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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 145 records · Page 8Linked to original sources
PubMed1992

A CNS specific proteoglycan associated with astrocytes in rat optic nerve.

A novel CNS specific keratan sulfate proteoglycan is identified by a monoclonal antibody (mAb) TED15. The antibody recognizes a carbohydrate epitope that is removed from the core protein following keratanase digestion. The relative molecular weight of the glycoprotein is not altered following digestion with heparinase, heparitinase or chondroitinase ABC. By immunoblot analysis, the TED15 antigen is differentially distributed in diencephalic derivatives, being present in the optic nerve but absent from the retina. Within the optic nerve, the TED15 antigen is associated with astrocytes, while in the retina no labeling of astrocytes of Müller cells is observed.

Animals↗
PubMed1992

End-stabilized microtubules observed in vitro: stability, subunit, interchange, and breakage.

We report a reliable method to prepare, in vitro, microtubules that are stabilized at both ends by axonemal structures, and report studies of their properties. Such "end-stabilized" microtubules neither grow nor shorten over times of several hours when tubulin subunits are present in the surrounding solution. When subunits are removed, the microtubules eventually break. Breakage occurs within a sinuous and flexible region, a few microns in length, that begins at a single point on the microtubule and grows. When breakage does occur, the resulting two free ends shorten very rapidly until the flexible part has depolymerized and the region of straight microtubule is reached. The remainder of the microtubule then shortens at rates comparable to those ordinarily observed in dynamic instability. Formation of the flexible region can be reversed if subunits are added to the buffer prior to breakage. End-stabilized microtubules are a useful tool for studying interactions of molecules with the microtubular wall. They may be a good model for interpreting stabilizing events that happen in the cell. A preliminary study of the effects of microtubule poisons on the wall is presented.

Alkaloids↗
PubMed1992

Two subtypes of HLA-B51 differing by substitution at position 171 of the alpha 2 helix.

Newly defined antigens of the B5, B35 cross-reacting group have been found in Japanese and North American Indians. Nucleotide sequencing of the alleles encoding the Japanese B5.35 antigen and the variant B5 antigen from the Piman Indians show them to be identical. This new allele, B*5102, differs from B*5101 by a single nucleotide substitution that changes residue 171 from histidine to tyrosine. Residue 171, which is part of the alpha 2 helix, is believed to contribute directly to peptide interaction in the A pocket of the binding groove and is either histidine or tyrosine in all HLA-A, B, C heavy chains. Tyrosine 171 is shared by B*5102, B*3501, B*3502, and B*5301 and must be responsible for the serological cross-reactivities of these molecules not shared with B*5101. Stimulation of lymphocytes from a B*5101 positive donor with B*5102 positive cells failed to generate cytotoxic T cells with specificity for the difference between these molecules. However, one out of five clones of cytotoxic T cells raised against B*5101 failed to lyse targets expressing B*5102. Substitution of histidine for tyrosine at residue 171 affected recognition of HLA-B35-restricted human minor histocompatibility antigen-specific T cell clones.

Amino Acid Sequence↗
PubMed1992

Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules bearing lambda light chains.

In order to evaluate binding specificities of anti-F(ab')2 antibodies from patients with systemic lupus erythematosus (SLE) and from normal healthy controls, F(ab')2 fragments were prepared from 24 IgG myelomas with defined isoelectric points, DNA-associated idiotypes, and kappa/lambda light chain types. Using ELISA and hemagglutination assays, anti-F(ab')2 antibodies from 12 healthy controls and 29 SLE patients were observed to exhibit preferential binding (lambda > kappa) to myeloma F(ab')2 fragments composed of lambda light chains (P < 0.0001). No correlation of anti-F(ab')2 binding and presence of cationic, neutral, or anionic isoelectric points or for DNA-associated idiotypes on monoclonal F(ab')2 was detected. Anti-F(ab')2 antibodies, often elevated in SLE during remission, show preferential specificity for F(ab')2 fragments bearing lambda light chains.

Adult↗
PubMed1992

HLA class II variation in the Gila River Indian Community of Arizona: alleles, haplotypes, and a high frequency epitope at the HLA-DR locus.

A genetic distribution for the HLA class II loci is described for 349 "full-blooded" Pima and Tohono O'odham Indians (Pimans) in the Gila River Indian Community. A high frequency epitope in the *DRw52 family was defined by reactions with 31 alloantisera, which we have designated *DR3X6. It segregates as a codominant allele at HLA-DR with alleles *DR2, *DR4, and *DRw8, and has the highest frequency yet reported for an HLA-DR specificity, 0.735. It forms a common haplotype with *DRw52 and *DQw3 that is a valuable marker for genetic admixture and anthropological studies. Phenotype and allele frequencies, and haplotype frequencies for two and three loci, are presented. Variation at these loci is highly restricted, the mean heterozygosity for HLA-DR and HLA-DQ being 0.361. The Pimans represent a contemporary model for the Paleo-Indians who first entered North America 20,000 to 40,000 years ago.

Alleles↗
PubMed1992

HLA class I variation controlled for genetic admixture in the Gila River Indian Community of Arizona: a model for the Paleo-Indians.

The genetic distribution of the HLA class I loci is presented for 619 "full blooded" Pima and Tohono O'odham Native Americans (Pimans) in the Gila River Indian Community. Variation in the Pimans is highly restricted. There are only three polymorphic alleles at the HLA-A locus, *A2, *A24, and *A31, and only 10 alleles with a frequency greater than 0.01 at HLA-B where *Bw48 (0.187), *B35 (0.173), and the new epitope *BN21 (0.143) have the highest frequencies. Two and three locus disequilibria values and haplotype frequencies are presented. Ten three-locus haplotypes account for more than 50% of the class I variation, with *A24 *BN21 *Cw3 (0.085) having the highest frequency. Gm allotypes demonstrate that little admixture from non-Indian populations has entered the Community since the 17th century when Europeans first came to this area. As a consequence many alleles commonly found in Europeans and European Americans are efficient markers for Caucasian admixture, while the "private" Indian alleles, *BN21 and *Bw48, can be used to measure Native American admixture in Caucasian populations. It is suggested that this distribution in "full blooded" Pimans approximates that of the Paleo-Indian migrants who first entered the Americas between 20,000 and 40,000 years ago.

Alleles↗
PubMed1992

Radiographic evaluation of crestal bone levels adjacent to nonsubmerged titanium implants.

Several parameters have been described to determine success or failure in long-term evaluations of dental implants. One of these parameters is the observation of changes in peri-implant bone levels. Studies on submerged implants have analyzed the bone level changes in the pre- and post-loading phases. No such data exist for intentionally nonsubmerged implants. The purposes of this study were: (1) to test the applicability and reproducibility of a simple computer-assisted method in the evaluation of changes in peri-implant bone levels; (2) to establish a baseline for the longterm radiographic follow-up; and (3) to evaluate changes in crestal bone levels adjacent to nonsubmerged ITI implants between the 1-year and 2-year examination. Standardized periapical radiographs were obtained from 80 implants at the 1-year and 2-year follow-up examinations after their placement. The implants were located in different jaw areas of 55 patients and supported single crowns or short-span fixed partial dentures. For each implant, the distance from implant shoulder to first crestal bone contact (DIB) was measured at the proximal surfaces with a digitizer/computer assembly. Statistically significant greater mean DIB were found at the 1-year (baseline) evaluation for: (1) maxillary sites overall (4.10 x 1.02 mm (SD)) compared with mandibular sites overall (3.61 +/- 1.03 mm); (2) maxillary anterior sites (4.08 +/- 0.97 mm) compared with mandibular posterior sites (3.60 +/- 1.05 mm); and (3) maxillary posterior sites (4.13 +/- 1.12 mm) compared with mandibular posterior sites. No statistically significant changes in DIB occurred in any of the jaw locations between the 1-year and 2-year evaluations.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗
PubMed1992

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Asian People↗
PubMed1992

Studies of antibody to herpes simplex virus Fc gamma-binding protein gE in patients with rheumatoid arthritis, juvenile rheumatoid arthritis and normal controls.

IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins.

Adult↗
PubMed1992

The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA-B46 haplotypes.

HLA haplotypes containing the HLA-B46 allele react with both anti-Cw1 and anti-Cw3 alloantisera, a pattern of reactivity defined as the Cw11 antigen and postulated to involve either a distinctive Cw11 allele or a duplicated HLA-C locus. From serological characterization of CIR cells transfected with B46 cDNA we now demonstrate that the anti-Cw3 reactivity with these haplotypes is solely due to the B46 molecule and not to an HLA-C molecule. Furthermore, isolation and characterization of HLA-C mRNA from cells expressing B46 strongly suggest that anti-Cw1 reactions are directed against the product of a conventional Cw1 allele. The antigenic cross-reactivities of B46 with B62 and Cw3 correlate with its chimaeric primary structure, which is identical to that of B62, except in the alpha 1 helix where it is identical to both Cw3 and Cw1. The structure, distribution and genetic linkage of B46 indicate it is of recent, Asian origin and is the result of a gene conversion, involving Cw1 as the donor gene and B62 as the recipient. These results demonstrate that the Cw11 antigen neither corresponds to a novel HLA-C allele nor a duplicated HLA-C locus, but to a combination of epitopes contributed by linked Cw1 and B46 alleles. The nucleotide sequence we previously and erroneously attributed to a distinct Cw11 allele is now demonstrated to encode Cw8. Isolation of the cDNA clone with this sequence from a library made from a cell homozygous for the B46 haplotype was probably an artefact of contamination.

Alleles↗
PubMed1992

Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss.

This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.

Administration, Oral↗
PubMed1992

Soft tissue reactions to non-submerged unloaded titanium implants in beagle dogs.

The soft tissue reactions to non-submerged unloaded titanium implants were examined. A total of 24 implants were placed in 6 beagle dogs. The implants differed in their crestal area by having either a rough sandblasted, a fine sandblasted, or a polished surface. After 3 months, all implants were firmly anchored in the bone and had no clinical signs of peri-implant inflammation. Undecalcified histologic sections demonstrated that all implants achieved osseointegration with direct bone contact. The epithelial structures showed a peri-implant sulcus with a non-keratinized sulcular epithelium and a junctional epithelium. None of the sections exhibited epithelial downgrowth to the alveolar crest. In the supracrestal area, a direct connective tissue contact to the implant post was observed. An approximately 50 to 100 microns wide zone of dense circular fibers was found close to the implant surface. It was free of blood vessels and resembled closely an inflammation-free scar tissue formation. This zone was surrounded by a looser connective tissue with a 3-dimensional network of collagen fibers running in different directions. No significant differences concerning soft tissue reactions were found between the 3 implant surfaces. In particular, the length of direct connective tissue contact was similar. Concerning bone reactions, a significantly shorter distance from the top of the implant to the most coronal bone-implant contact was observed for rough surfaces. It is concluded that non-submerged unloaded titanium implants achieved a complication-free tissue integration with a dense connective tissue in direct contact to the implant surface in the supracrestal area, and epithelial structures similar to those around natural teeth. The different surface textures did not influence the healing pattern of the soft tissues, but had an influence on the location of the most coronal bone-implant contact.

Alveolar Process↗
PubMed1992

Molecular mimicry--hypothesis or reality?

A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.

Arthritis↗
PubMed1992

Splenectomy as treatment for nonhealing soft tissue defect after total knee arthroplasty in a patient with Felty's syndrome.

We describe the apparent remarkable effect of splenectomy on wound healing in a patient with rheumatoid arthritis and Felty's syndrome. The patient had previously undergone a knee replacement with 4 months of failure of the surgical wound site to heal or close. The wound, which had broken down and dehisced on 3 separate occasions after plastic surgical attempts at closure, healed cleanly and without recurrence within 3 weeks of splenectomy and plastic repair at the same operation.

Aged↗
PubMed1992

The magnitude and origin of European-American admixture in the Gila River Indian Community of Arizona: a union of genetics and demography.

Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, md. The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on md yielded a fitted line m(a) = .922md, r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European-Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population.

Alleles↗
PubMed1992

Rheumatoid factors: historical perspective, origins and possible role in disease.

The recognition of antibodies by the immune system is more complex than previously believed. Rheumatoid factor (RF), a family of autoantibodies against gammaglobulin, has long been recognized as an important biologic marker for rheumatoid arthritis (RA). When RF contributes to the generation of the inflammatory aspects of RA, it probably does so by forming immune complexes that are themselves able to bring about the inflammatory response. Contrary to the widely accepted belief that RF somehow is triggered by recognition of self IgG, antibodies to viral Fc receptors may provide the initial stimulus for RF production in RA.

Aging↗
PubMed1991

Laboratory tests for rheumatic diseases.

A carefully taken history and thorough physical examination remain the most crucial aspects of diagnosing rheumatic disorders. Non-rheumatologic conditions also need to be kept in mind. Laboratory tests should be looked on as mostly supportive or confirmatory, because many of the tests are relatively nonspecific and may lack sensitivity. If their limitations are recognized, however, the tests can be invaluable tools when the clinician confronts the task of differentiating an array of rheumatologic disorders.

Adult↗