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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↗
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↗
PubMed1978

Globus and headache: common symptoms of the irritable bowel syndrome.

Persons with the irritable bowel syndrome (IBS) have a significantly higher prevalence of globus and migraine-like headache than age-matched control subjects. On the other hand, persons with organic disease of the esophagus or colon may have a reduced prevalence of functional symptoms involving the opposite end of the gastrointestinal tract. The dispersed pattern of symptoms in IBS suggests that some agent, such as a hormone, may be acting systemically.

Adolescent↗
PubMed1977

Symposium on diarrhea. 2. Clinical diagnosis of the causes of diarrhea.

Elucidation of the cause of diarrhea is facilitated by considering which of three principal determinants are of relevance in a particular case. These determinants relate to the onset (whether diarrhea is acute or chronic), to infection or an absence ofinfection and to the presence in the stool of blood or mucus, or both. Diagnosis is also facilitated by taking an accurate and full history, conducting a physical examination, performing sigmoidoscopy and, with proper care, attempting a therapeutic diagnosis. Findings from investigations should then enable one to arrive at a diagnosis. The diagnosis can be reached in an orderly fashion by classifying the types of diarrhea into eight categories: with respect to the acute or chronic onset a case of diarrhea may be noninfectious, without blood or mucus in the stool; noninfectious, with blood or mucus, or both; infectious, without blood or mucus; and infectious, with blood or mucus in the stool.

Acute Disease↗
PubMed1977

Evaluation of immunosuppressive potential of cryogenine using developing and established adjuvant arthritis in rats.

Both developing (Days --1-+12 relative to inoculation) and established (Days +18-+29) stages of Mycobacterium butyricum adjuvant-induced polyarthritis in rats were treated orally with cryogenine (100 mg/kg/day), a prototype anti-inflammatory (phenylbutazone, 100 mg/kg/day), or a prototype immunosuppressive (cyclophosphamide, 6 mg/kg/day). During developing adjuvant arthritis, cryogenine and phenylbutazone significantly reduced the nonimmune-mediated inflammation in the inoculated hindpaw. Neither cryogenine nor phenylbutazone provided protection against the development of the delayed-onset, immune-mediated inflammation and the reduction in growth rate seen after Day +12 in unmedicated rats. Cyclophosphamide failed to reduce the nonimmune-mediated inflammation, but it provided significant protection against both the delayed-onset, immune-mediated inflammation and the reduced growth rate. During established adjuvant arthritis, cryogenine and phenylbutazone were effective against the established inflammation, while cyclophosphamide was ineffective. These results confirm the known anti-inflammatory and immunosuppressive activities of phenylbutazone and cyclophosphamide, respectively, and indicate that cryogenine lacks immunosuppressive capability at the effective anti-inflammatory dosage level used.

Alkaloids↗
PubMed1977

Celiac axis compression: experience with 20 patients and a critical appraisal of the syndrome.

Twenty patients with celiac axis compression were treated surgically during a 5-year period. Fifteen remain asymptomatic, two are partially improved, two are unimproved, and one has been lost to follow-up. The main presenting symptom was upper abdominal pain--constant in some, intermittent in most--and the main diagnostic clue was a loud, localized systolic bruit in the midepigastrium. All had angiographic confirmation of the diagnosis. Ten had previous surgery (appendectomy, cholecystectomy, vagotomy, and pyloroplasty), without relief. The authenticity of celiac axis compression as a symptom-producing entity is difficult to establish objectively because the main treatable symptom is pain. However, eight of these patients gained weight, three have shown improvement in pancreatic function, and one of the unimproved patients still has an occluded celiac axis. A critical review of the literature of this controversial topic is included.

Adolescent↗