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  • 1
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Osteoporosis, a condition characterized by low bone mineral density (BMD) leading to bone fragility [1], is a major public health concern in Japan as well as in other countries. Although genetic predisposition seems to be a factor in the pathogenesis of osteoporosis [2–4], the precise cohort of genes that may be involved is not well defined. The COLIA1 and COLIA2 genes encode polypeptide constituents of collagen type Iα1 and Iα2, respectively. Both are important candidates as genetic regulators of BMD, since mutations in either gene result in osteogenesis imperfecta, a disorder characterized by severe osteoporosis [5]. Some patients with adult osteoporosis also carry mutations in COLIA1 or COLIA2 genes [6].
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Osteopenia and osteoporosis are common human conditions considered to result from the interplay of multiple genetic and environmental factors. Twin and family studies have yielded strong correlations between levels of bone mass and a number of genetic factors. The genes involved could regulate metabolism, formation and resorption of bone, all processes that determine bone mass. We tested 192 sibling pairs of adult Japanese women from 136 families for genetic linkage between osteopenia and allelic variants of four candidate genes (interleukin-6, interleukin-6 receptor, calcium-sensing receptor, and matrix gla protein) using qualitative and quantitative methods, and using as genetic markers dinucleotide-repeat polymorphisms present in or near each of those loci. The interleukin-6 locus showed evidence of linkage to osteopenia analyzed as a qualitative trait, with mean allele sharing of 0.40 (P=0.0001) in discordant pairs and 0.55 (P=0.04) in concordant affected pairs. Variation at this locus was also linked to decreased bone mineral density measured as a quantitative trait (P=0.02). Analyses limited only to the post-menopausal women showed similar or even stronger results. No other locus among those tested showed any evidence of linkage by either method. The results provided strong evidence that genetic variation at the interleukin-6 locus affects regulation of bone mineral metabolism and confers risk for osteopenia and osteoporosis in adult women.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-232X
    Keywords: Key words Tumor necrosis factor ; Dinucleotide repeat rheumatoid arthritis ; Obesity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Tumor necrosis factor alpha (TNFα) in activated monocytes exerts cytotoxic activity and has a variety of other biological effects. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the gene located at 6p21.3. High heterozygosity (0.80) makes this polymorphism a useful marker in the genetic study of disorders affecting immunological response and cell differentiation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-232X
    Keywords: Key words Progesterone receptor ; CA repeat ; Progesterone resistance ; Pseudocorpus luteum insufficiency ; Female endocrine system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the human progesterone receptor (PGR) gene. This polymorphism will be a useful marker in the genetic study of disorders affecting female endocrine systems, such as progesterone resistance and breast, uterine, and ovarian cancers.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-232X
    Keywords: Key wordsRET proto-oncogene ; TRK proto-oncogene ; Papillary thyroid carcinoma ; Rearrangement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Rearrangements of the RET and TRK proto-oncogenes, which generate fusion oncogenes, are frequent in papillary thyroid carcinomas in Caucasian populations. To determine the spectrum of gene rearrangements in Japanese patients, we systematically examined 40 papillary thyroid carcinomas for all possible types of gene fusion events involving RET or TRK genes. RET rearrangements were found in ten tumors (25%): ret/PTC1 had occurred in two tumors, ret/PTC2 in one, ret/PTC3 in six, and a novel RET rearrangement in the remaining patient. In this last patient, the 5′ novel sequence was fused in-frame to the RET amino acid sequence; thus, the fusion gene may encode a protein with a RET kinase domain at the carboxy terminus. The RET gene was fused to 5′ donor sequences at the beginning of exon 12 in all ten tumors. No rearrangements involving the TRK gene were found in this panel of carcinomas. Our results indicated that constitutive activation of the RET by gene rearrangement is a frequent mechanism of papillary thyroid carcinogenesis in Japanese adults.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-232X
    Keywords: Key words Interleukin 6 ; Bone mineral density ; Osteo-porosis ; Association study ; Microsatellite marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Twin studies have shown strong correlations between bone mass and genetic factors. Some of the genes involved could regulate bone metabolism and bone formation and resorption, all processes that determine bone mass. One candidate gene, interleukin 6 (IL-6), has been implicated in the pathogenesis of bone loss because it stimulates osteoclasts. We investigated a possible association between the CA repeat polymorphism at the IL-6 gene locus and the bone mineral density (BMD) of radial bone in 472 postmenopausal Japanese women. Genotypes were classified into six groups according to the number of CA repeats present, from 13 to 18. BMD was expressed as adjusted BMD, which was the body mass index (BMI)- and age-adjusted average BMD. The 73 women who possessed an A1 allele (134 bp, containing 18 repeats of CA) had significantly lower adjusted BMD than those participants (n = 399) who did not carry an allele of that size (mean ± SD values, 0.294 ± 0.064 vs 0.312 ± 0.061 g/cm2; P = 0.0221). This result suggests that genetic variation at the IL-6 gene locus is associated with some determinants of BMD in postmenopausal women.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-232X
    Keywords: Key words nuclear factor kappa-beta subunit 1 ; dinucleotide repeat ; immune response ; cell differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The transcriptional factor nuclear factor kappa-beta (NFKB) consists of a multicomponent protein complex that plays a major role in the regulation of many viral and cellular genes. The NFKB complex has two alternative DNA binding subunits. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the NFKB subunit 1 (NFKB1) gene located at 4q23–24. High heterozygosity (0.813) makes this polymorphism a useful marker in the genetic study of disorders affecting the immune response and cell differentiation.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of human genetics 44 (1999), S. 354-355 
    ISSN: 1435-232X
    Keywords: Key wordshSNF5/INI1 gene ; Single nucleotide polymorphism ; Malignant rhabdoid tumor ; Chromosome 22q11.2 ; Tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We found two single nucleotide polymorphisms at the hSNF5/INI1 gene located on 22q11.2, encoding a member of the chromatin-remodelling SWI/SNF multiprotein complexes. A guanine/adenine polymorphism at codon 299 in exon 7, and another guanine/adenine polymorphism at 39 bp upstream of exon 9 were identified. As the gene was recently identified as a tumor suppressor gene for malignant rhabdoid tumor, this polymorphism may be useful for the genetic study of susceptibility for human malignancies of various tissue origins.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1435-232X
    Keywords: Key words Hyperlipoproteinemia ; Lipoproteins ; LDL receptor ; Familial hypercholesterolemia ; Genetic diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Heterozygous familial hypercholesterolemia (FH) is a serious disorder causing twice normal low-density lipoprotein (LDL) cholesterol levels early in childhood and very early coronary disease in both men and women. Treatment with multiple medications together with diet can normalize cholesterol levels in many persons with FH and prevent or delay the development of coronary atherosclerosis. Previously published blood cholesterol criteria greatly under-diagnosed new cases of FH among members of known families with FH and over-diagnosed FH among participants of general population screening. Thus, there is a need for accurate and genetically validated criteria for the early diagnosis of heterozygous FH. In the course of investigations of coronary artery disease in Utah, we identified a family whose proband showed elevated plasma levels of LDL cholesterol. To carry out molecular genetic diagnosis of the disease, we screened DNA samples for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor gene (LDLR). Novel point mutations were identified in the proband: a C-to-T transversion at nucleotide position 631, causing substitution of tyrosine for histidine at codon 190 in exon 4 of the LDLR gene. The mutant allele-specific amplification method was used to examine 12 members of the family recruited for the diagnosis. This method helped to unequivocally diagnose 7 individuals as heterozygous for this particular LDLR mutation, while excluding the remaining 5 individuals from carrier status with FH.
    Type of Medium: Electronic Resource
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