Hyperlipoproteinemia enhances susceptibility to acute disseminated Candida albicans infection in low-density-lipoprotein-receptor-deficient mice

Recent studies have suggested the use of lipoproteins as an adjuvant treatment of lethal gram-negative infections. However, other important microorganisms for the etiology of sepsis, such as Candida species, grow better in lipid-rich environments. We investigated the effect of hyperlipoproteinemia on systemic candidiasis in low-density-lipoprotein-receptor-deficient (LDLR-/-) mice, in which the loss of the receptor results in a seven- to ninefold-higher plasma LDL level than that in their wild-type littermates (C57BL/6J). LDLR-/- mice died earlier, and the outgrowth of Candida albicans in the kidneys and livers of LDLR-/- mice was significantly higher compared with that of controls. After infection, circulating cytokine concentrations were significantly higher in LDLR-/- mice. In vitro, C. albicans grew better in plasma samples of LDLR-/- mice than in control plasma samples and peritoneal macrophages of LDLR-/- mice challenged with heat-killed C. albicans produced more cytokines than did those of controls. This latter phenomenon was probably due to increased binding of yeast cells to macrophages of LDLR-/- mice. These data suggest that hyperlipoproteinemia is deleterious in systemic candidiasis.     

Comparative analysis of antibiotic resistance, immunofluorescent colony staining, and a transgenic marker (bioluminescence) for monitoring the environmental fate of rhizobacterium

Field releases of the wild-type plant growth-promoting rhizobacterium Pseudomonas fluorescens 89B-27, its bioluminescent derivative GEM-8 (89B-27::Tn4431), and a spontaneous rifampin-resistant variant estimating the wild-type population. Seed and root samples were taken 0, 7, 14, 21, or 28, 35 or 42, and 70 days after planting in each year and processed for enumeration by spiral plating or immunofluorescent colony staining (IFC). In both years, the populations of 89B-27, R34, and GEM-8, as measured by IFC, were not significantly different (P > 0.05) from each other at each sampling time. However, the populations of R34 and GEM-8, as measured by spiral plating and differentiation based on their respective phenotypes, were significantly lower (P < 0.05) than the wild-type populations and their IFC-determined populations. These data indicate that traditional marker systems may underestimate populations and hence the survival and colonization of genetically marked bacteria.     

The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction. A prospective controlled study

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been contra-indicated for the treatment of patients with hepatocellular carcinoma (HCC) and main portal vein (MPV) obstruction because of the potential risk of hepatic insufficiency resulting from ischemia after TACE. The current controlled study was undertaken to assess the safety, efficacy, and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV. METHODS: Of a total of 47 patients, 31 were treated with TACE, and 16 who declined the procedures were untreated controls. Thirty-six patients (77%) had diffuse-type HCC and 11 (23%) had nodular-type HCC. During the first week after TACE immediate postprocedural complications were evaluated, and the development of hepatic insufficiency as a late complication was assessed at the end of the fourth week. The cumulative survival rate was estimated by the Kaplan-Meier method, and predictors of better prognosis were obtained by univariate and multivariate analyses. RESULTS: Although no patients showed clinical evidence of hepatic insufficiency as an immediate complication, transient fever and abdominal pain were common. Progressive hepatic insufficiency developed at the fourth week; however, there was no difference between the treated and untreated groups. The survival time of treated patients was statistically no longer than that of untreated patients. In the univariate analysis, tumor type and size, the pattern of iodized oil uptake in the tumor, and the presence of iodized oil uptake in the tumor thrombi at the MPV significantly influenced the prognosis. Tumor type, whether treated or not, was the most important prognostic factor patients with nodular-type HCC had significantly longer survival time (median, 11 months) than those with diffuse-type HCC (median, 4 months). Regarding the efficacy of TACE, there was no statistical difference in survival between treated and untreated diffuse-type HCC patients. In comparison, with nodular-type HCC it seemed that survival time was longer for TACE-treated patients (median, 30 months) than for untreated patients (median, 7 months). CONCLUSIONS: TACE may be a safe modality for the treatment of patients with HCC and MPV obstruction, provided that the patients have good hepatic function and collateral circulation around the MPV. However, TACE was not efficacious in the treatment of diffuse-type HCC. The authors recommend TACE for treating nodular-type HCC because of the potential benefit of prolonged survival.     

Effects of methylphenidate on oxytocin and vasopressin levels in pinealectomized rats during light-dark cycle

Although previous reports have shown that methylphenidate (MPH), in addition to its known behavioral effect, can influence the hypothalamo-pituitary-adrenal axis by increasing the plasma ACTH, the pineal gland seems to be involved in neuroendocrinological processes too, e.g., in hypothalamic synthesis and release of oxytocin (OXY) and vasopressin (AVP). Therefore, a study was performed to measure the OXY and AVP content of the hypothalamus, neurohypophysis, and plasma after application of MPH in the morning and evening in pinealectomized (PE) as well as sham-operated control (SO) rats. Pinealectomy influenced both the daily pattern (reversed in the neurohypophysis) and the levels of OXY and AVP. Starting from this different situation, application of MPH produced diverse effects. Hypothalamus: PE, increase in both hormones in the morning and evening; SO, decrease in morning OXY level. Neurohypophysis: PE, increase in morning OXY level; SO, decrease in both hormones even though in the morning only. Plasma: PE, decrease in morning OXY concentration; SO, increase in both hormones in the morning and decrease in the evening. The present results indicate that MPH application influences the hypothalamo-neurohypophysial system. Furthermore, the hypothesis has been supported that this influence may be dependent on the circadian activity of the pineal gland as well.     

Immunochemical identification and differential phosphorylation of alternatively spliced forms of the alpha 1A subunit of brain calcium channels

Biochemical properties of the alpha 1 subunits of class A brain calcium channels (alpha 1A) were examined in adult rat brain membrane fractions using a site-directed anti-peptide antibody (anti-CNA3) specific for alpha 1A. Anti-CNA3 specifically immunoprecipitated high affinity receptor sites for omega-conotoxin MVIIC (Kd approximately 100 pM), but not receptor sites for the dihydropyridine isradipine or for omega-conotoxin GVIA. In immunoblotting and immunoprecipitation experiments, anti-CNA3 recognized at least two distinct immunoreactive alpha 1A polypeptides, a major form with an apparent molecular mass of 190 kDa and a minor, full-length form with an apparent molecular mass of 220 kDa. The 220- and 190-kDa alpha 1A polypeptides were also specifically recognized by both anti-BI-Nt and anti-BI-1-Ct antibodies, which are directed against the NH2- and COOH-terminal ends of alpha 1A predicted from cDNA sequence, respectively. These data indicate that the predicted NH2 and COOH termini are present in both size forms and therefore that these isoforms of alpha 1A are created by alternative RNA splicing rather than post-translational proteolytic processing of the NH2 or COOH termini. The 220-kDa form was phosphorylated preferentially by cAMP-dependent protein kinase, whereas protein kinase C and cGMP-dependent protein kinase preferentially phosphorylated the 190-kDa form. Our results identify at least two distinct alpha 1A subunits with different molecular mass, demonstrate that they may result from alternative mRNA splicing, and suggest that they may be differentially regulated by protein phosphorylation.