Publications

The origin and exact stage of differentiation of the neoplastic cells that comprise hairy cell leukemia have remained uncertain. As Ig heavy and light chain genes must both undergo a DNA rearrangement during B-cell development but rarely do so within other hematopoietic lineages, we examined these genes in this leukemia. The neoplastic cells of all eight cases demonstrated rearranged heavy and light chain genes and, in two cases examined, contained the corresponding mRNA for heavy and light chain Ig. Consistent with this B-cell genotype, all cases displayed cell surface HLA-DR and B-cell-associated antigens. Unexpectedly, all cases demonstrated cell surface Tac antigen, which previously had been restricted predominantly to select T-cell malignancies and activated T cells. Prior studies suggested that the anti-Tac monoclonal antibody recognized a peptide associated with the binding of interleukin 2 (T-cell growth factor) in such T cells. Immunoprecipitation with anti-Tac and NaDodSO4/polyacrylamide gel electrophoresis revealed an antigen on leukemic hairy cells with a Mr of 53,000-57,000, identical in size to the receptor on activated T cells. This apparent biphenotypic status might reflect a transformation-associated expression of the Tac antigen in this leukemia. Alternatively, hairy cell leukemia may be a malignancy of a unique stage of normal B-cell differentiation in which the Tac antigen is expressed.

The effects of oral diltiazem (360 mg/day) on exercise tolerance, left ventricular performance, and plasma lactate and catecholamine levels were studied in 13 patients with atherosclerotic coronary artery disease in a placebo-controlled, randomized, double-blind protocol. Exercise duration to the onset of ischemic ST segment depression, time to angina pectoris, and time to peak exercise improved by 120, 174, and 144 sec, respectively (p less than .0001). Left ventricular ejection fraction, as determined by radionuclide angiography, increased in patients at rest from 52 +/- 11% (mean +/- SD) during placebo therapy to 58 +/- 11% during diltiazem therapy (p less than .001); at peak exercise ejection fraction increased from 44 +/- 11% during placebo treatment to 52 +/- 15% during diltiazem therapy (p less than .01). The mean plasma norepinephrine level in patients at rest increased from 498 +/- 221 pg/ml during placebo treatment to 667 +/- 272 pg/ml during diltiazem therapy (p less than .05). Resting standing blood pressure and supine and standing diastolic blood pressures decreased significantly with diltiazem. In all 10 patients followed over a long term, oral diltiazem caused persistent improvement in exercise performance at 12 to 20 weeks, without evidence of placebo effects. Thus, diltiazem is highly effective in divided doses of 360 mg/day for the therapy of chronic angina pectoris due to coronary artery disease.