Biomedical subjects

S L John

Publications and source records attributed to S L John.

6 recordsLinked to original sources

PubMed2001

Problems identified by tutors in a hybrid problem-based learning curriculum.

Problem-based learning (PBL) tutors (n = 27) were interviewed to identify problems they encountered in facilitating a hybrid PBL-lecture curriculum. Analysis of responses yielded six problems for students: "mini-lecturing," dysfunctional group dynamics, completing cases too quickly, superficial research, frustration with tutors who lack content expertise, and lack of support for PBL. These may arise because students lack problem-solving and interpersonal skills needed to benefit from PBL.

Curriculum↗

PubMed1999

A randomized trial of daily and thrice-weekly trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected persons. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)

We enrolled 2,625 human immunodeficiency virus-infected patients into a randomized trial to assess the efficacy and tolerability of daily vs. thrice-weekly trimethoprim-sulfamethoxazole (160 mg/800 mg) for prophylaxis of Pneumocystis carinii pneumonia (PCP). The rate of PCP was 3.5 and 4.1 per 100 person-years in the daily and thrice-weekly groups, respectively, with a relative risk (RR) of 0.82 (95% confidence interval [CI], 0.61-1.09; P = .16) (RR of <1.0 favors daily trimethoprim-sulfamethoxazole). The RR for PCP determined by on-treatment analysis was 0.59 (P = .03). The RR for death was 0.91 (P = .12); for bacterial pneumonia, 0.82 (P = .06); and for combined PCP and bacterial pneumonia, 0.84 (P = .04). Discontinuation due to adverse events occurred more commonly in the daily trimethoprim-sulfamethoxazole group (RR, 2.14; 95% CI, 1.73-2.66; P < .001). Overall estimates for efficacy end points favored daily trimethoprim-sulfamethoxazole, although rates of intolerance were higher among patients receiving that dose. Daily trimethoprim-sulfamethoxazole may offer advantages as a first choice for PCP prophylaxis; thrice-weekly dosing is an appropriate option for patients intolerant of the daily dose.

AIDS-Related Opportunistic Infections↗

PubMed1999

Corneal epithelial-specific cytokeratin 3 is an autoantigen in Wegener's granulomatosis-associated peripheral ulcerative keratitis.

PURPOSE: In a previous investigation it was demonstrated that circulating antibodies to a 66-kDa corneal epithelial antigen (BCEA-A) are associated with peripheral ulcerative keratitis (PUK) in patients with Wegener's granulomatosis (WG). The aim of this study was to identify BCEA-A. METHODS: The 66-kDa antigen was purified from a bovine corneal epithelial protein extract, using DE52 ion exchange chromatography. Purified protein was used to raise rabbit polyclonal antibodies. These antibodies were used to screen a bovine corneal epithelial cDNA expression library. Positive clones were purified and sequenced. Clones were identified by DNA sequence homology searches of the GenBank DNA database. RESULTS: A cDNA clone that demonstrated strong binding to both the rabbit polyclonal antibody and patient sera, showed 85% homology to rabbit cytokeratin 3 (K3). K3 is a basic cytokeratin specific to corneal epithelium. No bovine DNA sequence for K3 is available. However, bovine K3 is larger than rabbit K3, with a molecular weight of 66 kDa. Immunofluorescence using both patient sera and the rabbit antibody demonstrated a cytoplasmic binding pattern on human corneal epithelium. CONCLUSIONS: This evidence suggests that the 66-kDa autoantigen (BCEA-A) associated with PUK in WG is cytokeratin 3, and this may form the basis of a diagnostic/prognostic test.

Amino Acid Sequence↗

PubMed1998

Characterization of two corneal epithelium-derived antigens associated with vasculitis.

PURPOSE: In a previous investigation into corneal autoimmunity, it was demonstrated that a putative autoantigen, a protein of 66 kDa, present in bovine corneal epithelium, binds circulating autoantibodies in approximately 60% of patients with Wegener's granulomatosis (WG). The aim of the present study was to characterize and identify the 66-kDa protein. METHODS: A purification protocol was established for the 66-kDa protein using standard chromatography techniques. During the purification procedure it became clear that the 66-kDa protein detected in patients' sera was in fact two proteins, both running at 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, that eluted in different fractions on DE-52 chromatography columns. These two proteins have been labeled bovine corneal epithelial antigen-A and -B (BCEA-A and BCEA-B). Further investigations of antibody binding have demonstrated that patients' sera bind to either one or the other of these proteins with no cross-reactivity between them. Separated BCEA-A and BCEA-B protein extracts were immunoblotted with 27 WG patients' sera, 10 Churg-Strauss syndrome (CSS) patients' sera, 31 rheumatoid arthritis (RA) patients' sera, and 40 healthy control subjects' sera from the blood bank. RESULTS: Forty-six percent of WG patients' sera had antibodies to one of the 66-kDa antigens, whereas none of the healthy control subjects' sera had 66-kDa antibodies (P < 10(-5)). In the WG group, 31% were positive to BCEA-A (versus controls, P = 0.0023), and 15% were positive to BCEA-B. WG patients with peripheral ulcerative keratitis (PUK) had a significant association with anti-BCEA-A antibodies when compared with healthy control subjects (50%, P < 10(-6)). However, in the RA group with no eye disease there was an association with BCEA-A (25%, P = 0.011) but not in the RA group with PUK. The frequency of anti-BCEA-B antibodies was significantly increased in patients with CSS (60%, P < 10(-7)). CONCLUSIONS: In summary, it has been shown that vasculitis patients have antibodies to two 66-kDa corneal antigens and that autoantibodies to these antigens are mutually exclusive. It has also been shown that antibodies to BCEA-B are associated with CSS, whereas BCEA-A antibodies are associated with WG and RA.

Adult↗

PubMed1997

A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. RESULTS: The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events. CONCLUSIONS: Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis.

AIDS-Related Opportunistic Infections↗

PubMed1992

Corneal autoimmunity in patients with peripheral ulcerative keratitis (PUK) in association with rheumatoid arthritis and Wegener's granulomatosis.

Serum antibodies to the cornea were investigated in patients with peripheral ulcerative keratitis (PUK) in isolation or in association with a systemic disease (rheumatoid arthritis or Wegener's granulomatosis). Indirect immunofluorescence on bovine corneal sections demonstrated that antibodies bound to epithelial antigens in two distinct patterns: a lattice-like pattern, probably staining intercellular membrane antigens, and a diffuse pattern covering the entire surface of the epithelium. Both patterns were associated with PUK rather than systemic disease whilst the presence of the lattice pattern was more associated with the onset of the PUK. Immunoblotting of sera to corneal epithelial protein extracts demonstrated that a number of corneal antigens were targeted by antibodies. Two antigens, 54 kDa and 70 kDa, were of particular interest. Antibodies to the 54 kDa antigen, the major corneal-specific antigen, were also detected by enzyme-linked immunosorbent assay (ELISA). Longitudinal studies showed that these antibodies often first occurred after an episode of PUK. Antibodies to the 70 kDa antigen were related to the Wegener's granulomatosis rather than the PUK.

Adult↗