Genetic and Epigenetic Analysis of Recurrent Hydatidiform Mole

Familial biparental hydatidiform mole (FBHM) is a maternal‐effect autosomal recessive disorder in which recurrent pregnancy failure with molar degeneration occurs. The phenotype mimics molar pregnancy due to androgenesis, despite the normal genetic makeup of the conceptus. FBHM appears to result from a failure to establish correct maternal epigenetic identity at imprinted loci during oogenesis. Several women affected with FBHM have previously been shown to have biallelic mutations in the NLRP7 gene (NALP7). Here, we present the results of epigenetic and mutational analysis on FBHM patients from 11 families, 10 of them novel. We demonstrate a methylation defect at imprinted loci in tissue from four new FBHM cases. Biallelic NLRP7 mutations, including eight previously undescribed mutations, were found in all but one family. These results indicate for the first time that maternal imprints at some loci may be correctly specified in FBHM conceptions, since differential methylation of SGCE/PEG10 was preserved in all four cases. © 2009 Wiley‐Liss, Inc.     

Effect of aspirin on glucose-D transport in intestine of rat

Objective： The present study was designed to evaluate the effect a commonly prescribed Non Steroidal Anti Inflammatory Drug （NSAID） i.e. aspirin on brush border membrane in terms of changes in the intestinal transport level of glucose which is monosaccharide with absolute requirement in the body and hence its absorption is directly proportional on the morphology of the intestinal mueosa. Method： Albino rats （Rattus Norvegicus） were divided into two different groups, Group I （Control）, Group II （ aspirin-treated, 50 mg aspirin/kg of body weight）. The treatment was continued for 28 days. On the 29th day after overnight fasting, intestine was removed from animals of both groups. Changes in transport of glueose-D in intestine were studied. Result： The results indicated a significant decrease in the transport of glucose-D in aspirin treated group as compared to the control group. Conclusion： Cautious use of NSAID is recommended in commonly observed symptom such as headache and to those patients who are given as a prophylaxis for thrombosis.     

Clinical presentation and genotype of hepatitis delta in Karachi

AIM: To assess the clinical presentation and genotypes of delta hepatitis in local population. METHODS: In this prospective study, 39 consecutive patients who were positive for HBsAg and hepatitis D virus (HDV) antibody were included. The patients were divided in two groups on the basis of presence or absence of HDV RNA and a comparative study was done. Genotype of HDV was determined in PCR positive patients. RESULTS: Overall there is male dominance, in which 34 patients out of 39 (87.2%) were male. Twenty (51%) patients were from the adjacent areas of three provinces; Sindh, Punjab and Balochistan indicating the higher prevalence of delta hepatitis in this mid region of Pakistan. Patients of all age groups were affected with delta hepatitis (median 31.5 years, range 12-75). HDV RNA was detectable in 23 patients (59%). All the HDV strains belonged to genotypeⅠ. HBV DNA was detectable only in 3 cases who were also HBeAg and HDV RNA positive. Patients with detectable HDV RNA were younger than patients with undetectable RNA; mean age 29.7 ± 12.8 years vs 36.8 ± 15.2. There were no statistically significant differences in the clinical presentation and routine biochemical profile of patients with detectable or undetectable HDV RNA. Clinical cirrhosis was present in 19 (49%) patients; 12 with detectable RNA and 7 with undetectable HDV RNA (P = 0.748). Decompensated disease was seen in eight patients; five and three respectively from each group. Four patients with undetectable RNA and two patients with detectable RNA had normal ALT and ultrasound abdomen. CONCLUSION: HDV may infect at any age, usuallyyoung adult males. GenotypeⅠ is prevalent. With time some of the patients become HDV RNA negative or asymptomatic carrier. Most of the patients have suppressed HBV DNA replication. Significant numbers of patients have cirrhosis.     

Molecular genetic analysis of BAX and cyclin D1 genes in patients with malignant glioma

INTRODUCTION AND OBJECTIVES: Brain tumorigenesis is a complex process involving multiple genetic alterations. Cyclin D1 and BAX genes are two of the most important regulators in controlling the normal proliferation and apoptosis of cells, respectively. In this study, we analysed the possibilities of involvement of cyclin D1 and BAX genes in the gliomagenesis. METHODS AND RESULTS: In determining gene alterations of exon 4 of cyclin D1 gene and exon 6 of BAX gene, all samples were amplified by polymerase chain reaction (PCR) and subsequently by direct sequencing. Our results showed a frameshift mutation (G base deletion) at nucleotide 82 of codon 28 in exon 4 of the cyclin D1 gene and another frameshift mutation with a deletion of C base at nucleotide 153 of exon 6 of the BAX gene in two separate cases of a glioblastoma multiform (WHO Grade IV) sample. CONCLUSION: These findings suggest that both cyclin D1 and BAX genes alteration are rarely found in brain tumors. However, the alteration might cause a significant effect of the normal protein production and this might contribute to the development of brain tumorigenesis in Malaysian patients.     

Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. METHODS: We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. RESULTS: Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. CONCLUSIONS: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.     

Gastric corpus polyps associated with Proton Pump Inhibitors therapy

The prevalence of Gastroesophageal Reflux Disease (GERD) is rapidly rising in Asia. We describe here a case of 51 years old man who had surgery for esophageal leiomyoma and received long-term therapy with Proton Pump Inhibitors (PPIs) for persisting reflux symptoms. On Esophago-Gastroduodenoscopy (EGD) several sessile polyps were seen in the gastric corpus. Earlier EGD done 15 years back had not demonstrated those polyps. Sections revealed polypoid fragments of glandular epithelium with dilated glands and negative histology for H. pylori. Polymerase chain reaction for 16S ribosomal RNA gene (16S rRNA PCR) of H. pylori was also negative. This is the first report originating from an Asian country describing Fundal Gland Polyps (FGPs) in the corpus of stomach rather than fundus in a patient on long-term PPI therapy.