Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness

Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.     

Effective and safe therapy with coenzyme Q10 for cardiomyopathy

Summary Coenzyme Q₁₀ (CoQ₁₀) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ₁₀ for cardiomyopathy. Patients were selected on the basis of clinical criteria,X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%–85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%–30%) showed the highest increases (115%–210%) and those with higher ejection fractions (50%–80%) showed increases of approx. 10%–25% on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ₁₀ enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ₁₀. Clinical responses on therapy with CoQ₁₀ appear maximal with blood levels of approx. 2.5 µg CoQ₁₀/ml and higher during therapy.Abbreviations CHF Congestive heart failure - CO Cardiac output - CoQ₁₀ Coenzyme Q₁₀ - EF Ejection fraction - IC Impedance cardiography - NYHA New York Heart Association - STI Systolic time interval     

Biological activity of thymus preparations from sheep of different ages

Research Institute of Epidemiology, Microbiology, and Infectious Diseases, Ministry of Health of the Uzbek SSR. Department of Immunology, Central Research Laboratory, Medical Institute, Tashkent. Research Institute of Physicochemical Medicine, Ministry of Health of the RSFSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. M. Lopukhin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 3, pp. 308–309, March, 1988.     

胃癌的细胞增殖、DNA增殖分数和倍性与患者生存的关系

目的：探讨胃癌细胞增殖、DNA增殖分数(S+G2/M期)和倍性与胃癌患者生存和生物学特性的关系。 方法： 应用流式细胞术，分别分析胃癌细胞群体的增殖、DNA增殖分数和倍性。 结果： 胃癌细胞群体的增殖和增殖分数之间无明显相关关系(P>0.05)；它们与胃癌患者的生存亦无明显相关关系(P>0.05)。胃癌细胞群体的增殖和DNA倍性与胃癌临床病理参数之间无明显相关关系(P>0.05)。胃癌患者DNA二倍体组和异倍体组Kaplan-Meier生存曲线经Log-rank检验有统计学差异（P<0.05）。 结论： 胃癌细胞的增殖和增殖分数与胃癌患者的生存无明显关系； DNA倍性分析对胃癌预后的判断具有重要参考价值。     

Effect of NO-generating compound NaNO<Subscript>2</Subscript> on ultrastructure of synaptic vesicles of glutamatergic synapses

Ultrastructure of synaptic vesicles in axon terminals of granule cells from isolated cerebellum of Rana temporaria frogs under the influence of NO-generating compound NaNO₂ in various concentrations and electrical stimulation was evaluated by the method of electron microscopy. NO-generating compound in low concentration induced translocation of synaptic vesicles and formation of small clusters. The size and structure of synaptic vesicles remained unchanged under these conditions. Increasing the concentration of NaNO₂ led to swelling of synaptic vesicles, formation of arranged heaps from individual vesicles or fusion of their content. Electrical stimulation of the cerebellum in the presence of NaNO₂ increased damage to synaptic vesicles. These experimental data model some stages observed in stroke. The formation of clusters from synaptic vesicles is a compensatory and adaptive response maintaining the structure of synaptic vesicles and protecting neurons from high concentrations of glutamate. Glutamate produces a toxic effect on nerve cells and glial cells of the cerebellum under pathological conditions, which is accompanied by impairment of signal transduction from presynaptic to postsynaptic neurons. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 7, pp. 13–17, July, 2008     

Human placentae membrane receptor for IgG—i. Studies on properties and solubilization of the receptor

Characterization of the human placental membrane receptor for human ¹²⁵I-IgG is described. The receptor bound specifically both monomers and aggregates of human IgG. Human colostral IgA, bovine, sheep, pig, and horse IgG were not bound. No effect of pH in the range 6.6–7.4, ionic strength in the range 0.1–0.5, and temperature between 4 and 45°C on the binding was found. A water-soluble fraction containing the active receptor (glycoprotein fraction-PGP) was obtained from the placental membranes using lithium diiodosalicylate. The solubilized receptor interacted with IgG better at 4°C than at 20°C or 37°C. The results on replacement of monomeric IgG by aggregated IgG, and vice versa, suggest that both monomers and aggregates of human IgG, were bound to the same receptor sites. The apparent association constant for monomeric human IgG was 0.86 ± 0.2 × 10⁷ mole^?1, and 2.0 ± 0.16 × 10¹⁵ IgG molecules were bound per l mg of the membrane protein. Formaldehyde (0.1%), 2-mercaptoethanol (50 mM), and periodate (4 mM) showed no effect on the binding properties of the membrane-bound and on the solubilized receptor, as well. Higher concentrations of periodate (10 mM or 20 mM) decreased the binding of IgG to membranes but showed no effect on the water-soluble receptor. Both the membrane-bound and the solubilized receptor were sensitive to papain. Pronose abolished the receptor activity after prolonged proteolysis only. Neuraminidase did not affect the activity of the receptor. The decrease of the binding activity of the membrane-bound receptor by trypsin and phospholipase C was due to a release of a material containing an active receptor. No effect of trypsin or phospholipase C on the activity of solubilized receptor was observed. The results obtained suggest a protein character of the placental Fc receptor. After electrophoresis of ¹²⁵I-labeled solubilized receptor in polyacrylamide gel in the presence of SDS, 2 major protein peaks with molecular weights of 74,000 and 104,000 and 3 minor peaks with molecular weights of 56,000, 144,000, and 163,000 were found.     

Effect of age on cardiac index,stroke index and left ventricular ejection fraction at rest and during exercise as studied by radiocardiography

Radiocardiography was used to measure cardiac output, stroke volume and left ventricular ejection fraction at rest and during muscular exercise in relation with age in 148 healthy subjects (age range: 6–78 years). A clear dependence of these parameters on age was found. The mean annual decrease at rest was 22±9 ml/min/m² for cardiac index, 0.22±0.04 ml/m² for stroke index and 0.0017±0.0003 for left ventricular ejection fraction. Male subjects had significantly (p < 0.001) greater cardiac (9±4%) and stroke indices (11±23%) than females. During submaximal exercise cardiac index increased from 3.5±0.7 l/min/m' to 8.1±1.6 l/min/m² in male subjects (mean age: 32 years) and from 3.1±0.4 l/min/m² to 7.2±1.2 l/min/ m² in female subjects (mean age: 29 years). The corresponding increases in stroke index and left ventricular ejection fraction were: from 52±7 ml/m² to 62±9 ml/m². from 46±7 ml/m² to 51±9 ml/m² and from 0.66±0.08 to 0.79±0.05 and from 0.64±0.10 to 0.72±0.10. In subjects who were 60 years and older the increases of these parameters during exercise were considerably smaller.     

Effectiveness of divergent selection for open-field activity in rabbits and correlated response for body weight and fertility

Two lines deriving from the same rabbit stock were selected for 8 generations for high (H) or low (L) locomotor activity score in the open field (OFS). The divergent selection was most effective up to the 3rd generation in the H line and up to the 4th generation in the L line. In further generations a decrease of OFS in the H line and a floor effect (OFS = 0) in the L line were observed. The mean OFS increased significantly in consecutive trials in the H line, whereas this increase was non-significant in the L line. There was a negative and very high correlation between the latency to enter the open field and the OFS (–0.95 and –0.98 for the H and L line, respectively). The realized heritability of the OFS was 0.46 and 0.23 in generations 0–3 within the L and H line, respectively, and 0.44 and –0.06 in generations 0–8. As calculated on the basis of divergent selection, the heritability was 0.31 and 0.15 for generations 0–3 and 0–8, respectively. The L rabbits were heavier shortly before (4th wk, P < 0.001) and after (8th wk, P < 0.01) weaning, than those of the H line, whereas the H rabbits grew faster (P < 0.05) between the 4th and 20th wk of age. There was a tendency for decreasing weight gains in consecutive generations. Generally, a lower percentage of H females delivered litters than those of the L line, but this was due to a very low percentage of such females in the 3rd and 6th generations. It can be assumed that H and L lines represent different, i.e., active and passive, coping strategies. These lines of rabbits offer increased possibilities for physiologically and ethologically oriented studies, e.g., on the welfare of caged animals.     

Antigen-specific,CD4+CD25+ regulatory T cell clones induced in Peyer's patches

Since intestine is exposed to numerous exogenous antigens such as food and commensal bacteria, the organ bears efficient mechanisms for establishment of tolerance and induction of regulatory T cells (T(reg)). Intestinal and inducible T(reg) include T(r)1-like and T(h)3 cells whose major effector molecules are IL-10 and transforming growth factor (TGF)-beta. These antigen-specific T(reg) are expected to become clinical targets to modify the inflammatory immune response associated with allergy, autoimmune diseases and transplantation. In the present study, we characterized the antigen-specific T(reg) induced in the intestine by orally administering high-dose beta-lactoglobulin (BLG) to BALB/c mice. Seven days after feeding, only Peyer's patch (PP) cells among different organs exerted significant suppressive effect on antibody production upon in vitro BLG stimulation. This suppressive effect was also prominent in six BLG-specific CD4(+) T cell clones (OPP1-6) established from PP from mice orally administered with high doses of BLG and was partially reversed by antibodies to TGF-beta. Intravenous transfer of OPP2 efficiently suppressed BLG-specific IgG1 production in serum following immunization, indicating the role of such T(reg) in the systemic tolerance after oral administration of antigen (oral tolerance). OPP clones secrete TGF-beta, IFN-gamma and low levels of IL-10, a cytokine pattern similar to that secreted by anergic T cells. OPP clones bear a CD4(+)CD25(+) phenotype and show significantly lower proliferative response compared to T(h)0 clones. This lower response is recovered by the addition of IL-2. Thus, antigen-specific CD4(+)CD25(+) T(reg), which have characteristics of anergic cells and actively suppress antibody production are induced in PP upon oral administration of protein antigen.