Both sex and gonadal steroid hormones may influence the abuse-related behavioral effects of cocaine under some conditions, but there is considerable inconsistency in the literature. In the present study, rats were trained under a fixed ratio (FR) 5 schedule of food presentation and were then allowed to self-administer cocaine (1.0 mg/kg/injection) until behavior stabilized. Subsequently, complete dose-effect functions for cocaine self-administration (0.032-3.2 mg/kg/injection) were determined in female and male rats before and after gonadectomy, and in gonadectomized female and male rats before and during chronic treatment with estradiol or testosterone, respectively. Sex, gonadectomy, and gonadal hormones did not alter the shape or position of dose-effect functions for cocaine self-administration. These results suggest that sex, estrogen, and testosterone levels are not critical determinants of cocaine's reinforcing effects in rats under these conditions. This study differed from earlier studies in that complete dose-effect functions for cocaine were determined. These findings suggest that the behavioral training history, the unit dose of cocaine, and the schedule of reinforcement are important variables in studies of sex and gonadal hormone effects on cocaine self-administration.

Lymphoproliferated disorders involving large granular lymphocytes (LGL) can be divided into a common T-cell subset (CD3+, CD8+) and a rarer natural killer (NK)-cell subset (CD2+, CD3-). The immunophenotype, clinical pathologic features, and cytogenetic and molecular genetic analyses are reported for seven patients with NK-cell-LGL proliferation. The typical immunophenotype was CD2+, CD3-, CD4-, CD11b+, and CD16+ or CD56+. A low but variable percentage of cells were CD8+ or CD57+. Unusual phenotypes with CD2- (1 of 7), CD11b- (1 of 7), or CD16-/CD56- (1 of 7) cells were seen. Strong NK-cell activity was observed in all cases, indicating that none of the NK-cell markers (CD11b, CD16, CD56, CD57) is essential for NK-cell activity. One patient died shortly after diagnosis from coexistent refractory multiple myeloma and another patient died within 1 month from the LGL proliferation. The other patients had been followed for 12 to 70 months, with a median follow-up period of 38 months. There was no progression of their LGL proliferation. Lymphocyte counts varied from 3.3 x 10(3)/microL to 58.4 x 10(3)/microL at the time of diagnosis. Unexplained anemia and neutropenia were observed in one patient. Cytogenetic abnormalities were detected in two of four patients studied with t(6;12) in one and der(5), der(6), and der(11) in the other. The approximately T gamma and T beta genes were in the germline configuration and Epstein-Barr virus DNA was undetectable in five of five patients studied. Natural killer-cell LGL proliferations were morphologically indistinguishable from T-cell LGL proliferations. However, the two were immunophenotypically and genotypically distinct and NK-cell activity was consistently observed in the former. Most of the NK-cell proliferations also were chronic indolent disorders and the incidence of associated cytopenias seemed to be lower than T-cell LGL proliferations.

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Daily intraperitoneal injections of acetaldehyde for 10 days to adult rats produced distinct morphological and biochemical changes in the exocrine pancreas, without affecting the body weight, pancreatic weight, and DNA, RNA, and protein content of the pancreas. By electronmicroscopy, although the number and size of the acinar zymogen granules appeared to be the same between the saline- and acetaldehyde-treated rats, the zymogen granules of the latter group showed decreased osmiophilia. Acinar mitochondria of the acetaldehyde-treated rats were found to be slightly swollen with dense granules, and plasma membrane fragments were often seen in the acinar lumen. Administration of acetaldehyde significantly decreased immunoreactive cationic trypsin (ogen) and total amylase activity in the pancreas, but not in the serum, where amylase activity was markedly increased. Basal secretion of amylase, trypsinogen, and chymotrypsinogen from isolated dispersed pancreatic acini of acetaldehyde-treated rats was increased by 40-50%. Nicotine (5-25 mM) induced a profound increase in secretion of the same enzymes from isolated acini of both saline- and acetaldehyde-treated rats, but in the latter group there was a concomitant rise in LDH release. Furthermore, CCK-8 (1 nM), secretin (1 microM), and carbachol (10 microM) either alone or in combination with nicotine (12.5 mM) produced a profound stimulation in amylase, trypsinogen, and chymotrypsinogen secretion from acini of both groups of rats. On the other hand, secretion of 3H-pulse-labeled proteins from isolated acini of acetaldehyde-treated rats by nicotine was decreased by approximately 50% compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of mediastinal giant lymph-node hyperplasia, plasma-cell type, is described. The patient had progressive peripheral neuropathy for which no apparent cause was found. Giant lymph-node hyperplasia with associated peripheral neuropathy has not been reported previously.