Angiographically defined primary angiitis of the CNS: is it really benign?

Children with B-progenitor cell acute lymphoblastic leukemia whose lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates (MTXPGs) appear to have a good prognosis. This has been attributed to increased sensitivity of their blast cells to MTX. However, the proportion of children who are cured of B-progenitor cell acute lymphoblastic leukemia exceeds the number whose lymphoblasts accumulate high MTXPG levels. We report that lymphoblasts from patients with < 50 chromosomes who have translocations that involve the short arm of chromosome 12 accumulate low levels of MTXPGs. These patients appear to have an excellent survival because none of 14 patients with translocations affecting 12p has relapsed, 26-79 months following diagnosis.     

Glucose action 'beyond ionic events' in the pancreatic beta cell

For normal glucose homeostasis, insulin release by the pancreatic beta cell is vital. Until recently, it was thought that glucose-induced ionic events, such as closure of the ATP-sensitive K+ (KATP) channels, membrane depolarization, activation of the L-type voltage-dependent Ca2+ channels, Ca2+ influx and elevation of cytosolic free Ca2+, constitute the main signalling pathway in beta-cell stimulus-secretion coupling. However, since the discovery of 'non-ionic' glucose actions in the beta cell by the Aizawa and Henquin laboratories in 1991, data have accumulated that strongly indicate the physiological relevance of this signalling pathway. In this review, Toru Aizawa and colleagues discuss how the KATP channel-Ca2+ hypothesis was formulated, what was overlooked in the hypothesis, and then provide a comprehensive view of stimulus-secretion coupling in the beta cell, with an emphasis on non-ionic glucose actions.     

Immature chemodifferentiation of Purkinje cell synapses revealed by 5''-nucleotidase ecto-enzyme activity in the cerebellum of the reeler mouse

Data from child and adolescent emergency mental health screening episodes prior and subsequent to privatized Medicaid managed care in Massachusetts are used to investigate the relationship between payer source and disposition and to compare the match between clinical need and disposition level of care. Having Medicaid as the payer in the post-Medicaid managed care period decreased the odds of hospitalization by nearly 60%. None of the clinical need variables that contributed to hospitalization for Medicaid episodes in the pre-Medicaid managed care period were significant in the post-Medicaid managed care period. Multiple forces shaping professional standards, decision making, and quality of care are described. Public sector agencies must lay the groundwork for comprehensive evaluation prior to the implementation of privatized Medicaid managed care initiatives.     

An increase in intracellular cyclic AMP modulates nitric oxide production in IFN-gamma-treated macrophages

Macrophages treated with IFN-gamma alone are stimulated to produce nitric oxide. The level of nitric oxide production can be enhanced significantly when IFN-gamma treatment is combined with other agents (e.g., LPS, TNF-alpha, IL-2, etc.). We tested the hypothesis that cAMP plays a role in the IFN-gamma-induced activation of macrophages. Our experiments indicate that factors that increase the concentration of cAMP in the murine macrophage cell line ANA-1 can also enhance IFN-gamma-induced production of nitric oxide. PGE2 and cholera toxin increased the production of nitrite (an indicator of nitric oxide production) in IFN-gamma-treated ANA-1 macrophages by at least twofold. These factors produced no increase in nitric oxide production in the absence of IFN-gamma treatment. The increase in nitric oxide production corresponded to an increase in the accumulation of nitric oxide synthase mRNA without a change in stability of mRNA. Dibutyryl cAMP and Sp-cAMPs (a selective activator of cAMP-dependent protein kinase I and II) also increased nitric oxide production in IFN-gamma-treated macrophages. However, at very high concentrations (i.e., >100 microM), the stimulatory effect was decreased. These studies indicate that elevation of intracellular cAMP causes a dose-dependent, biphasic alteration of IFN-gamma-induced nitric oxide production in murine macrophages. Moreover, they suggest that agents that affect nitric oxide synthesis may do so via modulation of the cAMP second messenger system.     

Functional expression of three isoforms of human nitric oxide synthase in baculovirus-infected insect cells

Complementary DNAs encoding three human isoforms (neuronal, inducible, and endothelial) of nitric oxide synthase were cloned into the baculovirus expression vector pVL1392/1393. Transfection of Sf-9 insect cells with the recombinant baculovirus resulted in the expression of high levels of nitric oxide synthases. The expressed proteins of neuronal and inducible nitric oxide synthase were predominantly soluble, whereas the endothelial enzyme was for the most part, particulate. Recombinant enzymes were purified with 2',5'-ADP Sepharose affinity chromatography. The effects of reference enzymatic inhibitors (NG-methyl-L-arginine, NG-nitro-L-arginine and N-iminoethyl-L-ornithine) on recombinant expressed proteins were not significantly different from native nitric oxide synthase enzyme preparations. L-aminoguanidine was found to be much less potent in inhibiting recombinant or native human inducible nitric oxide synthase compared to the murine isoform. These findings indicate previously unappreciated interspecies differences in the action of nitric oxide synthase enzymatic inhibitors. The functional expression of human nitric oxide synthase isoforms in a heterologous expression system allowed screening of novel inhibitors. Studies indicated that S-ethylisothiourea and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine were potent novel inhibitors of human nitric oxide synthases.     

Topical progesterone as support for the luteal phase in induced cycles

e efficacy and tolerability of 2.5% natural vaginal progesterone as luteal phase support in pharmacologically induced cycles has been evaluated. MATERIALS AND METHODS: On the basis of the administered therapy, the population studied was subdivided at random into four different groups. Sixty patients came to the Sterility Autonomous Department of the Niguarda Ca' Granda Hospital in Milan from November 1994 to January 1996. Both ultrasonographic and plasmatic hormonal parameters have been evaluated on a monthly basis. RESULTS: The plasma progesterone levels and ultrasonographic endometrial thickness average values resulted more important in groups treated with topical progesterone; in these same groups a greater percentage of pregnancies was observed. CONCLUSIONS: The results obtained demonstrated that the drug studied can be recommended as a valid luteal phase support in pharmacologically induced cycles.