Vortex Shedding in Steady Flow Through a Model of an Arterial Stenosis and Its Relevance to Mural Platelet Deposition

In this study, the development of unsteady vortical formations in the separated flow region distal to a stenosis throat is presented and compared with the platelet deposition measurements, to enhance our understanding of the mechanisms involved in platelet kinetics in flowing blood. Qualitative and quantitative flow visualization and numerical simulations were performed in a model of a streamlined axisymmetric stenosis with an area reduction of 84% at the throat of the stenosis. Measurements were performed at Reynolds numbers (Re), based on upstream diameter and average velocity, ranging from 300 to 1800. Both the digital particle image visualization method employed and the numerical simulations were able to capture the motion of the vortices through the separated flow region. Periodic shedding of vortices began at approximately Re=375 and continued for the full range of Re studied. The locales at which these vortices are initiated, their size, and their life span, were a function of Re. The numerical simulations of turbulent flow through the stenosis model entailed a detailed depiction of the process of vortex shedding in the separated flow region downstream of the stenosis. These flow patterns were used to elucidate the mechanisms involved in blood platelet kinetics and deposition in the area in and around an arterial stenosis. The unsteady flow development in the recirculation region is hypothesized as the mechanism for observed changes in the distribution of mural platelet deposition between Re=300, 900, and 1800, despite only a marginal variation in the size and shape of the recirculation zone under these flow conditions. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8710+e     

Cardiometabolic health in Turner syndrome

Individuals with Turner syndrome (TS) have a higher morbidity and mortality compared to the general population. Diabetes and cardiovascular disease are the major contributors to this burden. Precursors to diabetes and cardiovascular disease make up what is known as metabolic syndrome, including abdominal obesity, hypertension, dyslipidemia, and elevated fasting glucose. These features of poor cardiometabolic health are also prevalent among women with TS. Youth with TS also exhibit many of these features, indicating that the pathogenesis of these cardiometabolic conditions may begin early in life. The etiology of the increased risk of cardiometabolic conditions in TS is likely multifactorial, involving genetics, epigenetics, hypogonadism, medical comorbidities, medications, and lifestyle. Counseling for the increased risk of cardiometabolic diseases as well as efforts to prevent or lower this risk should be routinely provided in the care of all patients with TS. Clinical practice guidelines are now available to guide screening and treatment of cardiometabolic conditions in girls and women with TS.     

淋巴细胞经TCR－CD3活化增殖作用的分析

本文探讨了抗ＣＤ３单抗诱导的淋巴细胞活化增殖及有关影响因素。实验结果表明：①淋巴细胞内钙升高是淋巴细胞活化增殖的重要条件，ＣＤ３ＭｃＡｂ引起的早期胞浆游离钙迅速升高主要由内质网释放钙离子所致，而淋巴细胞增殖不仅需要细胞内钙释放，还需要细胞外钙内流；②ＧＴＰ结合蛋白是淋巴细胞激活过程的一重要环节，经Ｇ蛋白作用物霍乱毒素作用后，淋巴细胞ＤＮＡ合成显著降低；③新霉素和ＰＳＳ可抑制ＰＬＣ和ＰｋＣ的活性，对淋巴细胞ＮＤＡ合成造成剂量依赖性抑制作用。此外，抗ＣＤ３ＭｃＡｂ诱导的淋巴细胞ＤＮＡ合成需要辅佐细胞的存在，高度纯化的Ｔ细胞对ＣＤ３ＭｃＡｂ的刺激不发生增殖反应。     

Preferential expansion of Ly-1 B and CD4 CD8 T cells in the polyclonal lymphocyte responses to murine T.cruzi infection

Acute murine infection with T.cruzi results in polyclonal lymphocyteresponses manifested by blast transformation of a large fractionof B, CD4+, and CD8+ cells. We describe here the finding ofsignificant increases in the splenic representation of minorpopulations, Ly-1+ B cells and CD4-CD8- T cells. These lymphocytepopulations might play an important role in the host response,as shown by T.cruzi infection of hosts that had been lethallyirradiated and reconstituted with autologous bone marrow. Underthese conditions, the splenic polyclonal PFC responses are nearlyabrogated, and not restored by the transfer of syngeneic peritonealcells which, however, reconstitute T15 idiotype production inthe same hosts. Control levels of PFC responses, however, arereconstituted by transfer of syngeneic splenic T cells. Sincebone marrow-reconstituted animals contain normal numbers ofCD4+ and CD8+ T cells which are actually activated by infection,these results suggest the participation of other T cell populationsin the host response to infection, as also suggested by themarked increases in T cell receptor and messages detectedin the spleen of infected animals. The implications of thesefindings in immunopathology of Chagas' disease are discussed.     

一个新的人B细胞活化抗原—5C5

用活化人B细胞株3D5细胞免疫小鼠和作为筛选的靶细胞,我们建立了产生单克隆抗体5C5的杂交瘤细胞株。此单抗识别的抗原5C5在25μg/ml anti-μ刺激的B细胞,于第10小时开始表达,亦即于G_1期开始表达。5C5细胞百分率随培养时间而增多。在PWM诱导下.外周血单一核细胞中5C5~ 细胞随培养时间而增加,至第3～4天达最高峰,然后减少,至第7天降至本底水平。5C5~ 细胞在不能为BCDF诱导分化至免疫球蛋白分泌细胞(ISC)的B细胞株3D5,Raji和Daudi阳性,但在能为BCDF诱导分化至ISC的CESS和SKW6细胞却不表达。这均表明5C5抗原表达于B细胞活化的早期和中期,但在B细胞终末分化阶段消失。在休止期B细胞、休止期T细胞、PHA激活的T细胞、单核细胞和中性粒细胞,以及在所检测的T细胞株和髓细胞株,5C5抗原均为阴性。~(125)I标记后用单抗5C5免疫沉淀提取的抗原,在还原与非还原条件下电泳,均只有分子量为52000的一条带,表明5C5是一个单链细胞表面蛋白。鉴于5C5抗原的分子量与文献中已报道的B细胞活化抗原分子量不同,以及5C5在细胞株表达的特点,它可能是一个新的人B细胞活化抗原。     

CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes

Human CD137 is a member of the tumor necrosis factor (TNF) receptor family and the homologue of murine 4-1BB. Recent studies have demonstrated that CD137 promotes accessory T cell activation, and regulates proliferation and survival of T lymphocytes. This study reports on the expression and function of CD137 in peripheral blood monocytes. While monocytes showed constitutive expression in 10 out of 18 healthy donors, CD137 was not expressed on resting T or B lymphocytes. Immobilized antibodies to CD137 markedly induced the production of IL-8 and TNF-alpha protein and mRNA, and led to inhibition of IL-10 expression by primary monocytes. Furthermore, cross-linking of CD137 on monocytes resulted in an increase of B lymphocyte apoptosis mediated by direct cell-cell contact of both cell populations. In conclusion, this study identified CD137 as a new receptor involved in monocyte activation by inducing a characteristic cytokine release profile. In addition, CD137 may play a role in monocyte-dependent control of B lymphocyte survival.     

The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves' disease: the role of CD8+ cells

The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves' disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves' disease.     

Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes

The C3b-binding receptor, CR1/CD35, supports CR2/CD21-mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i-Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1- and CR2-blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k(1)) for CR1 and CR2, operating independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(-1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13-fold over the C3i concentration range examined. The maximum association constant (K(a, max)=109+/-27.2 x 10(7) l/mole) was ca. 9- and 6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/-5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Metabolic and cardiovascular risk factors in Klinefelter syndrome

Klinefelter syndrome (KS), which normally presents with a 47,XXY karyotype, is the most common sex chromosome disorder in males. It is also the most common genetic cause of male infertility. KS subjects are typically tall, with small and firm testes, gynecomastia, broad hips, and sparse body hair, although a less evident presentation is also possible. KS is also characterized by a high prevalence of hypogonadism, metabolic syndrome (MetS) and cardiovascular disease. The aim of this article is to systematically review metabolic and the cardiovascular risk factors in KS patients. Hypogonadism has an important role in the pathogenesis of the changes in body composition (particularly visceral obesity) and hence of insulin resistance and MetS, but the association between KS and MetS may go beyond hypogonadism alone. From childhood, KS patients may show an increase in visceral fat with a reduction in lean body mass and an increase in glucose and impaired fat metabolism. Their increased incidence of congenital anomalies, epicardial adipose tissue, and thromboembolic disease suggests they have a higher risk of cardiovascular disease. There is conflicting evidence on the effects of testosterone therapy on body composition and metabolism.