CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

肝再生过程中肝和脑垂体纤维粘连蛋白表达的变化

目的；探讨大鼠肝大部分切除再生过程中肝和垂体内纤维粘连蛋白变化变化，方法：用免疫组织化学法观察鼠肝大部切除术０．５天，１天，１．５天，２天，３天，７天时，肝内和垂体远侧部滤泡状细胞细胞纤维粘连蛋白的变化，并用图像分析仪进行定量测定，结果：肝大部切除术后１．５天，肝内纤维粘连蛋白阳性染色增强，基平均光密度高于对照组（Ｐ〈０．０５）；术后２～３天，镜下可见纤维粘连蛋白染色呈强阳性，尤其在肝组织增生部位     

炎症因子对肾小球系膜细胞分泌IL—8的影响

目的：观察炎症因子ＩＬ－１及肿瘤坏死因子（ＴＮＦ）对人肾小球系膜细胞（ＨＭＣ）分泌ＩＬ－８的影响。方法：体外细胞培养技术及ＥＬＩＳＡ夹心法。结果：ＩＬ－１、ＴＮＦ均可诱导ＨＭＣ分泌ＩＬ－８，并呈剂量依赖性。结论：在一些炎症因子刺激下，ＨＭＣ可能通过分泌趋化因子ＩＬ－８参与肾脏炎症反应的启动和维持     

Assessment of HBV persistent infection in an adult population in Taiwan

In order to study the prevalence of hepatitis B virus (HBV) in the adult population of Taiwan, we screened for the presence of HBV DNA in 205 blood samples from adult (20-59-year-old) volunteers. According to the serological markers of HBV, samples were divided into three groups: group I (173 subjects) was negative for both HBsAg and HBeAg; group II (14 subjects) was positive for both HBsAg and HBeAg; and group III consisted of 18 subjects who were HBsAg-positive but HBeAg-negative. Plasma HBV DNA was not detected in group I, but it was found in 85.7% and 11.8% of samples in group II and group III, respectively. A free-form HBV DNA was found in 14.3% of the leukocyte samples in group II. Furthermore, an integrated form of HBV DNA was detected in the leukocytes of two cases of group I who remained healthy based on clinical data. HBV DNA was also detected in the spermatozoa and liver cells of one of the cases.     

Increase in the proportion of granulated CD56+ T cells in patients with malignancy.

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such CD56+ T cells were a minor population in the peripheral blood (< 10%), they were abundant in the liver (up to 50%), which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of gamma delta T cells than did CD56- T cells, contained double-negative CD4-8- cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.     

Circulating leucocyte subpopulations in sedentary subjects following graded maximal exercise with hypoxia

Summary Ten healthy sedentary subjects [age, 27.5 (SD 3.5) years; height, 180 (SD 5) cm; mass, 69.3 (SD 6.3) kg] performed two periods of maximal incremental graded cycle ergometer exercise in a supine position. Randomly ordered and using an open spirometric system, one exercise was carried out during normoxia [maximal oxygen consumption ( O_2max)=38.6 (SD 3.5) ml·min^–1·kg^–1; maximal blood lactate concentration, 9.86 (SD 1.85) mmol·l^–1; test duration, 22.6 (SD 2.7) min], the other during hypoxia [ O_2max=33.2 (SD 3.2) ml·min^–1· kg^–1; maximal blood lactate concentration, 10.38 (SD 2.02) mmol·l^–1; test duration, 19.7 (SD 2.8) min]. At rest, immediately (0 p) and 60 min (60 p) after exercise, counts of leucocyte subpopulations (flow cytometry), cortisol and catecholamine concentrations were determined. At 0 p in contrast to normoxia, during hypoxia there was no significant increase of granulocytes. There were no significant differences between normoxia and hypoxia in the increases from rest to 0 p in counts of monocytes, total lymphocytes and lymphocyte subpopulations [clusters of differentiation (CD), CD3⁺, CD4⁺CD45RO^–, CD4⁺CD45RO⁺, CD8⁺CD45RO^–, CD8⁺CD45RO⁺, CD3⁺HLA-DR⁺, CD3^–CD16/CD56⁺, CD3⁺CD16/CD56⁺, CD 19⁺] as well as adrenaline, noradrenaline and cortisol concentrations. The counts of CD3 ^–CD16/CD56⁺-and CD8 ⁺CD45RO⁺-cells increased most. At 60 p, CD3^–CD16/CD56⁺ and CD3⁺CD16/CD56⁺-cell counts were below pre-exercise levels and under hypoxia slightly but significantly lower than under normoxia. We concluded that the exercise-induced mobilization and redistribution of most leucocyte and lymphocyte subpopulations were unimpaired under acute hypoxia at sea level. Reduced increases of granulocyte counts during the study and reduced cell numbers of natural killer cells and cytotoxic, not major histocompatibility complex-restricted T-cells, only indicated marginal effects on the immune system.     

Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2

In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E₂ (PGE₂)mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 ,g/ml of water) or Indo (CIT; 10 g/ml) 5 days after s.c. transplantation of 5 × 10⁵ metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 g/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1⁺, Thy-1^–, Lyt-2^– phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20–23, 31–34) of IL-2 (15 000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1⁺, Thy-1^–, Lyt-2^–); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1⁺, Thy-1⁺ and Lyt-2⁺ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu + IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE₂ synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT. Thus, Ibu proved to be an excellent substitute for Indo in preventing metastasis and NK cell activation when given alone, and also in ameliorating established metastasis and activating lymphokine-activated killer cells when combined with IL-2.     

Amiloride enhances the secretion but not the synthesis of renin in renal juxtaglomerular cells

In this study we have examined a potential role of the sodium/proton exchange system in the regulation of renin secretion. We found that the inhibitors of the Na⁺/H⁺ antiport, amiloride (1 mM) and ethylisopro-pylamiloride (EIPA, 50 M), led to a 125% increase of renin secretion from cultured mouse juxtaglomerular cells. The stimulatory effect of EIPA on renin secretion was dependent on the extracellular concentrations of sodium and hydrogen ions. While lowering the extracellular pH from 7.3 to 7.0, and lowering [Na⁺]_e from 130 mM to 5 mM had no effect on basal renin release, it markedly attenuated or even blunted the effect of EIPA on renin secretion. The stimulatory effect of forskolin on renin secretion, however, was not altered by decreases of extracellular pH and of sodium. Inhibition of basal renin release was achieved with angiotensin II (1 M). In the presence of EIPA the inhibitory effect angiotensin II was markedly attenuated. Although effective on renin secretion, neither amiloride nor EIPA exerted a significant effect on the de novo synthesis of renin in cultured mouse JG cells. These findings are compatible with the idea that an amiloride-sensitive transport process, presumably the Na⁺/H⁺ exchanger, acts indirectly as an inhibitory signal transduction system for renin secretion from renal juxtaglomerular cells.     

Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions

An inward current characterized by a slow inactivation, was induced when the extracellular Ca^2– concentration was reduced by EGTA. It was suppressed by replacing external Na^– with Tris⁺ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na⁺ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 M for Ca²⁺ and 60 M for Mg²⁺. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa=7.5 or pCa>8, the single channel I-V relationship was linear and the slope conductance was 70–75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa=6 than at pCa=7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around –40 mV (pCa>8, with 5 M Bay K 8644 in the bath solution), which was decreased with increasing the Ca²⁺ concentration in the pipette solution. Noise power spectra of patch currents at pCa=6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca²⁺ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca²⁺ might be attributed to a rapid block by Ca²⁺.