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Retinoic acid signaling acts as a rheostat to balance Treg function

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Cellular & Molecular Immunology 2022年第7期19卷 820-833页

作者： Govindarajan Thangavelu Gabriela Andrejeva Sara Bolivar-Wagers Sujeong jin michael C.Zaiken michael Loschi Ethan G.Aguilar Scott N.Furlan Chrysothemis C.Brown Yu-Chi Lee Cameron McDonald Hyman Colby j.Feser Angela Panoskaltsis-Mortari Keli L.Hippen Kelli P.MacDonald William j.Murphy Ivan Maillard Geoffrey R.Hill David H.Munn Robert Zeiser Leslie S.Kean jeffrey C.Rathmell Hongbo Chi Randolph j.Noelle Bruce R.Blazar Department of Pediatrics Center for ImmunologyUniversity of MinnesotaMinneapolisMNUSA Center for Immunobiology Vanderbilt University Medical CenterNashville TNUSA Department of Pediatrics University of WashingtonSeattleWAUSA Fred Hutchinson Cancer Research Center SeattleWAUSA Howard Hughes Medical Institute Immunology Program and Ludwig CenterSloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Microbiology and Immunology.Geisel School of Medicine at Dartmouth Norris Cotton Cancer CenterLebanonUSA Department of Immunology Queensland Institute of Medical Research(QIMR)Berghofer Medical Research Institute and School of MedicineUniversity of QueenslandBrisbaneQLDAustralia Departmentof Dermatology School of MedicineUniversity of California DavisSacramentoCAUSA Division of Hematology/Oncology Department of MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPAUSA Georgia Cancer Center Augusta UniversityAugustaGAUSA Department of Haematology Oncology and Stem Cell TransplantationFaculty of MedicineFreiburg University Medical CentreFreiburgGermany Boston Children's Hospital and the Dana-farber Cancer Institute BostonMAUSA Department of Immunology St.Jude Children's ResearchHospitalMemphisTNUSA

Regulatory T cells(Tregs)promote immune homeostasis by maintaining self-tolerance and regulating inflammatory *** certain inflammatory conditions,Tregs can lose their lineage stability and *** studies have reported that ex vivo exposure to retinoic acid(RA)enhances Treg function and ***,it is unknown how RA receptor signaling in Tregs influences these processes in ***,we employed mouse models in which RA signaling is silenced by the expression of the dominant negative receptor(DN)RARαin all T *** the fact that DNRARαconventional T cells are hypofunctional,Tregs had increased CD25 expression,STAT5 pathway activation,mTORC1 signaling and supersuppressor ***,DNRARαTregs had increased inhibitory molecule expression,amino acid transporter expression,and metabolic fitness and decreased antiapoptotic *** function was observed when wild-type mice were treated with a pharmacologic pan-RAR ***,Treg-specific expression of DNRARαresulted in distinct phenotypes,such that a single allele of DNRARαin Tregs heightened their suppressive function,and biallelic expression led to loss of suppression and *** loss of Treg function was not cell intrinsic,as Tregs that developed in a noninflammatory milieu in chimeric mice reconstituted with DNRARαand wild-type bone marrow maintained the enhanced suppressive *** mapping suggested that maintaining Treg stability in an inflammatory milieu requires RA *** findings indicate that RA signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions in a dose-dependent manner.

关键词： Retinoic acid Tregulatory cells Autoimmunity Metabolism mTORC1 STAT5

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食品中单核细胞增多性李氏杆菌的研究现状

肉品卫生 1994年第4期 25-28页

作者： j.M.farber 柳增善

在食品安全性方面,单核细胞增多性李氏杆菌是每个人都关心的食源性病原菌,已出版了两本专著和发表许多综述。这里主要讨论三个方面的最新研究现状,即方法学、控制和法规方面的研究现状。在方法学上由于篇幅所限,只能作以简要探讨。

关键词：食品微生物李氏杆菌研究

Impact of COVID-19 on presentation,management,and outcomes of acute care surgery for gallbladder disease and acute appendicitis

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World journal of Gastrointestinal Surgery 2021年第8期13卷 859-870页

作者： Orly Nadell farber Giselle I Gomez Ashley L Titan Andrea T Fisher Christopher j Puntasecca Veronica Toro Arana Arielle Kempinsky Clare E Wise Kovi E Bessoff Mary T Hawn james R Korndorffer jr joseph D Forrester Micaela M Esquivel Department of Surgery Stanford University School of MedicinePalo AltoCA 94305United States

BACKGROUND The ongoing coronavirus disease 2019(COVID-19)pandemic has significantly disrupted both elective and acute medical *** from the early months suggest that acute care patient populations deferred presenting to the emergency department(ED),portending more severe disease at the time of ***,care for this patient population trended towards initial non-operative *** To examine the presentation,management,and outcomes of patients who developed gallbladder disease or appendicitis during the *** A retrospective chart review of patients diagnosed with acute cholecystitis,symptomatic cholelithiasis,or appendicitis in two EDs affiliated with a single tertiary academic medical center in Northern California between March and june,2020 and in the same months of *** were selected through a research repository using international classification of diseases(ICD)-9 and ICD-10 *** both years,313 patients were identified with either type of gallbladder disease,while 361 patients were identified with acute *** primary outcome was overall incidence of *** outcomes included presentation,management,complications,and 30-d re-presentation *** between different variables were explored using Pearson’s r correlation *** were compared using the Welch’s t-Test,Chi-squared tests,and Fisher’s exact test as *** Patients with gallbladder disease and appendicitis both had more severe presentations in *** respect to gallbladder disease,more patients in the COVID-19 cohort presented with acute cholecystitis compared to the control cohort[50%(80)vs 35%(53);P=0.01].Patients also presented with more severe cholecystitis in 2020 as indicated by higher mean Tokyo Criteria Scores[mean(SD)1.39(0.56)vs 1.16(0.44);P=0.02].With respect to appendicitis,more patients were diagnosed with a perforated appendix at presentation in 2020[20%(36)vs 16%(29);P=0.0

关键词： COVID-19 Cholecystitis Biliary colic Appendicitis Acute care surgery

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银屑病第三届国际银屑病讨论会论文汇编

临床自体肺动脉瓣移植:主动脉位置发生适应性重构的病理学证据

1983年

作者： Eugene M.farber M.D.Alvin j.Cox M.D.编张国威王光超等译

来源：汇雅图书（南通市图书馆... 评论

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世界核心医学期刊文摘（心脏病学分册） 2005年第3期1卷 59-60页

作者： Rabkin-Aikawa E. Aikawa M. farber M. F.j. Schoen 杜媛 Department of Pathology Department ofMedicine BrighamWomen's Hosp. HarvardM. BostonMA United States Dr.

Objective We studied the pathologic features, cellular phenotypes, and matrix remodeling of clinical pulmonary-to-aortic valve transplants functioning up to 6 years. Methods Nine autografts and associated vascular walls early(2-10 weeks) and late(3-6 years) postoperatively were examined by using routine morphologic methods and immunohistochemistry. In 4 cases autograft and homograft cusps were obtained from the same patients. Results Autografts had near-normal trilaminar cuspal structure and collagen architecture and viable valvular interstitial and endothelial cells throughout the time course. In contrast, cusps of homografts used to replace the pulmonary valves in the same patients were devitalized. In early autograft explants, 19.3%±2.4%of cuspal interstitial cells were myofibroblasts expressing α-actin. In contrast, myofibroblasts comprised only 6.0%±1.1%of cells in late explants and 2.5%±0.4%and 4.6%±0.8%of cells in normal pulmonary and aortic valves, respectively (P< .05). In early autografts only 12.0%±4.6%of endothelial cells expressed the systemic arterial endothelial cellmarker EphrinB2,whereas later explants had 85.6%±5.4%of endothelial cells expressing EphrinB2(P< .05). In early autografts 43.0%±8.8%of interstitial cells expressed metalloproteinase 13, whereas late autografts had 11.4%±2.7%of interstitial cells expressing matrix metalloproteinase 13 (P< .05). Collagen content in autografts was comparable with that of normal valves and was higher than that seen in homograft valves (P< .005). However, autograft walls were damaged, with granulation tissue (early) and scarring, with focal loss of normal smooth muscle cells, elastin, and collagen (late). Conclusions The structure of pulmonary valves transplanted to the systemic circulation evolved toward that of normal aortic valves. Key processes in this remodeling included onset of a systemic endothelial cell phenotype and reversible plasticity of fibroblast-like valvular interstitial cells to myofibroblast

关键词：肺动脉瓣自体移植物动脉瓣置换间质细胞免疫组化观察内皮细胞同种移植肌成纤维细胞 α-肌动蛋白平滑肌细胞

Systemic inflammation in colorectal cancer: Underlying factors,effects, and prognostic significance

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World journal of Gastroenterology 2019年第31期25卷 4383-4404页

作者： Anne E Tuomisto Markus j Makinen juha P Vayrynen Cancer and Translational Medicine Research Unit University of OuluOulu 90220Finland Department of Pathology Oulu University Hospital and Medical Research Center OuluOulu 90220Finland Department of Medical Oncology Dana-Farber Cancer Institute and Harvard Medical SchoolBostonMA 02115United States

Systemic inflammation is a marker of poor prognosis preoperatively present in around 20%-40%of colorectal cancer *** hallmarks of systemic inflammation include an increased production of proinflammatory cytokines and acute phase proteins that enter the *** the low-level systemic inflammation is often clinically silent,its consequences are many and may ultimately lead to chronic cancer-associated wasting,*** this review,we discuss the pathogenesis of cancer-related systemic inflammation,explore the role of systemic inflammation in promoting cancer growth,escaping antitumor defense,and shifting metabolic pathways,and how these changes are related to less favorable outcome.

关键词： Colorectal cancer Inflammation Prognosis Cytokine Chemokine C-reactive protein Glasgow prognostic score Cachexia Metastasis

K65(X80)管线钢断口分离及其对冲击韧性的影响

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焊管 2018年第2期41卷 65-68页

作者：方伟(编译) 邹斌(编译) 李为卫(编译) 吕华(编译) farber V M KHOTINOV V A MOROZOVA A N 中国石油集团石油管工程技术研究院西安710077 中国石油西部管道分公司乌鲁木齐830013 不详

为了研究K65(X80)钢断口分离对冲击韧性的影响,对不同生产厂家的4种典型K65(X80)高韧性管线钢进行了+20^-90℃夏比冲击试验,并对冲击试样断口分离形貌和尺寸进行了分析。结果表明,均匀韧性断口的高能量区长度Lh与冲击韧性A_(kV)直接相关... 详细信息

为了研究K65(X80)钢断口分离对冲击韧性的影响,对不同生产厂家的4种典型K65(X80)高韧性管线钢进行了+20^-90℃夏比冲击试验,并对冲击试样断口分离形貌和尺寸进行了分析。结果表明,均匀韧性断口的高能量区长度Lh与冲击韧性A_(kV)直接相关,考虑了试验温度下降时断口分离形式和数量的变化,确定了管线钢获得高冲击韧性(-60℃A_(kV)≥250 j/cm^2)的条件。

关键词：断口分离 X80钢冲击韧性断口表面夏比转变曲线

Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

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Genes & Diseases 2018年第1期5卷 46-48页

作者： Trevor E.Angell Le Min Tad j.Wieczorek F.Stephen Hodi Division of Endocrinology Diabetesand HypertensionBrigham and Women’s HospitalBostonMAUSA Department of Pathology Brigham and Women’s HospitalBostonMAUSA Department of Medical Oncology Dana-Farber Cancer InstituteBostonMAUSA

Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer *** antibodies targeting two such molecules,Programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4(CTLA-4)have shown clinical benefit in the treatment of advanced malignancies,including metastatic *** effects of these immune checkpoint inhibitors include immune-related adverse events(irAE),of which one of the most common is autoimmune *** thyroiditis is increasingly recognized,there are no reports of the pathological findings that occur in immunotherapy-induced *** present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features.A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab(PD-1 antagonist)plus ipilimumab(CTLA-4 antagonist)therapy.A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells,lymphocytes and CD163-positive *** case reports cytopathologic features found in immune checkpoint inhibitor related *** appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

关键词： Thyroiditis PD-1 CTLA-4 Ipilimumab Nivolumab Cytology

Leukemia:研究鉴定出与34种AML白血病亚群相关联的基因突变

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现代生物医学进展 2017年第15期17卷 I0002-I0003页

作者： A-K Eisfeld K Mrózek j Kohlschmidt D Nicolet S Orwick C j Walker K W Kroll j S Blachly A j Carroll j E Kolitz B L Powell E S Wang R M Stone A de la Chapelle j C Byrd C D Bloomfield The Ohio State University Comprehensive Cancer Center Columbus OH USA Alliance Statistics and Data Center Mayo Clinic Rochester MN USA Division of Hematology Department of Internal Medicine The Ohio State University Comprehensive Cancer Center Columbus OH USA Department of Genetics University of Alabama at Birmingham Birmingham AL USA Monter Cancer Center Hofstra North Shore-Long Island Jewish School of Medicine Lake Success NY USA Comprehensive Cancer Center of Wake Forest University Winston-Salem NC USA Department of Medicine Roswell Park Cancer Institute Buffalo NY USA Department of Medical Oncology Dana-Farber/Partners CancerCare Boston MA USA

针对成年急性髓细胞白血病（acute myeloid leukemia，AML）患者的一项新的大型研究将80种癌症相关基因突变与5种AML亚型相关联。这5种AML亚型可通过特异性的染色体异常加以确定。在未来，这些发现可能有助指导基因突变测试和治疗决策。

关键词：基因突变 AML 白血病关联亚群鉴定染色体异常髓细胞