Duplication 10q confirmed by DNA in situ hybridization

Partial duplication of 10q is a recognizable clinical entity. In most of the reported cases, the trisomic segment is identified by a balanced translocation state in a parent. Verification remains a problem in de novo cases. However, the recent availability of whole chromosome probes allows for confirmatory diagnosis of suspected cases. We describe a case of de novo duplication (10q) wiht verification using DNA in situ hybridization. © 1994 Wiley-Liss, Inc.     

The modulating effects of proinflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and immunoregulating cytokines IL-10 and transforming growth factor-beta (TGF-beta), on anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex

We assessed the roles of proinflammatory cytokines IFN-gamma and TNF-alpha, and immunoregulatory cytokines IL-10 and TGF-beta in the modulation of the anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex (MAIC). First, both IFN-gamma and TNF-alpha significantly reduced the bacterial growth in macrophages, indicating that these cytokines participate in up-regulation of macrophage anti-MAIC function. Second, although MAIC-infected macrophages produced substantial amounts of IL-10 and TGF-beta, neutralization of endogenous IL-10 and TGF-beta with anti-IL-10 and anti-TGF-beta antibodies, respectively, did not affect the intracellular growth of MAIC in macrophages from mice with BcgS (MAIC-susceptible) or BcgI (MAIC-resistant) genotype, regardless of the virulence of test MAIC strains. The same result was also obtained for macrophages stimulated with IFN-gamma or TNF-alpha. Third, in MAIC-infected mice, the growth of organisms at the sites of infection (lungs and spleens) was not affected by administration of anti-IL-10 or anti-TGF-beta antibodies. These findings indicate that, in the case of mice, endogenous IL-10 and TGF-beta are essentially ineffective in down-regulating macrophage anti-MAIC functions not only in vitro but also in vivo.     

IL-10 Secretion and Sensitivity in Normal Human Intestine and Inflammatory Bowel Disease

Interleukin-10 (IL-10) deficiency in gene knockout mice causes chronic enterocolitis. We hypothesized that inflammation in human inflammatory bowel disease might result from innate alterations in the IL-10 pathway. Serum, supernatants, and mRNA of peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) derived from inflamed (LPMC-i) and noninflamed colonic mucosa (LPMC-ni) were collected from patients with Crohn's colitis, ulcerative colitis, and controls. IL-10 protein concentrations and IL-10 mRNA were examined in response to PMA/CD3 or PHA stimulation. The response to rhIL-10 was assessed by inhibition of tumor necrosis factor-alpha (TNF-), IL-6, and interferon-gamma (IFN-) production. Serum IL-10 levels of inflammatory bowel disease (IBD) patients were within the normal range. IL-10 concentrations in supernatants from LPMC-i were significantly lower than from LPMC-ni or PBMC. No difference was seen between samples from ulcerative colitis and Crohn's disease. IL-10 mRNA was detected in 0/4 LPMC-i samples compared to 1/6 LPMC-ni and 6/6 PBMC. RhIL-10 inhibited TNF-, IL-6, and IFN- synthesis in PBMC. This effect was strongly diminished in LPMC. Disease-specific alterations were not detected. Our data suggest that LPMC derived from inflamed colonic mucosa have a reduced ability to produce and to respond to rhIL-10. A disease-specific alteration in the IL-10 pathway, however, was not found.     

Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation

Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy‐prone infants. Methods In a randomized double‐blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C‐reactive protein (CRP), total IgA and IgE, food‐specific IgA, IgG, and IgE, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, and IFN‐γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL‐10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy‐prone children supports the view that chronic, low‐grade inflammation protects from eczema. Probiotic‐induced low‐grade inflammation was characterized by elevation of IgE, IgA, and IL‐10, the changes typically observed in helminth infection‐associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.     

Absence of either gastric or intestinal phenotype in microscopic differentiated gastric carcinomas

Differentiated gastric carcinoma (DGC) corresponds roughly to the intestinal type of gastric carcinoma described by Laurén. It has been suggested that DGCs arise from intestinalized gastric mucosa, but recent findings regarding their mucin expression do not support this hypothesis. To evaluate the histogenetic relationship between DGCs and intestinal metaplasia, lesions that are as small as possible should be examined. Twenty-five DGCs, ranging in their greatest dimension from 0.4 to 2.7 mm, were collected and divided into two groups by size. Group A consisted of 13 lesions less than 1.4 mm across, and group B of 12 lesions 1.4 mm or more. The presence of mucin and a brush border was assessed by immunostaining with antibodies against human gastric mucin, pyloric-gland-type mucin, Muc-2 glycoprotein, and CD10 antigen, and the lesions were classified as having the gastric phenotype (G-type), intestinal phenotype (I-type), mixed gastric and intestinal phenotype (M-type), or null phenotype (N-type). Thirteen (52%) of the 25 lesions were N-type, 5 (20%) lesions were G-type, 5 (20%) were I-type, and 2 (8%) were M-type. Group A had a larger proportion of N-type lesions than B (10/13, or 77%, vs. 3/12, or 25%; p = 0.027, chi-square test for proportions). Group B had a larger proportion of G-type lesions than A (5/12, or 42%, vs. 0/13, or 0%; p = 0.033). The phenotypes of the carcinomas and their surrounding mucosa were unrelated. Therefore, DGCs may arise from gastric mucosa affected by intestinal metaplasia or not, without having either the gastric or intestinal phenotype.     

CD4+CD25+T细胞在系统性红斑狼疮中的表达及意义

目的：探讨CD4^＋ CD25^＋ T细胞、IL-10在系统性红斑狼疮（SLE）患者外周血的表达及临床意义。方法：入组30例SLE患者和20例正常对照者，其中活动性SLE患者17人，非活动性SLE患者13人。用流式细胞仪检测SLE患者和正常对照者的外周血CD4^＋ CD25^＋ T细胞阳性率，用酶联免疫吸附试验（ELISA）检测血清中IL-10浓度。结果：活动性和非活动性SLE患者CD4^＋ T细胞总数均低于正常对照者；活动性和非活动性SLE患者CD4^＋ CD25^＋ T细胞阳性率高于正常对照者；活动性SLE患者IL-10浓度显著高于非活动性SLE患者和正常对照者。SLE患者CD4^＋ CD25^＋ T细胞阳性率和血清IL-10浓度与补体C3、抗DNA抗体水平及SLEDAI积分均无相关性。结论：SLE患者外周血CD4^＋ CD25^＋ T细胞是活化T细胞的标志，IL-10分泌异常与SLE的发病有关。     

Genetic variations in five genes involved in the excitement of cardiomyocytes

We provide here 29 genetic variations, including 28 novel ones, in five genes that are potentially involved in the excitement of cardiomyocytes: we found 4 in KCNA10, 2 in KCNK1, 8 in KCNK6, 11 in SLC18A1 (VMAT1), and 4 in SLC6A2 (norepinephrine transporter). We also examined their allelic frequencies in a Japanese population of long QT syndrome-affected and nonaffected individuals. These data would be useful for genetic association studies designed to investigate acquired arrhythmias. Received: May 22, 2001 / Accepted: June 8, 2001     

Cross-regulatory role of interferon-gamma (IFN-gamma), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation.

This study examined the relationship of IL-4, IL-10 and IFN-gamma with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL-10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity. Cytokine neutralization was performed in egg-challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation. Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-10 and IL-5 increased by nearly two-, four-, five- and six-fold, respectively. Anti-IL-10 did not affect GR size or GR cytokines, but abrogated GR area by 40%, along with a reduction in local IL-4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60-70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits Th1 cells. IL-4 fosters Th2 cells differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function.     

Additive cytotoxicity of adriamycin and a naturally occurring growth inhibitor extracted from bovine aorta

A factor of nominal molecular weight 6K–10K Daltons, isolated from bovine aorta, has previously been shown to inhibit neovascularization and tumor growth in vivo and the growth of some tumor cells as well as endothelial cells in culture. This factor, termed A-10, was tested alone and in combination with Adriamycin against TA3Ha mammary adenocarcinoma cells in tissue culture. It was found to have cytotoxicity additive to that of Adriamycin in inhibiting the growth of these cells. In vitro and animal studies show that the sequence of Adriamycin A-10 is superior to either agent alone in delaying the appearance of palpable tumors after subcutaneous injection of 10⁵ pre-treated tumor cells in the tail of strain A mice. While the growth rate of the primary tumor was not affected by such treatment, survival was prolonged to a greater degree by the this sequence than by either of these agents used alone. A-10 treatment reduced the number of metastases to the adrenal gland but not to lung, liver, or lymph nodes. It did, however, reduce the size of metastases to para-aortic lymph nodes.