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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 163 records · Page 9Linked to original sources

Genetic variation in Arizona Mexican Americans: estimation and interpretation of admixture proportions.

Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedical, and evolutionary concerns. New genetic typings on 730 Arizona Mexican Americans for the HLA-A, HLA-B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each model. The following admixture estimates were obtained: Amerindian, 0.29 +/- 0.04; Spaniard, 0.68 +/- 0.05; and African, 0.03 +/- 0.02. The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion. An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.

Africa↗

Rheumatoid factors react with Fab fragments of monoclonal antibodies to herpes simplex virus types 1 and 2 Fc gamma-binding proteins.

Human polyclonal IgM rheumatoid factors (RF) were tested in an enzyme-linked immunosorbent assay with monoclonal antibodies (MAb) (II-481 and B10/A8) to glycoprotein E (gE), the Fc gamma-binding protein of herpes simplex virus type 1 (HSV-1), as well as with MAb 88-S to gE of HSV-2. Most of the RF reacted with II-481 and 88-S. Positive reactions were recorded for RF reacting with whole MAb II-481 and 88-S, as well as with their Fab, but not their Fc, fragments. Human monoclonal IgM RF isolated from mixed cryoglobulins showed a similar profile, with reactivity for both whole MAb II-481 and 88-S and for their Fab fragments. Reactivity with MAb to gE was observed regardless of the Gm specificity of the polyclonal RF and the cross-reactive idiotypes (6B6, 17.109, or G6) of the monoclonal RF. No positive reactions were noted between protein A and Fab fragments of any of the anti-gE MAb. These findings indicate that many RF may bear the internal image of the Fc gamma-binding regions of 2 different herpesviruses: HSV-1 and HSV-2.

Antibodies, Monoclonal↗

Kinky microtubules: bending and breaking induced by fixation in vitro with glutaraldehyde and formaldehyde.

We have employed video-enhanced light microscopy to study alterations of the overall shape of microtubules that are produced by the aldehyde fixation methods commonly employed to study them in vitro. Changes brought about by these methods include deformation and breakage. The severity of the effects depends on the fixative employed and increases with its concentration, and with the time of fixation. The changes are observed under a variety of conditions, such as brief exposure to 3.7% formaldehyde, or somewhat longer exposure to glutaraldehyde at concentrations as low as 0.05%. The observed distortion explains why microtubules usually appear curved or sinuous in electron micrographs while appearing relatively rigid and linear in video-enhanced light microscopy. The observed breakage implies that caution must be used in inferring length distributions from measurements of aldehyde-fixed microtubules.

Animals↗

Contrast enhancement as an aid to interpretation in digital subtraction radiography.

An initial study was performed to demonstrate the feasibility of pseudocolor contrast enhancement technique in digital subtraction radiography (DSR). DSR is an electronic image processing technique that has been shown to be of greater diagnostic value in the detection of small periodontal bone lesions than conventional radiography. Pseudocolor enhancement involves selectively assigning a unique color to each shade of gray present in a black-and-white subtracted image. Two image enhancement techniques were developed and tested in a phantom system consisting of extracted teeth set in blocks of plaster mixed with sawdust to simulate trabecular bone. It was found that experimentally induced periodontal lesions were more readily detected by the average clinician in both types of enhanced subtraction images than unenhanced subtractions. Furthermore, both enhancement techniques were of significantly greater diagnostic value for lesions smaller than 1.0 mm (p less than 0.001). The technique that colored an isolated area of interest was significantly more diagnostic at all depths tested (p less than 0.001 at 0.5 and 1.0 mm, and p less than 0.05 at 0.5 mm). Contrast enhancement may be a significant aid to the average clinician for the interpretation of DSR and the detection of small periodontal defects.

Chi-Square Distribution↗

Parallelism of serum anti-F(ab')2 and anti-cationic IgG reactivities in patients with systemic lupus erythematosus.

Cationic anti-DNA antibodies may be related to glomerular injury in murine lupus nephritis or in patients with systemic lupus erythematosus (SLE). Therefore, anti-cationic antibodies in SLE could include antibodies with regulatory function on such pathogenic cationic molecules. Since anti-F(ab')2 antibodies may be involved in the idiotype control of anti-DNA antibodies in some patients with inactive SLE, the present study was aimed to determine if SLE patients with significant serum levels of anti-F(ab')2 produce antibodies reacting with cationic IgG molecules. Three SLE sera with high titers of anti-F(ab')2 antibodies were individually adsorbed by sequential affinity chromatography on three Sepharose columns coupling normal IgG from Cohn Fraction II, pooled cationic IgG myeloma paraproteins displaying idiotypic anti-DNA markers (F4 and 8.12), and F(ab')2 fragment from allogeneic IgG, respectively. Eluates obtained from cationic IgG adsorption showed predominant anti-F(ab')2 reactivity. A similar profile was also detected in a serum from a normal control donor with high levels of anti-F(ab')2. Biotinylation of anti-cationic eluates showed that such antibodies were significantly more reactive with cationic than anionic or neutral IgG, confirming their apparent affinity for positively charged antigens on IgG molecules. Since anti-cationic absorptions were able to remove the anti-F(ab')2 activities in the SLE sera studied, it is possible that anti-cationic antibodies could function as immunoregulatory antibodies in the idiotypic control of some SLE autoreactive phenomena, including glomerular anti-DNA deposition.

Adult↗

Monoclonal antibodies against human anti-F(ab')2 antibodies react with light chain epitopes.

Anti-F(ab')2 antibodies affinity isolated from sera of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or normal SLE relatives were used to produce monoclonal antibodies (mAbs) in Balb/c and NZB mice. Four of five mAbs showed only primary light chain specificity. Only one mAb produced in an NZB mouse against anti-F(ab')2 from a single SLE patient showed anti-mu-chain specificity. Parallel identical control immunizations with IgG or a single human IgG kappa myeloma produced mAbs with a predominant gamma-chain/Fc fragment specificity. Anti-light chain specificity of mAbs was demonstrated to involve epitopes requiring tertiary structure of the entire light chain instead of antigens confined to Ckappa/lambda or Vkappa/lambda fragments. Anti-kappa specificity of three mAbs was extremely similar but not identical to that defined by anti-Km1 allotyping systems. No evidence was obtained with any of the mAbs produced for antigens unique to SLE or RA anti-F(ab')2 antibodies. The light chain antigenic prominence of many anti-F(ab')2 antibodies may reflect structural features shared by this group of immunoglobulins somehow important for their biologic function.

Animals↗

Effect of the NSAID piroxicam, topically administered, on the development of gingivitis in beagle dogs.

A single-blind investigation was designed to study the effects of piroxicam in preventing gingival inflammation and plaque formation in beagle dogs. Twelve 1-year-old beagles were brought to optimum oral hygiene and gingival health. Thereafter, they were fed a moist plaque-promoting diet and were divided into three groups. The first group received daily administration of 1.0 ml placebo gel (methylcellulose) painted on the teeth. The second group received 1.0 ml of gel containing 2 mg/ml piroxicam and the third group received 1.0 ml liquid containing 2 mg/ml of piroxicam. Placebo and test solutions were applied daily, and dogs were examined biweekly for evaluation of plaque accumulation, gingival inflammation, bleeding upon gentle probing and tooth staining. Data were analyzed using the Krushkal-Wallis test. Over the treatment period, plaque accumulation was substantial in all three groups and was not significantly different between the three groups. By week 2, the gingival index in the piroxicam-treated dogs was significantly lower than that of the placebo-treated group and remained so throughout the study, with the exception of wk 6 and 12 in the topical gel-treated group. Mean percent bleeding sites were also significantly less in the piroxicam-treated groups than in the control dogs. Staining of the teeth increased for all groups over the 16-wk treatment period. These data indicate that piroxicam can significantly inhibit the development of gingival inflammation in beagle dogs.

Administration, Topical↗

Use of digital radiography to demonstrate the potential of naproxen as an adjunct in the treatment of rapidly progressive periodontitis.

The effect of the non-steroidal anti-inflammatory drug, naproxen, in reducing periodontal disease activity was assessed in 15 patients with rapidly progressive periodontitis. All patients in this double-blind study were treated with scaling and root planing. Thereafter, 7 patients receiving 500 mg naproxen b.i.d. for 3 months, and 8 patients received placebo. Disease activity was assessed in three ways. First, alveolar bone height was determined using standardized radiography. Second, alterations in alveolar bone metabolism were assessed using 99m-Tc-methylene diphosphonate uptake prior to dosing and 3 months later. Finally, bone loss or gain was detected using digital subtraction radiography. In this study, conventional subtraction images were processed to isolate the area of change and superimpose the change on the original radiograph. This allowed determination of both the direction and location of osseous changes. There was significantly less bone loss as determined by analysis of bone height during the 3-month study in the naproxen-treated patients when compared to the placebo-treated patients (p less than 0.001). Radiopharmaceutical uptake was significantly reduced in the alveolar bone in patients receiving naproxen (p less than 0.03), whereas no significant change was observed in the placebo-treated patients. Furthermore, the subtraction radiographs showed a significant increase in the proportion of teeth demonstrating bone gain in the naproxen-treated group. These findings indicate that naproxen may be a useful adjunct to scaling and root planing in patients with rapidly progressive periodontitis.

Adolescent↗

Inhibition of alveolar bone loss in beagles with the NSAID naproxen.

The non-steroidal anti-inflammatory drug(NSAID) naproxen was studied in 11 beagle dogs over a 13-month period to determine its effect on the progression of periodontitis. Following a 6-month pretreatment period, 5 dogs received naproxen daily at a dosage of 2.0 mg/kg for 1 month, then 0.2 mg/kg for 6 months. Six control dogs received a gelatin capsule daily as placebo. Standardized radiographs were used to measure the rate of bone loss during the pretreatment and treatment periods. In the control dogs, the rate of bone loss was seen to increase during the treatment period although the increase was not statistically significant. In dogs treated daily with naproxen, the rate of bone loss in the treatment period was significantly less at 4 months of treatment; however, at 7 months the difference, though lower than pretreatment rate, was not significant. When the percent change in rate of bone loss during the overall 7-month treatment period was compared with pretreatment rate, the control dogs demonstrated a 38% increase in rate of bone loss during the treatment period contrasting with a 61% decrease in bone loss rate in naproxen-treated dogs. The data indicate that the non-steroidal anti-inflammatory drug naproxen can significantly inhibit alveolar bone loss in beagles. At 4 months of treatment the rate of bone loss in the naproxen-treated dogs was significantly less than pretreatment, but at 7 months of treatment the rate was no longer statistically significantly less than baseline. This probably reflects a dose response to naproxen treatment for, after 30 days of the treatment period, the naproxen dosage was reduced 10-fold due to tolerance by the beagle.

Alveolar Bone Loss↗

Detection of periodontal disease activity with a scintillation camera.

The goal of this study was to assess the ability of a scintillation camera method to detect areas of active bone loss due to periodontitis. Technetium 99m methylene diphosphonate was used as the bone-seeking radiopharmaceutical. Bone-seeking radiopharmaceutical uptake (BSRU) was imaged and quantified in alveolar bone regions of interest with a scintillation camera and a computer. Analysis of the sequential radiographs over six months constituted the basis for determination of sites of active disease. The study was composed of two parts. First, 18 subjects, nine with adult periodontitis and nine controls, were enrolled in a cross-sectional study to determine whether the quantitative scintillation amera methodology detected differences in BSRU in periodontitis vs. periodontally healthy patients. Second, the nine patients with periodontitis were studied longitudinally in order to determine whether the BSRU examination was indicative of bone loss subsequently measured radiographically. In the cross-sectional study, the mean uptake ratio for the periodontitis group was significantly higher than that for the control group (1.63 +/- 0.06 and 1.42 +/- 0.04, respectively, p less than 0.01, t test). From the longitudinal study, the mean patient scintillation image uptake ratios were highly correlated with the mean bone loss determined from serial radiographs (p less than 0.01). The accuracy, sensitivity, and specificity of the quantitative gamma camera method for detecting site(s) of active bone loss within the region of interest were assessed relative to the longitudinal radiographic data. The accuracy, sensitivity, and specificity were 85%, 90%, and 79%, respectively. Alveolar bone scintigraphy with a gamma camera and computer may provide a simple and valid technique for the immediate indication of areas of periodontal disease activity.

Adult↗

Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs.

The purpose of this study was to evaluate the early wound healing events of bone around press-fit titanium implants inserted with and without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I). Nine months prior to implant placement all mandibular premolar teeth were extracted in 8 beagle dogs. Subsequently, 40 specially manufactured titanium implants with 2 transverse holes in the apical section were press fit into precise recipient sites in the dogs' mandibles. The dogs were sacrificed at 7 and 21 days following implant placement yielding 12 PDGF-B/IGF-I treated and 8 control (placebo gel or non-treated) implants for each observation period. Coded undecalcified sections were analyzed for: 1) percentage of implant surface in contact with new bone; 2) percentage of peri-implant space filled with new bone; and 3) percentage of implant hole filled with new bone. An analysis of variance was used to determine significant differences among the treatment groups. At 7 days, the percentage of bone fill in the peri-implant spaces and the percentage of implant surface in contact with new bone were both significantly increased in PDGF-B/IGF-I treated sites (P less than 0.01 for both groups). There was less than 1.5% fill of the implant holes in both treated and control sites (no significant differences). At 21 days the percentage of bone fill in the peri-implant spaces was significantly increased in the PDGF-B/IGF-I treated sites (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing.

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolar Bone Loss↗

Rheumatoid factors may bear the internal image of the Fc gamma-binding protein of herpes simplex virus type 1.

Affinity-purified rheumatoid factors (RF) from 20 patients with rheumatoid arthritis were tested for their reactivity with the mAb II-481 against glycoprotein E (gE), the Fc gamma-binding protein of HSV-1, as well as with a panel of mAb against human Fc gamma R. All RF bound to mAb II-481 in preference to mAb IV.3 (anti-human Fc gamma RII) or MOPC 141 (control mAb) which belong to the same IgG2b subclass. Five RF showed strong reactivity with II-481. No significant reactivity was observed between RF and mAb against human Fc gamma R. Non-RF human IgM did not react with any of the mAb. Clear-cut binding to II-481 was also seen with monoclonal IgM-RF derived from MRL/1 mice (mRF-2). The reaction between RF and II-481 was completely inhibited by human IgG. It was also inhibited by BHK cell extract infected with HSV-1, and with purified gE. II-481 inhibited the binding of human IgG Fc to the infected cell extract, confirming that II-481 recognizes the Fc-binding site on gE. II-481 did not react directly with human IgG or Fc of IgG. mAb to human IgG2 showed stronger binding to II-481 than to MOPC 141, suggesting II-481 has conformational similarity to human IgG H chain. These results suggest that at least some RF bear the "internal image" of HSV-1 Fc gamma-binding protein and support the hypothesis that some RF may be generated as anti-idiotype antibodies against antiviral antibodies.

Animals↗

Microtubule solutions display nematic liquid crystalline structure.

We report a study of the spontaneous formation of ordered arrays of microtubules in solution. Form birefringence and anisotropic light-scattering appear rapidly and spontaneously when tubulin, initially present in homogeneous solution, self-assembles into microtubules. This phenomenon is reversible and occurs at protein concentrations of a few milligrams per ml, in the presence or absence of microtubule-associated proteins. Light and electron microscopic examination reveals that extensive regions of these birefringent solutions consist of nearly parallel microtubules. Measurement of the order parameter, S, yields a value of 0.81 +/- 0.05, indicating a high degree of alignment. Comparison of these observations to qualitative predictions developed from the theory of Onsager ((1949) Ann. N.Y. Acad. Sci. 51, 627-659) leads to the conclusion that microtubules form a nematic liquid crystalline phase in vitro under ordinary conditions. Simultaneous spectrophotometric observation of turbidity (a measure of microtubule assembly) and birefringence shows that the parallel ordering lags only slightly behind assembly, thus demonstrating that much microtubule growth must occur by addition of tubulin to the ends of microtubules that are already aligned. These observations of anisotropy are important to the understanding of microtubule dynamics in vitro.

Animals↗

Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis.

We have identified an inhibitor of the protein C anticoagulant pathway in the plasma of a patient with systemic lupus erythematosus and a history of recurrent deep vein thrombosis, fetal wastage, and seizures. The patient's plasma contained anticardiolipin antibodies as well as a weak lupus anticoagulant. Examination of this patient's plasma revealed normal levels of protein C and protein S antigen, normal levels of functional protein C, as well as essentially normal levels of every blood coagulation factor. In a modified prothrombin time assay, the activated protein C-mediated prolongation of the clotting time observed in normal plasma was not observed in this patient's plasma. Gel permeation chromatography of the patient's plasma revealed that the inhibitory material was a high molecular weight protein that coeluted with the IgM peak. The inhibitor did not appear to circulate as a complex with protein C, since the inhibitor could easily be separated from protein C during fractionation procedures, and did not interfere with the activation of protein C in plasma as assessed by a functional amidolytic assay. Our findings suggest that the recurrent thrombotic episodes observed in this patient may have occurred as a result of the patient's antiphospholipid antibody neutralizing specific phospholipids essential for the full expression of the anticoagulant activity of activated protein C.

Abortion, Habitual↗

Functional and morphological stasis during molecular evolution.

The evolutionary distance between two sets of proteins was estimated using the techniques of Miyata and Yasunaga (1980) and Kimura (1980). Human beta 2-microglobulin was compared with the homologous murine molecule, while human and equine alpha-globin were similarly treated. It was found that a large amount of molecular evolution has occurred in beta 2-microglobulin since its divergence from the common ancestor of mice and humans. Kimura's estimate of evolutionary distance, K, is 0.353, while those of Miyata and Yasunaga are KS = 0.708 and KA = 0.171. The respective values for human and equine alpha-globin are 0.152, 0.293, and 0.084. In spite of this molecular evolution, it is shown that murine beta 2-microglobulin can effect the expression of HLA class I antigens on the surface of human-mouse hybrid cells and that the tertiary structures of human and equine deoxyhemoglobin are nearly identical. These observations are discussed in the light of Kimura's theory of neutral allelic drift.

Amino Acid Sequence↗