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R C Williams

Publications and source records attributed to R C Williams.

At least 181 records · Page 10Linked to original sources
PubMed1990

Microtubule-associated proteins from Antarctic fishes.

Microtubules and presumptive microtubule-associated proteins (MAPs) were isolated from the brain tissues of four Antarctic fishes (Notothenia gibberifrons, N. coriiceps neglecta, Chaenocephalus aceratus, and a Chionodraco sp.) by means of a taxol-dependent, microtubule-affinity procedure (cf. Vallee: Journal of Cell Biology 92:435-442, 1982). MAPs from these fishes were similar to each other in electrophoretic pattern. Prominent in each preparation were proteins in the molecular weight ranges 410,000-430,000, 220,000-280,000, 140,000-155,000, 85,000-95,000, 40,000-45,000, and 32,000-34,000. The surfaces of MAP-rich microtubules were decorated by numerous filamentous projections. Exposure to elevated ionic strength released the MAPs from the microtubules and also removed the filamentous projections. Addition of fish MAPs to subcritical concentrations of fish tubulins at 0-5 degrees C induced the assembly of microtubules. Both the rate and the extent of this assembly increased with increasing concentrations of the MAPs. Sedimentation revealed that approximately six proteins, with apparent molecular weights between 60,000 and 300,000, became incorporated into the microtubule polymer. Bovine MAPs promoted microtubule formation by fish tubulin at 2-5 degrees C, and proteins corresponding to MAPs 1 and 2 co-sedimented with the polymer. MAPs from C. aceratus also enhanced the polymerization of bovine tubulin at 33 degrees C, but the microtubules depolymerized at 0 degrees C. We conclude that MAPs are part of the microtubules of Antarctic fishes, that these proteins promote microtubule assembly in much the same way as mammalian MAPs, and that they do not possess special capacities to promote microtubule assembly at low temperatures or to prevent cold-induced microtubule depolymerization.

Alkaloids↗
PubMed1990

Antibodies to the peptide from the plasmid-coded Yersinia outer membrane protein (YOP1) in patients with ankylosing spondylitis.

Seventy-five Norwegian patients with ankylosing spondylitis (AS) were studied for class-specific antibody response against synthetic peptide, P81, representing the sequence of plasmid-coded outer membrane protein of Yersinia (YOP1) containing four amino acid homology (TDRE) with HLA-B27 sequence. Ten (16.7%), five (8.3%) and seven (11.2%) of 60 male AS patients showed elevated anti-YOP1 P81 antibody of IgA, IgG, and IgM class, respectively, whereas for each isotype only one (4%) of 25 healthy male controls was positive. Differences were not observed between female patients and controls. In all isotypes, antibody-positive patients were more frequently found in patients with active disease. The anti-YOP1 P81 antibody levels of the patients were generally not correlated with the antibody levels against the peptide representing the hypervariable region of HLA-B27 (B27 peptide). However, in one patient the antibody was shown to react with both peptides by cross-inhibition analysis. Overall, it appears that any causal relationship between YOP1 and pathogenesis of AS is not strong. Immunogenicity and cross-reactivity of the YOP1 region encompassing the TDRE sequence particularly at the T cell level require further study.

Adhesins, Bacterial↗
PubMed1990

Sulfadiazines reduce gingivitis and plaque formation in beagle dogs.

The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on reducing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. 12 beagle dogs were scaled, root planed and pumiced to bring them to a similar level of gingival health, prior to placing them on a diet of Purina Dog Chow softened with canned gravy and molasses to promote the build-up of plaque and the initiation of gingivitis. At the end of 8 weeks, the dogs were determined to have substantial bacterial plaque accumulation and apparent gingivitis. Thereafter, 4 dogs were treated 2 x daily with topical applications of 3% zinc sulfadiazine; 4 dogs were treated with 2% silver sulfadiazine while 4 dogs were treated with placebo gel serving as control over a 14-week treatment period. By week 2, the zinc and silver sulfadiazine dogs showed a significant decrease in gingival index which was maintained throughout the study. Additionally, by week 2, the % of sites with bleeding was also seen to decrease significantly in the experimental groups. The plaque index remained consistent in all 3 groups until week 6 when the 2 experimental groups indicated significant decrease in plaque accumulation as compared to controls. Probing depths were also seen to decrease significantly in the experimental groups after 10 weeks of therapy. The mean stain index was similar in all 3 groups of dogs throughout the study. Data indicate that both zinc and silver sulfadiazine inhibit plaque formation and reduce existing gingivitis in beagle dogs.

Administration, Topical↗
PubMed1990

Sulfadiazines prevent plaque formation and gingivitis in beagles.

The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on developing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. Plaque and gingival indices were used to measure plaque formation and gingivitis. During a 2-wk baseline period each dog was brought to optimal gingival health with prophylaxis and tooth brushing. Thereafter, 4 dogs were treated twice daily with topical application of 3.0% zinc sulfadiazine; 4 dogs were treated with 2.0% silver sulfadiazine while 4 dogs treated with placebo gel served as controls over a 12-wk treatment period. At wk 2 of treatment, all three groups of dogs showed an increase in plaque build-up on their teeth from baseline. By wk 6, plaque accumulation on the teeth was significantly less in dogs treated with either ZnSD or AgSD compared to control dogs. At wk 2 of treatment, gingival inflammation was increased from baseline in all three groups. Thereafter, over the course of the 12-wk treatment period, gingival inflammation in the ZnSD and the AgSD treated dogs was significantly less than the placebo treated dogs. The data indicate that both ZnSD and AgSD inhibit developing plaque formation in beagles. This significant inhibition of plaque formation was accompanied by a significant reduction in gingival inflammation.

Administration, Topical↗
PubMed1990

Thyroid-stimulating antibody activity between different immunoglobulin G subclasses.

To investigate the distribution of thyroid-stimulating antibody (TSAb) activity between IgG subclasses, sera from 11 patients with Graves disease (including the National Institute of Biological Standards and Control (NIBSC) Research Standard, long acting thyroid stimulator-B) were fractionated by chromatography on affinity columns of monoclonal IgG subclass antibodies or protein A to deplete all but a single subclass. The resulting fractions were 98% or more pure for a single subclass. In all 11 patients, TSAb activity appeared to be confined to the IgG1 fraction as determined by cAMP production on addition of the fractions to the FRTL-5 rat thyroid cell line. In all of eight specimens from seven patients so tested, the whole serum activity was recovered in the IgG1 fraction, after adjusting for the recovery of the isotype from the column. TSAb activity in one serum comprised both lambda and kappa light chains but was IgG1 restricted. This IgG subclass restriction was not found when the same fractions were tested for thyroglobulin, microsomal/thyroid peroxidase, or tetanus toxoid antibody activity. Together with previous results showing marked restriction of both light chain usage and isoelectric point of TSAb, these results support the idea that Graves' disease may be the result of an oligo- or possibly monoclonal response at the B cell level.

Cyclic AMP↗
PubMed1990

Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid.

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.

Amino Acid Sequence↗
PubMed1989

The binding of isocolchicine to tubulin. Mechanisms of ligand association with tubulin.

Isocolchicine is a structurally related isomer of colchicine altered in the methoxytropone C ring. In spite of virtual structural homology of colchicine and isocolchicine, isocolchicine is commonly believed to be inactive in binding to tubulin and inhibiting microtubule assembly. We have found that isocolchicine does indeed bind to the colchicine site on tubulin, as demonstrated by its ability to competitively inhibit [3H]colchicine binding to tubulin with a KI approximately 400 microM. Isocolchicine inhibits tubulin assembly into microtubules with an I50 of about 1 mM, but the affinity of isocolchicine for the colchicine receptor site, 5.5 +/- 0.9 x 10(3) M-1 at 23 degrees C, is much less (approximately 500-fold) than that of colchicine. Unlike colchicine, isocolchicine binds rapidly, and the absorption and fluorescence properties of the complex are only modestly altered compared to free ligand. It is proposed that the binding of isocolchicine to tubulin may be rationalized either in terms of conformational states of colchicinoids when liganded to tubulin or by the structural requirements for C-10 substituents for high affinity binding to the colchicine receptor.

Animals↗
PubMed1989

End-to-end joining of taxol-stabilized GDP-containing microtubules.

By the use of the drug taxol, microtubules were assembled from tubulin that had GDP at its exchangeable nucleotide binding site. By means of dilution experiments and measurements of exchange of labeled subunits, it was determined that the rate of interchange of subunits between these microtubules and the solution is very slow: the upper limit of the dissociation rate constant was measured to be 0.2 subunit s-1 end-1. When they were broken into short pieces by gentle shearing, these microtubules were found to undergo a rapid subsequent spontaneous increase in length. This increase was attributed to end-to-end joining (also called annealing), because dynamic instability and other mechanisms involving either nucleotide hydrolysis or subunit interchange at the ends could be ruled out. To characterize the process, a diffusion-controlled joining mechanism was hypothesized, and a length-independent bimolecular rate constant, gamma, was defined. Length distributions were measured at a series of times after the initial shearing. By means of a novel iterative calculation, the best-fitting value of gamma was determined from the time-dependent changes in the length distributions. Fitting was carried out at each of three concentrations of microtubules. The resulting values show that end-to-end joining of microtubules is remarkably efficient and that gamma is concentration-dependent.

Algorithms↗
PubMed1989

Cross-reactive epitope with Klebsiella pneumoniae nitrogenase in articular tissue of HLA-B27+ patients with ankylosing spondylitis.

Synovial tissues from patients with ankylosing spondylitis or reactive arthritis were examined by an immunoperoxidase technique, using antisera to synthetic peptides representing antigens shared between HLA-B27.1 and Klebsiella pneumoniae nitrogenase. With either antiserum, all HLA-B27+ patients with synovial inflammation showed strong immunoperoxidase staining in synovial lining cells, vascular endothelium, and infiltrating inflammatory cells. These findings indicate that antigens showing cross-reactivity between HLA-B27.1 and Klebsiella nitrogenase epitopes are strongly expressed within inflamed synovial tissues of HLA-B27+ patients.

Arthritis↗
PubMed1989

Distribution of anti-F(ab')2 antibodies and the 16/6 idiotype in systemic lupus erythematosus (SLE) probands and kindreds.

Levels of serum anti-F(ab')2 antibodies and expression of the 16/6 anti-DNA idiotype were studied in 103 sera from first-degree relatives of 17 systemic lupus erythematosus (SLE) kindreds. Among healthy SLE relatives, 35.9% showed anti-F(ab')2 elevations and 24%, Id 16/6 expression. Forty-three and two-tenths percent of healthy SLE relatives with elevated anti-F(ab')2 also showed expression of 16/6; when Id 16/6 was positive, 16 of 25 relatives (64%) showed parallel elevations of anti-F(ab')2. However, within individual families, distribution patterns of elevated anti-F(ab')2 and Id 16/6 often did not coincide. Affinity-isolated anti-F(ab')2 from four members of a single SLE kindred showed relative enrichment for Id 16/6 in only two of the four individuals studied. Moreover, none of the isolated anti-F(ab')2 antibodies within this kindred or another kindred showing 16/6 Id expression reacted directly with 16/6 Id. Our studies suggest that whereas both anti-F(ab')2 and Id 16/6 are increased within SLE kindreds, expression of the two does not always coincide. Furthermore, anti-F(ab')2 antibodies do not show direct reactivity with Id 16/6. A number of anti-DNA idiotypic markers may play a role in idiotypic networks among such SLE kindreds.

Adolescent↗
PubMed1989

Isotype, distribution and target analysis of lymphocyte reactive antibodies in patients with human immunodeficiency virus infection.

Anti-lymphocyte (ALA) antibodies were investigated by using both microcytotoxicity and immunofluorescence analyses in 87 subjects with different clinical features of human immunodeficiency virus (HIV) infection. A similar mean percentage of killing in microcytotoxicity assays using heterologous lymphocytes as cellular target was recorded in four groups of patients, including 36 HIV-seropositive asymptomatic subjects, 34 patients with HIV-induced lymphadenopathy syndrome (LAS), 13 with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and 4 patients with the full-blown AIDS. Conversely, an increasing percentage of ALA-positive subjects paralleled the evolution of the HIV infection. The majority of ALA were IgM isotype with a significant reactivity against T cells. This specificity was indifferently directed to CD3+, CD4+, and CD8+ lymphocytes. In additional experiments employing enzymatic digestion of lymphocyte membrane antigens, we demonstrated that CD4 and CD8 receptors were digested by the pronase, whereas CD3 molecules were highly resistant. Subsequent flow cytometry analyses using these pronase-digested T cells showed that reactivity of ALA for their target was unchanged. Our data suggest that antigenic specificities of ALA in HIV infection are resistant to pronase treatment and are not related to CD4 and CD8 molecules.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Studies of anti-F(ab')2 antibodies and VH region distribution among SLE kindreds.

Genomic DNA samples from kindreds of patients with systemic lupus erythematosus were examined for VH region genotypes using probes representing JH and representative members of the human VH gene families (VHI-VHVI) in parallel with distribution of high levels of anti-F(ab')2 (generic anti-idiotype) in some non-affected SLE family members. Identical VH region genotypes were present in an SLE female proband and one unaffected normal male sibling. Three normal unaffected family members with elevated anti-F(ab')2 showed AB, AD, and AC (non-identical)VH genotypes. VH region genotype pattern distributions do not appear to directly correlate with production of high levels of anti-F(ab')2 in SLE families.

Autoantibodies↗
PubMed1989

A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration.

The combination of platelet-derived growth factor (PDGF) and insulin-like growth factor one (IGF-1) has previously been shown to enhance repair of soft tissue wounds. Here we report initial observations following application of PDGF and IGF-1 to periodontitis-affected teeth in beagle dogs. 1 micrograms of PDGF and IGF-1 in an aqueous gel was applied to the root surfaces of test teeth following open flap debridement. Control sites received the gel alone. Block biopsies of the teeth and surrounding bone were taken 2 weeks after treatment. Histologic analyses of control specimens revealed a long junctional epithelial attachment, and no new bone or cementum formation. In contrast, growth factor treated sites exhibited significant amounts of new bone and cementum formation. A nearly continuous layer of osteoblasts lined the newly formed bone, and there was a dense cellular "front" at the coronal extent of the new bone. These preliminary results suggest that in vivo application of the combination of PDGF and IGF-1 may enhance regeneration of the periodontal structures.

Alveolar Process↗
PubMed1989

Production of tumor necrosis factor/cachectin by peripheral blood mononuclear cells in patients with systemic lupus erythematosus.

Levels of tumor necrosis factor/cachectin (TNF alpha) assessed by ELISA were similar in the supernatant of cultures from peripheral blood mononuclear cells (PBMC) from either active or inactive systemic lupus erythematosus (SLE) patients and controls stimulated with mitogen alone. When PBMC were stimulated with mitogen plus phorbol 12-myristate-13-acetate (PMA), the amount of TNF alpha was significantly decreased in culture supernatants from active patients or from the entire group of SLE patients studied. However, spontaneous synthesis of TNF alpha in nonstimulated cultures was increased in the SLE patients. Interferon-gamma (IFN-gamma) enhanced TNF alpha synthesis in cultures from either SLE patients or controls stimulated by concanavalin A (Con A) alone, but depressed the high production of TNF alpha by normal PBMC stimulated with Con A plus PMA. IFN-gamma enhanced TNF alpha production in response to Con A plus PMA in 2 of 3 SLE patients.

Concanavalin A↗
PubMed1989

Presence of a non-HLA B cell antigen in rheumatic fever patients and their families as defined by a monoclonal antibody.

Numerous investigators have suspected that there is a genetic predisposition to rheumatic fever (RF). In this context we have recently produced a series of monoclonal antibodies directed against B cells obtained from RF patients one of which, labeled D8/17, identifies a B cell antigen present in 100% of all RF patients studied. While the highest percentage of positive cells were exhibited by RF probands (33.5% +/- SE), the percentage of cells in unaffected siblings and parents was 14.6 and 13%, respectively. The percentage of positive cells in APSGN probands, unaffected siblings, and parents was 2.96, 3.86, and 2.8%, respectively. A low level of B cells (5-7%) bearing the D8/17 marker was seen in control patients. The segregation pattern of the phenotypes defined by the percentage of D8/17 positive cells within HLA-typed RF families are consistent with an autosomal recessive mode of inheritance not associated with the human MHC system. We postulate that these phenotypes indicate the presence of at least one necessary genetic factor for susceptibility to RF.

Analysis of Variance↗
PubMed1989

Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen.

The treatment of human periodontal diseases relies on mechanical and antimicrobial suppression of the etiologic bacteria. The ability to alter the progression of periodontitis by additionally blocking host pathways involved in the destructive process is an area of current research. Prostaglandins and other metabolites of arachidonic acid are believed to be important host mediators of the bone resorption of diseases such as periodontitis. We have previously examined the effect of inhibitors of prostaglandin production, non-steroidal anti-inflammatory drugs (NSAIDs), on inhibiting alveolar bone loss in beagles. The present study was designed to examine the effect of the NSAID, flurbiprofen, on slowing the radiographic loss of alveolar bone in the human. Fifty-six individuals with radiographic evidence of alveolar bone loss were recruited for study. Forty-four patients remained in the study for the data analysis of loss of alveolar bone. Following a 6 month baseline pretreatment period to measure the radiographic progression of bone loss, half of the patients were administered flurbiprofen, 50 mg. b.i.d., while half were administered a placebo. All patients received a subgingival scaling and pumice by a hygienist every 6 months. The rate of alveolar bone loss in a 2 year treatment period was compared to the baseline 6 month pretreatment period within and between patient groups. Throughout the study, teeth exhibiting obvious loss of bone were exited from study and treated with conventional mechanical therapy. At the end of the pretreatment period both patient groups had a similar mean rate of alveolar bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗