Using a new high-resolution technique for chromosomal analysis, we have successfully studied biopsy specimens of lymph nodes from 42 of 44 patients with non-Hodgkin's lymphoma and have categorized them using the new international histologic formulation and immunologic markers. Abnormalities of the clonal chromosomes were detected in all 42 patients. Three recurrent chromosomal aberrations were found to correlate with certain histologic types: a translocation between chromosomes 18 and 14 in 16 of 19 patients with follicular lymphomas (small cleaved cell, mixed cell, and large cell); a translocation between chromosomes 8 and 14 in 5 of 6 patients with small noncleaved-cell (non-Burkitt's) or large-cell immunoblastic lymphoma; and a trisomy 12 in 4 of 11 patients with small-cell lymphocytic lymphoma. Our findings suggest that characteristic chromosomal defects occur in certain lymphoma subtypes and that high-resolution chromosomal analysis promises to become an important tool in improving our basic understanding of lymphoid cancers.
Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.
SummaryActivation of coagulation occurs at inflammatory sites following the ingress of mononuclear cells, and may result from alterations in the vessel wall. Since the monokine, interleukin 1, initiates diverse responses to inflammation, its ability to enhance vascular procoagulant activity was studied. Interleukin 1-treated cultured human endothelial cells acquired elevated levels of the procoagulant, tissue factor. This required de novo protein synthesis, was maximal at 2 h after exposure to interleukin 1, and resulted in persistently elevated cellular procoagulant activity. Tissue factor was later expressed (6-24 h) on the surface of uninjured endothelial cells. Endothelial cell procoagulant production and expression in response to interleukin 1 could be dissociated from endogenous prostaglandin metabolism, being insensitive to hydrocortisone, indomethacin, eicosatetrayionic acid and exogenous arachidonic acid. In addition, no increase in prostaglandin synthesis occurred during the interval in which tissue factor was synthesized. We therefore conclude that interleukin 1 stimulates endothelial synthesis and surface expression of tissue factor by a prostaglandin-independent mechanism.
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