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  • 1
    ISSN: 1573-7217
    Keywords: p73 ; mutation ; breast cancer ; sporadic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, a novel tumor suppressor gene, p73, was isolated and mapped to chromosome 1p36, a region commonly associated with loss of heterozygosity in neuroblastoma and other human malignancies, including breast cancer. The p73 gene shares considerable homology with the common tumor suppressor gene p53, both in composition and function. This study examines the potential participation of p73 in the pathogenesis of sporadic and hereditary breast cancers. Mutation analysis of 29 hereditary breast cancer cases revealed five independent silent mutations in the hereditary cases that are unlikely to play a role in tumor development. Mutation analysis of 48 sporadic breast tumors did not identify any unique variants. Eleven common polymorphisms scattered throughout the gene were also detected. Thus, mutations in the p73 gene appear to play little if any role in hereditary or sporadic breast cancer.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Chemistry of materials 7 (1995), S. 1957-1967 
    ISSN: 1520-5002
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 34 (1995), S. 4139-4146 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Journal of the American Chemical Society 117 (1995), S. 554-555 
    ISSN: 1520-5126
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Keywords Nitric oxide ; nitrogen monoxide ; insulin secretion ; glucose ; nitric oxide synthase ; alpha cell ; beta cell ; delta cell.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of cells. In the present study rat pancreatic islets were perifused with physiologically relevant glucose concentrations in the presence or absence of various NO-modulating agents. Perifusion in the presence of 0.1–1 mmol/l of the NO synthase inhibitor, NG-monomethyl-L-arginine or of 10 μmol/l of the NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), resulted in an inhibition of the early phase of glucose-stimulated insulin secretion by 60–65 % and 46 %, respectively. Light- and electron-microscopic studies revealed that pancreatic islets constitutively express NO-synthase in alpha and delta cells, where it is confined to the secretory granules. Therefore, these data indicate that NO may be important in the signal transduction pathway of the early phase of glucose-stimulated insulin secretion. [Diabetologia (1998) 41: 292–299]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Transporters associated with antigen processing molecules (TAP1 and TAP2) mediate the transfer of cytosolic peptides into the lumen of the endoplasmic reticulum for association with newly synthesized class I molecules of the major histocompatibility complex. Previous molecular and functional analyses of rat and human TAP2 homologues indicated major differences in gene diversification patterns and selectivity of peptides transported. Therefore, in this study, we analyzed the alleles of the gorilla TAP2 locus to determine whether the pattern of diversification resembled that in either of those two species. Sequence analysis of the TAP2 cDNAs from gorilla Epstein-Barr virus-transformed B-cell lines revealed four alleles with a genetic distance of less than 1%. The nucleotide substitutions distinguishing the alleles are confined to the 3′ half of the coding region and occur individually or within two small clusters of variability. Diversification of the locus appears to have resulted from point substitutions and recombinational events. Evolutionary-rate estimates for the TAP2 gene in gorilla and human closely approximate those observed for other hominoid genes. The amino acid polymorphisms within the gorilla molecules are distinct from those in the human homologues. The absence of ancestral polymorphisms suggests that gorilla and human TAP2 genes have not evolved in a trans-species fashion but rather have diversified since the divergence of the lineages.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The New World primate, the cotton-top tamarin (Saguinus oedipus), expresses major histocompatibility complex (MHC) class I molecules with limited diversity. The uniqueness of the cotton-top tamarin MHC class I loci may contribute to this species’ unusual susceptibility to viral infections and high incidence of ulcerative colitis. As a prelude to examining the effect of this limited MHC class I diversity on the tamarin CD8+ T-cell receptor (TCR) repertoire, we identified expressed tamarin TCR β chain (TCRB) cDNAs by anchored and inverse polymerase chain reaction. Sequence alignments and phylogenetic comparisons with human and rhesus macaque sequences identified homologues of 21 human variable (V) gene families. Only single variable region genes were identified in each of these tamarin VB families, with the exception of the VB 5, 9, and 13 families which were comprised of two or three distinct members. The multiple genes within these three VB families do not appear to have separate human homologues, but rather aligned equally well to a single human gene from their respective VB families. These genes appear to have arisen, therefore, by duplication of certain VB genes in the tamarin ancestors following their divergence from the lineage leading to Old World primates and hominoids. Homologues of 12 of the 13 human joining (J) region genes were also identified in the tamarin. Comparison of the proportion of nonsynonymous (pN) and synonymous (pS) substitutions occurring per site within tamarin variable region genes demonstrated a reduction in pN in the framework regions compared with pN in the presumed MHC contact regions (CDR1 and CDR2). Taken together, these findings illustrate that the TCR β chain-encoding genes of the cotton-top tamarin are similar in structure and degree of complexity compared with their Old World primate and human counterparts.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Rhesus macaques represent important animal models for biomedical research. The ability to identify macaque major histocompatibility complex (Mhc) alleles is crucial for fully understanding these models of autoimmune and infectious disease. Here we describe a rapid and unambiguous way to distinguish DRB alleles in the rhesus macaque using the polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and direct sequencing. The highly variable second exon of Mamu-DRB alleles was amplified using generic DRB primers and alleles were separated by DGGE. DNA was then reamplified from plugs removed from the gel and alleles were determined using fluorescent-based sequencing. Validity of this typing procedure was confirmed by identification of all DRB alleles for three macaques previously characterized by cloning and sequencing techniques. Importantly, our analysis revealed DRB alleles not previously identified in the three reference animals. Using this technique, we identified 40 alleles in fifteen unrelated macaques. On the basis of phylogenetic tree analyses, 14 new DRB alleles were assigned to 10 different Mhc-DRB lineages. Interestingly, two of the new DRB6 lineages had previously been identified in prosimians and pigtailed macaques. Whereas traditional DRB typing methods provide limited information, our new technique provides a simple and relatively rapid way of identifying DRB alleles for tissue typing, determining individual identification and studies of disease association and susceptibility. This new technique should also contribute to ongoing studies of Mhc function and evolution in many different species of nonhuman primates.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Although the functions of the molecules encoded by the classical MHC class I loci are well defined, no function has been ascribed to the molecules encoded by the non-classical MHC class I loci. To investigate the evolution and conservation of the non-classical loci, we cloned and sequenced HLA-E homologues in macaques. We isolated four E locus alleles from five rhesus monkeys and two E locus alleles from one cynomolgus monkey, which indicated that the E locus in macaques is polymorphic. We also compared the rate of nucleotide substitution in the second intron of the macaque and human E locus alleles with that of exons two and three. The rate of nucleotide substitution was significantly higher in the introns, which suggested that the E locus has evolved under selective pressure. Additionally, comparison of the rates of synonymous and non-synonymous substitutions in the peptide binding region versus the remainder of the molecule suggested that the codons encoding the amino acids in the peptide binding region had been conserved in macaques and humans over the 36 million years since macaques and humans last shared a common ancestor.
    Type of Medium: Electronic Resource
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