Biomedical subjects
J N Frame
Publications and source records attributed to J N Frame.
Waldenström macroglobulinemia with an IgM-kappa antiepidermal basement membrane zone antibody.
BACKGROUND: Waldenström macroglobulinemia, a lymphoplasmacytoid cell malignant neoplasm associated with a monoclonal IgM paraprotein, has been associated with a number of cutaneous manifestations. On rare occasions, IgM deposits have been demonstrated in the epidermal basement zone of patients with WM. OBSERVATIONS: We report the case of a patient with Waldenström macroglobulinemia and IgM-kappa paraprotein who had development of an eruption of pruritic papules and demonstrated the following unusual immunopathologic findings: (1) deposits of IgM-kappa in the epidermal basement membrane zone of lesional and nonlesional skin; (2) a circulating IgM-kappa antiepidermal basement membrane zone antibody; and (3) binding of this circulating IgM-kappa antiepidermal basement membrane zone antibody to both sides of 1 mol/L sodium chloride split skin. The cutaneous eruption cleared completely with oral psoralen with long-wave UV radiation in the A range (PUVA) therapy. CONCLUSIONS: We present a patient with Waldenström macroglobulinemia who had a distinctive papular eruption and immunopathologic findings suggesting that his paraprotein has specificity for the epidermal basement membrane zone.
Multicenter trials versus observational databases.
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Correction of severe heparin-associated thrombocytopenia with intravenous immunoglobulin.
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T cell depletion of human bone marrow. Comparison of Campath-1 plus complement, anti-T cell ricin A chain immunotoxin, and soybean agglutinin alone or in combination with sheep erythrocytes or immunomagnetic beads.
The aim of this study was to compare the extent of in vitro T cell depletion and recovery of hematopoietic progenitor cells achieved with five methods of T cell depletion. Bone marrow samples from the same source were treated with monoclonal antibody Campath-1 (CP1) and human complement, XomaZyme-H65 (anti-T cell ricin A chain immunotoxin), or soybean agglutinin (SBA) alone or in combination with sheep erythrocytes (EAET) or a cocktail of immunomagnetic beads (B) directly coated with anti-CD2, anti-CD3, or anti-CD8 monoclonal antibodies. Residual T cells were enumerated by limiting dilution analysis, EAET rosetting, and proliferative responses to phytohemagglutinin. The results of this study demonstrated the following reductions in BM T cells as detected by limiting dilution analysis (mean % control): SBA+B (99.9%), SBA+EAET (99.8%), CP1+C' (99.4%), anti-T cell ricin A chain immunotoxin (99.0%), and SBA alone (94.2%). Neither PHA response nor enumeration of residual EAET rosettes provided discriminating differences in the degree of T cell depletion by treatment method when T cell reductions exceeded 99.0% by LDA. These results demonstrate the ability of CP1+C', XomaZyme-H65, and SBA plus sheep erythrocyte or magnetic bead depletion to achieve a greater than 99% reduction of BM T cells and the importance of limiting dilution analysis in defining differences in T cell numbers when depletion exceeded 99%.
Optimal conditions for in vitro T cell depletion of human bone marrow by Campath-1a plus complement as demonstrated by limiting dilution analysis.
Quantitations of residual T cells by limiting dilution analysis (LDA), immunofluorescence analysis, sheep red cell rosetting, and proliferative responses to phytohemagglutinin were done to identify treatment conditions that maximized the ex vivo T cell depletion (TCD) of human bone marrow (BM) with the rat monoclonal antibody Campath-1 (CP1) and complement (C'). Different treatment approaches achieved levels of TCD varying from 0.4 to 2.6 log10. However, under optimal treatment conditions, a mean (+/- SEM) log10 TCD of 2.60 +/- 0.12 was demonstrated by LDA. Concentrations of CP1 ranging from 5 micrograms to 300 micrograms/10(7) cells/ml achieved equally effective TCD as determined by LDA. An inverse relationship between the concentration of BM cells/ml and the extent of TCD was observed. Additional C' treatment did not increase TCD as detectable by LDA. Mean recoveries of CFU-GM (day 7), CFU-GM (day 14), CFU-GEMM, and BFU-E growth following CP1 + C' were 51, 43, 42, and 45% respectively. These results demonstrate the importance of cell concentration and treatment conditions for maximizing the depletion of BM T cells with CP1 + C'.
Debrisoquine metabolism and lung cancer risk.
Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize debrisoquine identifies individuals at increased risk for lung cancer in a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hospital, was conducted at the National Naval Medical Center (Bethesda, MD) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate debrisoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% confidence interval, 0.3-1.2). The lack of an association was not confounded by control diagnoses, medications used within 1 month of debrisoquine administration, smoking, stage, or histology of lung cancer. No relationship was found among either heavy smokers or light and nonsmokers. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lung cancer risk in these data.