Preparation and evaluation of 99mTc(V)-DMSA complex: studies in medullary carcinoma of thyroid

Consequent to the promising results reported with 99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways: from freshly prepared reagents, through the use of a two component kit and use of the standard renal DMSA kit by a modified recipe. The 99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays

Sister chromatid exchange (SCE) and chromosomal aberration studies have been used to monitor human populations for genotoxic exposure to chemical substances. These monitoring techniques involve collection of blood and/or bone marrow from the exposed subjects and culturing cells for one or two cell cycles with various treatments in culture. The results obtained from such in vivo/in vitro studies may lead to an over- or underestimation of the damage that could occur in vivo. In the present study, which uses a mouse model, the in vivo/in vitro cytogenetic assays (SCEs and chromosomal aberrations) have been compared with similar in vivo systems in bone marrow and spleen cells treated with various doses of cyclophosphamide (CPA). The results indicate a significant difference in CPA-induced cytogenetic endpoints between in vivo and in vivo/in vitro conditions in both organs. However, linear relationships were found between CPA dose and cytogenetic end point analyzed under both conditions. Based on these results it appears that the in vivo/in vitro assay is a useful technique for indicating potential in vivo damage of chemicals.     

Liposarcomatous differentiation in diffuse pleural mesothelioma.

A case history is presented of a woman who died eight hours after hospital admission with severe breathlessness. At necropsy the right lung was encased in a thickened pleura with a large tumour. Histological examination of the tumour showed pleural mesothelioma with liposarcomatous differentiation. The lungs showed changes of asbestosis and the asbestos fibre count was significantly raised. Liposarcomatous differentiation in pleural mesothelioma has not been reported previously.     

Human papilloma virus infection in Indian nasopharyngeal carcinomas in relation to the histology of tumour

Nasopharyngeal carcinoma (NPC) is a rare malignancy world-wide. It shows an increasing trend in the southern parts of India. Genetic alterations brought about by environmental factors, HPV and EBV are thought to be crucial for NPC carcinogenesis. This study reports for the first time the incidence of HPV infection in NPC in Southern India. Detection of HPV was carried out in 36 NPC and 10 adenoid lesions by immunohistochemical analysis. 38.8% of NPC were positive for HPV with higher positivity in WHO Type I and WHO Type II cancers. One among 10 adenoid lesions also showed presence of HPV. The patients belonged to low socio-economic status and had exposure to either tobacco or alcohol alone or in combination or kitchen smoke.     

High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity

It has been reported that hepatitis B virus (HBV) mutants carrying mutations in the pre-S region can be found in infected patients. In this study, we investigated the prevalence of the HBV variant with the pre-S mutant in different geographic regions, including countries with low and high levels of endemic HBV infection, and analyzed the correlation with clinical findings. We examined 387 HBV DNA-positive serum samples from individuals among 12 countries, consisting of Vietnam, Myanmar, Thailand, China, Korea, Nepal, Japan, Russia, Spain, United States, Bolivia, and Ghana. HBV pre-S mutants were detected in 71 (18.3%) of 387 serum samples tested. This mutant was the most prevalent in Vietnam (36%), followed by Nepal (27.3%), Myanmar (23.3%), China (22.4%), Korea (14.3%), Thailand (10.5%), Japan (7.7%), and Ghana (4.3%). In contrast, no case with this mutation was found in Russia, Spain, United States, and Bolivia. Among the HBV deletion mutations, 15.5% (11 of 71) occurred in the pre-S1 and 46.5% (33 of 71) in the pre-S2 regions. Eight (11.3%) cases had a mutation in both the pre-S1 and pre-S2 regions. In addition, a point mutation at the pre-S2 starting codon was observed in 19 (26.7%) cases. The detection rate of the HBV mutant in patients with hepatocellular carcinoma was significantly higher than in other patients (P < 0.05). Furthermore, these mutants were found more frequently in genotype B (25%) and genotype C (24.5%) than in the other genotypes (P < 0.05). Our results indicated that there was a high prevalence of HBV pre-S mutation in regions of endemic HBV infection in Asia. Furthermore, the pre-S mutation appeared to be correlated with hepatocellular carcinoma and HBV genotypes.     

Mutations in VMK1, a mitogen-activated protein kinase gene, affect microsclerotia formation and pathogenicity in Verticillium dahliae

Verticillium dahliae is an important soil-borne fungal pathogen that causes vascular wilt diseases in a large variety of important crop plants. Due to its persistence in the soil, control of Verticillium wilt relies heavily on soil fumigation. The global ban on methyl bromide, a highly effective soil fumigant, poses an urgent need to develop alternative control measures against Verticillium wilt; and these might be more forthcoming with a better understanding of the molecular and cellular mechanisms that underpin the pathogenicity of V. dahliae. In this study, we assessed the role in growth, development, and pathogenicity of VMK1, a gene encoding a mitogen-activated protein (MAP) kinase (hence, Verticillium MAP Kinase 1). Disruption of VMK1 via Agrobacterium tumefaciens-mediated transformation, in two V. dahliae isolates, one from lettuce and the other from tomato, resulted in severely reduced virulence in diverse host plants, suggesting that VMK1 is essential for pathogenicity and that the MAP kinase-mediated signaling pathway has a conserved role in fungal pathogenicity. The vmk1 mutants also exhibited reduced conidiation and microsclerotia formation, suggesting that the gene is important for multiple cellular processes. P.R. and R.G.B. equally contributed to the work     

Potentiation of human alpha4beta2 neuronal nicotinic receptors by a Flustra foliacea metabolite

The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function.