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Biomedical subjects

S Gu

Publications and source records attributed to S Gu.

At least 19 recordsLinked to original sources

Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10.

Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P=1.39 x 10(-10), odds ratio (OR)=9.43), especially with Chlamydophila psittaci (P=2.81 x 10(-7), OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P=8.03 x 10(-5), OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.

Adult↗

Scalar interaction limits from the beta-nu correlation of trapped radioactive atoms.

We have set limits on contributions of scalar interactions to nuclear beta decay. A magneto-optical trap provides a localized source of atoms suspended in space, so the low-energy recoiling nuclei can freely escape and be detected in coincidence with the beta. This allows reconstruction of the neutrino momentum, and the measurement of the beta-nu correlation, in a more direct fashion than previously possible. The beta-nu correlation parameter of the 0(+)-->0(+) pure Fermi decay of (38)K(m) is a =0.9981+/-0.0030+0.0032 / -0.0037, consistent with the standard model prediction a =1.

Journal Article↗

Novel search for heavy nu mixing from the beta+ decay of 38mK confined in an atom trap.

A new technique, full neutrino momentum reconstruction, is used to set limits on the admixture of heavy neutrinos into the electron neutrino. We measure coincidences between nuclear recoils and positrons from the beta decay of trapped radioactive atoms and deduce the neutrino momentum. A search for peaks in the reconstructed recoil time-of-flight spectrum as a function of positron energy is performed. The admixture upper limits range from 4 x 10(-3) to 2 x 10(-2) and are the best direct limits for neutrinos (as opposed to antineutrinos) for the mass region of 0.7 to 3.5 MeV.

Journal Article↗

Characterization of two novel KRAB-domain-containing zinc finger genes, ZNF460 and ZNF461, on human chromosome 19q13.1-->q13.4.

This study reports the cloning and characterization of two novel human zinc finger protein cDNAs (ZNF460 and ZNF461) from a fetal brain cDNA library. The ZNF460 cDNA is 3,135 bp in length encoding a 562-amino-acid polypeptide and the ZNF461 cDNA is 2,548 bp encoding a 563-amino-acid protein. Both of the proteins contain a KRAB A+B box and eleven C2H2 type zinc finger motifs. ZNF461 shows high similarity with the rat GIOT-1 gene (GIOT1). The ZNF460 gene mapped to 19q13.4 with 3 exons, and ZNF461 mapped to 19q13.1 with 6 exons. Both of the two genes are ubiquitously expressed in normal human tissues and the abundance of the ZNF460 mRNA is relatively low.

Amino Acid Sequence↗

The development-associated cleavage of lens connexin 45.6 by caspase-3-like protease is regulated by casein kinase II-mediated phosphorylation.

Gap junctions are important in maintaining lens transparency and metabolic homeostasis. In this paper, we report that the gap junction-forming protein, connexin (Cx) 45.6, was specifically truncated during lens development and that the majority of the truncated fragments were located in the differentiated lens fibers. When isolated lens membranes were treated by caspase-3, the truncated fragments of Cx45.6 were reproduced, and this truncation occurred at the COOH terminus of Cx45.6. Moreover, when primary lens cells were treated with apoptosis-inducing reagents, Cx45.6 was cleaved similarly as the in vitro treatment by caspase-3, and this cleavage was blocked by a caspase-3 inhibitor. These results suggest that caspase-3 is responsible for the development-associated cleavage of Cx45.6. The cleavage site of Cx45.6 was identified between amino acid residues Glu(367) and Gly(368). We have shown previously that Ser(363) is an in vivo phosphorylated site by casein kinase II, and this specific phosphorylation leads to a rapid turnover of Cx45.6. Interestingly, we found here that when Ser(363) was phosphorylated by casein kinase II, the cleavage of Cx45.6 catalyzed by caspase-3 was inhibited. This study, for the first time, demonstrates that a connexin can be a direct target of an apoptotic protease and that cleavage by caspase-3-like protease leads to the development-associated truncation of a lens connexin. Finally, caspase-3-mediated cleavage can be regulated by casein kinase II-mediated phosphorylation, suggesting that Cx45.6 turnover and specific cleavage by caspase-3-like protease is alternatively modulated.

Animals↗

A novel human amino acid transporter, hNAT3: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization.

Amino acid transporters are proteins that transport amino acids across the membrane. We report here the isolation and characterization of a novel human cDNA clone encoding a protein of 547 amino acids. This protein shares approximately 50% amino acid sequence homology with the amino acid transporters mouse mNAT and its orthologs, rat SN1 and human g17, and mouse GlnT/ATA1 and ATA2. Expression of this cRNA in Xenopus oocytes revealed that the strongest transport activities were specific for l-alanine. In addition, hNAT3 is a Na(+)- and pH-dependent, low-affinity transporter and partially tolerates substitution of Na(+) by Li(+). Since this protein has sequence and functional similarities to the previously identified system N amino acid transporters, we named this protein hNAT3. The genomic DNA sequence encoding the transcript of hNAT3 spans over 14 kb with 16 exons and 15 introns. Using fluorescence in situ hybridization, we mapped the hNAT3 gene to human chromosome 12q12-q13. By RT-PCR of embryonic and adult human tissues, hNAT3 was detected to be predominantly expressed in the liver and to a much lesser extent in the muscle, kidney, and pancreas. The data obtained in this study are likely to offer critical clues for identification of amino acid transporter-associated diseases.

Alanine↗

Cloning and expression pattern of the human NDRG3 gene.

We report the cloning and expression pattern of a novel N-myc downstream-regulated gene 3 (NDRG3), located on human chromosome 20q11.21-11.23. The NDRG3 cDNA is 2588 base pair in length, encoding a 363 amino acid polypeptide highly related to mouse Ndr3 protein. Northern blot reveals that NDRG3 is highly expressed in testis, prostate and ovary. By in situ hybridization, the NDRG3 mRNA was localized to the outer layers of seminiferous epithelium, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗

Characterization of an N-system amino acid transporter expressed in retina and its involvement in glutamine transport.

We report here on the characterization of a mouse N-system amino acid transporter protein, which is involved in the transport of glutamine. This protein of 485 amino acids shares 52% sequence homology with an N-system amino acid transporter, mouse N-system amino acid transporter (mNAT) and its orthologs. Because this protein shares a high degree of sequence homology and functional similarity to mNAT, we named it mNAT2. mNAT2 is predominately expressed in the retina and to a slightly lesser extent in the brain. In the retina, it is located in the axons of ganglion cells in the nerve fiber layer and in the bundles of the optic nerve. Functional analysis of mNAT2 expressed in Xenopus oocytes revealed that the strongest transport activities were specific for l-glutamine. In addition, mNAT2 is a Na(+)- and pH-dependent, high affinity transporter and partially tolerates substitution of Na(+) by Li(+). Additionally, mNAT2 functions as a carrier-mediated transporter that facilitates efflux. The unique expression pattern and selective glutamine transport properties of mNAT2 suggest that it plays a specific role in the uptake of glutamine involved in the generation of the neurotransmitter glutamate in retina.

Acetyltransferases↗

Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the itpa gene.

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC ). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose protein sequence has not been determined before. At the optimal pH of 10.0, recombinant hITPase hydrolyzed ITP, dITP, and xanthosine 5'-triphosphate to their respective monophosphates whereas activity with other nucleoside triphosphates was low. K(m) values for ITP, dITP, and xanthosine 5'-triphosphate were 0.51, 0.31, and 0.57 mm, respectively, and k(cat) values were 580, 360, and 640 s(-1), respectively. A divalent cation was absolutely required for activity. The gene encoding the hITPase cDNA sequence was localized by radiation hybrid mapping to chromosome 20p in the interval D20S113-D20S97, the same interval in which the ITPA inosine triphosphatase gene was previously localized. A BLAST search revealed the existence of many similar sequences in organisms ranging from bacteria to mammals. The function of this ubiquitous protein family is proposed to be the elimination of minor potentially mutagenic or clastogenic purine nucleoside triphosphates from the cell.

Amino Acid Sequence↗

Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells.

Chemokines and their receptors control the emigration of leukocytes during inflammation. The role of the RANTES (regulated on activation normal T-cell expressed and secreted) receptors CCR1 and CCR5 in the selective recruitment of monocytes, T(H)1-like T-cell clones, and peripheral T cells enriched for CD45RO(+) "memory" cells were tested in a system in which arrest under flow conditions is triggered by RANTES immobilized to activated endothelium. With the use of selective nonpeptide receptor antagonists or blocking antibodies, it was found that the RANTES-induced arrest of these cells was mediated predominantly by CCR1. In contrast, CCR5 mainly contributed to the spreading in shear flow, and both CCR1 and CCR5 supported transendothelial chemotaxis toward RANTES. The data in this study reveal specialized roles of apparently redundant receptors in distinct steps of leukocyte trafficking and suggest that not all receptors currently used to define mononuclear cell subsets are involved in their direct recruitment from the circulation.

Cell Adhesion↗

Cloning and characterization of a novel human leptin receptor overlapping transcript-like 1 gene (LEPROTL1).

A new full-length cDNA encoding a novel protein was isolated from our human fetal brain cDNA library. The cDNA consists of 2701 bp and has a putative open reading frame encoding 131 amino acids which possesses a JAK binding site (Pro(46)-Ile-Pro(48) which is preceded by a cluster of hydrophobic residues) and is highly homologous to the leptin receptor gene-related protein (OB-RGRP). Northern blot analysis showed that this new gene is widely expressed in human tissues and radiation hybrid mapping placed the gene to human chromosome 8p21.1-8p21.2.

Amino Acid Sequence↗

Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II.

The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3(+) lymphocytes over Th1-type CXCR3(+)/CCR5(+) leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune response in vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.

CCR5 Receptor Antagonists↗

Transitions in functional status among older people in Wuhan, China: socioeconomic differentials.

The vast majority of research on socioeconomic status (SES) and old-age disability is based on data derived from the developed nations. This study evaluates the external validity of current findings by examining old-age disability in China, a developing nation. The direct, indirect, and total effects of SES on disability transitions were ascertained during a 3-year period in a probability sample of 2,943 people aged 60 years or older in Wuhan, China. As SES measures, education and urban residence exert distinct direct and indirect effects on functional transitions with complicated underlying mechanisms. SES has differential effects on functional transitions depending on one's prior functional state. Furthermore, the generally positive effects of SES are partially offset by negative indirect effects

Aged↗

PDZ-binding kinase participates in spermatogenesis.

A cDNA clone denoted SPK (spermatogenesis-related protein kinase) was isolated from human fetal brain cDNA library. The deduced protein was 99% identical to human PDZ-binding kinase (PBK), which is a mitotic kinase. Its isoform, which is about 300 bp longer at 3' end, was also isolated in this study. SPK gene was assigned to human chromosome 8p21.2 by radiation hybrid. Northern blot analysis indicated that SPK mRNA was predominantly expressed in testis. SPK mRNA was localized to the outer cell layer of seminiferous tubules by in situ hybridization, suggesting involvement of it in the process of spermatogenesis.

Amino Acid Sequence↗

A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues.

We report the cloning and characterization of a novel human hydroxysteroid dehydrogenase like gene (HSDL1) located on human chromosome 16q24.2. The HSDL1 cDNA is 3407 base pair in length, encoding a 309 amino acid polypeptide related to human 17beta-HSD3. Northern blot reveals that the HSDL1 is highly expressed in testis and ovary. In situ hybridization indicates that the expression of HSDL1 is predominantly increased in the prostate cancer tissue compared with the normal prostate tissue, which suggests that the gene expression is important to the arising of prostate cancer.

Amino Acid Sequence↗

Correlation of rectum-associated lymph nodules with the development of experimentally induced acute colonic inflammation in rats.

BACKGROUND AND AIMS: The mechanisms of inflammation in ulcerative colitis occurring initially in the rectum and then extending throughout the colon are still unknown. The aim of this study is to investigate the correlation of rectum-associated lymph nodules (RALN) and the development of a dextran sulfate sodium-induced experimentally acute colonic inflammation in rats. METHODS: We immunohistochemically analyzed the lymph nodules in the rectal region of rats using monoclonal antibodies to specific markers. RESULTS: Rectum-associated lymph nodules resembled the Peyer's patches, where CD4+, CD8+ lymphocytes and Mar 1+ macrophages were observed. After the administration of dextran-sulfate sodium (DSS), RALN showed hypertrophy with an increase in the number of CD4+, CD8+, and interleukin (IL)-2R+ lymphocytes in the periphery, as well as Mar 1+ macrophages in the entire region. Concurrently, platelet/endothelin cell adhesion molecule-1 (PECAM-1+) blood vessels, including high-endothelial venules (HEV), were increased in number in the interfollicular areas. Furthermore, a number of small lymph nodules varying in size were observed in the upper region of the rectum. Some of them were initially confined to the lamina propria mucosae, and became large enough to extend deeper into the tela submucosa. These DSS-induced lymph nodules contained large numbers of CD4+ lymphocytes, IL-2R+ lymphocytes, and Mar 1+ macrophages. CONCLUSIONS: The pathological changes of ulcerative colitis were well correlated with the development of both RALN and DSS-induced lymph nodules. The immunological reaction that occurred in DSS-induced lymph nodules is significantly associated with the expansion of colitis from the lower region of rectum to the upper region of rectum and colon.

Animals↗