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Biomedical subjects

R C Williams

Publications and source records attributed to R C Williams.

At least 109 records · Page 6Linked to original sources
PubMed1994

Elevations of neutrophil proteinase 3 in serum of patients with Wegener's granulomatosis and polyarteritis nodosa.

OBJECTIVE: To determine serum levels of proteinase 3 (PR3) in normal subjects and patients with Wegener's granulomatosis (WG), polyarteritis nodosa (PAN), chronic renal failure, and systemic lupus erythematosus (SLE). METHODS: Serum levels of PR3 were measured by enzyme-linked immunosorbent assay employing a monospecific rabbit polyclonal antibody against PR3. RESULTS: Quantifiable levels of PR3 were detected in all serum samples examined, including those of normal subjects. Marked elevations of serum PR3, which decreased with treatment, were found in patients with active WG. Patients with PAN, SLE, and chronic renal failure also showed elevated levels of PR3. CONCLUSION: Quantitating serum PR3 may be useful in the management of patients with WG and other connective tissue diseases.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Dynamic instability of microtubules from cold-living fishes.

The dynamic instability of microtubules free of microtubule-associated proteins from two genera of cold-living fishes was measured, by means of video-enhanced differential-interference-contrast microscopy, at temperatures near those of their habitats. Brain microtubules were isolated from the boreal Atlantic cod (Gadus morhua; habitat temperature approximately 2-15 degrees C) and from two austral Antarctic rockcods (Notothenia gibberifrons and N. coriiceps neglecta; habitat temperature approximately -1.8 to + 2 degrees C). Critical concentrations for polymerization of the fish tubulins were in the neighborhood of 1 mg/ml, consistent with high interdimer affinities. Rates of elongation and frequencies of growth-to-shortening transitions ("catastrophes") for fish microtubules were significantly smaller than those for mammalian microtubules. Slow dynamics is therefore an intrinsic property of these fish tubulins, presumably reflecting their adaptation to low temperatures. Two-dimensional electrophoresis showed striking differences between the isoform compositions of the cod and the rockcod tubulins, which suggests that the cold-adapted microtubule phenotypes of northern and southern fishes may have arisen independently.

Animals↗
PubMed1994

Tissue distribution of antigen(s) defined by monoclonal antibody D8/17 reacting with B lymphocytes of patients with rheumatic heart disease.

Monoclonal antibody D8/17 originally prepared by immunization of mice with B cells from a patient with rheumatic heart disease (RHD) reacts with epitopes expressed on significantly elevated proportions of B cells (10-35%) from all patients with acute rheumatic fever or rheumatic heart disease. This B cell marker does not segregate with any known HLA or DR phenotype. We have examined the reactivity of D8/17 with a broad assortment of human tissues, using indirect immunofluorescence. Strong positive reactivity of D8/17 was observed with cardiac muscle, skeletal muscle, and smooth muscle of blood vessels. Positive fluorescent staining was also noted in cell membranes of hepatocytes and cells lining bile canaliculi as well as in epithelial cells of skin, esophagus, and cervix. D8/17 mAb binding to cardiac muscle was markedly diminished by preincubation of mAb with KH B cell line originally established from an RHD patient. D8/17 mAb binding to human heart was also inhibited by preincubation with myosin and tropomyosin but not by actin. Using the D8/17 mAb in immunoblots, positive binding was noted by the antibody to recombinant type M6 protein, vimentin, and myosin. Our findings indicate that the B cell antigen reacting with mAb D8/17 may be related to contractile proteins present in heart, skeletal and smooth muscle, and may also share epitopes with some components of group A streptococci.

Antibodies, Monoclonal↗
PubMed1994

Changes in rheumatoid factor and monoclonal IgG antibody specificity after site-specific mutations in antigenic region of beta 2-microglobulin.

Antigenic epitopes on the SKDWSFY region (positions 57-63) of human beta 2-microglobulin (beta 2m) reacting in ELISA with polyclonal and monoclonal human IgM rheumatoid factors (RF) as well as with monoclonal mouse IgG anti-beta 2m antibodies were studied after site-specific mutation of single or double beta 2m amino acid residues. Single site-specific mutations at lysine 58 and serine 61 produced a major decrease (50-100%) in reactivity of polyclonal IgM RF with beta 2m. Mutations at serine 57, tryptophane 60, and phenylalanine 62 also induced substantial decrements (25-49%) in IgM RF reactivity. beta 2m mutants containing double amino acid mutations including one residue outside the SKDWSFY region along with four different mutations at tryptophane 60 also often showed marked decrements in IgM RF anti-beta 2m reactivity. Site-specific mutations at virtually all residues within the SKDWSFY beta 2m region produced a major decrease in reactivity of two of three monoclonal human IgM RF. Results with nine murine IgG anti-beta 2m mAbs often showed an entirely different profile. Site-specific mutation of aspartic acid at position 59 produced a 50-100% decrease in binding of nine mAbs. Serine at position 61 and tyrosine at 63 also appeared to represent important residues for antigenic determinants reacting with anti-beta 2m mAbs. Results of mapping discrete epitopes using glycine substitution within overlapping 7-mers of beta 2m linear sequence compared with site-specific mutation of single beta 2m residues were similar in many instances, but also often showed marked differences. A marked change in antigenic contribution of single amino acid residues to beta 2m antigenic epitopes frequently depended on what residues were mutated to. Our findings emphasize that single residues within a small seven amino acid, solvent-accessible antigenic stretch of primary beta 2m sequence vary considerably in their contribution to the reactive antigenic structures for IgM RF as well as monoclonal IgG antibodies.

Amino Acid Sequence↗
PubMed1994

Expression of F4, 8.12, 3I, and 16/6 anti-DNA idiotype-related antigens on cationic human IgG myeloma proteins.

One hundred cationic isolated human IgG myeloma proteins were studied for expression of four anti-DNA idiotypic (Id) markers F4, 3I, 8.12, and 16/6. Forty-three of 100 myelomas showed the presence of at least one anti-DNA idiotype. Twenty-seven were F4 positive, 18 were 16/6 positive, 8 were 3I positive, and 7 were positive for 8.12. Two different anti-DNA idiotypic markers were found together on the same 14 myeloma proteins and 3 myelomas showed three different anti-DNA Ids. Anti-DNA activity was found on only 1 of 100 myelomas but not associated with presence of an anti-DNA Id. Ten myelomas showed anti-F(ab')2 activity and 6 of these also showed the presence of an anti-DNA Id marker. When myeloma proteins expressing anti-DNA Ids were compared in direct competition ELISAs with known Id-positive human IgG anti-DNA antibodies, much less inhibition was recorded in comparison to known human anti-DNA antibodies. Our findings indicate that human IgG myeloma proteins may show positive reactions with anti-DNA idiotypic antibodies but do not express the complete anti-DNA idiotypic antigenic complex.

Antibodies, Antinuclear↗
PubMed1994

Inhibition of peri-implant bone loss with the nonsteroidal anti-inflammatory drug flurbiprofen in beagle dogs. A preliminary study.

There is increasing interest in how pathways of tissue destruction around dental implants are similar as for teeth and how these pathways can be modulated to slow loss of supporting bone. The purposes of this study were to develop a short-term animal model to study the effect of the nonsteroidal anti-inflammatory drug flurbiprofen, on slowing the rate of induced peri-implant bone resorption. A total of 20 cylindrical titanium implants were placed in 2 beagle dogs using a low-trauma surgical technique. During the 3-month healing period without functional loading of the implants, daily oral hygiene was performed to maintain a Gingival Index of 0 to 0.5. At completion of the healing period, a baseline evaluation was performed which included the uptake of the bone-seeking radiopharmaceutical (BSRU) 99mtechnetium-tin-diphosphonate (99mTc-Sn-MDP) in peri-implant bone and standardized radiographs. Peri-implantitis was induced with 4-0 silk ligatures, cessation of oral hygiene and soft diet. One beagle was given 0.02 mg/kg of flurbiprofen by mouth; the other received a placebo. BSRU and radiographic height of bone were remeasured to calculate the rate of bone loss during the 60-day treatment period. The percent rate of bone loss during the study period was calculated from the radiographs using a computer-assisted method. The radiopharmaceutical uptake for the flurbiprofen-treated implants remained unchanged. However, BSRU for placebo-treated implants was significantly increased from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Bone Loss↗
PubMed1994

Rheumatoid-factor-reactive sites on CH2 established by analysis of overlapping peptides of primary sequence.

Polyclonal IgM rheumatoid factors (RF) from ten patients with rheumatoid arthritis (RA) isolated on IgG affinity columns were studied for their reactivity with overlapping 7-mer peptides representative of solvent accessible regions of the CH2 domains of IgG using a pin-ELISA assay. A panel of nine monoclonal RF from RA patients' B cells were studied in parallel. Four peptides SVFLFPP (239-245), KFNWYVD (274-280), NSTYRVVSV (297-305) and VLTVLHQNWL (305-314) reacted with most RF. Glycine substitution showed that tryptophanes at 277 and 313, tyrosine at 278, valines at 279 and 305, and leucine 314 represented important residues for RF reactivity. Assays using monoclonal IgM RF produced from RA synovial B cells or peripheral blood B cells frequently showed a restricted spectrum of reactivity for CH2 epitopes, which often were identical to those binding to polyclonal IgM RF. Combinations of synthetic 7-mer peptides representing RF-reactive CH2 or CH3 epitopes produced as much as 60-90% inhibition of RF binding to IgG when peptides were preincubated with RF in free solution before completion of the reaction of RF with IgG on the ELISA plate.

Amino Acid Sequence↗
PubMed1994

Streptococcus pyogenes type M12 protein shows selective binding to some human immunoglobulin G3 myeloma proteins.

Purified, recombinant M12 protein from Streptococcus pyogenes CS24 has recently been demonstrated to bind human immunoglobulin G3 (IgG3). The binding site for IgG has been localized to an internal peptide encoded by a PvuII fragment of the gene emm12. We have investigated the ability of an isolated recombinant M12 protein consisting of the peptide encoded by the PvuII fragment to bind various monoclonal human IgG3 myeloma proteins representing a number of both Caucasian and Oriental IgG3 Gm(allotypic) phenotypes. Of nine Caucasian IgG3 myeloma proteins, only two bound strongly to the recombinant M12 protein in enzyme-linked immunosorbent assays. The allotypic phenotypes of the reactive proteins were IgG3m(b+)(g-) and IgG3m(b-)(g+). No binding was seen for seven IgG3 myeloma proteins of Oriental origin with G3m(st+)(u-)(b+)(g-), G3m(st-)(u+)(b+)(g-), G3m(st-)(u+)(b-)(g+), and G3m(st-)(u-)(b-)(g+) phenotypes. The binding of human IgG3 to M12 protein seems to be related to features other than its Gm allotypic markers. Selective reactivity of IgG3 myeloma proteins with M12 protein may provide another way to subclassify human IgG3 molecules. The biological significance of the selective reactivity is not known.

Animals↗
PubMed1994

Antimyenteric neuronal antibodies in scleroderma.

The pathogenesis of gastrointestinal (GI) dysmotility in scleroderma is incompletely understood, although previous studies have proposed a neuropathic mechanism. We studied patients with scleroderma as compared with other connective tissue disease patients and normal controls for the presence of circulating antibodies to myenteric neurons. Serial dilutions of sera were overlaid on rat intestine, double-labeled with antineurofilament antibody as a myenteric plexus marker, and imaged using indirect immunofluorescence techniques. High titer sera (> or = 1:50) from 19 out of 41 scleroderma patients stained myenteric neurons, whereas none of 22 normals or 5 patients with idiopathic GI dysmotility were positive. Although 6 out of 20 SLE and 6 out of 10 mixed connective tissue disease patients' sera stained myenteric plexus neurons, when positive sera were absorbed with calf thymus extract to remove antinuclear antibody, 15 scleroderma sera, 0 SLE, and 2 mixed connective tissue disease patients retained positive staining of myenteric neurons. Western blotting using actin and neuronal intermediate filament preparations failed to show immunoreactivity with scleroderma sera containing antimyenteric neuronal antibodies. Paraneoplastic sera associated with GI dysmotility stained myenteric neurons in a different pattern than seen with scleroderma sera. A positive correlation between the presence of Raynaud's phenomenon and antimyenteric neuronal antibodies was observed in scleroderma patients. Our results indicate that IgG antibodies reacting with myenteric neurons are present in many patients with scleroderma. Although the neuronal antigen has not yet been identified, the presence of myenteric neuronal antibodies in patients with GI dysmotility and scleroderma suggests a neuropathic process.

Adolescent↗
PubMed1994

Studies of protein A and herpes simplex virus-1 induced Fc gamma-binding specificities. Different binding patterns for IgG3 from Caucasian and Oriental subjects.

Herpes simplex virus type 1 (HSV-1) expresses a receptor that binds the Fc portion of IgG. This HSV-1 Fc gamma-binding protein is, like protein A of Staphylococcus aureus, known to bind human IgG1, IgG2 and IgG4 but not IgG3 subclasses. However, IgG3 with the allotype Gm(s+)(t+), prominent in the Oriental population, reacts with protein A. This prompted us to investigate the reactivity of Oriental IgG3 monoclonal myeloma proteins of various allotypes with the HSV-1 Fc gamma-binding protein. Of seven Oriental IgG3 myeloma proteins with allotypes Gm(s+)(t+)(u-)(b+)(g-), Gm(s-)(t-)(u+)(b+)(g-) and Gm(s-)(t-)(u+)(b-)(g+), all reacted with the HSV-1 Fc gamma-binding protein. This was in contrast to negative reactions obtained with three IgG3 myeloma proteins of Caucasian origin with Gm(b+)(g-) or Gm(b-)(g+) phenotypes. The same binding pattern, i.e. binding of IgG3 of Oriental but not of Caucasian origin, was found with protein A. The binding of the monoclonal Oriental IgG3 proteins was again independent of the G3m phenotype. These findings support the concept that the HSV-1 Fc gamma-binding protein A have a similar binding site on the IgG molecule. All monoclonal IgG3 proteins derived from Oriental subjects with or without histidine at position 435 bound to HSV Fc gamma-binding protein. This suggests that Oriental IgG3 myeloma proteins with Gm(s-)(t-) phenotypes have additional critical amino acid residue substitutions important for HSV Fc gamma binding different from those already known.

Asian People↗
PubMed1994

Longitudinal radiographic study of crestal bone levels adjacent to non-submerged dental implants.

To investigate changes in alveolar crestal bone levels adjacent to dental implants prior to and after functional loading, dental radiographs of 103 implants from consecutively treated patients were taken at four time-points: immediately after surgical insertion, at 3-6 months after surgery, at 12 months, and at 24 months after surgery. A computer-assisted method was used to measure the percent of bone change (%BC) relative to the shoulder-apex length of the implants at mesial and distal sites. Differences in the mean rates of %BC between the pre-loading period (3-6 months post-surgery) and the post-loading periods PLP1 and PLP2 (6-12 months and 12-24 months post-surgery, respectively) were evaluated. Rates of % BC during PRE, PLP1, and PLP2 were also determined for locations (maxilla or mandible) and types (screw or press-fit). Significantly higher rates of % bone loss per month were found for all implants during PRE compared with PLP1 and PLP2, and during PLP1 compared with PLP2. During PRE, maxillary implants had a significantly higher rate of bone loss compared with mandibular implants. During PLP1, mandibular implants showed some further loss, whereas maxillary implants exhibited a small but significant gain. No significant difference was found during PLP2. Bone loss adjacent to press-fit implants was significantly higher than that adjacent to the screw type during PRE, while no difference was found during the post-loading periods.

Alveolar Bone Loss↗
PubMed1994

Periodontal regeneration with bioresorbable membranes.

A critical point for the success of guided tissue regeneration is the rate of degradation of the bioresorbable membrane. An ideal bioresorbable membrane must allow selective repopulation of the root surface by cells from the periodontal ligament before it is degraded and replaced by the healing connective tissues of the periodontium. Freeze-dried dura mater, microfibrillar collagen, bovine type I collagen, human type I collagen, polylactic acid, and polyglactin 910 have been used in clinical human studies. Microfibrillar collagen did not form an effective barrier to epithelial migration. Freeze-dried dura mater has shown limited improvement in the treatment of proximal infrabony defects and equal results to expanded polytetrafluorothylene in the treatment of mandibular class II furcations. Cross-linked type I collagen and polylactic acid have shown significant improvement in the treatment of proximal infrabony lesions and class II furcations. More clinical studies done by independent investigators are needed to support the value of these bioresorbable materials in the regeneration of the periodontal tissues.

Animals↗
PubMed1993

Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment.

The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the VH4-21 gene segment, a member of the human VH4 family. This gene segment is utilized by essentially all cold agglutinin (CA) Abs with I/i specificity isolated from patients with CA disease stemming from chronic lymphoproliferative disorders. In this study, mutational analysis of a CA has been used to determine the structural basis for 9G4 binding to Abs utilizing the VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 family member that is associated neither with Abs having CA activity nor with Abs that react with 9G4. The results indicate that the motif AVY at amino acid positions 23-25 in FR1 defines the 9G4 idiotope. Reaction of these recombinant Abs with a polyclonal rabbit anti-CA antiserum absorbed to render it specific for a CA CRI also maps predominantly to FR1. These findings indicate that the solvent-exposed FR1 plays an important role in eliciting an immune response to Igs.

Agglutinins↗
PubMed1993

Microtubule-associated protein 2 alters the dynamic properties of microtubule assembly and disassembly.

The influence of microtubule-associated protein 2 (MAP2) on the dynamics of microtubule assembly and disassembly from axonemal fragments was characterized in vitro in solutions of pure tubulin and varying concentrations of MAP2. A mechanistic description of interactions between MAP2 and individual microtubules was developed from analysis of recorded images obtained by video-enhanced differential-interference-contrast light microscopy. MAP2 decreased the rates and lengths of shortening events and decreased the frequency of transitions between growth and shortening over a wide range of concentrations, thereby producing the increases in net microtubule growth previously described by light-scattering techniques. Increases in rates and lengths of elongation phases, as well as rescue frequencies (i.e. transition from shortening to growth), were observed under conditions in which microtubules are expected to be saturated with MAP2. During early stages of nucleated assembly, MAP2 greatly increased the number of microtubules growing from a given axoneme and caused elongation of "curved" structures which may be sheet-like microtubules.

Animals↗
PubMed1993

Taxol-induced flexibility of microtubules and its reversal by MAP-2 and Tau.

When microtubules, ordinarily quite rigid structures, are treated in vitro with the anti-tumor drug taxol, they rapidly develop a wavy appearance and become strikingly flexible. A quantitative measure of their flexibility, the reciprocal statistical length, lambda, increases by an order of magnitude when taxol is bound. Subsequent addition of either of the microtubule-associated proteins MAP-2 or tau causes the flexibility to disappear. It can be restored again by removing the microtubule-associated protein. These results show that taxol changes microtubular structure substantially, probably by weakening the interactions between protofilaments, and that microtubule-associated proteins reverse these effects, possibly by bridging protofilaments. This structural change and the accompanying flexibility may contribute importantly to taxol's cytotoxic activity.

Animals↗
PubMed1993

Rheumatoid factors from patients with rheumatoid arthritis react with tryptophan 60 and 95, lysine 58, and arginine 97, on human beta 2-microglobulin.

OBJECTIVE: To define precise epitopes on human beta 2-microglobulin (beta 2m) reacting with polyclonal IgM rheumatoid factors (RF) from patients with rheumatoid arthritis (RA). METHODS: Ten polyclonal RF were tested for their human beta 2m epitope-binding specificities using the entire 99-amino acid sequence synthesized as overlapping 7-mers in an enzyme-linked immunosorbent assay. Glycine substitution for each residue within RF-reacting linear regions was employed to define major reactive sites. RESULTS AND CONCLUSION: Major beta 2m residues contributing to RF reactivity were tryptophans at positions 60 and 95, lysine at 58, and arginine at position 97.

Amino Acid Sequence↗