqueaks plasm platonist platonism pleura pleurae pleuras pleural pneumoconiosis pneumoconioses pochard pochards pollack pollack pollard pollarded polonaise polyandry polyandrous polyanthus polyclonal polygyny polygynous polymorphous polymorphously polymorphic polysemous polysemic polysemy pomade pomades pomeranian pomeranians pooper poopers poppadom poppadoms poppycock porker porkers porphyry porphyries portage portages portaged portaging posset postulant postulants potboiler potboilers pratfall pratfalls preponderant preponderantly pretzel pretzels prickle prickles prickled prickling primp primps primped primping progestogen progestogenic prokaryote prokaryotic procaryotic prolactin proline prolix prolixly prolixity proof proofs proofing proofed propylene protease proteinase protoplasm protoplasmic prunus psephology psephological psephologist psychoanalyse psychoanalyses psychoanalysing psychoanalysed psychoanalyse psychoanalyses psychoanalysing psychoanalysis psychoanalyze psychoanalyzes psychoanalyzing psychoanalyzed psychoanalist psychodrama psychodramatic psychodramas pube pubes puck puck puerperal puerperally pupate pupates pupated pupating pupation purine purl purls purled purling putto putti pyracantha pyrexia pyrimidine pyromaniac pyromaniacal pyromania pyroxene pyroxenic pyroxenoid quadraphonic quadraphonics quarterdeck quarterdecks quattrocento rabelaisian raddle raddles raddled raddling radiograph radiographic radiographically radioisotope radioisotopic radioisotopically raillery railleries ramekin rangy rangier rangiest ranginess raster rasters ratbag ratbags ratiocination ratiocinative rawhide rebarbative rebarbatively recto rectos remaster remasters remastered remastering rennet retinoblastoma retinoblastomas retinoblastomata retrogression retroviral retrovirus retroviral retsina revetment revetments rhea rheology rheological rheologically rheologist rhinitis rhombus rhyolite ribonucleic ribosome ribosomes ribosomal riffle riffles riffled riffling rive rives rived riven roadster roadsters rogation rondo rondos rotarian roulade roulades roust rousts rousted rousting rubicund rubicundity rumba rumbas rhumba rhumbas rummy runaround runtime ruritanian ruritania sacerdotal sacerdotally sacrum sacra safflower sagittarian sagittarius salicylate salix salvia samizdat sampan sandbag sandbags sandbagged sandbagging sandbagger sarsaparilla sassenach sassenachs sate sates sated sating satinwood schmuck schmucks scilla scrapie screwball screwballs scullion scullions scumbag scumbags scurf scurfy sealion sedum seersucker segue segues segued segueing seine seines seined seining seiner seisin seismography seismographic seismographer seismology seismological seismologist selvedge selvedge semiquaver semiquavers senescence senescent sensorimotor sephardic sephardim septum septa seraglio seraglios seropositive sexology sexologist shebang shebeen sheepfold sheepfolds shiatsu shiner shiners shortsighted shortsightedly shortsightedness showjumping showjumper sicko sickos sidereal sideswipe sideswipes sideswiped sideswiping silverfish simmental simmentals simplex siskin siskins skirl skirls skirled skirling slapdash slather slathers slathered slathering sluggard sluggards smalltalk smidgeon smidgeons smidge smidges smorgasbord smorgasbords snick snicks snicked snicking snitch snitches snitched snitching sociopath sociopathic somnambulist somnambulism somnambulistic somnambulistically sooth sou sous sough soughs soughed soughing soundbite soundbites souse souses soused sousing southpaw southpaws spay spays spayed spaying spectrophotometry spectrophotometric spectrophotometrical spectrophotometrically spermatozoon spermatozoa spermatozoal sphygmomanometer sphygmomanometers sphygmomanometry spindrift splenetic splenetically splosh sploshes sploshed sploshing sprog sprogs spurge spurges squaw squaws standoff standoffs standoffish standpipe standpipes staphylococcus staphylococci 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TEC-/- BTK-/- double mutant T cells exhibit severely impaired T cell activitity. RLK-/-ITK-/- double mutant celles exhibit severely imparired Th2 responses. Grb2(+/-) mice disrupt T cell signaling networks and development. Dendric cells and macrophages of MEK3 deficient mice have impaired IL12 production. Bam32(-/-) B cell develop normally but have impaired T-independent antibody responses in vivo. T-cell and B-cell of RAP1A deficient mice impair integrin-mediated cell adhesion. T-cell of WASP deficient mice impair the proliferaction and antigen receptor cap formation in response to anti-CD3zeta stimulation. T-cell of SHB defective mice impair the phosphorylation of LAT and consequently the activation of MAP kinase pathways. B-cell of 3BP2 (-/-) deficient mice have defective in proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to BCR ligation. B-cell of Vav2(-/-) deficient mice are defective in the ability to switch immunoglobulin class. T-cell of Vav1(-/-) deficient mice exhibit impaired antigen receptor signaling. Vav1(-/-)Vav2(-/-) mice exhibit greatly reduced the mature B-cells. Vav-1-/-Vav-2-/- B cells were unresponsive to BCR-driven proliferation in vitro and to thymus-indepen-dent antigen in vivo. Fyn-deficient mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. T cell from mice deficient in LCK is required for normal signal transduction through the TCR. T cells from mice deficient in SLAP-130/Fyb show markedly impaired proliferation. B cell of chicken deficient ITK reduce IP3 generation and phospholipase C gamma 2 tyrosine phosphorylation. T cell of mice deficient ITK reduce IP3 generation and phospholipase C gamma 1 tyrosine phosphorylation. T cell of mice deficient ITK have failure of Th2 development. Mice deficient in ITK have reduced proliferative responses to MHC stimulation and to anti-TCR cross-linking Mutations in Btk cause X-linked immunodeficiency. Gads(GRAP2) has a role in thymocyte proliferaction for maturation of T-cells. Gads(GRAP2) has a role for homeostatic proliferaction in B cells. Grap negatively regulates T-cell proliferation. Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transuduction. B cell signaling causes tyrosine phosphorylation of Gab1, and in turn SHP2 bind to Gab1 Gab1 phosophorylation potentiate the phosphorylation of Akt, PI3K-dependent response. RasGRP1 mediates Ras activation following TCR stimulatioin. RasGRP1 and RasGRP3 induces RAS activation in B-cell to response to T-cell stimulation. Grb2-hSos1-PLCgamma1-p36/p38-ZAP70 complexes localize in the vicinity of TCR-zeta Gads(Grap2) plays an important role in T-cell signaling via its association with SLP-76 and LAT. Lck is required for normal signal transduction through the TCR. ZAP-70 plays crucial roles in T-cell activation and development. Syk triggers cellular activation in T-cell. TEC-/- BTK-/- double mutant T cells exhibit severely impaired T cell activitity. 1 J Exp Med. 2000 Dec 4;192(11) 1611-24. Severe B cell deficiency in mice lacking the tec kinase family members Tec and Btk. Ellmeier W, Jung S, Sunshine MJ, Hatam F, Xu Y, Baltimore D, Mano H, Littman DR. Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine. wilfried.ellmeier@univie.ac.at The cytoplasmic protein tyrosine kinase Tec has been proposed to have important functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypic alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double-deficient mice were generated. These mice exhibited a block at the B220(+)CD43(+) stage of B cell development and displayed a severe reduction of peripheral B cell numbers, particularly immunoglobulin (Ig)M(lo)IgD(hi) B cells. Although Tec/Btk(null) mice were able to form germinal centers, the response to T cell-dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compensate for Btk may also explain phenotypic differences in X-linked immunodeficiency (xid) mice compared with human X-linked agammaglobulinemia (XLA) patients. Publication Types Research Support, Non-U.S. Gov't PMID 11104803 [PubMed - indexed for MEDLINE] RLK-/-ITK-/- double mutant celles exhibit severely imparired Th2 responses. 1 Nat Immunol. 2001 Dec;2(12) 1183-8. Mutation of Tec family kinases alters T helper cell differentiation. Schaeffer EM, Yap GS, Lewis CM, Czar MJ, McVicar DW, Cheever AW, Sher A, Schwartzberg PL. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. The Tec kinases Rlk and Itk are critical for full T cell receptor (TCR)-induced activation of phospholipase C-gamma and mitogen-activated protein kinase. We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type 1 (TH1) and TH2 cytokines. Consistent with these biochemical defects, Itk-/- mice did not generate effective TH2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired Rlk-/-Itk-/- mice were able to mount a TH2 response and produced TH2 cytokines in response to this challenge. In addition, Rlk-/-Itk-/- cells showed impaired TCR-induced repression of the TH2-inducing transcription factor GATA-3, suggesting a potential mechanism for TH2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4+ TH cell differentiation. Publication Types Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. PMID 11702066 [PubMed - indexed for MEDLINE] Grb2(+/-) mice disrupt T cell signaling networks and development. 1 Nat Immunol. 2001 Jan;2(1) 29-36. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T, Chan AC. Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA. The developmental processes of positive and negative selection in the thymus shape the T cell antigen receptor (TCR) repertoire and require the integration of multiple signaling networks. These networks involve the efficient assembly of macromolecular complexes and are mediated by multimodular adaptor proteins that permit the functional integration of distinct signaling molecules. We show here that decreased expression of the adaptor protein Grb2 in Grb2+/- mice weakens TCR-induced c-Jun N-terminal kinase (JNK) and p38, but not extracellular signal-regulated kinase (ERK), activation. In turn, this selective effect decreases the ability of thymocytes to undergo negative, but not positive, selection. We also show that there are differences in the signaling thresholds of the three mitogen-activated protein kinase (MAPK) families. These differences may provide a mechanism by which quantitative differences in signal strength can alter the balance of downstream signaling pathways to induce the qualitatively distinct biological outcomes of proliferation, differentiation or apoptosis. PMID 11135575 [PubMed - indexed for MEDLINE] Dendric cells and macrophages of MEK3 deficient mice have impaired IL12 production. 1 EMBO J. 1999 Apr 1;18(7) 1845-57. Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. Lu HT, Yang DD, Wysk M, Gatti E, Mellman I, Davis RJ, Flavell RA. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. The p38 mitogen-activated protein kinase (MAPK) pathway, like the c-Jun N-terminal kinase (JNK) MAPK pathway, is activated in response to cellular stress and inflammation and is involved in many fundamental biological processes. To study the role of the p38 MAPK pathway in vivo, we have used homologous recombination in mice to inactivate the Mkk3 gene, one of the two specific MAPK kinases (MAPKKs) that activate p38 MAPK. Mkk3(-/-) mice were viable and fertile; however, they were defective in interleukin-12 (IL-12) production by macrophages and dendritic cells. Interferon-gamma production following immunization with protein antigens and in vitro differentiation of naive T cells is greatly reduced, suggesting an impaired type I cytokine immune response. The effect of the p38 MAPK pathway on IL-12 expression is at least partly transcriptional, since inhibition of this pathway blocks IL-12 p40 promoter activity in macrophage cell lines and IL-12 p40 mRNA is reduced in MKK3-deficient mice. We conclude that the p38 MAP kinase, activated through MKK3, is required for the production of inflammatory cytokines by both antigen-presenting cells and CD4(+) T cells. PMID 10202148 [PubMed - indexed for MEDLINE] Bam32(-/-) B cell develop normally but have impaired T-independent antibody responses in vivo. 1 Immunity. 2003 Oct;19(4) 621-32. Bam32 links the B cell receptor to ERK and JNK and mediates B cell proliferation but not survival. Han A, Saijo K, Mecklenbrauker I, Tarakhovsky A, Nussenzweig MC. Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA. Bam32 is an adaptor protein recruited to the plasma membrane upon B cell receptor (BCR) crosslinking in a phosphoinositol 3-kinase (PI3K)-dependent manner; however, its physiologic function is unclear. To determine its physiologic function, we produced Bam32-deficient mice. Bam32(-/-) B cells develop normally but have impaired T-independent antibody responses in vivo and diminished responses to BCR crosslinking in vitro. Biochemical analysis revealed that Bam32 acts in a novel pathway leading from the BCR to MAPK/ERK Kinases (MEK1/2), MAPK/ERK Kinase Kinase-1 (MEKK1), extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (p38). This pathway appears to be initiated by hematopoietic progenitor kinase-1 (HPK1), which interacts directly with Bam32, and differs from all previously characterized BCR signaling pathways in that it is required for normal BCR-mediated proliferation but not for B cell survival. PMID 14563325 [PubMed - indexed for MEDLINE] T-cell and B-cell of RAP1A deficient mice impair integrin-mediated cell adhesion. 1 Mol Cell Biol. 2006 Jan;26(2) 643-53. Rap1A-deficient T and B cells show impaired integrin-mediated cell adhesion. Duchniewicz M, Zemojtel T, Kolanczyk M, Grossmann S, Scheele JS, Zwartkruis FJ. Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, D-14195 Berlin, Germany. Studies in tissue culture cells have demonstrated a role for the Ras-like GTPase Rap1 in the regulation of integrin-mediated cell-matrix and cadherin-mediated cell-cell contacts. To analyze the function of Rap1 in vivo, we have disrupted the Rap1A gene by homologous recombination. Mice homozygous for the deletion allele are viable and fertile. However, primary hematopoietic cells isolated from spleen or thymus have a diminished adhesive capacity on ICAM and fibronectin substrates. In addition, polarization of T cells from Rap1-/- cells after CD3 stimulation was impaired compared to that of wild-type cells. Despite this, these defects did not result in hematopoietic or cell homing abnormalities. Although it is possible that the relatively mild phenotype is a consequence of functional complementation by the Rap1B gene, our genetic studies confirm a role for Rap1A in the regulation of integrins. PMID 16382154 [PubMed - indexed for MEDLINE] T-cell of WASP deficient mice impair the proliferaction and antigen receptor cap formation in response to anti-CD3zeta stimulation. 1 Immunity. 1998 Jul;9(1) 81-91. Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation. Snapper SB, Rosen FS, Mizoguchi E, Cohen P, Khan W, Liu CH, Hagemann TL, Kwan SP, Ferrini R, Davidson L, Bhan AK, Alt FW. Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA. The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-independent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3epsilon stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-Ig stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans. PMID 9697838 [PubMed - indexed for MEDLINE] T-cell of SHB defective mice impair the phosphorylation of LAT and consequently the activation of MAP kinase pathways. 9 Sep 24;274(39) 28050-7. Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells. Lindholm CK, Gylfe E, Zhang W, Samelson LE, Welsh M. Department of Medical Cell Biology, Box 571, Biomedicum, Uppsala University, S-75123 Uppsala, Sweden. Stimulation of the T cell antigen receptor (TCR) induces tyrosine phosphorylation of numerous intracellular proteins. We have recently investigated the role of the adaptor protein Shb in the early events of T cell signaling and observed that Shb associates with Grb2, linker for activation of T cells (LAT) and the TCR zeta-chain in Jurkat cells. We now report that Shb also associates with phospholipase C-gamma1 (PLC-gamma1) in these cells. Overexpression of Src homology 2 domain defective Shb caused diminished phosphorylation of LAT and consequently the activation of mitogen-activated protein kinases was decreased upon TCR stimulation. In addition, the Shb mutant also blocked phosphorylation of PLC-gamma1 and the increase in cytoplasmic Ca(2+) following TCR stimulation. Nuclear factor for activation of T cells is a major target for Ras and calcium signaling pathways in T cells following TCR stimulation, and the overexpression of the mutant Shb prevented TCR-dependent activation of the nuclear factor for activation of T cells. Consequently, endogenous interleukin-2 production was decreased under these conditions. The results indicate a role for Shb as a link between the TCR and downstream signaling events involving LAT and PLC-gamma1 and resulting in the activation of transcription of the interleukin-2 gene. PMID 10488157 [PubMed - indexed for MEDLINE] B-cell of 3BP2 (-/-) deficient mice have defective in proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to BCR ligation. 1 Mol Cell Biol. 2006 Jul;26(14) 5214-25. 3BP2 deficiency impairs the response of B cells, but not T cells, to antigen receptor ligation. de la Fuente MA, Kumar L, Lu B, Geha RS. Division of Immunology, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA. The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-gamma (PLC-gamma); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development, proliferation, cytokine secretion, and signaling in response to T-cell receptor (TCR) ligation were all normal in 3BP2(-/-) mice. 3BP2(-/-) mice had increased accumulation of pre-B cells in the bone marrow and a block in the progression of transitional B cells in the spleen from the T1 to the T2 stage, but normal numbers of mature B cells. B-cell proliferation, cell cycle progression, PLC-gamma2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to B-cell receptor (BCR) ligation were all impaired. These results suggest that 3BP2 is important for BCR, but not for TCR signaling. PMID 16809760 [PubMed - indexed for MEDLINE] B-cell of Vav2(-/-) deficient mice are defective in the ability to switch immunoglobulin class. 1 Nat Immunol. 2001 Jun;2(6) 542-7. Comment in Nat Immunol. 2001 Jun;2(6) 482-4. Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation. Doody GM, Bell SE, Vigorito E, Clayton E, McAdam S, Tooze R, Fernandez C, Lee IJ, Turner M. Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, UK. B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation. PMID 11376342 [PubMed - indexed for MEDLINE] T-cell of Vav1(-/-) deficient mice exhibit impaired antigen receptor signaling. 1 Nature. 1995 Mar 30;374(6521) 474-7. Defective T-cell receptor signalling and positive selection of Vav-deficient CD4+ CD8+ thymocytes. Fischer KD, Zmuldzinas A, Gardner S, Barbacid M, Bernstein A, Guidos C. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. During lymphocyte development, cellular proliferation and positive and negative selection events ensure the production of T and B lymphocytes bearing highly diverse, but self-tolerant, repertoires of antigen receptors. These processes are initiated when engagement of growth-factor receptors, or the T and B lymphocyte antigen receptors, induces tyrosine phosphorylation of specific SH2- and SH3-domain-containing cytoplasmic proteins, including Vav. Here we show that vav-/- embryonic stem cells generate only limited numbers of immature and mature T and B lymphocytes in the RAG-2 blastocyst complementation assay. Furthermore, Vav-deficient T lymphocytes showed severely impaired antigen receptor signalling. Finally, we demonstrate that Vav-dependent signalling pathways regulate maturation, but not CD4/CD8 lineage commitment, during T-cell-receptor-mediated positive selection of immature CD4+ CD8+ precursors into mature CD4+ CD8- or CD4- CD8+ T cells. PMID 7700360 [PubMed - indexed for MEDLINE] Vav1(-/-)Vav2(-/-) mice exhibit greatly reduced the mature B-cells. Vav-1-/-Vav-2-/- B cells were unresponsive to BCR-driven proliferation in vitro and to thymus-indepen-dent antigen in vivo. 1 Nat Immunol. 2001 Jun;2(6) 548-55. Comment in Nat Immunol. 2001 Jun;2(6) 482-4. Compensation between Vav-1 and Vav-2 in B cell development and antigen receptor signaling. Tedford K, Nitschke L, Girkontaite I, Charlesworth A, Chan G, Sakk V, Barbacid M, Fischer KD. Abteilung Physiologische Chemie, Universitat Ulm, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. Vav-1 and Vav-2 are closely related Dbl-homology GTP exchange factors (GEFs) for Rho GTPases. Mutation of Vav-1 disrupts T cell development and T cell antigen receptor-induced activation, but has comparatively little effect on B cells. We found that combined deletion of both Vav-1 and Vav-2 in mice resulted in a marked reduction in mature B lymphocyte numbers. Vav-1(-/-)Vav-2(-/-) B cells were unresponsive to B cell antigen receptor (BCR)-driven proliferation in vitro and to thymus-independent antigen in vivo. BCR-stimulated intracellular calcium mobilization was greatly impaired in Vav-1(-/-)Vav-2(-/-) B cells. These findings establish a role for Vav-2 in BCR calcium signaling and reveal that the Vav family of GEFs is critical to B cell development and function. PMID 11376343 [PubMed - indexed for MEDLINE] Fyn-deficient mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen. 1 Cell. 1992 Sep 4;70(5) 751-63. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Appleby MW, Gross JA, Cooke MP, Levin SD, Qian X, Perlmutter RM. Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195. Considerable evidence supports the hypothesis that the nonreceptor protein tyrosine kinase p59fyn participates in signal transduction from the T cell receptor (TCR). To examine this hypothesis in detail, we have produced mice that lack the thymic isoform of p59fyn but retain expression of the brain isoform of the protein. fynTnull mice exhibit a remarkably specific lymphoid defect thymocytes are refractile to stimulation through the TCR with mitogen or antigen, while peripheral T cells, following what appears to be a normal maturation sequence, reacquire significant signaling capabilities. These data confirm that p59fynT plays a pivotal role in TCR signal transduction and demonstrate that additional developmentally regulated signaling components also contribute to TCR-induced lymphocyte activation. PMID 1516132 [PubMed - indexed for MEDLINE] Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. 1 Nature. 1992 May 14;357(6374) 161-4. Comment in Nature. 1993 Jan 21;361(6409) 213. Profound block in thymocyte development in mice lacking p56lck. Molina TJ, Kishihara K, Siderovski DP, van Ewijk W, Narendran A, Timms E, Wakeham A, Paige CJ, Hartmann KU, Veillette A, et al. Ontario Cancer Institute, University of Toronto, Canada. The protein Lck (p56lck) has a relative molecular mass of 56,000 and belongs to the Src family of tyrosine kinases. It is expressed exclusively in lymphoid cells, predominantly in thymocytes and peripheral T cells. Lck associates specifically with the cytoplasmic domains of both CD4 and CD8 T-cell surface glycoproteins and interacts with the beta-chain of the interleukin-2 receptor, which implicates Lck activity in signal transduction during thymocyte ontogeny and activation of mature T cells. Here we generate an lck null mutation by homologous recombination in embryonic stem cells to evaluate the role of p56lck in T-cell development and activation. Lck-deficient mice show a pronounced thymic atrophy, with a dramatic reduction in the double-positive (CD4+CD8+) thymocyte population. Mature, single-positive thymocytes are not detectable in these mice and there are only very few peripheral T cells. These results illustrate the crucial role of this T-cell-specific tyrosine kinase in the thymocyte development. PMID 1579166 [PubMed - indexed for MEDLINE] T cell from mice deficient in LCK is required for normal signal transduction through the TCR. 1 Cell. 1992 Aug 21;70(4) 585-93. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Straus DB, Weiss A. Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143. Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR. PMID 1505025 [PubMed - indexed for MEDLINE] T cells from mice deficient in SLAP-130/Fyb show markedly impaired proliferation. 1 Science. 2001 Sep 21;293(5538) 2263-5. Coupling of the TCR to integrin activation by Slap-130/Fyb. Peterson EJ, Woods ML, Dmowski SA, Derimanov G, Jordan MS, Wu JN, Myung PS, Liu QH, Pribila JT, Freedman BD, Shimizu Y, Koretzky GA. The Abramson Family Cancer Research Institute, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. SLAP-130/Fyb (SLP-76-associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb-deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals. PMID 11567141 [PubMed - indexed for MEDLINE] B cell of chicken deficient ITK reduce IP3 generation and phospholipase C gamma 2 tyrosine phosphorylation. 1 J Exp Med. 1996 Jul 1;184(1) 31-40. A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2. Takata M, Kurosaki T. Department of Oncology and Immunology, Wyeth-Ayerst Research, Pearl River, New York 10965, USA. Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. Recent studies have shown that Btk is tyrosine phosphorylated and activated upon B cell antigen receptor (BCR) stimulation. To elucidate the functions of this kinase, we examined BCR signaling of DT40 B cells deficient in Btk. Tyrosine phosphorylation of phospholipase C (PLC)-gamma 2 upon receptor stimulation was significantly reduced in the mutant cells, leading to the loss of both BCR-coupled phosphatidylinositol hydrolysis and calcium mobilization. Pleckstrin homology and Src-homology 2 domains of Btk were required for PLC-gamma 2 activation. Since Syk is also required for the BCR-induced PLC-gamma 2 activation, our findings indicate that PLC-gamma 2 activation is regulated by Btk and Syk through their concerted actions. PMID 8691147 [PubMed - indexed for MEDLINE] T cell of mice deficient ITK reduce IP3 generation and phospholipase C gamma 1 tyrosine phosphorylation. 1 J Exp Med. 1998 May 18;187(10) 1721-7. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells. Liu KQ, Bunnell SC, Gurniak CB, Berg LJ. Program of Immunology, Division of Medical Sciences, Harvard University, Boston, Massachusetts 02115, USA. Itk, a Tec family tyrosine kinase, plays an important but as yet undefined role in T cell receptor (TCR) signaling. Here we show that T cells from Itk-deficient mice have a TCR-proximal signaling defect, resulting in defective interleukin 2 secretion. Upon TCR stimulation, Itk-/- T cells release normal amounts of calcium from intracellular stores, but fail to open plasma membrane calcium channels. Since thapsigargin-induced store depletion triggers normal calcium entry in Itk-/- T cells, an impaired biochemical link between store depletion and channel opening is unlikely to be responsible for this defect. Biochemical studies indicate that TCR-induced inositol 1,4,5 tris-phosphate (IP3) generation and phospholipase C gamma1 tyrosine phosphorylation are substantially reduced in Itk-/- T cells. In contrast, TCR-zeta and ZAP-70 are phosphorylated normally, suggesting that Itk functions downstream of, or in parallel to, ZAP-70 to facilitate TCR-induced IP3 production. These findings support a model in which quantitative differences in cytosolic IP3 trigger distinct responses, and in which only high concentrations of IP3 trigger the influx of extracellular calcium. PMID 9584150 [PubMed - indexed for MEDLINE] T cell of mice deficient ITK have failure of Th2 development. 1 Immunity. 1999 Oct;11(4) 399-409. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells. Fowell DJ, Shinkai K, Liao XC, Beebe AM, Coffman RL, Littman DR, Locksley RM. Department of Medicine, University of California San Francisco 94143, USA. Naive Itk-deficient CD4+ T cells were unable to establish stable IL-4 production, even when primed in Th2-inducing conditions. In contrast, IFNgamma production was little affected. Failure to express IL-4 occurred even among cells that had gone through multiple cell divisions and was associated with a delay in the kinetics and magnitude of NFATc nuclear localization. IL-4 production was restored genetically by retroviral reconstitution of Itk or biochemically by augmenting the calcium flux with ionomycin. In vivo, Itk-deficient mice were unable to establish functional Th2 cells. Development of protective Th1 cells was unimpeded. These data define a nonredundant role for Itk in modulating signals from the TCR/CD28 pathways that are specific for the establishment of stable IL-4 but not IFNgamma expression. PMID 10549622 [PubMed - indexed for MEDLINE] Mice deficient in ITK have reduced proliferative responses to MHC stimulation and to anti-TCR cross-linking 1 Immunity. 1995 Dec;3(6) 757-69. Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk. Liao XC, Littman DR. Department of Microbiology and Immunology, University of California, San Francisco 94143-0414, USA. Itk is a T cell protein tyrosine kinase (PTK) that, along with Btk and Tec, belongs to a family of cytoplasmic PTKs with N-terminal pleckstrin homology domains. Btk plays a critical role in B lymphocyte development. To determine whether Itk has an analogous role in T lymphocytes, we used gene targeting to prepare mice lacking expression of Itk. Such animals had decreased numbers of mature thymocytes, an effect most clearly observed in mice expressing T cell receptor (TCR) transgenes. Mature T cells from Itk-deficient mice had reduced proliferative responses to allogeneic MHC stimulation and to anti-TCR cross-linking, but responded normally to stimulation with phorbol ester plus ionomycin or with IL-2. These results provide genetic evidence that Itk is involved in T cell development and also suggest that Itk has an important role in proximal events in TCR-mediated signaling pathways. PMID 8777721 [PubMed - indexed for MEDLINE] Mutations in Btk cause X-linked immunodeficiency. 1 Semin Immunol. 1998 Aug;10(4) 309-16. Btk function in B cell development and response. Satterthwaite AB, Li Z, Witte ON. Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095-1662, USA. Mutations in Bruton's tyrosine kinase (Btk) result in the B cell immunodeficiencies XLA in humans and Xid in mice. Both the maintenance of peripheral B cell numbers and their response to B cell antigen receptor (BCR) crosslinking depend on Btk. Btk integrates signals from multiple cell surface receptors, including BCR and G-protein coupled receptors. These Btk dependent signals control B cell proliferation and survival by mediating Ca2+ flux, activating JNK and p38 and inducing cell cycle regulatory genes. Publication Types Review PMID 9695187 [PubMed - indexed for MEDLINE] Gads(GRAP2) has a role in thymocyte proliferaction for maturation of T-cells. 1 Science. 2001 Mar 9;291(5510) 1987-91. Requirement for the SLP-76 adaptor GADS in T cell development. Yoder J, Pham C, Iizuka YM, Kanagawa O, Liu SK, McGlade J, Cheng AM. Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA. GADS is an adaptor protein implicated in CD3 signaling because of its ability to link SLP-76 to LAT. A GADS-deficient mouse was generated by gene targeting, and the function of GADS in T cell development and activation was examined. GADS- CD4-CD8- thymocytes exhibited a severe block in proliferation but still differentiated into mature T cells. GADS- thymocytes failed to respond to CD3 cross-linking in vivo and were impaired in positive and negative selection. Immunoprecipitation experiments revealed that the association between SLP-76 and LAT was uncoupled in GADS- thymocytes. These observations indicate that GADS is a critical adaptor for CD3 signaling. PMID 11239162 [PubMed - indexed for MEDLINE] Gads(GRAP2) has a role for homeostatic proliferaction in B cells. 1 Eur J Immunol. 2005 Apr;35(4) 1184-92. Expression and function of the adaptor protein Gads in murine B cells. Yankee TM, Draves KE, Clark EA. Department of Immunology, University of Washington, Seattle, USA. tyankee@kumc.edu Nearly all hematopoietic receptors are dependent on adaptor proteins for the activation of downstream signaling pathways. The Gads adaptor protein is expressed in many hematopoietic tissues, including bone marrow, lymph node, and spleen. Using intracellular staining, we detected Gads protein in a number cells, including B cells, T cells, NK cells, monocytes, and plasmacytoid DC, but not in macrophages, neutrophils, or monocyte-derived DC. In the B cell compartment, Gads was first expressed after immature B cells leave the bone marrow and was down-regulated after B cell antigen receptor (BCR) ligation. Female Gads(-/-) mice had increased numbers of splenic B cells, as compared to female Gads(+/+) mice, suggesting a role for Gads in B cell homeostasis. Although B cell production and turnover of splenic B cell subsets appeared normal in Gads(-/-) mice, homeostatic proliferation was significantly impaired in Gads(-/-) B cells. Whereas BCR ligation can induce apoptosis in wild-type transitional stage 1 (T1) B cells, Gads(-/-) T1 B cells were resistant to BCR-induced apoptosis. Gads(-/-) B cells also showed increased BCR-mediated calcium mobilization. We conclude that Gads may have a negative regulatory role in signaling through survival pathways, and is necessary for normal homeostatic proliferation in B cells. PMID 15761845 [PubMed - indexed for MEDLINE] Grap negatively regulates T-cell proliferation. 1 Mol Cell Biol. 2002 May;22(10) 3230-6. Grap negatively regulates T-cell receptor-elicited lymphocyte proliferation and interleukin-2 induction. Shen R, Ouyang YB, Qu CK, Alonso A, Sperzel L, Mustelin T, Kaplan MH, Feng GS. Program in Signal Transduction Research, The Burnham Institute, La Jolla, California 92037, USA. Grb-2-related adaptor protein (Grap) is a Grb2-like SH3-SH2-SH3 adaptor protein with expression restricted to lymphoid tissues. Grap(-/-) lymphocytes isolated from targeted Grap-deficient mice exhibited enhanced proliferation, interleukin-2 production, and c-fos induction in response to mitogenic T-cell receptor (TCR) stimulation, compared to wild-type cells. Ectopic expression of Grap led to a suppression of Elk-1-directed transcription induced by the Ras/Erk pathway, without having effects on gene expression mediated by Jnk and p38 mitogen-activated protein kinases. Together, these data suggest that Grap, unlike Grb2, acts as a negative regulator of TCR-stimulated intracellular signaling by downregulating signal relay through the Ras/Erk pathway. PMID 11971956 [PubMed - indexed for MEDLINE] Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transuduction. 1 J Biol Chem. 2001 Nov 30;276(48) 45175-83. Epub 2001 Sep 25. Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules. Yamasaki S, Nishida K, Hibi M, Sakuma M, Shiina R, Takeuchi A, Ohnishi H, Hirano T, Saito T. Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. To maintain various T cell responses and immune equilibrium, activation signals triggered by T cell antigen receptor (TCR) must be regulated by inhibitory signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has been shown to be involved in the downstream signaling from cytokine receptors. We investigated the functional role of Gab2 in TCR-mediated signal transduction. Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2 mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding capacity also impaired the inhibitory activity, and the pleckstrin homology domain-deletion mutant revealed a crucial function of the pleckstrin homology domain for localization to the plasma membrane. These results suggest that Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transduction by mediating the recruitment of inhibitory molecules to the TCR signaling complex. PMID 11572860 [PubMed - indexed for MEDLINE] B cell signaling causes tyrosine phosphorylation of Gab1, and in turn SHP2 bind to Gab1 Gab1 phosophorylation potentiate the phosphorylation of Akt, PI3K-dependent response. 1 J Biol Chem. 2001 Apr 13;276(15) 12257-65. Epub 2001 Jan 22. The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase. Ingham RJ, Santos L, Dang-Lawson M, Holgado-Madruga M, Dudek P, Maroun CR, Wong AJ, Matsuuchi L, Gold MR. Departments of Microbiology and Immunology and Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. B cell antigen receptor (BCR) signaling causes tyrosine phosphorylation of the Gab1 docking protein. This allows phosphatidylinositol 3-kinase (PI3K) and the SHP2 tyrosine phosphatase to bind to Gab1. In this report, we tested the hypothesis that Gab1 acts as an amplifier of PI3K- and SHP2-dependent signaling in B lymphocytes. By overexpressing Gab1 in the WEHI-231 B cell line, we found that Gab1 can potentiate BCR-induced phosphorylation of Akt, a PI3K-dependent response. Gab1 expression also increased BCR-induced tyrosine phosphorylation of SHP2 as well as the binding of Grb2 to SHP2. We show that the pleckstrin homology (PH) domain of Gab1 is required for BCR-induced phosphorylation of Gab1 and for Gab1 participation in BCR signaling. Moreover, using confocal microscopy, we show that BCR ligation can induce the translocation of Gab1 from the cytosol to the plasma membrane and that this requires the Gab1 PH domain as well as PI3K activity. These findings are consistent with a model in which the binding of the Gab1 PH domain to PI3K-derived lipids brings Gab1 to the plasma membrane, where it can be tyrosine-phosphorylated and then act as an amplifier of BCR signaling. PMID 11278704 [PubMed - indexed for MEDLINE] RasGRP1 mediates Ras activation following TCR stimulatioin. RasGRP1 and RasGRP3 induces RAS activation in B-cell to response to T-cell stimulation. 1 Immunol Lett. 2006 May 15;105(1) 77-82. Epub 2006 Feb 20. The role of RasGRPs in regulation of lymphocyte proliferation. Coughlin JJ, Stang SL, Dower NA, Stone JC. Department of Biochemistry, University of Alberta, Edmonton, Alta., Canada T6G 2H7. RasGRP1 links TCR signaling to Ras in T cells, while both RasGRP1 and RasGRP3 link BCR signaling to Ras in B cells. T cells deficient in RasGRP1 have defective proliferative responses as do B cells deficient in both RasGRP1 and RasGRP3, confirming the importance of Ras activation in lymphocyte proliferation. While aged Rasgrp1-/- mice develop late-onset autoimmunity characterized by splenomegaly and the presence of anti-nuclear antibodies (ANA), the additional loss of RasGRP3 expression inhibits this phenotype. We show here that the autoimmunity in Rasgrp1-/- mice is T cell dependent. Compared to wildtype, Rasgrp1-/- T cells induce greater in vitro B cell proliferation that is due, at least in part, to increased production of interleukin-4 (IL-4). Rasgrp1 Rasgrp3 double mutant B cells are less responsive to this T cell stimulation. The reduced double mutant B cell proliferative response was paralleled by decreased induction of cyclin D2 upon stimulation with IL-4 and anti-IgM. Taken together these results suggest that double mutant mice fail to generate autoimmunity due to their decreased B cell cyclin D2 accumulation, and thus proliferation, in response to the elevated levels of IL-4 produced by mutant T cells. PMID 16530850 [PubMed - indexed for MEDLINE] Grb2-hSos1-PLCgamma1-p36/p38-ZAP70 complexes localize in the vicinity of TCR-zeta 1 J Biol Chem. 1995 Aug 4;270(31) 18428-36. Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR. Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB. Department of Medicine, UCLA School of Medicine 90024, USA. Signaling by the T-cell antigen receptor (TCR) involves both phospholipase C (PLC)-gamma 1 and p21ras activation. While failing to induce Shc/Grb2 association, ligation of the TCR/CD3 receptor in Jurkat T-cells induced hSos1-Grb2 complexes. In addition to hSos1, Grb2 participates in the formation of a tyrosine phosphoprotein complex that includes 145-, 95-, 70-, 54-, and 36-38-kDa proteins. p145 was identified as PLC-gamma 1 and p70 as the protein tyrosine kinase, ZAP-70. Although of the same molecular weight, p95 was not recognized by an anti-serum to p95 Vav. The SH2 domains of Grb2 and PLC-gamma 1 were required for the formation of this protein complex. In anti-CD3-treated cells, Grb2 redistributed from the cytosol to a particulate cell compartment along with p36/p38, ZAP-70, and PLC-gamma 1. Part of the Grb2 complex associated with the particulate compartment could be extracted with Nonidet P-40, while the rest was Nonidet P-40 insoluble. In both the detergent-soluble and -insoluble fractions, Grb2 coimmunoprecipitated with the zeta-chain of the TCR. Taken together, these results indicate that anti-CD3 induces Grb2-hSos1-PLC-gamma 1-p36/p38-ZAP70 complexes, which localize in the vicinity of TCR-zeta. PMID 7629168 [PubMed - indexed for MEDLINE] Gads(Grap2) plays an important role in T-cell signaling via its association with SLP-76 and LAT. 1 Curr Biol. 1999 Jan 28;9(2) 67-75. The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. Liu SK, Fang N, Koretzky GA, McGlade CJ. Department of Medical Biophysics, University of Toronto, The Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Research Institute, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. BACKGROUND The adaptor protein Gads is a Grb2-related protein originally identified on the basis of its interaction with the tyrosine-phosphorylated form of the docking protein Shc. Gads protein expression is restricted to hematopoietic tissues and cell lines. Gads contains a Src homology 2 (SH2) domain, which has previously been shown to have a similar binding specificity to that of Grb2. Gads also possesses two SH3 domains, but these have a distinct binding specificity to those of Grb2, as Gads does not bind to known Grb2 SH3 domain targets. Here, we investigated whether Gads is involved in T-cell signaling. RESULTS We found that Gads is highly expressed in T cells and that the SLP-76 adaptor protein is a major Gads-associated protein in vivo. The constitutive interaction between Gads and SLP-76 was mediated by the carboxy-terminal SH3 domain of Gads and a 20 amino-acid proline-rich region in SLP-76. Gads also coimmunoprecipitated the tyrosine-phosphorylated form of the linker for activated T cells (LAT) adaptor protein following cross-linking of the T-cell receptor; this interaction was mediated by the Gads SH2 domain. Overexpression of Gads and SLP-76 resulted in a synergistic augmentation of T-cell signaling, as measured by activation of nuclear factor of activated T cells (NFAT), and this cooperation required a functional Gads SH2 domain. CONCLUSIONS These results demonstrate that Gads plays an important role in T-cell signaling via its association with SLP-76 and LAT. Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways. PMID 10021361 [PubMed - indexed for MEDLINE] Lck is required for normal signal transduction through the TCR. 1 Cell. 1992 Aug 21;70(4) 585-93. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Straus DB, Weiss A. Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco 94143. Signaling through the T cell antigen receptor (TCR) results both in rapid increases in tyrosine phosphorylation on a number of proteins and in the activation of the phosphatidylinositol pathway. It is not clear how stimulation of the TCR leads to these signaling events. Mutants of the Jurkat T cell line have been previously isolated that fail to show increases in calcium following receptor stimulation. Analysis of one of these mutants, JCaM1, which is defective in the induction of tyrosine phosphorylation, revealed a defect in the expression of functional lck tyrosine kinase. The lack of lck activity was caused in part by a splicing defect. Expression of the lck cDNA in JCaM1 restores the ability of the cell to respond to TCR stimulation. These results indicate that lck is required for normal signal transduction through the TCR. PMID 1505025 [PubMed - indexed for MEDLINE] ZAP-70 plays crucial roles in T-cell activation and development. Syk triggers cellular activation in T-cell. 1 Mol Cell Biol. 1998 Mar;18(3) 1388-99. Genetic evidence for differential coupling of Syk family kinases to the T-cell receptor reconstitution studies in a ZAP-70-deficient Jurkat T-cell line. Williams BL, Schreiber KL, Zhang W, Wange RL, Samelson LE, Leibson PJ, Abraham RT. Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA. T-cell antigen receptor (TCR) engagement activates multiple protein tyrosine kinases (PTKs), including the Src family member, Lck, and the Syk-related PTK, ZAP-70. Studies in ZAP-70-deficient humans have demonstrated that ZAP-70 plays crucial roles in T-cell activation and development. However, progress toward a detailed understanding of the regulation and function of ZAP-70 during TCR signaling has been hampered by the lack of a suitable T-cell model for biochemical and genetic analyses. In this report, we describe the isolation and phenotypic characterization of a Syk- and ZAP-70-negative somatic mutant derived from the Jurkat T-cell line. The P116 cell line displays severe defects in TCR-induced signaling functions, including protein tyrosine phosphorylation, intracellular Ca2+ mobilization, and interleukin-2 promoter-driven transcription. These signaling defects were fully reversed by reintroduction of catalytically active versions of either Syk or ZAP-70 into the P116 cells. However, in contrast to ZAP-70 expression, Syk expression triggered a significant degree of cellular activation in the absence of TCR ligation. Transfection experiments with ZAP-70-Syk chimeric proteins indicated that both the amino-terminal regulatory regions and the carboxy-terminal catalytic domains of Syk and ZAP-70 contribute to the distinctive functional properties of these PTKs. These studies underscore the crucial role of ZAP-70 in TCR signaling and offer a powerful genetic model for further analyses of ZAP-70 regulation and function in T cells. PMID 9488454 [PubMed - indexed for MEDLINE]
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} /** Infomation styling **/ #trackinfo .info_header th { padding .3em .5em; background-color #D8D8D8; font-size 95%; } #trackinfo .infomation_show_btn_wrapper { float right; font-size 12px; user-select none; } #trackinfo .infomation_show_btn { cursor pointer; } #trackinfo .info_content td { padding 0 0 0 5px; height 0; transition .3s; } #trackinfo .info_content ul { padding 0; margin 0; max-height 0; list-style initial; transition .3s; } #trackinfo .info_content li { opacity 0; visibility hidden; margin 0 0 0 1.5em; transition .3s, opacity .2s; } #trackinfo .info_content.infomation_show td { padding 5px; height 100%; } #trackinfo .info_content.infomation_show ul { padding 5px 0; max-height 50em; } #trackinfo .info_content.infomation_show li { opacity 1; visibility visible; } #trackinfo .info_content.infomation_show li nth-of-type(n+2) { margin-top 10px; } /** Lyrics styling **/ #lyrics { font-size 1.06em; line-height 1.6em; } .not_in_card, .inaudible { display inline; position relative; } .not_in_card { border-bottom dashed 1px #D0D0D0; } .tooltip { display flex; visibility hidden; position absolute; top -42.5px; left 0; width 275px; min-height 20px; max-height 100px; padding 10px; border-radius 5px; background-color #555; align-items center; color #FFF; font-size 85%; line-height 20px; text-align center; white-space nowrap; opacity 0; transition 0.7s; -webkit-user-select none; -moz-user-select none; -ms-user-select none; user-select none; } .inaudible .tooltip { top -68.5px; } span hover + .tooltip { visibility visible; top -47.5px; opacity 0.8; transition 0.3s; } .inaudible span hover + .tooltip { top -73.5px; } .not_in_card span.hide { top -42.5px; opacity 0; transition 0.7s; } .inaudible .img { display inline-block; width 3.45em; height 1.25em; margin-right 4px; margin-bottom -3.5px; margin-left 4px; background-image url(https //img.atwikiimg.com/www31.atwiki.jp/touhoukashi/attach/2971/7/Inaudible.png); background-size contain; background-repeat no-repeat; } .not_in_card after, .inaudible .img after { content ; visibility hidden; position absolute; top -8.5px; left 42.5%; border-width 5px; border-style solid; border-color #555 transparent transparent transparent; opacity 0; transition 0.7s; } .not_in_card hover after, .inaudible .img hover after { content ; visibility visible; top -13.5px; left 42.5%; opacity 0.8; transition 0.3s; } .not_in_card after { top -2.5px; left 50%; } .not_in_card hover after { top -7.5px; left 50%; } .not_in_card.hide after { visibility hidden; top -2.5px; opacity 0; transition 0.7s; } /** For mobile device styling **/ .uk-overflow-container { display inline; } #trackinfo.mobile { display table; float none; width 100%; margin auto; margin-bottom 1em; } #trackinfo.mobile th { text-transform none; } #trackinfo.mobile tbody tr not(.media) th { text-align left; background-color unset; } #trackinfo.mobile td { white-space normal; } document.addEventListener( DOMContentLoaded , function() { use strict ; const headers = { title アルバム別曲名 , album アルバム , circle サークル , vocal Vocal , lyric Lyric , chorus Chorus , narrator Narration , rap Rap , voice Voice , whistle Whistle (口笛) , translate Translation (翻訳) , arrange Arrange , artist Artist , bass Bass , cajon Cajon (カホン) , drum Drum , guitar Guitar , keyboard Keyboard , mc MC , mix Mix , piano Piano , sax Sax , strings Strings , synthesizer Synthesizer , trumpet Trumpet , violin Violin , original 原曲 , image_song イメージ曲 }; const rPagename = /(?=^|.*