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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 253 records · Page 14Linked to original sources
PubMed1985

Release of exchangeably bound guanine nucleotides from tubulin in a magnesium-free buffer.

The number of moles of guanine nucleotides (denoted GXP), either guanosine 5'-triphosphate (GTP) or guanosine 5'-diphosphate (GDP), bound to a mole of phosphocellulose-purified tubulin after gel filtration into a variety of nucleotide-free buffers has been measured (H. B. Croom, J. J. Correia, and R. C. Williams, Jr., unpublished results). All buffers we have studied that promote reduction of the number of bound nucleotides to fewer than two per tubulin dimer also eventually cause irreversible loss of activity of the protein. However, in 0.1 M 1,4-piperazinediethanesulfonic acid (pH 6.9) and 2 mM dithioerythritol (with no Mg2+), tubulin rapidly releases approximately 0.4 mol of bound nucleotides during two successive gel filtrations requiring less than 0.5 h and regains the ability to polymerize when magnesium and GTP are immediately added to the buffer. No change in conformation detectable by circular dichroism or sedimentation velocity accompanies this reversible process. (Upon prolonged incubation in the buffer, however, tubulin undergoes irreversible changes according to apparent first-order kinetics with a half-life of approximately 8 h. These changes include the irreversible release of nucleotide, a loss of the ability to polymerize, and a decrease in molar ellipticity between 210 and 240 nm.) The nucleotide which is reversibly released in this buffer comes from that population which exchanges readily with [3H]GTP in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

GM allotypes in Native Americans: evidence for three distinct migrations across the Bering land bridge.

We report the results of typings, for immunoglobulin G allotypes, of 5392 Native Americans from ten samples, the typings having been performed over the last 20 years. Four cultural groups are represented: the Pimans-Pima and Papago; the Puebloans-Zuni and Hopi; the Pai-Walapai; and the Athabascans-Apache and Navajo. The haplotype Gm1;21 has the highest frequency in each population while Gm1,2;21 is polymorphic in all except the Hopi. The Mongoloid marker Gm1;11,13 is found primarily in the Athabascans. The Caucasian haplotype Gm3;5,11,13 is found at polymorphic frequencies in several of the populations but its frequency is very low or absent among nonadmixed individuals. Although Nei's standard genetic distance analysis demonstrates genetic similarity at the Gm and Km loci, the heterogeneity that does exist is consistent both with what is known about the prehistory of Native Americans and traditional cultural categories. When the current Gm distributions are analyzed with respect to the three-migration hypothesis, there are three distinct Gm distributions for the postulated migrants: Gm1;21 and Gm1,2;21 for the Paleo-Indians 16,000 to 40,000 years ago; Gm1;21, Gm1,2;21, and Gm1;11,13 for the second wave of Na-Dene hunters 12,000 to 14,000 years ago; and Gm1;21 and Gm1;11,13 for the Eskimo-Aleut migration 9,000 years ago. The Pimans, Puebloans, and the Pai are descendents of the Paleo-Indians while the Apache and Navajo are the contemporary populations related to the Na-Dene. Finally, the Gm distribution in Amerindians is found to be consistent with a hypothesis of one migration of Paleo-Indians to South American, while the most likely homeland for the three ancestral populations is found to be in northeastern Asia.

Chromosome Mapping↗
PubMed1985

Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis.

Synovial tissues were studied, using immunofluorescence techniques, for localization of lymphocytic infiltrates and immune reactants, including C3, C5b-9, C9, and Ia antigen. Tissue distribution of interleukin-2 (IL-2) and gamma-interferon was also determined, using mouse monoclonal antibodies. IL-2 was found in association with OKT8 and OKT4 T cells, and gamma-interferon was noted in association with T cells, B cells, and macrophages. Staining both for IL-2 and for gamma-interferon was surprisingly faint in view of the intensity of lymphocytic infiltration.

Arthritis, Rheumatoid↗
PubMed1985

Rheumatic fever-associated B cell alloantigens as identified by monoclonal antibodies.

Mice immunized with B lymphocytes obtained from patients who had had well-documented rheumatic fever in the past yielded 2 monoclonal antibodies, termed 83S19.23 and 256S10, which identified certain alloantigens present on the B cells of these patients. The frequency of the B cell marker detected by clone 83S19.23 in rheumatic fever patients was found to be 59%, 77%, and 74% in India, New Mexico, and New York, respectively. Monoclonal antibody 256S10 identified 75% of those rheumatic fever patients who were nonreactive to clone 83S19.23. Thus, the 2 antibodies identify approximately 92% of all rheumatic fever patients and suggest the presence of a diallelic genetic marker for susceptibility to rheumatic fever.

Antibodies, Monoclonal↗
PubMed1985

IgM, IgA and IgG rheumatoid factors in patients with rheumatoid arthritis and normal donors.

IgM, IgA, and IgG Rheumatoid Factors (RF) were measured by ELISA assay in serum from 26 patients with definite rheumatoid arthritis (RA) and 11 normal controls. IgM-RF was assayed by ELISA, radioimmunoassay, and also by the standard latex fixation test in all sera from RA patients. In patients with RA quantitative amounts of IgM, IgA, and IgG-RF as estimated by ELISA were highly correlated. Significant correlations were found between a physician's rating of disease activity and IgG-RF (r = 0.44; p less than .02) and IgA-RF (r = 0.38; p = .06 but not for IgM-RF as measured in any of the three assays.

Adult↗
PubMed1985

Salmonella typhimurium mitogen induces proliferation of human B lymphocytes.

The maturation of human B lymphocytes can be described as a sequence of activation, proliferation, and differentiation into immunoglobulin-secreting cells. A variety of mitogens which are T cell dependent or independent have been employed to study this process. These moieties generally induce B-cell activation and proliferation followed by differentiation, making the study of initial events difficult. This study characterizes the mitogenic activity of Salmonella typhimurium mitogen (STM), a protein fraction of S. typhimurium. Glass-nonadherent peripheral blood lymphocytes were rosetted with affinity-purified rabbit anti-human F(ab')2-coupled ox erythrocytes and separated on a Ficoll-Hypaque gradient. This population of B lymphocytes, when cultured in dilutions of STM showed dose-dependent proliferation by [3H]thymidine incorporation. Maximal proliferation occurred on Day 7 using STM at 100 micrograms/ml (control, 5692 +/- 1704 cpm; STM, 58,541 +/- 5655 cpm). On Day 7 the percentage of blast cells by Giemsa stain was 14 +/- 4% in control cultures and 52.5 +/- 8.7% with STM. ELISA quantitation of IgG and IgM in culture supernatants revealed no secretion above unstimulated controls. When B lymphocytes were enriched by a negative selection technique, significant proliferation was not observed. STM is a novel B lymphocyte mitogen which induces proliferation but not activation or differentiation of human B lymphocytes into immunoglobulin-secreting cells.

B-Lymphocytes↗
PubMed1985

Discrepancy in the expression of autoantibodies in healthy aged individuals.

Sera from 50 healthy old subjects and from 51 young controls were tested by ELISA assays for a panel of autoantibodies, including IgM RF, anti-DNA, anti-F(ab')2, antithyroglobulin, anti-human albumin, anti-human hemoglobin, anti-secretory component from human IgA, and anti-gliadin. In vitro production of anti-DNA as well as anti-F(ab')2 antibodies were measured after stimulation of PBMC by pokeweed mitogen (PWM) in 12 healthy elderly subjects and 11 young controls. Sera from elderly donors contained threefold higher amounts of IgM RF than young controls (P less than 0.001). On the contrary, the levels of anti-DNA as well as anti-F(ab')2 antibodies were similar in both groups (P less than 0.3 for the two determinations). Anti-DNA and anti-F(ab')2 antibodies were also measured in supernates of PWM-stimulated glass nonadherent PBMC cultures from both old and young healthy donors without finding any significant difference between the two groups. Additional ELISA tests were also performed in both elderly and young control sera to detect antibodies against six other different antigens. No significant difference was found in the percentages of positive sera between the two groups. This discrepancy in production of IgM RF compared to other autoantibodies in healthy elderly subjects does not provide support for a general increase of autoantibodies with aging. The biological significance of an increase in IgM RF with aging remains to be determined.

Aged↗
PubMed1985

Nuclear medicine. An indicator of "active" alveolar bone loss in beagle dogs treated with nonsteroidal anti-inflammatory drug.

Nuclear medicine was used to assess the activity of alveolar bone loss in beagle dogs treated with the nonsteroidal anti-inflammatory drug flurbiprofen. Radiographic measurements of the rate of bone loss were taken during a 6-month "pretreatment" period and a 9-month treatment period. During the treatment period six dogs received a placebo, and six dogs received orally 0.02 mg/kg flurbiprofen daily for 9 months. In addition, each dog received periodontal surgery in one half of the mouth at the end of the pretreatment period. The rate of alveolar bone loss was significantly decreased in the treatment period in the flurbiprofen-treated dogs (P less than 0.001). Measurements of bone-seeking radiopharmaceutical uptake were taken 3 months after the initiation of therapy. The single measurement of uptake was compared to the rate of bone loss determined from repeated radiographs taken during the 9-month treatment period. Bone-seeking radiopharmaceutical uptake was an accurate indicator of "active" bone loss in 83.5% of the teeth studied.

Alveolar Process↗
PubMed1985

Healing of spontaneous periodontal defects in dogs treated with xenogeneic demineralized bone.

This study was undertaken to histologically, clinically and radiographically evaluate the sequence of healing following implantation of bovine demineralized bone powder (DBP) into severe, spontaneous periodontal defects in beagle dogs. Eight dogs with documented severe periodontitis were treated surgically following initial debridement. One quadrant in each arch was treated with conventional flap surgery and the others were treated with surgery followed by DBP implantation. Animals received postoperative debridement and clinical and radiographic evaluation. Two dogs were sacrificed at 1, 3, 6 or 12 months postoperatively, and the jaws were evaluated histologically. Clinically, DBP was well tolerated by recipients. No evidence of localized inflammatory response or delayed hypersensitivity reaction was noted. Significant reductions in gingival inflammation were noted in both experimental and control sites at 1 month postoperatively compared to preoperative scores. Equivalent periodontal pocket reduction was noted between test and experimental sites and remained significant at 12 months. Radiographically, no differences were noted in the rate of bone loss between control and test sites. Histologic evaluation demonstrated the presence of DBP at 1 month following implantation, but the material was replaced with new bone by the next sacrifice period. Periodontal ligament fibers of standard orientation were seen extending from DBP-induced bone to the root surface by 1 month after implantation. An intact epithelial attachment appeared to be present 1 month after the implantation of DBP. No differences in root surfaces were detected between test and control groups. Ankylosis was a rare finding, noted equally between test and control sites. DBP did not appear to predispose to external root resorption. In later stages, histologic evidence of advancing periodontitis was noted equally in both control and experimental groups. While DBP successfully induced new bone formation, the inability to adequately maintain the periodontal tissues due to bacterial accumulation in this model combined with recurrent pocket formation, precluded any conclusion regarding long-term advantage. Based on these findings, clinical trials of this or similar materials are recommended.

Alveolar Process↗
PubMed1985

Studies of streptococcal membrane antigen--binding cells in acute rheumatic fever.

Blood specimens from patients with rheumatic heart disease in both India and New Mexico were typed for the presence of B cell alloantigen 883 by use of a mouse monoclonal antibody with identical specificity to the original 883 human alloantiserum. Strong relative segregation was recorded for 883 positive B cell typing in patients with rheumatic heart disease in both geographic locations as compared with that in normal unaffected controls. In patients with acute rheumatic fever, studies of actual B-lymphocyte membrane binding by anti-883 monoclonal antibody and sonicated group A streptococcal membrane antigens showed separate but contiguous localization on isolated cell surfaces. Although physically distinct, 883 B cell alloantigen and sonicated group A streptococcal membrane antigens moved together in cell capping studies after incubation at 37 degrees C. These findings reaffirm the apparent close association between 883 B cell alloantigen and rheumatic heart disease. They also demonstrate that the B cell alloantigen 883 itself is physically distinct from but very close to sites on antigen-reactive B cells actually binding to group A streptococcal membrane antigens.

Acute Disease↗
PubMed1985

Family distribution of anti-F(ab')2 antibodies in relatives of patients with systemic lupus erythematosus.

Recently we reported an inverse relationship between the levels of anti-F(ab')2 antibodies and disease activity in systemic lupus erythematosus (SLE). The present study focused on anti-F(ab')2 antibodies in unaffected relatives of SLE patients. Sixty sera from first degree family members from 11 SLE families and 49 sera from 8 control families were studied. Percentage of SLE family members with anti-DNA antibodies (15%) was higher than than control family sera (8%, P less than 0.05). Anti-F(ab')2 antibodies were measured using ELISA assays. The SLE family sera had higher amounts of anti-F(ab')2 antibodies than the normal control family group (P = 0.0051). In an effort to determine if anti-F(ab')2 antibodies found in high titres in the sera of some SLE family members had specificity for the F(ab')2 fragment of anti-DNA antibodies of the SLE relative patients, DNA-anti-DNA inhibition experiments were performed using anti-F(ab')2 prepared from the relative in parallel with anti-F(ab')2 prepared from normal controls with equivalent high titres of serum anti-F(ab')2. Inhibition exhibited by anti-F(ab')2 of first degree relatives was higher than that obtained from control normal donors (P less than 0.02). Such differences in inhibition were not recorded using a control tetanus toxoid-anti-tetanus toxoid assay. In direct binding ELISA experiments, peroxidase-conjugated anti-F(ab')2 antibodies from the same first degree relative showed high relative specificity against purified anti-DNA antibodies of his SLE proband when compared to those obtained against different anti-DNA antibodies isolated from unrelated SLE patients (P less than 0.001). Such a substantial difference was not observed in parallel experiments using peroxidase conjugated anti-F(ab')2 antibodies from normal controls unrelated to SLE subjects.

Adolescent↗
PubMed1985

Immunofluorescence studies of cardiac valves in infective endocarditis.

Mitral and aortic valves removed at emergency cardiac surgery from a patient with infective endocarditis caused by Streptococcus viridans were studied by immunofluorescence to ascertain the extent and pattern of various immune reactants within the large valvular vegetations. Heavy intravalvular deposits of IgG as well as bacterial antigen were present. Much more focal interstitial IgM and C3 deposits were noted within vegetations and valve substance. Diffuse endocardial and subendocardial deposition of C5b-C9 and C9 complement neoantigens was present. Direct staining of valvular tissues and vegetations for rheumatoid factor showed extensive interstitial tissue deposition. These findings emphasize the large amounts of immune reactants and constituents of immune complexes present in valves and vegetations of patients with infective endocarditis.

Adult↗
PubMed1985

Antibodies to lymphocyte membrane preparations in systemic lupus erythematosus.

IgG and IgM antilymphocyte antibodies were determined in sera from patients with systemic lupus erythematosus (SLE) by an ELISA method using isolated lymphocyte plasma membranes as antigens. Lymphocyte membranes prepared from T or B cell lines or normal peripheral blood showed a high degree of purity by enzyme assay and electron microscopic monitoring. Sera from patients with active SLE showed high IgG and IgM ELISA reactivity against T and B cell plasma membranes compared with normal sera. IgM antibodies to lymphocyte membranes showed a correlation with microcytotoxicity results. Serial studies showed a relationship of antimembrane antibody to disease activity in some patients, but not in others. The ELISA method for antilymphocyte antibody assay provides a sensitive technique for monitoring reactivity against antigens retained in isolated lymphocyte membrane preparations.

Adsorption↗