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Biomedical subjects

J Welsh

Publications and source records attributed to J Welsh.

At least 145 records · Page 8Linked to original sources
PubMed1981

Bone pathology and parathyroid gland activity in hypocalcemic magnesium-deficient chicks.

Growing chicks fed magnesium-deficient (150 ppm Mg) diets for 14 or 21 days developed significant hypomagnesemia and hypocalcemia compared to control chicks fed 1,000 ppm Mg. The hypocalcemia was accompanied by significant parathyroid gland hyperactivity, suggesting that magnesium deficiency did not impair parathyroid gland function. Despite parathyroid gland hyperactivity, however, bone resorption was decreased in the magnesium-deficient chicks, although bone formation was not affected by magnesium depletion. The decrease in bone resorption in the magnesium-deficient chicks was correlated with significant bone magnesium depletion and resulted in increased bone calcium content. These findings suggested that the development of hypocalcemia in magnesium-deficient chicks was related to decreased bone resorption, due to impaired osteocytic function rather than parathyroid gland insufficiency. The results also offer an explanation for the decrease in skeletal responsiveness to PTH which has been reported during magnesium depletion.

Animals↗
PubMed1981

Uveitis, vitreous humor, and klebsiella. I. Binding studies with rabbit antisera.

Uveitis occur in a proportion of patients with ankylosing spondylitis, and an increased faecal isolation of the Gram-negative micro-organism Klebsiella pneumoniae has been reported from such patients. Immunological cross-reactivity between K. pneumoniae and bovine vitreous humour has been studied by 2 different antibody binding techniques: I125-labelled antigen binding assay with and without carrier, and beta-galactosidase enzyme-immunoassay. Sera from rabbits immunised with whole klebsiella micro-organisms or klebsiella extracts were found to bind labelled vitreous humour antigens to a greater extent (p less than 0.001) than sera from rabbits immunised with Escherichia coli, Streptococcus pyogenes, and phi X 174 virus or sera from the same rabbits before immunisation. It is suggested klebsiella micro-organisms may carry antigenic determinants which resemble vitreous humour antigens.

Animals↗
PubMed1981

Uveitis, vitreous humour, and klebsiella. II. Cross-reactivity studies with radioimmunoassay.

Radioimmunoassay with calf and cow vitreous humour-I125 and rabbit antivitreous humour serum has been employed to investigate the immunological cross-reactivity of vitreous humour with bacterial and mammalian tissue antigens. Klebsiella ultrasonicate preparation at a dose fo 10 000 micrograms/ml was found to inhibit the binding of vitreous humour by 25-100% (p less than 0.001), compared with an inhibition of 5-30% by a similar quantity of E. coli ultrasonicate preparation. Equivalent amounts of Streptococcus pyogenes antigen, bovine haemoglobin, and hyaluronic acid had no inhibitory effect, while horse spleen ferritin was found to inhibit vitreous humour binding between 0 and 10%. These results indicate that klebsiella micro-organisms have antigens which partially resemble some eyeball components. It is suggested that acute anterior uveitis of ankylosing spondylitis may be produced by anti-Gram-negative bacterial antibodies binding to cross-reacting eye antigens.

Animals↗
PubMed1980

Ankylosing spondylitis, HLA-B27 and Klebsiella. I. Cross-reactivity studies with rabbit antisera.

Sera from rabbits immunized with HLA-B27 lymphocytes showed increased activity against klebsiellal enterobacter antigens using immunodiffusion, bacterial agglutination (P less than 0.025), haemagglutination (P less than 0.001) and radiobinding assays (P less than 0.001). Immunoprecipitin lines were also produced by these antilymphocyte sera against extracts from Yersinia enterocolitica and Shigella sonnci microorganisms. Rabbit anti-klebsiella sera had lymphocytotoxic activity against HLA-B27 lymphocytes obtained from patients with ankylosing spondylitis (P less than 0.001). These results suggest partial cross-reactivity between some antigens found in several Gram-negative microorganisms and HLA-B27 lymphocytes.

Agglutination Tests↗
PubMed1980

Ankylosing spondylitis, HLA-B27 and Klebsiella. II. Cross-reactivity studies with human tissue typing sera.

Human monospecific HLA B27 typing sera have been shown to have increased binding activity for klebsiella extracts by haemagglutination (P less than 0.001), radiobinding assay (P less than 0.025) and radiolabelled antigen competition assay (P less than 0.02) when compared to non-B27 tissue typing sera. These observations are in agreement with those of studies using rabbit sera, suggesting that HLA B27 lymphocytes may exhibit partial cross-reactivity with bacterial antigens found in some Gram-negative microorganisms such as klebsiella. It is suggested ankylosing spondylitis may occur as a result of immunological damage following infection by Gram-negative bacteria carrying antigens having stereochemical similarity to self antigens.

Agglutination Tests↗
PubMed1977

America 1976.

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Communication↗
PubMedDate not supplied

Functions of 1alpha,25-dihydroxyvitamin D(3) in mammary gland: from normal development to breast cancer.

This review examines the role of 1alpha,25(OH)(2)D(3) (1,25D) and the vitamin D(3) receptor in growth regulation of normal and transformed mammary epithelial cells. 1,25D exerts both anti-proliferative and pro-apoptotic functions in transformed mammary cells such as MCF-7. The anti-proliferative effects of 1,25D have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21, p27, cyclins and Rb. The pro-apoptotic effects of 1,25D involve alterations in the relative ratios of the bcl-2 family members which regulate mitochondrial integrity. In MCF-7 human breast cancer cells, 1,25D mediated apoptosis is associated with translocation of the pro-apoptotic protein Bax to the mitochondria, generation of reactive oxygen species, dissipation of the mitochondrial membrane potential and release of cytochrome c. These mitochondrial events trigger apoptosis in a caspase-independent manner, since caspase inhibitors do not rescue 1,25D treated cells from death. The potential role of 1,25D in growth and differentiation of normal mammary epithelial cells has been examined in VDR null mice. Initial data indicates a significant decrease in ductal differentiation in VDR null mice compared to age matched wild type mice, reflected as an increased number of undifferentiated terminal end buds in the VDR null mouse. These data suggest that 1,25D promotes differentiation during early mammary gland development. In summary, our studies suggest an expanding role for the vitamin D(3) endocrine system in control of proliferation, differentiation and apoptosis of mammary epithelial cells.

Animals↗
PubMedDate not supplied

Changes in posterior disc bulging and intervertebral foraminal size associated with flexion-extension movement: a comparison between L4-5 and L5-S1 levels in normal subjects.

BACKGROUND CONTEXT: No previous study has used magnetic resonance imaging (MRI) to evaluate changes of posterior disc bulging and intervertebral foraminal size in the normal spine with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. PURPOSE: To determine changes in posterior disc bulging and intervertebral foraminal size with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. STUDY DESIGN: An in vivo study of magnetic resonance kinematics with spine flexion extension. METHODS: Spines of three volunteers with no history of low back pain were scanned in neutral, flexion, and extension positions in a vertically open MRI system. MRI was repeated after 6 hours of normal activity and an additional 4 hours of heavy activity with a weighted vest. Posterior bulging of the intervertebral disc and the size of intervertebral foramen were measured at the L4-5 and L5-S1 levels. RESULTS: With spine flexion, posterior bulging of the discs increased at L4-5 in eight of nine measurements (three different spine-loading states for each of three subjects) and L5-S1 discs in six of nine measurements. In most cases, posterior bulging decreased with extension. No significant difference was noted in the degree of disc bulge between levels. Foraminal size at L4-5 increased with flexion and decreased with extension, and the extent of these changes was greater at the L4-5 level than at L5-S1. CONCLUSIONS: This pilot study demonstrates two distinct behavior characteristics of the normal spine with flexion-extension movement.

Adult↗
PubMedDate not supplied

Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens.

1,25-Dihydroxycholecalciferol D3 (1,25(OH)2D3), the active metabolite of vitamin D, is a potent inhibitor of breast cancer cell growth both in vivo and in vitro. We have shown that MCF-7 cells treated with 100 nM 1,25(OH)2D3 exhibit characteristic apoptotic morphology (pyknotic nuclei, chromatin and cytoplasmic condensation, nuclear matrix protein reorganization) within 48 h. In the experiments reported here, we examined the interactions between 1,25(OH)2D3 and the antiestrogen 4-hydroxytamoxifen (TAM), which also induces apoptosis in MCF-7 cells. Our data suggest that TAM significantly potentiates the reduction in cell number induced by 1,25(OH)2D3 alone. Combined treatment with 1,25(OH)2D3 and TAM enhances the degree of apoptosis assessed using morphological markers that identify chromatin and nuclear matrix protein condensation. We have selected a subclone of MCF-7 cells resistant to 1,25(OH)2D3 (MCF-7D3Res). These cells express the vitamin D receptor and exhibit doubling times comparable to the parental MCF-7 cells, even when grown in 100 mM 1,25(OH)2D3. Treatment of both parental and resistant MCF-7 cells with TAM induces apoptosis and clusterin. These data emphasize that apoptosis can be induced in MCF-7 cells either by activation of vitamin-D-mediated signalling or disruption of estrogen-dependent signalling.

Apoptosis↗
PubMedDate not supplied

Great expectations.

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Adult↗