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Biomedical subjects

W C Watson

Publications and source records attributed to W C Watson.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Bacterial L-form isolation from inflammatory bowel disease patients.

This study was designed to investigate a possible relationship between bacterial L forms and inflammatory bowel disease. Homogenates of intestinal mucosal biopsies from Crohn's disease, ulcerative colitis, and control patients underwent bacterial culture on hypertonic media designed for the recovery of L-form bacteria and parental organisms. L forms were recovered from 24 of 71 Crohn's disease, 51 of 121 ulcerative colitis, and 2 of 140 control biopsy specimens. These isolation rates are significantly different when Crohn's disease biopsy specimens (p less than 0.001) and ulcerative colitis biopsy specimens (p less than 0.001) are compared with controls. Six different L-form types were recovered, of which the most common were Escherichia coli and Streptococcus fecalis. No marked differences were observed in L-form recovery rates or L-form types recovered between Crohn's disease and ulcerative colitis patients. Drug treatment of inflammatory bowel disease patients did not affect L-form recovery rates or the type of L forms recovered. The results suggest either that L forms are involved in the causation of inflammatory bowel disease or that their presence in mucosal biopsy tissues is a result of the disease process.

Biopsy↗

"Bingo brain".

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Aged↗

Prostaglandin E2 tablets prevent aspirin-induced blood loss in man.

A double-blind study was performed to determine the effect of prostaglandin E2 (PGE2) tablets on aspirin-induced blood loss in 20 healthy male volunteers. All subjects took aspirin, and 9 in the control group and 11 in the treatment group received placebo and PGE2 respectively. One tablet of PGE2, 0.5 mg, was given four times daily for five days. Two tablets of unbuffered aspirin (640 mg) were given four times daily for four days commencing one day after the start of the PGE2 or placebo. Fecal blood loss was measured using 51Cr-labeled red cells. There was no significant difference in serum salicylate levels. There was a significant increase in fecal blood loss in control subjects on the third and fourth days on aspirin and for 4 days following aspirin ingestion. In the treatment group, fecal blood loss was prevented by PGE2.

Adolescent↗

Aortoenteric fistula. Incidence, presentation recognition, and management.

Twenty-two patients developed one or more aortoenteric fistulae following aortic reconstruction with a dacron graft. Endoscopy was performed on 11 of these patients on 17 occasions and a preoperative diagnosis was made in eight patients. Fistulous communication was most common between the aorta and duodenum (60%), and a further 30% penetrated into the jejunum and ileum. The mean period from operation to time of diagnosis was 36 months and the mean length of bleeding was 25 days, allowing ample time for preoperative evaluation. Surgery was performed on 21 of the 22 patients with an overall mortality of 77%. The best surgical results were obtained with graft resection, closure of the aorta, and maintenance of circulation by an axillofemoral graft.

Adult↗