Search PubMed⌕ Search

Biomedical subjects

W C Watson

Publications and source records attributed to W C Watson.

At least 19 recordsLinked to original sources
PubMed1992

Collagen-induced arthritis in rats. Examination of the epitope specificities of circulating and cartilage-bound antibodies produced by outbred and inbred rats using cyanogen bromide-derived peptides purified from heterologous and homologous type II collagens.

To determine the number and location of antibody binding epitopes on type II collagen, outbred and inbred rats were immunized with chick, bovine, human, and rat type II collagen (CII, BII, HII, and RII); all sera were assayed for reaction with a panel of CB peptides purified and renatured from the immunizing collagen and from RII. Antibody reaction patterns (profiles) varied among individual outbred rats but were essentially constant over time and changed little after boosting. The strongest antibody reactions were to CB11, CB9-7, and CB12 followed by CB8, CB10, and CB6. Antibody profiles varied depending on the species of collagen used for immunization and the strain of rat immunized. Except for CB10, where antibodies were largely specific for heterologous collagens, antibodies reactive with all other CB peptides cross-reacted strongly with renatured rat CB peptides. Sera from inbred BB rats immunized with BII, CII, or HII reacted best with CB11, unlike antisera to RII that reacted strongly with CB9-7. Inbred LEW, COP, WKY, F344, and BUF rats immunized with BII reacted strongest with CB9-7 and variably with CB11 and CB12. BBxLEW F1 hybrid rats reacted almost equally with CB11 and CB9-7 producing an antibody profile intermediate to those elicited in the parent strains. Finally, antibodies reactive with rat CB11, CB9-7, and CB12 could be eluted from normal rat cartilage incubated in anti-BII serum; antibody eluate profiles generally paralleled the profile produced by the sera applied to cartilage. Taken together, these findings indicate that multiple antibody-reactive epitopes on type II collagen may be instrumental in the initiation of collagen-induced arthritis in rats, particularly shared or cross-reactive epitopes located within CB11, CB9-7, CB12, and CB8.

Animals↗
PubMed1991

Immunity to type XI collagen in mice. Evidence that the alpha 3(XI) chain of type XI collagen and the alpha 1(II) chain of type II collagen share arthritogenic determinants and induce arthritis in DBA/1 mice.

To determine whether native bovine type XI collagen (BXI) is arthritogenic, five strains of inbred mice were immunized with BXI/CFA. Arthritis was not observed in any of these strains, though it was prevalent in DBA/1 and B10.RIII controls immunized with bovine type II collagen (BII). Antisera from BXI-immunized mice reacted with mouse type XI collagen (MsXI), weakly with the alpha-chains of BXI, and minimally with mouse type II collagen (MsII). However, antisera to BII reacted with MsII and MsXI, indicating antibodies to conformation-independent epitopes shared by alpha 1(II) and alpha 3(XI). Mice immunized with BXI containing a small amount of BII developed arthritis much like those immunized with BII; sera from these mice reacted with MsXI and MsII. Delayed-type hypersensitivity responses differed from IgG responses, i.e., BXI elicited responses to alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II); BII, to alpha 3(XI) and alpha 1(II) exclusively. To determine whether alpha 1(XI), alpha 2(XI), alpha 3(XI), and alpha 1(II) are arthritogenic, DBA/1J mice were immunized with each alpha-chain. Arthritis was seen in mice injected with alpha 3(XI) or alpha 1(II). Sera to both alpha-chains reacted similarly with MsII and peptide fragment alpha 1(II)-CB11. Epitope mapping using polyclonal and mAb to type II collagen revealed that all polyclonal and 11 of 14 mAb reacted with alpha 3(XI) and alpha 1(II), whereas three mAb reacted only with alpha 1(II). In conclusion, BXI is immunogenic but not arthritogenic in five strains of mice, whereas alpha 3(XI) and alpha 1(II) are arthritogenic and immunogenic in DBA/1 mice and share greater than or equal to 11 epitopes recognized by autoantibody.

Animals↗
PubMed1991

SWR mice are resistant to collagen-induced arthritis but produce potentially arthritogenic antibodies.

SWR mice are resistant to collagen-induced arthritis but produce antibodies to type II collagen. To determine if these antibodies have arthritogenic potential, serum from collagen-immunized mice was concentrated and passively transferred to DBA/1 mice. The recipients developed severe arthritis within 72 hours. To evaluate the role of complement, SWR mice were bred with congenic inbred B10.D2/oSn (complement deficient) and B10.D2/nSn (complement normal) mice. Collagen-immunized (SWR x B10.D2/nSn)F1 mice had high levels of C5 and were susceptible to arthritis, while (SWR x B10.D2/oSn)F1 mice were deficient in C5 and were resistant to arthritis.

Animals↗
PubMed1990

Human HLA-DR beta gene hypervariable region homology in the biobreeding BB rat: selection of the diabetic-resistant subline as a rheumatoid arthritis research tool to characterize the immunopathologic response to human type II collagen.

Collagen arthritis (CA), an autoimmune model of rheumatoid arthritis (RA), has been studied in various animals. However, it has not been studied in an animal with a genetic background relevant to RA. We selected rats from a diabetic-resistant (DR) subline of the diabetic BB rat because they have an autoimmune disease-prone background, but not the immunodeficiencies of the diabetic BB rat, and the third hypervariable region (HVRIII) of the BB RT1.D beta gene appeared to encode a nucleotide sequence of the human HLA DR beta gene, which has been reported to be associated with susceptibility to RA. We synthesized oligonucleotide primers flanking the RT1.D beta HVRIII, cloned polymerase chain reaction-amplified DNA into M13mp18, and confirmed the presence of the susceptibility sequence (SS) (RRRAA) by the dideoxy sequencing method in a colony of DR BB/Wor-UTM rats. When immunized with human type II collagen (CII) in incomplete Freunds adjuvant (IFA), arthritis developed rapidly by day 10 with 100% incidence. Light and electron microscopy revealed an unusually severe and aggressive, bidirectional pattern of cartilage resorption by synovial and subchondral mononuclear and multinucleated inflammatory cells. These findings coincided with a predominant humoral response to the cyanogen bromide (CB) 11 fragment of the human CII molecule by the pathogenic IgG2a isotype. This study provides further support to the role of CA as a relevant RA model, the specific roles of the CB11 fragment as a major site of arthritogenic epitopes, and of antibody mechanisms in the pathogenesis of CA. Furthermore, the identification of an RA SS in an immune response gene of the DR BB rat presents a novel opportunity to determine with an animal model the role of other antigens as well as this SS in RA.

Amino Acid Sequence↗
PubMed1988

Collagen autoimmunity and arthritis.

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen-induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.

Animals↗
PubMed1987

Passive transfer studies with type II collagen antibody in B10.D2/old and new line and C57Bl/6 normal and beige (Chediak-Higashi) strains: evidence of important roles for C5 and multiple inflammatory cell types in the development of erosive arthritis.

C5-normal B10.D2/new line mice were susceptible to passively transferred arthritis from purified type II collagen antibody, and in vitro studies demonstrated that, when bound to cartilage, this antibody readily activated complement C5 to C5a. C5-deficient B10.D2/old line mice failed to develop passively transferred arthritis, despite the deposition of antibody and C3 along the cartilage surface. C57Bl/6 mice were susceptible to passively transferred arthritis, which was characterized in histopathologic studies as an erosive synovitis involving multiple inflammatory cell types. In contrast, neither clinical nor histologic evidence of arthritis was observed in C57Bl/6 mice with the beige mutation (Chediak-Higashi syndrome).

Animals↗
PubMed1987

Filterability of L-forms.

We investigated the recovery of L-forms through micropore filtration. The findings indicate that L-form recovery and viability are a function of filter size and preparation technique. Current methods in use for L-form isolation appear to give erroneously low results, underestimating the potential role of L-forms in human disease.

Bacteria↗
PubMed1986

Assessment of the potential pathogenicity of type II collagen autoantibodies in patients with rheumatoid arthritis. Evidence of restricted IgG3 subclass expression and activation of complement C5 to C5a.

IgG subclass analysis by enzyme-linked immunosorbent assay of the autoantibody to native type II collagen, detected in 9 patients with classic or definite rheumatoid arthritis, demonstrated a predominance of IgG3 autoantibody. Gm allotyping revealed no obvious association with a particular phenotype. In comparative studies, IgG antibodies to the capsular polysaccharides of pneumococci and tetanus toxoid protein in these same patients consisted predominantly of IgG2 and IgG4. Purified type II collagen autoantibody from 3 of these patients activated complement C5 to C5a when bound to human cartilage in vitro, as measured by radioimmunoassay. These results represent direct evidence of a potential pathogenic role for this autoantibody in rheumatoid arthritis.

Animals↗
PubMed1986

Colonoscopic polypectomy.

Colonoscopic polypectomy is well established as an outpatient procedure. In skilled hands it is essentially safe. The components of a satisfactory therapeutic outcome are good bowel preparation, adequate sedation analgesia, an experienced operator and the proper range of equipment. In this two year series of 71 patients (176 polyps) there were no fatalities, no perforations and only two minor bleeds. Eighty percent of the polyps were of the tubuloadenomatous or tubulovillus type. Carcinoma was present in 6% and their outcome is described in detail. The commonest presentation of colonic polyps was rectal bleeding or occult blood in the stools (56%). Two or more polyps were present in 60% of patients. Seventy percent were located distal to the splenic flexure and the rest proximally. Fifteen percent were over 2 cm in maximum diameter. Policies for the type and frequency of follow-up are a matter for ongoing discussion.

Adult↗
PubMed1985

Genetic susceptibility to murine collagen II autoimmune arthritis. Proposed relationship to the IgG2 autoantibody subclass response, complement C5, major histocompatibility complex (MHC) and non-MHC loci.

Analysis of the IgG autoantibody subclass response in the collagen II autoimmune arthritis (CII AIA)-susceptible D1 strain mice revealed that the onset of disease was associated with a predominance of IgG2a autoantibody. In a comparative study, resistance in the B6 strain was associated with a deficient IgG2a autoantibody response. B6 IgG1, 2b, and 3 autoantibody responses generally overlapped those of arthritic D1 mice, and estimates of antibody crossreactivity and affinity were similar for both strains. In crosses between D1 and B6, arthritis developed only in those F1 mice with IgG2a autoantibody responses approximating or exceeding those in arthritic D1 mice. Additional studies with B6 and B10 strains suggested an alternate role for the IgG2b autoantibody response. In inbred strains with known genetic backgrounds, a dissociation between the magnitude of the total IgG autoantibody response and the percent of total as IgG2a was demonstrated. The H-2q, Ig-1c D1 strain was a high-total and high-percent IgG2a responder, while the H-2d, Ig-1c D2 strain was a low-total but high-percent IgG2a responder. The H-2b, Ig-1b B6 strain was a low-total and low-percent IgG2a responder, while the H-2b/q, Ig-1b/c (B6D1)F1 hybrid was a low-total but high-percent IgG2a responder. A further dissociation between high-percent IgG2a autoantibody responsiveness and the H-2 haplotype was demonstrated by the H-2 congenic B10.D2/n (H-2d, Ig-1b) strain, in which a low-percent IgG2a response was observed to differ from the D2 strain. High-percent IgG2a autoantibody responsiveness also appeared to be inherited as a dominant trait based upon high responses in all (B6D1)F1 hybrids and backcrosses to D1. These findings suggest that the H-2 haplotype is involved in the total IgG autoantibody response but that the relative fraction of the total response as IgG2a is independent of the H-2 haplotype and possibly related to Igh-C genes. C5-deficient SWR (H-2q, Ig-1c) mice were found to have a high total autoantibody response to mouse CII and IgG2a comparable to arthritic D1 mice, but these mice did not develop arthritis. Based upon these observations, we conclude that susceptibility to CII AIA requires the interaction of multiple genes, both major histocompatibility complex (MHC) and non-MHC, which influence the magnitude (total IgG) and the quality (IgG subclass) of the autoimmune response and the availability of appropriate mediators (C5) to initiate the inflammatory reaction.

Animals↗
PubMed1985

Analysis of dimethyl sulfoxide immunosuppression in the rat model of collagen II autoimmune arthritis: an effect dependent upon intraperitoneal administration and associated with toxicity.

The effect of the route of administration of dimethyl sulfoxide on humoral immunity and arthritis was evaluated in the rat model of collagen II autoimmune arthritis. Intraperitoneal administration of 5 g/kg/day (days 0-12) reduced serum anti-collagen II IgG levels, delayed the onset of arthritis, but induced sterile peritonitis in all of the treated animals. The same dose given subcutaneously did not alter humoral or clinical parameters. Lower intraperitoneal doses (0.04 and 0.25 g/kg/day), although non-toxic, were similarly ineffective. Subcutaneous (5 g/kg/day) or topical treatment (both hindpaws dipped twice daily into 70% dimethyl sulfoxide) of established disease (days 16-27) produced a mild anti-inflammatory effect without any immunosuppression. We suggest that the apparent suppression of autoimmunity by dimethyl sulfoxide is dependent upon intraperitoneal administration and a toxic dose of the agent.

Administration, Topical↗
PubMed1985

Management of adenocarcinoma in a columnar-lined esophagus.

Of 89 patients diagnosed between 1973 and 1983 as having at least 3 cm of columnar-lined esophagus, 22 were found to have adenocarcinoma. There was no difference in sex ratio, smoking, or the use of alcohol between the benign and adenocarcinoma groups. The patients with adenocarcinoma were older (63 years versus 57 years) and had a higher frequency of dysphagia (64% versus 46%), gastrointestinal bleeding (36% versus 24%), extended columnar-lined esophagus (94% versus 28%), and epithelial dysplasia (68% versus 10%). Heartburn was less frequent in the adenocarcinoma group (59% versus 79%), but when it occurred, it was of longer duration (mean, 18.8 years versus 10.9 years). In 2 patients, progression from benign columnar-lined esophagus to early adenocarcinoma was observed. Of the patients with adenocarcinoma, 2 received palliative treatment without resection and died four and nine months later. Six underwent partial esophagogastrectomy with 1 postoperative death. Four had residual columnar-lined esophagus at the resection margins. In one of them, stricture developed and in one, anastomotic recurrence of adenocarcinoma; 1-year survival was 50%. Fourteen patients underwent total thoracic esophagectomy with no operative deaths, strictures, or anastomotic recurrences; 1-year survival was 5 of 6. Surgical staging revealed that 63% had transmural spread and 55%, lymph node involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

Chest pain--esophageal, cardiac, or both?

The esophagus may be the origin of chest pain clinically indistinguishable from that of ischemic heart disease. In some patients the esophageal origin of the pain may only be recognized by pharmacological provocation during manometry. We describe nine patients with chest pain which could be explained by disorders of esophageal motility--diffuse spasm in four, high pressure lower esophageal sphincter in three, and "nutcracker esophagus" in two. Methacholine provoked the pain and manometric abnormalities in five patients who had normal baseline tracings. However, seven patients given methacholine developed ischemic changes on the electrocardiogram. In one patient these were typical of Prinzmetal's variant angina. The manometric and electrocardiographic abnormalities were reversed by intravenous atropine. Ischemic heart disease and esophageal motor disorders may occur concomitantly and pose a dilemma in diagnosis and management.

Aged↗