CHH with Early-Onset CAD

The patient with congenital hypogonadotropic hypogonadism (HH) shows low serum levels of androgen, which is a group of sex hormones including testosterone, caused by the decreased gonadotropin release in the hypothalamus. Recent reports showed androgens exert protective effects against insulin resistance or atherosclerotic diseases, such as diabetes mellitus or coronary artery disease. However, whether the juvenile hypogonadism affects the diabetes or cardiovascular disease is unclear. We report a case of a middle-aged man with congenital HH who had severe coronary artery disease complicated with metabolic disorders

Importance of the interferon-α system in murine large intestine indicated by microarray analysis of commensal bacteria-induced immunological changes

Abstract Background Although microbiota play a critical role in the normal development and function of host immune systems, the underlying mechanisms, especially those involved in the large intestine (LI), remain unknown. In the present study, we performed transcriptome analysis of the LI of germ-free (GF) and specific pathogen-free (SPF) mice of the IQI strain, an inbred strain established from ICR mice. Results GeneChip analysis, quantitative real-time RT-PCR, and reconfirmation using bacteria-inoculated GF mice revealed differences in the expression levels of several immune-related genes, such as cryptdin-related sequences (CRS), certain subsets of type 1 interferon (IFN)-related genes, class Ib MHC molecules, and certain complements. LI expressed no authentic cryptdins but predominantly expressed CRS2, 4, and 7. The mRNA levels of IFN-related genes, including Irf7, Isgf3g, Ifit1 and Stat1, were lower in SPF- and flora-reconstituted mice. When an oral IFN-α inducer tilorone analog, R11567DA, was administered to SPF mice, IFN-α was induced rapidly in the LI at 4 h, whereas no IFN-α protein was detected in the small intestine (SI) or blood. In situ hybridization and immunohistochemistry suggested that the IFN-α production originated from Paneth cells in the SI, and portions of lamina proprial CD11b- or mPDCA1-positive cells in the LI. Conclusion The present study suggests that microbial colonization, while inducing the expression of anti-microbial peptides, results in the down-regulation of certain genes responsible for immune responses, especially for type I IFN synthesis. This may reflect the adaptation process of the immune system in the LI to prevent excessive inflammation with respect to continuous microbial exposure. Further, the repertoire of anti-microbial peptides and the extraordinary role of interferon producing cells in the LI have been found to be distinct from those in the SI.</p

A microarray analysis of gnotobiotic mice indicating that microbial exposure during the neonatal period plays an essential role in immune system development

Abstract Background Epidemiological studies have suggested that the encounter with commensal microorganisms during the neonatal period is essential for normal development of the host immune system. Basic research involving gnotobiotic mice has demonstrated that colonization at the age of 5 weeks is too late to reconstitute normal immune function. In this study, we examined the transcriptome profiles of the large intestine (LI), small intestine (SI), liver (LIV), and spleen (SPL) of 3 bacterial colonization models—specific pathogen-free mice (SPF), ex-germ-free mice with bacterial reconstitution at the time of delivery (0WexGF), and ex-germ-free mice with bacterial reconstitution at 5 weeks of age (5WexGF)—and compared them with those of germ-free (GF) mice. Results Hundreds of genes were affected in all tissues in each of the colonized models; however, a gene set enrichment analysis method, MetaGene Profiler (MGP), demonstrated that the specific changes of Gene Ontology (GO) categories occurred predominantly in 0WexGF LI, SPF SI, and 5WexGF SPL, respectively. MGP analysis on signal pathways revealed prominent changes in toll-like receptor (TLR)- and type 1 interferon (IFN)-signaling in LI of 0WexGF and SPF mice, but not 5WexGF mice, while 5WexGF mice showed specific changes in chemokine signaling. RT-PCR analysis of TLR-related genes showed that the expression of interferon regulatory factor 3 (Irf3), a crucial rate-limiting transcription factor in the induction of type 1 IFN, prominently decreased in 0WexGF and SPF mice but not in 5WexGF and GF mice. Conclusion The present study provides important new information regarding the molecular mechanisms of the so-called "hygiene hypothesis".</p

Four hours after oral administration of R11567DA at 100 mg/kg, the small and large intestines were removed, homogenized, and centrifuged

The amounts of IFN-αs were measured by ELISA as described in Materials and Methods. Data represent mean ± SEM (n = 3). LI, large intestine; SI, small intestine, N.D., not detected (under detection limit), *, p < 0.0001 vs SI. Without R11567DA treatment, IFN-αs were not detected in any tissues or sera. This experiment was repeated twice with similar results.<p><b>Copyright information:</b></p><p>Taken from "Importance of the interferon-α system in murine large intestine indicated by microarray analysis of commensal bacteria-induced immunological changes"</p><p>http://www.biomedcentral.com/1471-2164/9/192</p><p>BMC Genomics 2008;9():192-192.</p><p>Published online 26 Apr 2008</p><p>PMCID:PMC2408602.</p><p></p

Cryostat sections of colonic tissues from mice 4 hr after the administration of saline or R11567DA

Sections were multi-labeled with anti-ISG and anti-CD11b, anti-CD11c, anti-mPDCA1 or DAPI. A, ISG15 signals were observed in colonic lamina propria of R11567DA-treated mice while saline treatment produced no signal. B, C. Portions of ISG15cells (green) were co-stained (yellow) with anti-CD11b antibody (red). Nuclei were visualized by DAPI staining (blue) in Panel B. D, ISG15CD11cdouble positive cells (yellow) were scarcely found. E, In addition to ISG15CD11bdouble-positive cells (yellow), ISG15mPDCA1double positive cells (white) were found. However, more than half of ISG15cells was stained by neither anti-CD11b nor anti-mPDCA1 antibodies (data not shown).<p><b>Copyright information:</b></p><p>Taken from "Importance of the interferon-α system in murine large intestine indicated by microarray analysis of commensal bacteria-induced immunological changes"</p><p>http://www.biomedcentral.com/1471-2164/9/192</p><p>BMC Genomics 2008;9():192-192.</p><p>Published online 26 Apr 2008</p><p>PMCID:PMC2408602.</p><p></p

Importance of the interferon-α system in murine large intestine indicated by microarray analysis of commensal bacteria-induced immunological changes-1

Ted in Paneth cells. In the large intestines, the signals were detected in the discrete cells distributed in lamina propria, though further examination is necessary to elucidate whether these signals were generated from the same cells, and to determine their cellular identity. Five sections per tissue were prepared from each of 8 mice. Representative photographs were shown.<p><b>Copyright information:</b></p><p>Taken from "Importance of the interferon-α system in murine large intestine indicated by microarray analysis of commensal bacteria-induced immunological changes"</p><p>http://www.biomedcentral.com/1471-2164/9/192</p><p>BMC Genomics 2008;9():192-192.</p><p>Published online 26 Apr 2008</p><p>PMCID:PMC2408602.</p><p></p