Ethanol induced changes in superoxide anion and nitric oxide in cultured microglia

Induction of oxidative stress has been implicated as a causative factor in fetal alcohol syndrome although the source of reactive oxygen species is not clear. One potential source is the microglia, the CNS macrophage, which generate superoxide anion as part of their normal immune function. Our data indicate that chronic exposure to ethanol alters the function of cultured neonatal hamster microglia by inducing superoxide anion production in resting (nonstimulated) cells. An increase in superoxide anion was seen at 24 or 48 hr of ethanol treatment but was not seen during acute exposures of up to 3 hr. This effect was dose dependent and was maximal at 20 mM ethanol. Treatment with ethanol did not directly activate the respiratory burst seen in microglia and did not act as a priming agent to enhance phorbol-ester-stimulated superoxide anion production. Lipopolysaccharide-mediated priming of microglial superoxide anion production was also not affected by exposure to 20 mM ethanol for 24 hr. Ethanol treatment, however, did depress nitric oxide (NO) levels in hamster microglia which had been stimulated to produce NO by polyinosinic:polycytidylic acid (poly I:C). Uptake of latex beads was increased by 24 hr of exposure to ethanol. The overall action of ethanol on neonatal hamster microglia is to shift the balance between the production of superoxide anion and NO. Because NO is protective to mammalian cells, these changes predict that oxidative stress in the CNS would be enhanced.     

The empirical antibiotic therapy of patients with acute leukemias: the results of a multicenter study

AIM: To evaluate efficacy of ampicilline/sulbactame and fluconasole in the regimen of empirical antibiotic therapy in patients with acute leukemia. MATERIALS AND METHODS: The trial covered 14 hematological departments of Russia and 1 of Ukraine. Acute myeloid leukemia patients were included. 92 cases of fever in 56 patients with analysis of efficacy in 66 cases were considered. At the first stage of empirical antibiotic therapy, cefoperason (4 g/day) and gentamycin (240 mg/day) were administered. If no response was reached, ampicilline/sulbactam (7.5 g/day) was added. This was the second stage. If no response occurred for 5 days the three drugs were joined by fluconasol (400 mg followed by 200 mg). RESULTS: Fever of unclear genesis was cured in 82% (28 of 34), clinical infection--in 80% (20 of 25), microbiologically confirmed infection--in 4 of 7 cases. A complete response to the empirical antibiotic therapy was registered in 52 of 66 cases (79%). 7(10.5%) patients died of infectious complications. 7(10.5%) received other antibiotics.     

Dissection of signaling pathways and cloning of new signal transducers in tyrosine kinase-induced pathways by genetic selection

We used genetic strategies which have been proven valuable to decipher signaling pathways in comparatively simple organisms such as Drosophila and Caenorhabditis elegans, to dissect signaling network activated by tyrosine kinases in mammals. The strategy was developed further towards a generally applicable expression cloning system to identify signal transducers in tyrosine kinase pathways. This system is based on the ability of downstream acting genes to rescue the transformation phenotype of partial loss-of-function mutants of BCR-ABL which still retain tyrosine kinase activity. Using this strategy we have previously shown that overexpression of c-Myc and Cyclin D1 can rescue a signaling defective SH2 mutant of BCR-ABL for transformation. In an unbiased approach to identify new compensating genes, a cDNA library was introduced by retroviral infection into fibroblasts which express the BCR-ABL SH2 mutant. CDNA clones, capable of rescuing the SH2 mutant for transformation should result in colony formation in soft agar. A PCR approach was used to recover these compensating genes from the genomic DNA of the transformed fibroblasts. Sequencing analysis of the initial cDNAs identified three known genes, the adapter molecule Shc, the kinases SPRK and p38 MAPK. These genes have been found to interact functionally with BCR-ABL for fibroblast and hematopoietic cell transformation. Currently, we are constructing and screening new libraries to identify novel genes which complement the BCR-ABL SH2 mutant. Our results demonstrate that this cloning approach is an effective means of identifying and characterizing signaling molecules that function in specific signaling pathways. This in turn may identify specific targets for mechanism-based therapeutic intervention to block altered signaling.     

Thymidine phosphorylase (platelet-derived endothelial cell growth factor), microvessel density and clinical outcome in hepatocellular carcinoma

BACKGROUND/AIMS: Angiogenesis plays an important role in tumor growth and metastasis. It is regulated by angiogenic factors. Thymidine phosphorylase (platelet-derived endothelial cell growth factor) is one such factor. Although the significance of platelet-derived endothelial cell growth factor has been studied for several types of tumor, the expression of platelet-derived endothelial cell growth factor and its correlation with microvessel density or clinicopathological factors in hepatocellular carcinoma are unknown. We evaluated microvessel density and platelet-derived endothelial cell growth factor expression in hepatocellular carcinoma to determine whether microvessel density and platelet-derived endothelial cell growth factor expression are correlated with the clinicopathological factors of hepatocellular carcinoma. METHODS: Using immunohistochemical staining with anti-platelet-derived endothelial cell growth factor antibody and the ELISA method, we evaluated the correlation among platelet-derived endothelial cell growth factor expression, microvessel density and clinicopathological factors in 84 hepatocellular carcinoma patients. Microvessels were stained with anti-human von Willebrand factor (anti-Factor VIII) and anti-CD34. RESULTS: In the surrounding liver, there was a significant correlation between microvessel density and platelet-derived endothelial cell growth factor expression (p=0.002), and hepatitis C virus-positive livers had higher microvessel densities than otherwise (p=0.003). However, this correlation was not found for hepatocellular carcinoma, but hepatitis C virus-positive tumors had higher expression of platelet-derived endothelial cell growth factor (p=0.018). Microvessel density in hepatocellular carcinoma obtained by Factor VIII staining inversely affected the recurrence-free survival rate (p=0.0416), but the microvessel density by CD34 staining was not a significant predictor. CONCLUSIONS: This study indicates that platelet-derived endothelial cell growth factor may not be a major regulator of angiogenesis of hepatocellular carcinoma, but this enzyme may play an important role in hepatocarcinogenesis cooperating with hepatitis C virus. Also, the density, not of sinusoid-like vessels, but of larger vessels in hepatocellular carcinoma could be a prognostic factor for hepatocellular carcinoma.     

The efficacy of treating patients with allergic diseases at a health resort with a gastroenterologic profile

45 allergic patients were treated in gastrointestinal sanatorium. Balneological and speleo modalities were employed. The clinical symptoms and humoral immunity indicated high efficacy of such treatment. The complex is recommended for introduction in gastrointestinal sanatoria.     

Development of mother-infant attachment scale

A 15 item mother-infant attachment scale was developed. It is a simple, brief and easy to comprehend even by the illiterate rural woman. The split half reliability was found to be 0.83 and there was high internal consistency. It has high face and construct validity. The babies separated for longer period had shown lesser attachment subsequently, compared to those who had no separation.     

Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset

Hyperammonemia and encephalopathy developed in an 11-year-old girl with chronic interstitial lung disease and cholesterol casts in her lung biopsy specimen. She had decreased plasma levels of ornithine, lysine, and arginine and excessive urinary excretion of lysine and arginine, consistent with the diagnosis of lysinuric protein intolerance. Analysis of plasma and urinary amino acids should be considered in the diagnostic evaluation of patients with interstitial lung disease of uncertain origin.