A persistent T cell expansion in the peripheral blood of a normal adult male: a new clinical entity?

A dramatic and persistent T cell expansion in a healthy adult male was initially identified, using anti-T cell receptor for antigen (TCR)-specific MoAbs. The expanded T cells were found to be expressing TCR containing V alpha 12.1 and V beta 5.2, and they composed approximately one third of all the CD8+ T cells. The cells were shown to be not only non-activated (HLA-DR-, IL-2R-) but also of 'virgin' cell type (CD45RA+/CD45RO-) and they persisted over the observation period of more than one and a half years. Various T and B cell markers, and all other laboratory and physical parameters analysed, were normal. The expanded CD8+ T cells were further characterized by polymerase chain reaction (PCR) amplification, using V beta- and C beta-specific primers, followed by hybridization with J beta-specific probes. Close to 90% of the V alpha 12.1+ V beta 5.2+ T cells were found to utilize the J beta 2.5 gene segment, thus strongly suggesting the expanded T cells to be monoclonal. The condition may constitute a T cell counterpart to 'monoclonal gammopathy of undetermined significance' (MGUS), and by analogy we suggest it should be designated 'monoclonal T cell expansion of undetermined significance' (MTUS).     

Local production of IgA- and IgM-rheumatoid factors in adult periodontal disease

The enzyme-linked immunospot assay was used to enumerate both the number and the frequency of spontaneous IgG, IgA, and IgM immunoglobulin-secreting cells and IgA- and IgM-rheumatoid factor (RF)-producing cells present in the gingivae and peripheral blood of adult periodontitis patients. Cells from 29 patients were incubated on plates coated with human IgG, Fc, or F(ab)₂ fragments and on plates coated with class-specific antihuman antibodies and secreted antibodies were subsequently visualized by means of an immunoenzymatic procedure. The data indicate that (1) IgA-RF- and IgM-RF-secreting cells are frequently present in the gingiva of adult periodontitis patients; (2) production of RF in gingivae of adult periodontitis patients occurs in the absence of demonstrable RF production by simultaneously obtained peripheral blood mononuclear cells, suggesting that local autoimmune reactions may occur in this disease; and (3) lack of correlation between IgA-RF and IgM-RF production in diseased gingiva suggests that the two RF isotypes are regulated independently of each other.     

Progressive dilated cardiomyopathy in a patient with longstanding and complete prednisone-induced hematological remission of idiopathic hypereosinophilic syndrome

Summary A female patient is described in whom the diagnosis of idiopathic hypereosinophilic syndrome (HES) with heart disease and peripheral neuropathy was made at the age of 32 years. Although prednisone induced a prompt and longstanding complete hematological remission, progressive and eventually intractable heart failure developed, and the patient died 6 years later. Endomyocardial biopsy at diagnosis showed infiltration with intact and disintegrated eosinophils and Charcot-Leyden crystals. Echocardiographic follow-up (including Doppler-Echocardiography) revealed mitral regurgitation with thickening and impaired motility of the posterior mitral leaflet, as well as progressive dilated cardiomyopathy. At autopsy, a diffuse interstitial fibrosis with patchy prominence in an eccentric hypertrophic and highly dilated heart was found. There were no significant endocardial thickening and no mural thrombi. In contrast to the findings of the initial endomyocardial biopsy, autopsy revealed no eosinophilic infiltrate.In this case, eosinophil-induced heart disease manifested as dilated cardiomyopathy, without endocardial fibrosis as originally described by Löffler. We speculate, that eosinophils have been deposited predominantly in the myocard at an early stage of disease, and — activated locally — secreted their granule proteins producing an initial damage to capillary endothelial cells and myocytes. After prednisone-induced clearance of eosinophils from blood and tissues, progressive, self-perpetuating interstitial fibrosis of the myocard and loss of myocytes eventually resulted in end-stage dilated cardiomyopathy.Abkürzungsverzeichnis HES idiopathic hypereosinophilic syndrome - UBBC unsaturated vitamin B₁₂ binding capacity - ECP eosinophil cationic protein - MBC major basic protein - EDD end-diastolic diameter of the left ventricle - LA left atrium diameter - LVEDP left ventricular end-diastolic pressure - NIH National Institutes of Health     

Action of nifedipine of BAY K8644 is dependent on calcium channel state in single smooth muscle cells from rabbit ear artery

The actions of nifedipine or BAY K 8644 were studied on barium currents recorded from single, collagenase- and elastase-dispersed, smooth muscle cells from the rabbit ear artery using the whole-cell configuration of the patch-clamp technique. Nifedipine (3M) caused a reduction in the barium current (I_Ba) evoked by steps to potentials positive of-10mV. This was characterized by a pronounced initial block, an increase in the rate of current decay during the voltage-clamp step, but by no increase in block if pulses were repeated every 600ms. Rapid extracellular application of nifedipine (1M) during the sustained current component (using a new concentration-jump technique) was found to have no effect on I_Ba over 4s at +20mV, but after returning to the holding potential (-60mV) for 10s, sustained I_Ba was subsequently abolished. BAY K 8644 (1M) increased I_Ba at all potentials, and on rapid application during the sustained current component markedly potentiated I_Ba. The results suggest that nifedipine binds with high affinity to the closed, available state of the Ca⁺⁺ channels but they do not suggest binding to the open or inactivated states. The effect of BAY K 8644 is consistent with high affinity binding to the open or inactivated and to the closed, available states.     

促肝细胞生长素诱导人肝癌细胞（BEL－7402）凋亡

本文从细胞学、ＤＮＡ凝胶电泳、流式细胞术三方面研究促肝细胞生长素（ｐＨＧＦ）在体外对肝癌细胞增殖活性的影响。结果表明：ｐＨＧＦ对肝癌ＢＥＬ－７４０２细胞增殖有抑制作用，并存在剂量和时间相关性。其４８ｈ的半数抑制浓度（ＩＤ５０）为０．３７ｍｇ／ｍｌ±０．０４ｍｇ／ｍｌ。而３７℃灭活的ｐＨＧＦ对ＢＥＬ－７４０２细胞增殖在１５ｈ无抑制作用，在２４和４８ｈ抑制作用很弱（ＩＤ５０＞１．５ｍｇ／ｍｌ）。ＤＮＡ凝胶电泳结果表明，ｐＨＧＦ可诱导ＢＥＬ７４０２细胞产生细胞凋亡（Ａｐｏｐｔｏｓｉｓ）。流式细胞术（ＦＣＭ）结果显示：ｐＨＧＦ抑制ＢＥＬ－７４０２细胞增殖过程是先使细胞停留在Ｇ０／Ｇ１期，继而诱导细胞产生凋亡。后两项结果均显示ｐＨＧＦ对人肝癌细胞凋亡的诱导里时间和剂量相关性。     

Pituitary choristoma composed of corticotrophs and adrenocortical cells in the sella turcica

A pituitary tumour composed of well-differentiated corticotrophs and adrenocortical cells is reported. Sections of the tumour revealed a mixture of small round cells with amphophilic or basophilic periodic acid-Schiff (PAS)-positive cytoplasm and large spherical and oval cells with abundant, granular, partly vacuolated PAS-negative cytoplasm. The small cells contained type 1 cytokeratin-positive microfilaments, numerous 250–500 nm endocrine-type secretory granules immunoreactive for adenocorticotropic hormone (ACTH) and -lipotropin. The large cells possessed ample cytoplasm filled with abundant vesicular smooth endoplasmic reticulum, numerous mitochondria possessing tubulovesicular cristae and frequent dense bodies. They lacked the features of pituitary endocrine cells or folliculostellate cells and were found to contain a panel of steroidogenic dehydrogenases and hydroxylases. The tumour was classified as a choristoma, in which two distinct cells types, corticotrophs and adrenocortical cells, were mixed. We suggest that, under continued ACTH stimulation, uncommitted stem cells may differentiate into adrenocortical cells. Alternatively, the presence of adrenocortical cells may be the result of heterotopia.     

慢性丙型肝炎时贮脂细胞的定量研究

应用免疫组化等方法，对慢性迁延性丙型肝炎肝组织中呈结蛋白阳性的贮脂细胞进行了定量的研究结果；结蛋白阳性的细胞数量与同阶段的乙型肝炎相比显著减少；电镜观察可见肝窦中有较多的枯否细胞，肝细胞间隙及窦周胶原纤维的沉积。我们认为，在丙型肝炎早期纤维化中，贮脂细胞可能并非主要导致纤维化的效应细胞，这和乙型肝炎有所不同。     

Inhibitory effect of plasma obtained from hypophysectomized and control women on the assay of bioactive luteinizing hormone

The purpose of this study was to determine the effect of components of female plasma on the value of bioactive luteinizing hormone (LH), especially in the presence of low immunological LH value. Using both an immunoradiometric assay (IRMA) and rat Leydig cell bioassay, immunoreactive (I) and bioactive (B) LH were assessed in plasma collected from women during a gonadotrophin releasing hormone (GnRH) test performed on day 7 of a spontaneous cycle. Two modes of response to an acute administration of GnRH were defined: normal production of gonadotrophins (group I) and excessive secretion (group II) associated with a significant difference in the B/I-LH ratio between the two groups. The B/I-LH ratio did not vary with sampling time during the test in either group. The addition of LH-free plasma collected from hypophysectomized women caused a 30% decrease in testosterone production compared to control values (in the presence or absence of hLH standard). A partial restoration of testosterone production was observed if plasma was first treated with PEG 12%. The inhibitory factor(s) was also present in plasma from ovulatory women, even after treatment by an antibody against the entire LH molecule. The effect of normal (A) or low I-LH plasma (B) on testosterone production varied strongly according to the plasma volume added to the bioassay, as well as to plasma treatments. Diethylether treatment caused a 50% decrease in testosterone secretion for plasma B (but not for A) whereas a diminution of the steroidogenesis is observed after a PEG treatment of plasma A (but not for B), suggesting that different inhibitory factors are present in plasmas A and B. Therefore the LH bioactivity measured in the rat Leydig cell assay, in terms of testosterone output, seems to represent a balance between the LH molecule and the presence of inhibitory factors in the plasma.     

人肿瘤细胞TH2类细胞因子的逆转与NK抗性变化的研究

目的研究促使人肿瘤细胞中ＴＨ２类细胞因子表达向ＴＨ０型的逆转及逆转后的肿瘤细胞对ＮＫ抗性的变化。方法首先用ＭＴＴ方法对悬浮培养的肿瘤细胞株ＤＢ大淋巴细胞瘤、Ｋａｒｐａｓ淋巴瘤、Ｍｉｃｈａｅｌ淋巴瘤、Ｒａｊｉ、ＨＬ６０和Ｋ５６２进行了ＮＫ杀伤敏感性的筛选。选择ＮＫ不敏感的Ｋａｒｐａｓ淋巴瘤和ＨＬ６０，用ｒｈＩＦＮγ、ｒｈＩＬ－１２和抗ＩＬ－１０ＭｃＡｂ经不同组合对其进行由ＴＨ２类细胞因子表达向ＴＨ１类细胞因子表达的促逆转研究，并观察促逆转后的肿瘤细胞对ＮＫ抗性的变化。结果ＲＴ－ＰＣＲ结果表明，经上述不同细胞因子组合诱导后，Ｋａｒｐａｓ淋巴瘤细胞均从表达ＴＨ２类细胞因子为主向ＴＨ０型逆转，并且各组逆转后的肿瘤细胞对ＮＫ的抗性均有不同程度的减弱。结论ＴＨ１类细胞因子（如ＩＦＮγ）、ＴＨ２类细胞因子拮抗剂（如ＩＬ－１０单抗）和ＩＬ－１２不同程度地促进肿瘤细胞表达的细胞因子由ＴＨ２型向ＴＨ０／ＴＨ１型逆转。促逆转后可以改善肿瘤细胞对机体杀伤作用的敏感性，提高抗肿瘤免疫能力     

Photoelectric recording of mechanical responses of cardiac myocytes

A method to monitor contraction of isolated myocytes by transmicroscopic photometry is illustrated. Two photodiodes are mounted inside an inverse microscope used for visual control of a cell. Illumination of one diode varies in proportion to changes in cell length. The contraction signal is amplified in a comparator circuit. Spatial resolution of the device is in the order of 1 m which corresponds to about 5% of cell shortening in the fully activated state of contraction. The method was tested on isolated myocytes from guinea-pig ventricle. Optical records of contraction in response to action potentials or during voltage clamp compare well with the contractile behaviour of multicellular preparations.