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11.
Correction of a suppressor cell deficiency in four patients with familial mediterranean fever by in vitro or in vivo colchicine 下载免费PDF全文
We have previously reported that three patients with familial Mediterranean fever (FMF) had deficient concanavalin A (Con A) activated suppressor cell inhibition of the proliferation of healthy volunteers' phytohaemagglutinin stimulated responder cells. When these three FMF patients were treated with long term oral colchicine (2 mg/day), their Con A activated suppressor cell deficiency was corrected and FMF attacks prevented. In the present report, the effect of in vitro as well as in vivo colchicine treatment on the suppressor cell function of these three FMF patients as well as one more FMF patient was tested to determine whether colchicine can directly increase suppressor cell function rather than colchicine's preventing FMF attacks by unknown mechanisms which only indirectly results in a correction of the suppressor cell deficiency. Long term oral colchicine treatment corrected the suppressor cell deficiency in the four FMF patients (5±2%, 35±5%, and 46±4% for mean ±s.e.m.% suppression for 0, 1 and 2 mg/day of oral colchicine, respectively). Oral colchicine treatment corrected their suppressor cell deficiency within one week of commencing treatment and even corrected one of the FMF patient's suppressor cell deficiency while he still had some FMF attacks on 1 mg/day of colchicine. Suppressor cells from two of the in vivo untreated FMF patients cultured with 10-5 M colchicine plus Con A significantly (P<0·01) suppressed proliferation (36±5%) as compared to their suppressor cells cultured only with Con A (4±7%). Furthermore, these in vivo untreated FMF patients' suppressor cells cultured with 10-5 M colchicine (without Con A) often suppressed as compared to their suppressor cells cultured in medium. Thus colchicine appears to directly correct these FMF patients' suppressor cell deficiency. These observations raise the possibility that colchicine may be therapeutically useful in treating patients with other diseases associated with an absolute or relative deficiency of suppressor cell function. 相似文献
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Ethan A. Carver Kathleen F. Oram Thomas Gridley 《Anatomical record (Hoboken, N.J. : 2007)》2002,268(2):90-92
Saethre‐Chotzen syndrome is a common autosomal dominant form of craniosynostosis, the premature fusion of the sutures of the calvarial bones of the skull. Most Saethre‐Chotzen syndrome cases are caused by haploinsufficiency for the TWIST gene. Mice heterozygous for a null mutation of the Twist gene replicate certain features of Saethre‐Chotzen syndrome, but have not been reported to exhibit craniosynostosis. We demonstrate that Twist heterozygous mice exhibit fusions of the coronal suture and other cranial suture abnormalities, indicating that Twist heterozygous mice constitute a better animal model for Saethre‐Chotzen syndrome than was previously appreciated. Anat Rec 268:90–92, 2002. © 2002 Wiley‐Liss, Inc. 相似文献
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Ethan M. Shevach Rebecca S. McHugh Ciriaco A. Piccirillo Angela M. Thornton 《Immunological reviews》2001,182(1):58-67
Summary: Depletion of the minor (∼10%) subpopulation of CD4+ T cells that co-expresses CD25 (interleukin (IL)-2 receptor α-chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4+ T cells with anti-CD25 and complement results in the development of organ-specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4+ CD25+ cells. CD4+ CD25+ -mediated protection of autoimmune gastritis does not require the suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-β. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4+ CD25+ T cells are also powerful suppressors of the activation of both CD4+ and CD8+ T cells in vitro . Suppression is mediated by a cell contact-dependent, cytokine-independent T–T interaction. Activation of CD4+ CD25+ via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4+ or CD8+ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4+ CD25+ T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4+ or CD8+ effector cells to suppress the development of autoimmune disease. 相似文献
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D Ilfeld E Feierman O Kuperman S Kivity M Topilsky L Netzer M Pecht N Trainin 《Immunology》1984,53(3):595-598
We examined the effect of oral colchicine (1-2 mg/day) on four healthy volunteers' T cell subsets. Colchicine significantly (P less than 0.01) decreased the mean (+/- SD) percent of OKT3+ total T cells (from 70 +/- 16 to 47 +/- 13), OKT4+ helper/inducer T cells (from 44 +/- 9 to 24 +/- 6), and OKT8+ suppressor/cytotoxic T cells (from 27 +/- 7 to 17 +/- 7), but did not significantly affect the OKT4:OKT8 ratio (from 1.64 +/- 0.21 to 1.48 +/- 0.45) or concanavalin A-induced suppressor cell function (from 44 +/- 9% to 47 +/- 13%). Thus, colchicine non-selectively decreased the circulating helper/inducer and suppressor/cytotoxic T cells. 相似文献
17.
Peter J. Littrup M.D. Alex M. Aisen M.D. Ethan M. Braunstein M.D. William Martel M.D. 《Skeletal radiology》1985,14(3):159-163
Magnetic resonance images (MRI) of 22 patients with roentgenographically normal hips were reviewed retrospectively and the findings categorized according to age. With increasing maturity, the MR intensity of the femoral heads on spin echo images increased, as marrow fat became a dominant tissue in the head. The femoral head pattern was relatively inhomogeneous, with a broad band of diminished intensity extending in a posteromedial to anterolateral direction, corresponding to the pattern of trabecular bone. The femoral capital epiphyses were visible in younger patients as structures of bright intensity which remained evident through early adulthood. The articular cartilage of the hip joint was noted as a distinctive halo around the femoral head. An understanding of the MR pattern of the normal hip will aid in the early recognition of pathologic conditions, such as osteonecrosis. 相似文献
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We report mean severe acute respiratory syndrome coronavirus 2 serial intervals for Montana, USA, from 583 transmission pairs; infectors’ symptom onset dates occurred during March 1–July 31, 2020. Our estimate was 5.68 (95% CI 5.27–6.08) days, SD 4.77 (95% CI 4.33–5.19) days. Subperiod estimates varied temporally by nonpharmaceutical intervention type and fluctuating incidence. 相似文献
19.
Carlos R Ferreira Dillon Kavanagh Ralf Oheim Kristin Zimmerman Julian Stürznickel Xiaofeng Li Paul Stabach R Luke Rettig Logan Calderone Colin MacKichan Aaron Wang Hunter A Hutchinson Tracy Nelson Steven M Tommasini Simon von Kroge Imke AK Fiedler Ethan R Lester Gilbert W Moeckel Björn Busse Thorsten Schinke Thomas O Carpenter Michael A Levine Mark C Horowitz Demetrios T Braddock 《Journal of bone and mineral research》2021,36(5):942-955
Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
20.
Angela B. Smith Cleo A. Samuel Sean D. McCabe Allison Deal Mattias Jonsson Dana E. Mueller Zahra M. Mahbooba Antonia V. Bennett Arlene E. Chung Matthew E. Nielsen Hung-Jui Tan Eric Wallen Raj Pruthi Andrew Wang Ethan Basch Bryce B. Reeve Ronald C. Chen 《Urologic oncology》2021,39(1):77.e1-77.e8
ObjectiveTo assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time.Subjects/Patients and MethodsWe recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy.Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time.ResultsSixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046).ConclusionsReported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care. 相似文献