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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 487 records · Page 27Linked to original sources

Lymphocytotoxic antibody in inflammatory bowel disease. A family study.

The prevalence of lymphocytotoxic antibody in inflammatory bowel disease is 40 per cent. Twenty-seven of 90 relatives of 23 probands with the disease (30 per cent) demonstrated lymphocytotoxic antibody, as contrasted with only three of 69 control family members (4 per cent) (P less than 0.0001). Decreased lymphocytotoxicity against lymphocytes from patients with inflammatory bowel disease as compared to normal donor lymphocytes previously demonstrated in the serum of probands was also observed in the serums from family members of the probands. Nineteen of the 48 household contacts of probands (40 per cent) were positive for antibody, whereas eight of 42 nonhousehold contacts (19 per cent) demonstrated it (P less than 0.05). Eight of 16 spouses (50 per cent) of probands showed antibody. The increased prevalence of lymphocytotoxic antibody in family members of probands and its occurrence mainly in household contacts (consanguineous and non-consanguineous) may indicate the exposure of probands and their family members to a common environmental agent.

Adult↗

The two-step reversible denaturation of lactate dehydrogenase at low pH.

Upon exposure to conditions of low pH, beef B4 lactate dehydrogenase rapidly loses enzymatic activity, but this process can be completely reversed yielding 100% of the original activity if the enzyme is immediately returned to neutral conditions. As the time of exposure to low pH is increased, the fraction of activity recovered declines to a values of 50--60% and remains nearly constant over a period of many hours. Correlated with this behavior is a change in the kinetics of the recovery of activity. Recovery of activity has been shown to be a second-order process for enzyme exposed to low pH for brief periods of time (Anderson, S., and Weber, G. (1966), Arch. Biochem. Biophys. 116, 207). After several minutes at low pH recovery of activity is found to become first order and to occur at a considerably slower rate. Gel filtration chromatography at low pH separates the protein into two fractions. The lower molecular weight fraction is found to be primarily monomeric, as indicated by equilibrium ultracentrifugation, and is capable of recovering enzymatic activity. The higher molecular weight fraction is generated from the lower molecular weight fraction, and is incapable of recovering activity. These results are interpreted to indicate that the enzyme exists sequentially in three denatured forms at low pH, the first two capable of being restored to the native state, and the third irreversibly denatured.

Animals↗

Inhibitors of leukocyte chemotaxis in alcoholic liver disease.

Twenty-one of 42 patients (50 per cent) with alcoholic liver disease showed serum chemotactic inhibitory activity (CIA). CIA was not related to any single biochemical or histologic feature in the patients studied. The frequency of CIA was greatest in those with active infection. Serial studies demonstrated that CIA may be a transient phenomenon, associated with active alcoholic liver disease or appearance of infection. Nine of 15 patients showed skin test anergy; CIA was present in 8 of these 9 patients. Serum immunoglobulin A (IgA) and G (IgG) concentrations were significantly higher in patients with CIA when compared to those without CIA. Sucrose density gradient centrifugation of serums showing CIA yielded three peaks of inhibitory activity. Two had sedimentation coefficients of 10.7S and 6.8S, and the third was approximately 3S. The two higher molecular weight inhibitors were predominant in the 50 per cent ammonium sulfate precipitate. Immunoabsorption by anti-IgA but not by anti-IgG or IgM columns removed the ammonium sulfate precipitable chemotactic inhibitors. The appearance of chemotactic inhibitors in patients with alcoholic liver disease may have relevance to their apparent susceptibility to serious infections.

Adult↗

Studies of human lymphocytes in the newborn and the aged.

Proportions and absolute numbers of T and B lymphocytes were determined among 30 newborn infants and group of 77 elderly patients 60 to 95 years of age. Total lymphocytes in the cord blood of the newborn showed a distinct elevation in total numbers of T and B lymphocytes (p less than 0.005) as compared to that in blood from normal adult controls, reflecting the relative lymphocytosis of infancy. Proportions of cord blood T lymphocytes as reflected by the sheep cell rosette technic were considerable lower than those in lymphocytes from normal adult controls, however, proportions of cord blood T lymphocytes as determined by indirect immunofluorescence were not significantly different from those in controls. Old people showed a significant reduction in total numbers of lymphocytes (p less than 0.005) when compared with those in normal adult controls 18 to 51 years of age. Moreover, there was a significant increase in the relative proportions of peripheral blood B lymphocytes in the elderly although the absolute numbers of B lymphocytes in the elderly although the absolute numbers of B cells did not differ from those in younger controls. A significant decrease in total numbers of T cells as measured both by sheep cell rosettes and indirect immunofluorescence was recorded among older patients (p less than 0.001). In addition, there was a broad increment in the incidence of various autoantibodies (anti-nuclear, andi-IgG, antismooth muscle, antimitochondrial and antiparietal cell) among the old people studies. No direct correlation could be determined between relative B-cell percentage increase or T-cell decrease and the presence of various autoantibodies in individual patients. Diminution in total lymphocyte counts as well as absolute numbers of T cells in the elderly may provide the cellular basis for an increased susceptibility to neoplasia and infection.

Adolescent↗

Inhibition of streptococcal attachment to receptors on human buccal epithelial cells by antigenically similar salivary glycoproteins.

Preparations of salivary glycoproteins inhibited the attachment of certain indigenous oral streptococci to human buccal epithelial cells and fostered the desorption of previously attached bacteria. The adherence-inhibiting and desorptive activities of the glycoproteins correlated with their ability to aggregate these organisms. Pretreatment of glycoprotein preparations with certain blood group antisera impaired their adherence-inhibiting effect, suggesting that components with blood group substance reactivity were involved. Pretreatment of buccal epithelial cells with certain blood group antisera or concanavalin A masked the receptors associated with the attachment of Streptococcus sanguis SG1. The association of blood-group-reactive substances with the receptors involved in bacterial attachment may provide a basis for understanding the distinct specificities that bacteria exhibit for attaching to different tissues, organs, and hosts. Antiserum raised in rabbits to human epithelial cells also exhibited receptor-masking activity, and absorption of this serum with homologous salivary glycoproteins removed the antibodies responsible. These observations indicate that some salivary glycoproteins are antigenically similar to components on the epithelial cell surfaces they bathe. It is suggested that by mimicking the receptors present on epithelial cells, the mucinous glycoproteins of secretions may competitively inhibit the sorption of infectious agents and facilitate their removal after they are attached. These activities help to explain how mucinous glycoproteins augment the cleansing action of secretions.

Absorption↗

Peripheral blood and intestinal lymphocyte sub-populations in Crohn's disease.

Immunofluorescent technques were utilized to study the nature and distribution of cells forming the inflammatory infiltrate in Crohn's disease. Tissue from resected ileum (one patient) or colon (one patient) when compared with corresponding control tissues contained increased numbers of B and T lymphocytes. B-cells of IgG class predominated in the mucosal lamina propria, whereas T-cells were prominent in the deeper layers of inflamed bowel. Inflammatory cells bearing Fc receptors were also present in these tissues. Decreased peripheral blood T-cell numbers returned to normal after resection of the involved bowel in the two patients studied. Impaired cellular immunity in Crohn's disease may thus result from T-cell sequestration in or loss from involved segments of intestine.

Adolescent↗

Peripheral blood T and B lymphocytes during acute rheumatic fever.

Proportions and total numbers of thymus-derived (T) and bone marrow-derived (B) peripheral blood lymphocytes were studied in 53 patients with acute rheumatic fever, diagnosed on the basis of modifified Jones criteria. An elevation in both proportions and absolute numbers of cells bearing surface Ig was found in most patients, particularly during the first 7 days after onset. Conversely, T-cell proportions and numbers were often found to be depressed early in the acue phases of rheumatic fever. Proportions of cells bearing surface Ig did not correlate with another B-cell marker, the aggregated gamma globulin receptor, suggesting that such cells bearing surface Ig were not all B lymphocytes. Incuvation for 20 h at 37 per cent C of cells showing high proportions of surface Ig-bearing surface Ig in both normal and rheumatic fever subjects, although there was no appreciable increment in proportions of lymphocytes expressing T-cell markers. Patients with initial attacks showed higher percentages and total numbers of Ig-bearing lymphocytes (P smaller than 0.01) than did those with rneumatic fever recurrences. Elevations in numbers and proportions of peripheral blood lymphocytes bearing Ig appeared to correlate with the relative acute nature of the rheumatic fever attack.

Acute Disease↗

Localization of T and B cells and alpha fetoprotein in hepatic biopsies from patients with liver disease.

Peripheral blood and hepatic tissue T- and B-lymphocyte distributions, serum alpha fetoprotein (AFP) concentrations, and hepatic AFP were studied in 46 patients undergoing diagnostic percutaneous liver biopsy. The patients included 26 with alcoholic liver disease, 13 with nonalcoholic hepatitis or cirrhosis, and 7 with either normal histology or minor nonspecific changes. Serum AFP was determined by radioimmunoassay and hepatic tissue AFP by indirect immunofluorescence. Peripheral blood T lymphocytes were identified by the sheep red-cell rosette technique; and B lymphocytes by fluoresceinated anti-immunoglobulin antisera and IgG aggregates. Tissue identification of T lymphocytes was accomplished using an extensively absorbed rabbit antihuman thymocyte antiserum and indirect immunofluorescence; tissue B lymphocytes were identified using pepsin F (ab')2 fragments of rabbit IgG antibodies to human immunoglobulins. T lymphocytes predominanted in hepatic lymphoid infiltrates from patients with alcoholic liver disease (91+/-4%), whereas in patients with chronic active or chronic persistant hepatitis, viral hepatitis, or cryoptogenic cirrhosis proportions of T and B lymphocytic infiltrates were similar (50+/-15%). Hepatic tissue AFP was detected in 9 of 18 patients with alcoholic hepatitis; serum AFP concentration was increased in only 1 of these 9 patients. Tissue AFP was not observed in the remaining biopsy material nor were serum AFP concentrations increased. Peripheral blood T-cell numbers were significantly decreased in patients with alcoholic liver disease (P less than 0.01) and in nonalcoholic hepatitis or cirrhosis (P less than 0.025). A close relationship between peripheral blood T-lymphocytopenia and hepatic T-cell infiltrates was observed in patients with alcoholic liver disease; this relationship was less apparent in patients with nonalcoholic hepatitis or cirrhosis.

B-Lymphocytes↗

Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus.

Antigen-ginding lymphocytes capable of binding native DNA (DNA-ABC) were identified in the peripheral blood of normal controls and patients with systemic lupus erythematosus (SLE) by autoradiography with 125I-nDNA. 12 patients with active SLE had 404 +/- 273 (mean +/- SD) DNA-ABC/105 lymphocytes, while 7 inactive SLE patients and 13 normals had 120 +/- 48 and 48 +/- 36, respectively. All three groups were significantly different from one another (p less than 0.01). No significant correlation was detected between the quantity of anti-native DNA (nDNA) antibody and number of DNA-ABC; however, most patients with large amounts of anti-nDNA antibody had both active disease and large numbers of DNA-ABC. Numbers of DNA-ABC and lymphocytes with surface immunoglobulin (Ig) did not change significantly after an 18-h incubation at 37degreeC. After depletion of B-lymphocytes by passage over bead columns coated with a complex of IgG and anti-IgG, the great majority of DNA-ABC were removed in both normal subjects and SLE patients. Labeling lymphocytes sequentially with 125I-nDNA, followed by an indirect fluorescence technique for identification of surface Ig, indicated that the great mahority of radiolabeled cells had surface Ig by fluorescence microscopy in four normals (average 93%) and five patients with active SLF (average 82%). The predominance of nDNA-sensitive B-lymphocytes in the peripheral blood of both normals and SLE patients is consistent with the concept that the induction of the anti-nDNA antibody response is due to the stimulation of preexisting nDNA-specific B lymphocytes by mechanisms other than those necessarily involving participation of nDNA-specific T lymphocytes.

Antibodies, Antinuclear↗

Smooth muscle antibody in heroin addicts.

The occurrence of autoantibodies and the concentrations of serum immunoglobulins were studied in 102 heroin addicts, 20 former addicts who had abstained from heroin for 1 year or more, and 40 normal control subjects. Antibodies to smooth muscle (46%) and lymphocytotoxic antibodies (30%) were detected in the active heroin users, and there was a significantly positive correlation between these autoantibodies. Absorption experiments strongly suggested antigenic cross-reactivity between smooth muscle and lymphocyte membrane antigens. The presence of smooth muscle antibody in addicts was not clearly correlated with signs of active liver disease. The occurrence of smooth muscle antibody (10%) and lymphocytotoxic antibodies (15%) was significantly lower in the former heroin addicts than among active drug users. A significant elevation of IgM was found in the active heroin addicts. Gamma-M globulin was lower among the former heroin addicts but still elevated when compared with normal controls.

Antibodies↗