Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus

Leptin, the protein product of the adipose tissue-specific ob (obese) gene (1), reduces the body weight, adiposity and food intake of obese ob/ob mice on peripheral or central injection (2, 3, 4). [125I]leptin binding has been detected in mouse choroid plexus (5), from which a leptin receptor gene was expression cloned (5). The gene has at least 6 splice variants (6, 7). Leptin receptor mRNA was localized in the hypothalamus by in situ hybridization being particularly abundantly expressed in the arcuate nucleus (8). There is evidence linking the physiological effects of injected leptin with hypothalamic neuropeptide Y (9, 10) (NPY), which has potent central effects on food intake and energy balance (11), and is also expressed in the arcuate nucleus. Here we report dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus, where the majority of cells examined expressed both genes. This provides the first direct evidence that leptin acts on cells that express NPY mRNA.     

Uterine activity patterns in uterine rupture: a case-control study

The effects of methylprednisolone therapy on the susceptibility of dystrophin-deficient myofibers to contraction-induced injury were evaluated in the mdx mouse diaphragm model of Duchenne dystrophy. Mdx myofibers were abnormally vulnerable to injury induced by high-stress eccentric contractions. However, methylprednisolone therapy did not significantly alter the degree of contraction-induced injury. These data suggest that beneficial effects of corticosteroid therapy in Duchenne dystrophy are unlikely to be related to a change in the threshold for contraction-induced myofiber damage.     

A randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy

BB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.     

Changes in fetal plasma corticotropin-releasing hormone during androstenedione-induced labor in the rhesus monkey: lack of an effect on the fetal hypothalamo-pituitary-adrenal axis

Androstenedione infusion to pregnant monkeys leads to premature labor and live delivery. Androstenedione-induced labor also increased placental CRH messenger RNA and peptide to concentrations observed at term in pregnant monkeys. Placental CRH may modulate fetal pituitary-adrenal function during pregnancy in primates. This study tested the hypothesis that androstenedione-induced premature delivery in pregnant monkeys results from androstenedione-induced increases in placental CRH, which stimulate premature activation of the fetal pituitary-adrenal axis. The hypothesis was tested by comparing fetal umbilical vein (FUV) plasma CRH, ACTH, dehydroepiandrosterone sulfate, and cortisol concentrations at cesarean section in fetuses from mothers undergoing spontaneous, term labor (group I), with those in fetuses from mothers undergoing androstenedione-induced, premature labor (group II) and with those from mothers not in labor (group III). In addition, gestation-related changes in maternal plasma CRH concentrations were investigated, and CRH immunoactivity was characterized by Sephadex G50 chromatography in pooled maternal plasma extracts. FUV CRH concentrations were similarly elevated in group I and group II fetuses, compared with group III fetuses. Despite similar FUV blood gases in all fetuses, FUV ACTH and dehydroepiandrosterone sulfate concentrations were higher in group I fetuses than in group II or group III fetuses. The majority of CRH immunoactivity coeluted with synthetic human CRH. Maternal plasma CRH concentrations showed a modest increase with gestation in the rhesus monkey. These data: 1) demonstrate that androstenedione treatment of pregnant monkeys at 0.8 of gestation elevates fetal plasma CRH to similar concentrations measured at term; 2) do not support the hypothesis that androstenedione-induced delivery in the monkey results from premature activation of the fetal pituitary-adrenal axis by placental CRH; but 3) do support a role for activation of the fetal hypothalamo-pituitary-adrenal axis in association with spontaneous term labor in the monkey; and 4) demonstrate important interprimate species differences in maternal CRH physiology.     

Suc-Phe-Leu-Phe-SBzl--a new substrate for functional study of Escherichia coli ATP-dependent Lon-proteinase and its modified forms

A new efficient substrate, Suc-Phe-Leu-Phe-SBzl, was proposed for studying the function of the Escherichia coli ATP-dependent Lon protease and its modified forms. The kinetic parameters of hydrolysis of the substrate were determined. The esterase activity of protease Lon was found to be nucleotide-regulated.     

Reaction of different cell populations in mouse thymus to a single gamma-irradiation

Acute care facilities are no longer viewed as the center of the health care network. Efforts to reduce hospital length of stay will continue to spur the growth of care delivered in homes. With the downsizing of many hospitals, the need for nurses in acute care settings will decline. Many acute care nurses are finding themselves seeking employment opportunities in home health care settings. The purpose of this study was to examine nurses' experiences when they change from hospital-based practice to home health care nursing. The qualitative mode of inquiry was used to conduct taped-recorded interviews of 25 baccalaureate-prepared nurses in a large metropolitan area. Stressors experienced by the nurses were identified as well as adaptations required to minimize role stress. Continuing education programs can provide information and skills needed to improve nurses' competencies to function in a health care system projected to be more community-based, which includes home health care.     

Use of tests for acidification of methyl-alpha-D-glucopyranoside and susceptibility to efrotomycin for differentiation of strains of Enterococcus and some related genera

A total of 107 Enterococcus strains, 10 Vagococcus fluvialis strains, and 8 Lactococcus garvieae strains were tested for acidification of methyl-alpha-D-glucopyranoside (MGP) and susceptibility to 100-microg efrotomycin (EFRO) disks. All 26 strains of Enterococcus casseliflavus, including 3 nonmotile and 2 nonpigmented strains, acidified MGP and were resistant to EFRO. All 22 strains of Enterococcus gallinarum, including 5 nonmotile strains, also acidified MGP and were resistant to EFRO. None of the 26 strains of Enterococcus faecium acidified MGP, and all were susceptible to EFRO. Although all 12 Enterococcus faecalis strains were also negative in the MGP test, they were resistant to EFRO. Other enterococcal strains gave variable results. All 10 strains of V. fluvialis and all 8 strains of L. garvieae gave positive and negative results, respectively, in the MGP test and were, respectively, resistant and susceptible to EFRO. These results indicate that tests of the production of acid from MGP and susceptibility to EFRO can be used as adjunct tests in the identification of typical and atypical strains of enterococci in the clinical microbiology laboratory.