Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs

To study the receptor specificity of modern human influenza H1N1 and H3N2 viruses, the analogs of natural receptors, namely sialyloligosaccharides conjugated with high molecular weight (about 1500 kDa) polyacrylamide as biotinylated and label-free probes, have been used. Viruses isolated from clinical specimens were grown in African green monkey kidney (Vero) or Madin-Darby canine kidney (MDCK) cells and chicken embryonated eggs. All Vero-derived viruses had hemagglutinin (HA) sequences indistinguishable from original viruses present in clinical samples, but HAs of three of seven tested MDCK-derived isolates had one or two amino acid substitutions. Despite these host-dependent mutations and differences in the structure of HA molecules of individual strains, all studied Vero- and MDCK-isolated viruses bound to Neu5Ac alpha2-6Galbeta1-4GlcNAc (6'SLN) essentially stronger than to Neu5Acalpha2-6Galbeta1-4Glc (6'SL). Such receptor-binding specificity has been typical for earlier isolated H1N1 human influenza viruses, but there is a new property of H3N2 viruses that has been circulating in the human population during recent years. Propagation of human viruses in chicken embryonated eggs resulted in a selection of variants with amino acid substitutions near the HA receptor-binding site, namely Gln226Arg or Asp225Gly for H1N1 viruses and Leu194Ile and Arg220Ser for H3N2 viruses. These HA mutations disturb the observed strict 6'SLN specificity of recent human influenza viruses.     

Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.     

Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Pulmonary hypertension with elevated pulmonary vascular resistance is a common cardiovascular complication associated with increased morbidity and mortality in preterm infants with chronic lung disease. Injury to the developing pulmonary circulation results in structural and functional abnormalities of the pulmonary vasculature. Animal studies have demonstrated that disruption of angiogenesis may contribute to the failure of normal alveolarisation in chronic lung disease. Levels of vascular endothelial growth factor in bronchoalveolar lavage fluid are lower in infants with chronic lung disease compared to preterm controls. Supplemental oxygen is commonly used to prevent and treat pulmonary hypertension, although optimal arterial oxygen saturation levels remain uncertain. Other vasodilators such as inhaled nitric oxide appear promising, but as yet have not been evaluated in the form of randomised controlled trials. Further studies are required to investigate the long-term effectiveness of pulmonary vasodilator therapy.     

Relationship of Quality of Life with Disability Grade in Obsessive Compulsive Disorder and Dysthymic Disorder

Background:

There is paucity of information on the relationship of quality of life (QOL) in obsessive compulsive disorder (OCD) and dysthymic disorder (DD) with disability grade in India.

Aim:

To assess the relation of QOL with disability level in OCD and DD.

Materials and Methods:

This hospital based study was conducted in a medical institution in Davanagere, Karnataka, India. Data was collected by using Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) criteria, WHO QOL BREF and IDEAS. Relationship between disability grade and QOL was assessed by independent sample t test.

Results:

Mild disabled OCD patients had a significantly better QOL in the Q1 domain i.e. perception on quality of life as compared to moderately disabled patients (P < 0.05), while in other domains of QOL, there was no statistically significant difference (P > 0.05). But, QOL score in physical domain showed significant difference across disability grades (56.00, SD = 6.89; 48.50, SD = 12.28) in DD, but not in other domains.

Conclusion:

Perception of QOL is better in those with mild disability in OCD, but in DD, physical domain of QOL score is more in mild disability compared to moderate disability.     

Analysis of N-ras gene mutation and p53 gene expression in human hepatocellular carcinomas

AIM:To study the relationship between N-ras gene mutation and p53 gene expression in the carcinogenesis and the development of human hepatocellular carcinomas (HCC).METHODS:The N-ras gene mutation and the p53 gene expression were analyzed in 29 cases of HCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and immunohistochemistry.RESULTS:Thirteen cases of HCCs were p53 positive (44.8%), which showed a rather high Cpercen-tage of p53 gene mutation in Guangxi. The aberrations at N-ras codon 2-37 were found in 79.31% of HCCs and 80.77% of adjacent non-tumorous liver tissues. More than 2 point mutations of N-ras gene were observed in 22 cases (75.86%). Twelve cases (41.37%) of HCCs showed both N-ras gene mutation and p53 gene expression.CONCLUSION:N-ras gene and p53 gene may be involved in the carcinogenesis and the development of HCC.That 38% of HCCs with N-ras gene mutation did not express p53 protein indicates that some other genes or factors may participate in the carcinogenesis and the development of HCC.     

Polymeric inhibitor of influenza virus attachment protects mice from experimental influenza infection

Synthetic sialic acid-containing macromolecules inhibit influenza virus attachment to target cells and suppress the virus-mediated hemagglutination and neutralize virus infectivity in cell culture. To test the protective effects of attachment inhibitors in vivo, mice were infected with mouse-adapted influenza virus A/Aichi/2/68 (H3N2) and treated with synthetic polyacrylamide-based sialylglycopolymer PAA-YDS bearing moieties of (Neu5Acalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1)2-3,6Manbeta1-4GlcNAcbeta1-4GlcNAc. Single intranasal inoculations with PAA-YDS 30 min before or 10 min after infection increased the survival of mice (P<0.01). Multiple treatments with aerosolized PAA-YDS on days 2-5 post infection also increased survival (P<0.01), alleviated disease symptoms, and decreased lesions in the mouse lungs. These data suggest that synthetic polyvalent inhibitors of virus attachment can be used for prevention and treatment of influenza.     

Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns

In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2-63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted.