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The gene expression of myeloperoxidase (MPO), CD3 epsilon, and CD3 delta molecules, the gene rearrangement of T-cell receptor (TCR) delta, gamma, and beta and immunoglobulin heavy (IgH) chain, and the expression of cell-surface antigens were investigated in seven cases of CD7+ CD5- CD2- and four cases of CD7+ CD5+ CD2- acute lymphoblastic leukemia or lymphoblastic lymphoma (ALL/LBL) blasts, which were negative for cytochemical myeloperoxidase (cyMPO). More mature T-lineage blasts were also investigated in a comparative manner. In conclusion, the CD7+ CD5- CD2- blasts included four categories: undifferentiated blasts without lineage commitment, T-lineage blasts, T-/myeloid lineage blasts, and cyMPO-negative myeloblasts. The CD7+ CD5+ CD2- blasts included two categories; T-lineage and T-/myeloid lineage blasts. The 11 cases were of the germ-line gene (G) for TCR beta and IgH. Four cases were G for TCR delta and TCR gamma. The others were of the monoclonally rearranged gene (R) for TCR delta and G for TCR gamma or R for both TCR delta and TCR gamma. The expression or in vitro induction of CD13 and/or CD33 antigens correlated with the immaturity of these neoplastic T cells, since it was observed in all 11 CD7+ CD5- CD2- and CD7+ CD5+ CD2-, and some CD7+ CD5+ CD2+ (CD3- CD4- CD8-) cases, but not in CD3 +/- CD4+ CD8+ or CD3+ CD4+ CD8- cases. CD3 epsilon mRNA, but not CD3 delta mRNA, was detected in two CD7+ CD5- CD2- cases, while mRNA of neither of the two CD3 molecules was detected in the other tested CD7+ CD5- CD2- cases. In contrast, mRNA of both CD3 epsilon and CD3 delta were detected in all CD7+ CD5+ CD2- cases, indicating that CD7+ CD5- CD2- blasts at least belong to T-lineage. The blasts of two CD7+ CD5- CD2- cases with entire germ-line genes and without mRNA of the three molecules (MPO, CD3 epsilon, and CD3 delta) were regarded as being at an undifferentiated stage prior to their commitment to either T- or myeloid-lineage. The co-expression of the genes of MPO and CD3 epsilon in a CD7+ CD5- CD2- case MPO, CD3 epsilon, and CD3 delta in a CD7+ CD5+ CD2- case suggested the presence of some overlapping phase for T- and myeloid-lineage commitment during immature stages of differentiation. This helps understand the conversion of some T-ALL/LBL cases to acute myeloblastic leukemia (AML).(ABSTRACT TRUNCATED AT 400 WORDS)

Abundant inflammatory cells such as polymorphonuclear leucocytes and macrophages accumulated and adhered to the endothelial surface of glomerular and intertubular veins and capillaries in rat kidneys after administration of bacterial lipopolysaccharide (LPS). There was also damage to both endothelial cells and proximal tubular cells, including intracytoplasmic oedema, and an increase in the number of lysosomes in the proximal tubular cells in the LPS-treated samples. Immunocytochemistry was used to demonstrate tumour necrosis factor (TNF) and leukotriene (LTR) in both LPS-treated and control samples. Immunoreactive LTR seen in the lysosomes of inflammatory cells attached to the endothelial cell surface may indicate the onset of endothelial cell damage. Positive immunoreactive TNF and LTR were seen on the endothelial cell surface only in the LPS-treated samples, indicating that TNF and LTR may enhance the adhesion of leucocytes to endothelium. Positive reactions of TNF and LTR in lysosomes of the mesangial cells suggest that lysosomes of such cells may be involved in the synthesis and storage of TNF and LTR. In addition to these reaction sites, lysosomes of proximal tubular cells were immunoreactive for LTR. These endogenous LTRs may be implicated in the degeneration of the proximal tubular cells.

One aim of our study was to characterize in intact rats the pharmacologic effects of carvedilol. After 3 days of continuous intravenous (i.v.) infusion of carvedilol (0.5 mg/kg/h), the positive chronotropic and inotropic effects of i.v. bolus injections of isoproterenol (0.1, 0.3, and 1 microgram/kg) and phenylephrine (3, 10, and 30 micrograms/kg), respectively, were measured and compared with those obtained in rats that received a continuous i.v. infusion of 0.9% NaCl, prazosin (0.1 mg/kg/h), and propranolol (0.5 mg/kg/h). The chronotropic response to isoproterenol was less blunted in carvedilol-treated animals than in propranolol-treated animals. The pressure response to phenylephrine was attenuated only moderately. Thus, carvedilol had beta-receptor blocking actions on intact rat heart that were similar to but not as pronounced as those of propranolol. Because it reduced diastolic aortic pressure (DAP) and left ventricular systolic pressure (LVSP), it also had a moderate vasodilating effect. Carvedilol (continuous i.v. infusion of 0.25 and 0.5 mg/kg/h) antagonized the effects of norepinephrine (NE, i.v. infusion of 0.2 mg/kg/h for 3 days) on heart function and heart weight in a dose-dependent manner. It also attenuated markedly the norepinephrine (NE)-induced increase in the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (PPP), although a 37% stimulation persisted.

After administration of bacterial lipopolysaccharide, there is an increase in the number of leucocytes which adhere to the endothelial cell surface of the hepatic vessels and pass through the endothelial layer by comparison with controls. There is also marked endothelial cell damage including intracytoplasmic oedema, increased numbers of autophagic vacuoles and dilatation of the intercellular junction in LPS-treated samples. The presence of immunocytochemical products of leukotriene (LTR) and tumour necrosis factor (TNF) was examined using in both LPS-treated and control samples. Immunoreactions of LTR which were seen in specific granules of neutrophils and monocytes attached to the endothelial cell surface may indicate the onset of endothelial cell damage. Positive immunoreactions of TNF on the endothelial cell surface, seen only in LPS-treated samples, indicate that TNF may enhance the passage of blood cells through the endothelia and also increase the endocytotic activity of the liver parenchymal cells, as revealed by the present marker experiment using horseradish peroxidase. Positive reactions of TNF in lysosomes of the endothelial cells suggest that they are able to produce TNF and transport it to the cell surface.

We report an 82-year-old Japanese female with acute myelomonocytic leukemia with dysplastic marrow eosinophilia (FAB M4Eo) exhibiting a partial deletion of the long arm of chromosome 5, del(5)(q13q31) and a derivative chromosome 16 with a breakpoint at band 16q22, in addition to 5q−. The patient had a history of a preleukemic phase for several months with marked dysplasia in trilineage marrow cells, in addition to leukemic features compatible with M4Eo. These findings strongly suggested that the leukemic cells in this case were derived from a preleukemic clone with a del(5q).