Suppressor-cell dysfunction in children with histiocytosis-X

Suppressor-cell activity of peripheral blood mononuclear cells were examined and lymphocyte subsets analyzed in children with histocytosis-X and in healthy, age-matched subjects. Suppressor-cell function was assessed by two methods, the indomethacin stimulation of mitogen-activated cultures and the concanavalin A-inducible suppressor-cell assay. The results of these two assays indicate that children with active disease have significantly decreased suppressor-cell activity. Additionally, the percentage and absolute number of OKT8⁺ lymphocytes were decreased in children with active disease. Suppressor-cell activity and lymphocyte subsets returned to normal, baseline levels with disease remission. This study documents for the first time suppressor-cell dysfunction and supports previous investigations in which suppressor T lymphocytes are deficient in children with active disease. These findings may explain certain clinical manifestations seen in children with histiocytosis-X.     

IgE and atopy in perinatally HIV-infected children

Elevated serum immunoglobulin E (IgE) and increased prevalence of atopy is reported in patients infected with human immunodeficiency virus (HIV). The elevated serum IgE may be attributed to polyclonal stimulation of B cells or IgE production against allergens, viruses, fungi and bacteria. This study investigates the prevalence of atopy in perinatally HIV-infected children, and the relationships between serum IgE (and other serum immunoglobulins) with atopy, CD4+ cell count and HIV-disease stage. Serum immunoglobulin levels, epicutaneous skin test for common aeroallergens, clinical Centers for Disease Control and Prevention (CDC) classification, CD4+ cell counts and allergy history were extracted from the charts of perinatally HIV-infected children on highly active antiretroviral therapy. The prevalence of atopy (52%) and the pattern of aeroallergen sensitivity were comparable with the US pediatric population. Serum IgE levels did not correlate with clinical disease stage. However, in non-atopic patients, serum IgE levels increased with disease progression (p = 0.02). There was an inverse relationship between the prevalence of elevated serum IgE levels and atopy with progression of disease (p = 0.019). Serum IgE did not correlate with atopy, CD4+ cell count, or duration of HIV infection or levels of serum immunoglobulins. This is the first study to show no increased prevalence of atopy in perinatally HIV-infected children compared with the general population. In advanced stages of HIV, elevated serum IgE may be specific for antigens other than those known as allergens.     

Enhancing and suppressive effects of tumour necrosis factor/cachectin on growth of Trypanosoma musculi

The effect of human recombinant TNF on the growth of T. musculi has been investigated. When added to parasites cultured in vitro, TNF inhibited their growth. In the presence of thioglycollate-elicited peritoneal exudate cells, the opposite effect was seen and TNF enhanced the growth of trypanosomes in vitro. Similarly, administration of TNF in vivo during the course of infection led to a net increase in the parasite population. It is suggested that TNF exerts a direct antitrypanosomal effect while simultaneously promoting the growth of the parasite through an indirect effect mediated via the host's cells, possibly the macrophages.     

尿流式细胞学在诊断移植肾急性排斥反应中的应用价值

目的：探讨尿流式细胞学在诊断移植肾急性排斥反应中的临床应用价值。方法：对43例肾移植受者的116份尿样本进行尿流式细胞学分析，并将急性排斥组和肾功能稳定组的分析结果进行比较。结果：急性排斥反应组尿淋巴细胞总数以及HLA－DR^ 淋巴细胞数显著增多，与肾功能稳定组比较，P＜0．01，CD8^ 细胞亦增多（P＜0．05），而CD3^ ,CD4^ ,CD19^ 细胞数变化两组差异不显著（P＞0．05），在诊断移植肾急性排斥反应上，HLA－DR阳性样本和淋巴细胞数阳性样本的诊断敏感性和特异性分别达95．2％，90．5％，和92．6％，87．4％，结论：尿流式细胞学分析可反映移植肾内的免疫状态，尿淋巴细胞数的显著增多和尿HLA－DR^ 淋巴细胞增多可以作为诊断急性排斥反应的有意义指标。     

母血中胎儿有核红细胞的荧光原位杂交法在产前诊断中的可行性探讨

探讨荧光原位杂交法（FISH）对母血中胎儿有核红细胞（NRBC）进行无创性产前诊断的可行性。20例孕龄15-20周的孕妇外周血经不连续密度梯度离心、制片、显微镜下识别并共计数NRBC及定位，然后行Y染色体的FISH检测。结果发现10例孕男性胎儿的孕妇外周血细胞涂片中每例均有阳性杂交信号出现；阳性率为60％（24/40）。10例孕女性胎儿的孕妇外周血细胞涂片中1例出现阳性杂交信号；阴性率为95％（38/40），假阳性率仅为5％（2/40）。结果提示FISH法对于用母血中分离到的胎儿细胞进行染色体异常的无创性产前遗传学检查具有重要意义。     

Sarcoidosis and primary biliary cirrhosis

Summary An unusual case of a woman with primary biliary cirrhosis and cutaneous sarcoidosis is described. The factors that allow a specific diagnosis of each condition are presented and the literature pertaining to such complex and unusual cases is presented.This work was supported in part by a grant from the Gastroenterology Medical Research Foundation of Southwestern Pennsylvania.     

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models. Here we show that blocking the 4-1BB pathway significantly inhibited rejection of intestinal allografts by CD8+ but not CD4+ T cells. This effect was associated with significantly decreased expression of the genes encoding TNFalpha and secondary lymphoid chemokine (SLC) within the spleens of recipient mice. Disruption of the 4-1BB pathway also impaired the priming of alloantigen-specific CD8+ T cells and the accumulation of recipient dendritic cells within the spleen. These data directly demonstrate an important role for 4-1BB in allograft rejection; particularly rejection mediated by CD8+ T cells. Our data suggest that in addition to providing a direct costimulatory signal to T cells, the 4-1BB pathway may regulate other important steps in the immune response such as the migration of T cells and dendritic cells.     

DIFF33H参与TRAIL诱导的人Jurkat T淋巴细胞白血病细胞凋亡调控

目的：研究DIFF33H在人T淋巴细胞白血病细胞Jurkat凋亡中的表达规律及其生物学功能。方法：采用PCR扩增DIFF33H cDNA，Northern blot分析DIFF33H的mRNA表达，MTT法测定细胞凋亡。结果：在重组可溶性TRAIL诱导的人T淋巴细胞白血病细胞Jurkat凋亡过程中，DIFF33H mRNA的表达水平随着Jurkat细胞的凋亡而下降，并对重组可溶性TRAIL的作用具有浓度和时间的依赖性。在抗肿瘤药物5-FU诱导肿瘤细胞凋亡过程中，DIFF33H的mRNA表达水平也显著下降。结论：DIFF33H参与人T淋巴细胞白血病细胞Jurkat凋亡的调控。     

Biological characterization of glutaraldehyde-modified Parietaria judaica pollen extracts

BACKGROUND: Allergoids are widely used in specific immunotherapy (SIT) for the treatment of IgE-mediated allergic diseases, but all techniques for standardization of conventional allergic extracts may not be appropriate for standardization of a glutaraldehyde (GA)-modified extract because of the unique characteristics of these extracts. OBJECTIVE: To assess an accurate methodology for standardization of chemically modified extracts. METHODS: GA-modified extracts from Parietaria judaica pollen were purified by diafiltration. Biochemical properties were investigated by determination of amino groups, chromatography, and SDS-PAGE. The IgE-binding activity was determined by skin prick test, enzyme allergosorbent test inhibition, basophil activation, and histamine release tests. Peripheral blood mononuclear cells (PBMCs) from P. judaica pollen-allergic subjects were stimulated with either native or allergoid extracts, and proliferation was measured. RESULTS: Biochemical data indicated a high degree of allergen polymerization resulting in extract components higher than 100 kDa. IgE-binding activity, both in vivo and in vitro, was reduced by more than 99.8%. Both allergen and allergoid induced PBMC proliferation and synthesis of blocking IgG antibodies at similar rates. Moreover, no evidence of introduction of new determinants by chemical modification was found. CONCLUSIONS: The preparation of GA-modified extracts by diafiltration is faster and more reliable than previous chromatographic methods. These modified extracts have drastically reduced their allergenicity while maintaining their immunogenicity, and therefore they can be used in safer and shortened schedules of SIT.     

Lymphocyte T helper-specific reactivity in sustained responders to interferon and ribavirin with negativation (seroreversion) of anti-hepatitis C virus.

BACKGROUND: Seroreversion, negativation of anti-hepatitis C virus previously positive, is sometimes found in some chronic hepatitis C-sustained responders (SRs) to antiviral therapy. AIMS: To determine the probability of seroreversion in SR treatment with Interferon and Ribavirin, and lymphocyte T helper (CD4+) reactivity to HCV antigens. METHODS: Thirty SR were followed on average for 54.8 months. Anti-HCV was tested by third generation test. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and cultured to evaluate CD4+ proliferation in response to 2 microg/ml of eight HCV recombinant antigens from core, NS3, NS4, NS5 regions. RESULTS: Seroreversion was verified in 23% of patients (7/30), appearing at 47.5+/-24.0 months. The probability of anti-HCV loss in this group was 25% at 56 months after ending therapy. In 57% (4/7), anti-HCV returned to positive. These 7 SR patients with seroreversion also showed weaker CD4+ reactivity in 5% of tests (3/56) than the remaining 23 anti-HCV-positive SRs who showed stronger reactivity in 18% of tests (33/184), P=0.036. CONCLUSIONS: One-quarter of the SR showed seroreversion of anti-HCV and weaker CD4+ specific HCV proliferation than those who remained anti-HCV positive. The data suggest that complete viral eradication is a possible and achievable clinical objective.