Binding of glycerol by microtubule protein.
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Biomedical subjects
Publications and source records attributed to R C Williams.
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Some gram-negative bacteria isolated from the urinary tract have on their surfaces antigens identical to or similar to those of human blood groups A, B, or (H) O. Human isoantibodies to these antigens appear to play some part in the immunologic response to urinary infections. It is postulated from this observation that human isoantibodies A and B persist because they are important segments in resistance to infections rather than reactions to other human tissues (as in transfusions or transplantation). To further assess the relationship between bacterial antigens similar to those of blood groups A or B and host isoantibody response we performed an in-depth study of this relationship in 13 patients with urinary infection of upper or lower tracts. Isoantibody of the immunoglobulin M class appeared to be the antibody which reacted with both bacteria and human erythrocytes. Patients with infections of the upper tracts had proportionately more cross-reacting anti-B antibody than those with lower tract infections, but the amounts of anti-A antibody were roughly equivalent in both types of infection. Response of a given host was genetically predetermined. Some deficiency in host recognition of bacterial antigens was noted since only 4 of 13 patients recognized bacterial A or B antigens while all normals did so. Study of the defined crossreactions between bacterial and blood group antigens offers further opportunities for definition of the genetic components of immunity to urinary infections.
An on-line computerized optical absorption scanner for the analytical ultracentrifuge has been developed and tested. It makes direct use of the instantaneous photomultiplier output, which is digitized and averaged by the computer. It incorporates a stepping motor to drive the photomultiplier, two analog-to-digital converters, and a device which monitors precessional movement of the rotor. The scanner has been employed chiefly in sedimentation equilibrium experiments, and techniques have been devised to correct for the adverse effects of inhomogeneities of apparent absorbance which arise from the cell windows. Correction for rotor movements which occur during the scan is also possible. The completed apparatus is a successful one, and provides a significant improvement in precision, speed and convenience over the commercially available scanners. The limitations on precision inherent in the present design are examined, and it is concluded that the combined effects of window inhomogeneities and rotor movement lead to uncertainty of the measured absorbance which is unlikely to be reduced below +/- 0.001 A.
Prior sc immunization of BALB/c mice with 1 mg isolated M component of MOPC-11 mouse myeloma resulted in significant relative immunity to subsequent sc or ip challenge with 10(4) living cells from the same plasmacytoma. However, challenges of 10(5) and 10(6) tumor cells overcame immune status engendered by preimmunization with M component. Despite evidence for the specificity of the immunity induced by one isolated M component as opposed to another, no clear cytotoxic antibody, cell-mediated tumor-cell lysis, or predominance of either humoral or cell-mediated immune mechanisms were demonstrated. These findings were compatible with a relatively slight tumor-specific antigenicity of M components expressed on tumor surfaces, compared with the tumor specificity of other tumor-related, cell-surface antigens.
Tissue typing was performed on lymphocytes of sixty-two patients with guttate psoriasis, in forty-four of whom this was the first manifestations of the disease. In 84% of cases, the guttate psoriasis was preceded by a clinical infection. A highly significant excess of antigen W17 (HLA-BW17) was found in patients when compared with healthy population. In common with some other studies antigens HL-A13 (HLA-B13), W15 (HLA-BW15) and W21 (HLA-BW21) were found in excess but these became non-significant after correction for the number of antigens studied. 68% of patients who had guttate psoriasis de novo, subsequently developed persistent plaque psoriasis.
Sera from patients with inflammatory bowel disease (IBD) showing broad lymphocytotoxic or lymphocyte-binding activity were subjected to additional analysis to further characterize their properties. Lymphocytotoxins appear to be antibodies predominantly of IgM class as determined by [1] 2-mercaptoethanol sensitivity, [2] serum fractionation by sucrose density gradient sedimentation, Sephadex G-200 filtration, and DEAE ion exchange chromatography, and [3] absorption by anti-Ig immunoadsorbent columns. Lymphocyte-binding antibody was found to be IgG, IgA, and IgM, as determined by indirect immunofluorescent staining of acetone-fixed lymphocytes. Individual IBD sera showed marked variability in occurrence of cytotoxic and binding antibodies when tested against the same donor panel of lymphocytes. These studies emphasize the marked heterogeneity of anti-lymphocyte antibodies occurring in IBD.
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Serum chemotactic inhibitory activity (CIA) was studied in 46 patients with various systemic diseases, using a system consisting of normal human leukocytes as indicator cells and 10% fresh normal serum as a control chemotactic attractant. It was shown, as previously reported, that an association exists between CIA and skin test anergy. Heat treatment of sera at 56 C for 30 min increased both the incidence and the degree of chemotactic inhibition observed in these patients. The effects of heat treatment of sera containing CIA on other chemotactic attractants (C3a, bacteria-derived chemotactic factor (BF), and casein) are shown. Before heat treatment, some sera suppressed chemotaxis mediated by BF in the absence of suppression of normal serum-mediated chemotaxis, indicating the possible involvement of more than one system of inhibition. Multiple systems were further supported by data indicating that room temperature incubation resulted in a loss of CIA as measured by normal serum-mediated chemotoxis with no apparent decrease in the inhibition of BF -mediated chemotaxis. Separation of sera containing CIA by Sephadex G-200 showed chemotactic inhibitory activity to be increased in both the void volume region. Experiments showed that heat treating before separation resulted in similar increases in both peaks, implying the presence of an antagonist to CIA. Experiments demonstrating that sera containing CIA do not suppress casein-mediated chemotaxis by means of an irreversible inactivation of chemotactic factor are included along with experiments demonstrating a cellular mode of action. The possible presence of two systems of chemotactic inhibition, one acting directly upon chemotactic factors and one interacting with the responding cell, are discussed.
The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection.
Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.
The prevalence of lymphocytotoxic antibody was studied in 131 relatives of 10 patients with Hodgkin's disease. The study group contained nine families, five of which had two subjects with Hodgkin's disease. One hundred twenty-eight control family members were studied in parallel. Lymphocytotoxic antibody was present in 35.5% of all family members of patients with Hodgkin's disease, and in 8.6% of controls (P less than 0.01). Lymphocytotoxic antibody appeared primarily in consanguineous relatives irrespective of close personal household contact with the probands. The prevalence of the antibody was equal in both first- and second-degree relatives. These findings suggest at least a genetic and possibly an environmental influence in the genesis of lymphocytotoxic antibody among relatives of patients with Hodgkin's disease.
Serum IgE concentrations were elevated in thirty-seven out of sixty-seven patients (55%) with acute or chronic liver disease of widely differing aetiology. The mean IgE concentrations in these patients showed an eight-fold increase above that observed in control subjects. Increased IgE levels in patients with liver disease occurred in the absence of eosinophilia, clinical evidence of atopy or other known causes of IgE elevation. No IgE-containing plasma cells were detected in the liver biopsies from thirty-two of the sixty-seven patients tested. Peripheral blood T cells were significantly decreased from normal in the patients with liver disease, but no correlation emerged between serum IgE levels and absolute peripheral blood T-cell numbers. These findings emphasize the importance of liver disease as a significant cause of serum IgE elevation.
Glomerulonephritis developed in a 42-year-old man with subacute bacterial endocarditis caused by an alpha-hemolytic Streptococcus. The patient showed hypocomplementemia and an elevated serum rheumatoid factor titer. Immunofluorescence microscopy of a renal biopsy specimen demonstrated granular deposits of IgM and C3 in all glomeruli studied. With the indirect immunofluores(ence technique and specific antiserum, the antigen in glomerular deposits was observed to correspond to the organism found in the blood cultures. These findings can be taken as further evidence that the glomerulonephritis of subacute bacterial enoocarditis represent an immune-complex disease.
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