Cardiovascular risk factors in subjects with Helicobacter pylori infection

Background. It has been proposed that Helicobacter pylori infection is related to cardiovascular disease, although this has not been fully investigated. The aim of this study was to investigate whether H. pylori in‐fection is associated with cardiovascular risk factors. Subjects and Methods. One thousand six hundred and fifty people undergoing annual medical checks at Shimane Institute of Health Science between September 1998 and August 1999 were enrolled. Gender, age, body mass index, habitual smoking and drinking, systolic and diastolic blood pressure, serum level of total cholesterol, triglyceride, high‐density lipoprotein cholesterol (HDLC), blood glucose, leukocyte count and hemoglobin were compared between H. pylori seropositive and seronegative cases. Results. In H. pylori seropositive individuals, HDLC was significantly lower than that in seronegative individuals. After adjustment for possible confounding factors (gender, age, BMI, smoking and drinking habits), mean HDLC in H. pylori‐seropositive and seronegative individuals were 56.1 and 58.2 mg/dl, respectively (p < .005). The percentage of the elderly (over 50 years old) individuals with HDLC < 35 mg/dl in H. pylori seropositive and seronegative groups were 7.4% and 4.7%, respectively (p < .001). In addition, the lower HDLC level was accompanied by an increased leukocyte count. Conclusion. Long‐term infection with H. pylori may have an important role in decreasing the serum HDLC concentration.     

Stromal-derived factor 1 expression in the human thymus

Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoietic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HC). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes.     

Mechanism of action of combined short-term CTLA4Ig and anti-CD40 ligand in murine systemic lupus erythematosus

Short-term combination therapy with the costimulatory antagonists CTLA4Ig and anti-CD40 ligand induces prolonged suppression of disease onset in New Zealand Black/New Zealand White F(1) systemic lupus erythematosus-prone mice. To determine the mechanism for this effect, 20- to 22-wk-old New Zealand Black/New Zealand White F(1) mice were treated with six doses each of CTLA4Ig and anti-CD40 ligand Ab over 2 wk. Combination-treated mice, but not mice treated with either agent alone, had prolonged survival and the production of pathogenic IgG anti-dsDNA Ab was suppressed. Twenty weeks after completion of treatment the frequency of activated B cells producing anti-dsDNA Ab was decreased, and the abnormal transition of T cells from the naive to the memory compartment was blocked. Combination treatment partially suppressed class switching and decreased the frequency of somatic mutations in the V(H)BW-16 gene, which is expressed by pathogenic anti-DNA Abs. Treated mice were still able to respond to the hapten oxazolone when it was given 8 wk after treatment initiation, and they mounted a somatically mutated IgG anti-oxazolone response that was noncross-reactive with dsDNA. Fifty to 60% of previously treated mice, but only 14% of previously untreated mice, responded within 2-3 wk to a second course of therapy given at the onset of fixed proteinuria and remained well for a further 3-4 mo. Although this treatment had no immediate effect on serum anti-dsDNA Abs or on the abnormal T cell activation observed in sick mice, 25% of treated mice lived for >18 mo compared with 5% of untreated controls. These results suggest that the effect of costimulatory blockade in remission induction must be mediated by a different mechanism than is demonstrated in the disease prevention studies.     

pilG Gene cluster and split pilL genes involved in pilus biogenesis,motility and genetic transformation in the cyanobacterium Synechocystis sp. PCC 6803

The unicellular motile cyanobacterium Synechocystis sp. PCC 6803 exhibits phototactic motility that depends on the type IV-like thick pilus structure. By gene disruption analysis, we showed that a gene cluster of slr1041, slr1042, slr1043 and slr1044, whose predicted products are homologous to PatA, CheY, CheW and MCP, respectively, was more or less required for pilus assembly, motility and natural transformation competency with extraneous DNA. By sequence homology, the missing cheA-like gene in this cluster was identified as novel split genes, slr0073 and slr0322, at separate loci on the genome. This was confirmed by non-motile phenotype of their disruptants. Unique hyperpiliation was observed in the slr1042 and slr0073 disruptants, suggestive of their specific interaction with pilT1. The genes, thus identified as pil genes in this study, were designated pilG (slr1041), pilH (slr1042), pilI (slr1043), pilJ (slr1044), pilL-N (slr0073) and pilL-C (slr0322).     

Y-chromosomal red-green opsin genes of nocturnal New World monkey

The X-chromosomal locality of the red-green-sensitive opsin genes has been the norm for all mammals and is essential for color vision of higher primates. Owl monkeys (Aotus), a genus of New World monkeys, are the only nocturnal higher primates and are severely color-blind. We demonstrate that the owl monkeys possess extra red-green opsin genes on the Y-chromosome. The Y-linked opsin genes were found to be extremely varied, in one male appearing to be a functional gene and in other males to be multicopy pseudogenes. These Y-linked opsin genes should offer a rare opportunity to study the evolutionary fate of genes translocated to the Y chromosome.     

A zigzag chain coordination polymer consisting of silver(I) ion having square planar geometry

Silver(I) complexes of hexakis(tolylsulfanyl)benzene (htsb), [Ag(htsb)](PF₆) (1), have been prepared and their molecular structures were determined by X-ray crystallography. In 1, the silver ion prefers a square planar coordination geometry comprized of four S atoms from two different htsb molecules and producing a zigzag chain structure of AgS in the silver coordination polymer. Based on the thermo-gravimetry analysis results, two tolylsulfanyl groups were easily eliminated at approximately 211 °C. However, [Ag(htsb)(2-butanone)] (PF₆) (2), which were obtained by the reactions in different solvents, showed a different colors and thermal degradation behaviors.     

Syntheses and crystal structures of mononuclear [2.2]paracyclophane complexes of rhodium and iridium supported by the pentamethylcyclopentadienyl ligand [M(η-pcp)(η-C5Me5)](BF4)2 (M=Rh and Ir)

Mononuclear [2.2]paracyclophane complexes of Rh and Ir, [M(η⁶-pcp)(η⁵-C₅Me₅)](BF₄)₂ (M=Rh (1) and Ir (2); pcp=[2.2]paracyclophane) were crystallized and their structures were first characterized crystallographically. On both pcp complexes the metal atom is bonded to the benzene ring on one side of the pcp ligand in the η⁶-coordination mode. The metal atom is also supported by the η⁵-C₅Me₅ ligand to afford a triple-decker sandwich structure. In Rh pcp complex 1 the average RhC(pcp) and RhC(C₅Me₅) distances are 2.284(2) and 2.161(2) Å, respectively. The average C(pcp)C(pcp) distance of 1.407(4) Å with the Rh atom is longer than that (1.388(4) Å) without a Rh atom. Similarly, the average IrC(pcp) and IrC(C₅Me₅) distances in Ir pcp complex 2 are 2.275(3) and 2.174(3) Å, respectively. The average C(pcp)C(pcp) distance of 1.410(4) Å with the Ir atom is longer than that (1.388(4) Å) without an Ir atom. It is interesting that the average interannular distances of 2.97 Å for 1 and 2 between two decks of the pcp ligand are shorter than that (3.09 Å) of the metal-free pcp ligand, indicative of the decrease of the repulsive π-interaction between benzene rings. The Rh pcp complex gave the well-resolved ¹H NMR signals of [Rh(η⁶-pcp)(η⁵-C₅Me₅)]²⁺, whereas the Ir pcp complex exhibited two kinds of ¹H NMR signals which were assigned as [Ir(η⁶-pcp)(η⁵-C₅Me₅)]²⁺ and [Ir₂(η⁶-pcp)(η⁵-C₅Me₅)₂]⁴⁺ in (CD₃)₂CO at 23 °C.     

Gene amplification profiling of esophageal squamous cell carcinomas by DNA array CGH

Gene amplification is one of the basic mechanisms that lead to overexpression of oncogenes. DNA array comparative genomic hybridization (CGH) has great potential for comprehensive analysis of both a relative gene-copy number and altered chromosomal regions in cancers, which enables us to identify new amplified genes and unstable chromosomal loci. We examined the amplification status in 32 esophageal squamous cell carcinomas (ESCCs) and 13 ESCC cell lines on 51 frequently amplified loci in a variety of cancers by both DNA array CGH and Southern blot analyses. The 1p34 locus containing MYCL1, 2p24 (MYCN), 7p12 (EGFR), and 12q14 (MDM2) were amplified in one of the 32 cases (3%), and the 17q12 locus (ERBB2) and 8p11 (FGFR1) in two of the 32 cases (6%), while only the 11q13 locus (Cyclin D1, FGF4, and EMS1) was frequently amplified (28%, 9/32), demonstrating this locus to be a major target in ESCCs. One locus, 8q24 (c-MYC) was found to be amplified only in the cell lines. Eight out of 51 loci (15.7%) were found to be amplified in at least one of the 32 primary ESCCs or the 13 ESCC cell lines, suggesting that chromosomal loci frequently amplified in a type of human cancer may also be amplified in other types of cancers. This paper is the first report of an application of DNA array CGH to ESCCs.     

Downregulation of bcl-xL is relevant to UV-induced apoptosis in fibroblasts

Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells. The caspase group of proteases is required for the apoptosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. These results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of fibroblasts.