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Biomedical subjects

F Ward

Publications and source records attributed to F Ward.

16 recordsLinked to original sources

Conservation of genes encoding HLA-B5 and B35 cross-reactive group antigens in various races.

HLA-B5 and B35 CREG antigens include HLA-B35, B51, B52, B53, and B78. Recent studies suggest that the genes encoding the HLA-B5, B35 CREG, and HLA-B58 antigens share a common ancestor. We sequenced the exons of the genes encoding HLA-B51, B53, and B58 from American black individuals and the gene HLA-B52 encoding from an Arabic individual, and compared them with previously reported sequences of HLA-B51 (B*5101) and HLA-B52 (B*5201) from Japanese, HLA-B53 (B*5301) from an Algerian, and HLA-B58 (B*5801) from a Sardinian. The sequences of the genes from the American black and Arabic individuals were identical to those from the other races. These findings support the hypothesis that these antigens have evolved prior to divergence of the major ethnic groups.

Base Sequence

Effects of Escherichia coli lipopolysaccharide on nitrate synthesis and on nitrosation of proline in rats.

Male Ola:SD rats were fed purified diets containing 5 or 20% lactalbumin as the protein source, with or without concomitant administration of Escherichia coli lipopolysaccharide (50-250 micrograms/kg, ip), and changes in 24-hr urinary nitrate excretion, plasma urea, plasma-nitrate pool size and 24-hr urinary nitrosoproline excretion were measured. Urinary nitrate and urinary 14C-nitrosoproline excretion (after oral [14C]proline administration) were significantly greater for rats receiving the high-protein diet compared with those on the low-protein diet. The co-administration of lipopolysaccharide increased nitrate excretion in both diet groups (although the increase was greatest (relatively) in the animals fed 5% lactalbumin), but did not significantly alter urinary nitrosoproline excretion by either group. Plasma urea concentrations and plasma-nitrate pool size were increased by a high-protein diet and/or lipopolysaccharide administration. These findings suggest that treatments which alter the availability of nitrate in vivo are not necessarily associated with increased nitrosation of proline.

Animals

Lack of gastric mucosal protection by sucralfate during long-term aspirin ingestion in humans.

The ability of sucralfate to prevent gastric mucosal erosions caused by long-term aspirin ingestion was studied in 19 normal human subjects. A placebo-controlled, double-blind, crossover design was used to study the capacity of 4 g sucralfate daily to lessen the noxious effect on gastric mucosa of 3.6 g aspirin daily for 14 days. Gastric mucosal injury was assessed by endoscopic scoring of erosions. There was no significant difference in mean erosion scores or the degree of partial mucosal protection between the two groups. It was concluded that sucralfate lacks a mucosal protection capacity at the dosage studied in human subjects ingesting large doses of aspirin over a two-week period.

Adult

Protective effect of sucralfate against aspirin-induced damage to the human gastric mucosa.

Sucralfate, an agent that heals peptic ulcers in humans, has been shown to reduce aspirin-induced gastric mucosal damage in experimental animals. It has been suggested that the protective effect of sucralfate is due to stimulation of local prostaglandin production. The purpose of this study was to establish whether sucralfate was capable of reducing aspirin-induced gastric damage in humans. The effect of 1 g of sucralfate or identical placebo was studied in random order in eight healthy subjects. To determine if the effect of sucralfate was related to local prostaglandin synthesis, a second series of studies was performed in which prostaglandin production was inhibited with indomethacin 50 mg given orally eight hours before sucralfate. In each subject, all studies were performed at least one week apart. Following an overnight fast, upper gastrointestinal endoscopy was performed, with sucralfate or placebo given orally 30 minutes before ingestion of 1,200 mg of soluble aspirin in 50 ml of water. Both endoscopist and subject were unaware of the test agent. Ninety minutes after aspirin ingestion, endoscopy was again performed and gastric mucosal lesions were counted and graded to derive an erosion score. Results are expressed as mean +/- SEM. Aspirin produced endoscopic changes (score of 2.75 +/- 0.49) that were significantly (p less than 0.05) inhibited by sucralfate (score of 1.13 +/- 0.44). The protective effect of sucralfate was abolished by pretreatment with indomethacin (scores of 2.88 +/- 0.55 and 1.88 +/- 0.40, respectively). These results demonstrate that sucralfate significantly protects the human gastric mucosa against the acute damaging effects of aspirin. This effect is abolished by indomethacin, suggesting that the protective action of sucralfate on the gastric mucosa of humans may be related to stimulation of endogenous prostaglandins.

Aspirin

Electrodermal activity as an index of motion sickness.

Sweating in the absence of thermal stimulation is one of the cardinal symptoms of motion sickness. But since sweating is closely related to electrodermal activity this may be a potentially useful index of the intensity of motion sickness. In order to evaluate this possibility, the correlations between electrodermal activity and a range of signs and symptoms of motion sickness were examined in four experiments, in which a total of 170 subjects were exposed to a cross-coupled force environment. Although increases in skin conductance did not correlate with specific single indices of motion sickness, correlations with a questionnaire based on several signs and symptoms varied from 0.89 (p less than 0.001) to 0.11 (N.S.). It is concluded that skin conductance potentially offers a valid and very precise measure of motion sickness, but that it is sensitive to extraneous factors only some of which are currently understood.

Female

Long-term culture and characterization of alloreactive T-cell infiltrates from renal needle biopsies.

Long-term T-cell lines have been established by culturing renal needle biopsies from kidney recipients undergoing graft rejection. These cultures are maintained in the presence of Interleukin 2, with weekly addition of irradiated donor lymphocytes as a source of antigen. The cells express T-cell markers, T3, T4, and T8, T-cell growth factor (IL2) receptor, and HLA-DR antigens. In one cell line, J2, the T4 and T8 antigens are found on two separate cell populations. This line is also shown to specifically kill Epstein Barr Virus transformed donor cells. This cytotoxicity is directed against HLA-B35 determinant and has been maintained in vitro for over 6 months.

Antibodies, Monoclonal

Screening tests for antibodies to cytomegalovirus: an evaluation of five commercial products.

Four hundred and ninety two samples of serum from blood donors were screened for the presence of antibodies specific to cytomegalovirus using radioimmunoassay, a modified complement fixation test, and five commercially available tests: the Cetus CMV IHA, Abbott CMV total AB EIA, Cytomegalisa Stat EIA, Enzygnost EIA, and Virenz G-CMV EIA. A wide variation in results was found, with only 53.5% of the sera giving total concordance by all methods. Rates of seropositivity in the different tests ranged from 34.9% to 59.3%, with sensitivities ranging from 75.2% to 99.1% compared with the radioimmunoassay. Of 211 sera which gave positive results with four or more of the tests, none was negative by the radioimmunoassay and Abbott EIA, three were negative in Cetus IHA and Enzygnost EIA, and 11 were negative in the modified complement fixation test. Virenz G and Cytomegalisa Stat EIAs, however, gave 40 (19%) and 49 (23.2%), respectively, as negative. The results confirmed the reliability of the radioimmunoassay for the detection of the antibody status to CMV, but this test is too elaborate for a screening procedure. The Abbott EIA and Cetus IHA were found to be the most suitable for this purpose in spite of high false positive rates.

Antibodies, Viral

The polyglandular failure syndrome: disease inheritance, HLA type, and immune function.

The occurrence of disease and the inheritance of histocompatibility leukocyte antigens (HLA) were evaluated in 11 patients with the polyglandular failure syndrome and 42 of their relatives. The gene frequency of the HLA-B8 allele (seven of 22) and the HLA-A1, B8 haplotype phenotype frequency (five of 11) were increased in patients with polyglandular failure as compared with a control population. Eleven of 42 relatives had a polyglandular failure illness. Disease prevalence correlated with HLA inheritance in some families, but not all. Patients and diseased relatives had a high incidenceof immunologic dysfunction: autoantibodies, including antinuclear antibodies; elevated serum immunoglobulins (three of 16); abnormal skin tests (four of nine). Polyglandular failure appears to be an HLA-B8-associated syndrome with a high prevalence of disease in relatives. Immunologic dysfunction resulting from a gene(s) on chromosome 6, in linkage dysequilibrium with the HLA-B8 allele, may be a factor in the pathogenesis of polyglandular failure illnesses.

Addison Disease

Hereditary C5 deficiency in man: genetic linkage studies.

Genetic linkage studies were performed on the only reported kindred with genetic deficiency of the fifth component of complement (C5). Thirty family members in four generations were studied for C5 defiency and 32 genetic marker systems. Of these marker loci, 13 were informative in this pedigree. Most importantly, C5 deficiency was excluded (lod score greater than -2.0) from linkage with the major histocompatibility locus (HLA) from a recombination frequency of greater than 15% (in females). Other marker systems excluded from linkage with C5 deficiency included the ceruloplasmin and Duffy loci at a recombination frequency of less than 15%, and the erythrocyte glyoxalase, MN, and Lewis loci at a recombination frequency of less than 5%. The most positive lod score (1.07, theta=0.05) was for linkage between C5 and haptoglobin, but this score does not reach statistical significance. Thus, among the genes for complement components which can be mapped because of deficiency states or polymorphic gene products, C5 joins C1r, C3 and C6 in not being closely linked to HLA. In contrast, close HLA linkage has been demonstrated for C2, C4, properdin factor B and, in one of two families, C8.

Adolescent

The pathology of the lung in byssinotics.

A report of the gross and microscopic appearances in the lungs and the weights of the cardiac ventricles in 43 subjects receiving industrial benefit for byssinosis is presented. In 27 (63%) there was no significant emphysema, in 10 (23%) there were varying amounts of centrilobular emphysema, and panacinar emphysema was found in six (14%). Other changes were of non-specific nature, but most cases showed heavy black dust pigmentation, often associated with centrilobular dilatation of distal air spaces.

Aged