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Biomedical subjects

C J Welsh

Publications and source records attributed to C J Welsh.

49 records · Page 3Linked to original sources
PubMed1986

Experimental induction of rheumatoid factor and joint lesions in rabbits after intravenous injections of killed bacteria.

Rabbits receiving repeated intravenous injections of killed bacteria (Escherichia coli or Bacillus subtilis) developed IgM rheumatoid factor which reacted with autologous heat-aggregated IgG. In addition, 5/7 'Old English' and 7/8 'Sandy Lop' rabbits receiving killed E. coli developed rheumatoid-like synovial lesions. 'Old English' rabbits developed lesions of a more severe nature. Three of eight 'Sandy Lop' rabbits injected with killed B. subtilis had high levels of rheumatoid factor but only mild joint lesions.

Animals↗
PubMed1986

Synovitis associated with serum IgM rheumatoid factor arising spontaneously in 'Old English' rabbits.

This paper reports the spontaneous development of synovitis in 'Old English' rabbits concurrent with serum IgM rheumatoid factor. Female rabbits developed lesions at a higher incidence than males (42% compared with 17%) and the pathology was of a more severe nature. In the female rabbits synovitis was associated with concurrent high serum IgM rheumatoid factor and high serum antibody levels to Pasteurella multocida. There was no histological evidence that the joints were directly infected.

Animals↗
PubMed1986

Comparison of the arthritogenic properties of dietary cow's milk, egg albumin and soya milk in experimental animals.

The arthritogenic effect of dietary cow's milk, egg albumin and soya milk were compared in Old English rabbits. The 12-week cow's milk feeding regimen produced the highest incidence of significant joint lesions. Lesions were evident but mild at 5 weeks and the synovitis had resolved by 32 weeks. It is suggested that the transient nature of the synovitis may be due to the development of specific secretory IgA antibodies which were detectable in faecal pellet extracts. Sandy Lop rabbits were less susceptible to the arthritogenic effect than were Old English rabbits. Dietary ovalbumin was less arthritogenic than cow's milk despite high titres of serum and synovial fluid antibodies and immune complexes. The rabbits were 'tolerant' to dietary soya due probably to pre-existing levels of soya protein in their diet. Lewis and Wistar strain rats, CBA, Balb/c and C57/BL6 mice fed on cow's milk for 3 months did not develop serum antibodies or synovial lesions. It is suggested that this allergic synovitis is not a model for early rheumatoid joint disease because of the transience of the lesions and lack of stimulation of rheumatoid factor. It may well, however, be a model for the arthralgia seen in patients with certain food allergies.

Animals↗
PubMed1985

Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. I. Joint pathology.

Rheumatoid-like lesions developed in 9 of 25 (36%) Old English rabbits drinking cow's milk for 12 weeks. The incidence of lesions in male and female animals was similar. The majority of rabbits drinking cow's milk developed increased numbers of nucleated cells and raised percentages of T lymphocytes in their synovial fluids, compared to control rabbits. The cell counts and T cell percentages correlated with the severity of the histological lesions. No evidence of glomerulonephritis was observed in any of the experimental animals.

Animals↗
PubMed1985

Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. II. Antibody responses to bovine serum proteins.

Thirty-six percent of Old English rabbits fed pasteurized cow's milk developed early rheumatoid-like synovial lesions. All rabbits drinking milk developed high titres of serum and synovial fluid Clq-binding activity. This has been shown to be due to specific antibody to Clq, produced in response to Clq in cow's milk. In addition, these rabbits responded to other bovine proteins present in cow's milk, including conglutinin, beta-lactoglobulin and IgG. There was no correlation between serum or synovial fluid titres of antibody to bovine milk proteins and synovial lesions.

Animals↗
PubMed1984

Production and preliminary characterization of monoclonal antibodies to human liver-specific lipoprotein (LSP).

Monoclonal antibodies (mc/anti-LSP) have been prepared by polyethylene glycol fusion of P3/NS1/Ag4-1 myeloma cells with spleen cells from Balb/c mice hyperimmunized with human liver-specific membrane lipoprotein (LSP). Ten hybridomas, cloned by limiting dilution, produced mc/anti-LSP reacting (by ELISA) with human LSP but not with normal human plasma proteins nor with a variety of other proteins likely to co-purify with LSP. Three of these ( A15 /7, A9/63 and B20 ), producing high-titre IgG1 mc/anti-LSP, were biosynthetically radiolabelled and used as index antibodies. By competitive inhibition of binding of the index antibodies to LSP in an immunoradiometric assay, the ten hybridoma products were classified into four distinct groups according to their specificities for different epitopes in LSP. None of the index antibodies reacted, on ELISA, with glutaraldehyde-fixed PLC/PRF/5, Chang, Daudi or HSB-2 cell lines nor with human peripheral blood leucocytes. However, A15 /27 (but not A9/63 or B20 ) reacted with saponin-permeabilized PLC/PRF/5 and Chang cells and also with rabbit LSP. The results emphasize the polyantigenic nature of LSP and indicate that at least one of the mc/anti-LSP ( A15 /27) recognises a species cross-reactive antigen that is present in liver-derived cell lines.

Animals↗
PubMed1982

Increasing the levels of ether-linked lipids in L-M cells by glyceryl ether supplementation depresses growth and choline utilization.

To gain insight into the role of alkyl-linked lipids in biological systems, we added hexadecylglycerol (a precursor of complex ether-linked lipids) to medium required for the growth of L-M cells in culture. L-M fibroblasts cultured through several generations in the presence of hexadecylglycerol grow at a reduced rate. Experimental cells at their sixth passage, with 2 microgram supplement/ml, double at 50% the rate of control cell populations. Hexadecylglycerol (10 microgram/ml) added 1 day after cell passage does not retard growth; however, within 1 h it decreases the incorporation of choline into the choline glycerophosphatide fraction. Inhibition is specific for choline; ethanolamine incorporation is not affected. The inhibition of choline utilization by hexadecylglycerol-treated cells is dose-dependent and reaches a maximum 12 h after supplementation. Cellular uptake of choline is reduced (approx. 17%) but not as much as the incorporation of choline into the phospholipids (approx. 60% at 12 h). The assimilation of ether lipid precursor into cellular phospholipids was followed by incubating cells with [1-14C]hexadecylglycerol. Incorporation of radioactivity into cellular phospholipids begins to plateau after 24 h, whereas the interference of hexadecylglycerol with choline metabolism could be detected as early as 1 h. The majority of the radioactivity recovered from cells incubated with labeled hexadecylglycerol is localized in the microsomal fraction (56%), where the label was distributed as free hexadecyglycerol, alkylacyl-phospholipids and alkyldiacylglycerols. These results show that the supplementation of a glyceryl ether to L-M fibroblast growth media selectively inhibits the utilization of choline for choline glycerophospholipid biosynthesis and causes a reduction in cell growth rate when cells are continually passaged in the presence of the glyceryl ether.

Choline↗
PubMed1981

Fatty acid metabolism in phorbol ester-differentiating human leukemia cells.

Human promyelocytic leukemia cells (HL-60) undergo differentiation when treated with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). As the primary target for TPA action is membranes, studies were undertaken to determine whether phorbol ester exposure would influence fatty acid metabolism in these cells. In cells incubated with labeled fatty acids for 1 hr, the percentage of distribution of lipid radioactivity is highest in the phospholipid fraction of control cultures, whereas in TPA-supplemented cells, substantially more label is associated with triacylglycerols. The specific activity of phospholipids and triacylglycerols was lower in treated than in control cells; however, the amount of cellular triacylglycerols increased 3.2-fold (lipid per mg protein). The increase in the amount of cellular phospholipids in TPA-treated cells is not as pronounced (approximately 50% above control), and this only occurs at higher concentrations of TPA. At early times after TPA exposure, there is no stimulation of the cellular uptake of labeled fatty acids; however, differentiating cells (24 to 48 hr of TPA), when incubated with label, contained more radioactivity than did control cultures. Cells treated with TPA for 48 hr show a marked decrease in the conversion of [1-14C]stearic acid to monoenoic product (22% of control); this decrease is dose dependent and occurs within 24 to 48 hr of treatment. Although the phospholipid fatty acid composition of differentiating cells was similar to control cells, acyl groups of triacylglycerols isolated from treated cells showed a marked decrease in the percentage of unsaturates. These data provide evidence which demonstrates that TPA treatment of HL-60 cells has a profound effect on fatty acid metabolism. The lack of an effect of TPA on fatty acid metabolism after short-term exposure to the promoter suggests that the modifications observed may be the result of cellular differentiation rather than a direct effect exerted by the presence of TPA in the culture media.

Carcinogens↗
PubMed1980

Alterations in lipid metabolism induced by 12-O-tetradecanoylphorbol-13-acetate in differentiating human myeloid leukemia cells.

Several aspects of lipid metabolism were evaluated in differentiating human myeloid leukemia (HL-60) cells after treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Modifications accompanying the phorbol ester-induced differentiation include an increase in the incorporation of acetate into free fatty acids and neutral lipids, an increase in the amount of neutral glycerolipids, and a selective incorporation of long-chain fatty alcohols into triacylglycerols and ether-linked alkyldiacylglycerols. Additionally, an enhanced stimulation of phospholipid metabolism, as measured by the incorporation of 32P and labeled precursors of the polar head groups, could be detected within 4 hr after treatment of cells with the tumor promoter. 4-O-Methyltetradecanoylphorbol-13-acetate, an analog with poor tumor-promoting activity, failed to elicit any activity on phospholipid metabolism.

Animals↗
PubMedDate not supplied

Modification of lipid acyl groups by serum deprivation does not affect phorbol ester-induced differentiation of human leukemia cells.

12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, can induce differentiation of human promyelocytic leukemia cells grown in a serum-free environment. Removal of serum produces altered acyl group composition of cellular phospholipids, most notably, marked decreases in the polyunsaturated fatty acid content. Although higher amounts of TPA are required to induce differentiation in serum-free cell populations, induction assessed by morphological and enzymatic markers in similar to the "macrophage-like' differentiated state reported for cells grown in a serum-rich medium.

Cell Differentiation↗
PubMedDate not supplied

Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.

Animals↗