Pancreatic cancer is a highly aggressive disease with rapid invasion and early encasement of blood vessels. Hence, levels of circulating nucleic acids and tumor-associated mutations in them may have clinical importance. We analyzed the levels of circulating tumor DNA and oncogenic k-ras mutation in plasma of patients with pancreatic cancer and correlated their levels with survival and clinicopathological parameters. Higher levels of plasma DNA (>62 ng/mL) was found to associate significantly with lower overall survival time (p=.002), presence of vascular encasement (p=.030) and metastasis (p=.001). However, k-ras mutation status did not correlate with any of the clinicopathological parameters or survival. We conclude that circulating DNA in plasma can be an important predictor of prognosis in pancreatic cancer.
The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.
Clinically visceral leishmaniasis is suspected in only a fraction of infected persons, as the majority of these may not have clinical manifestations and remain asymptomatic. There is scanty information on diagnosing latent infections and predicting disease in asymptomatic persons. We therefore carried out a study on asymptomatic contacts of patients with visceral leishmaniasis and post-kala-azar dermal leishmaniasis by using methods for detection of antibody to recombinant K39 (rK39) antigen. A total of 240 patients with leishmaniasis and 150 asymptomatic contacts were tested for anti-rK39 immunoglobulin G (IgG) and IgA antibodies. Fifty-five asymptomatic persons were found to be seropositive. These individuals were monitored every 3 months for 1 year. On follow-up, 43.9% of the asymptomatic seropositive contacts developed kala-azar within the first 3 months, and a cumulative total of 69% developed kala-azar within 1 year. The rest remained asymptomatic and self-healed the infection. The sensitivity and specificity of rK39 enzyme-linked immunosorbent assay (ELISA) and dipstick tests were 100%, while an in-house-developed latex agglutination test had 80% sensitivity. The antibody profile showed that the IgG anti-rK39 antibodies reached a titer of up to 10 ؊6 within 6 months of infection, started declining thereafter, and completely disappeared in 2 to 3 years in successfully treated cases. Significant titers of IgA antibodies were detectable a little earlier than those of IgG antibodies and were undetectable after 6 months. The study showed that mass screening of family members and contacts by using anti-rK39 ELISA could be a highly reliable tool for early diagnosis and to plan prophylactic treatment of latently infected asymptomatic carriers to eradicate kala-azar.
Visceral leishmaniasis (VL) is a disease that has both zoonotic and anthroponotic etiologies. In India, VL is endemic, considered to be anthroponotic, and caused by Leishmania donovani . Anthroponotic diseases are maintained by transmission from human to human and to a lesser extent from human to animals. Serum samples from 1,220 animals from 7 human VL endemic districts of Bihar, India, were tested for antibodies to a recombinant kinetoplast antigen (rK39 antigen) present in amastigotes of visceralizing Leishmania species, i.e., L. donovani complex. Additionally, PCR was used to examine samples positive by rK39 antigen serology. Antibodies to rK39 indicative of VL were detected in 33 of 1,220 animals. Thirty-one of 867 goats (Capra hircus), 1 of 161 cattle (Bos indicus), and 1 of 54 wild rats (Rattus sp.) were positive by rK39 serology. None of 106 chickens (Gallus domesticus), 26 sheep (Ovis aries), 3 water buffaloes (Bubalus bubalus), or 3 dogs (Canis familiaris) was positive by rK39 serology. Leishmania donovani DNA was detected by PCR in 20 rK39 positive blood samples from goats and 1 sample from a cow. The present study indicates that goats are potential animal reservoirs of human VL in India.
A genomewide transcriptome assay of two subtropical genotypes of maize was used to observe the expression of genes at seedling stage of drought stress. The number of genes expressed differentially was greater in HKI1532 (a drought tolerant genotype) than in PC3 (a drought sensitive genotype), indicating primary differences at the transcriptional level in stress tolerance. The global coexpression networks of the two genotypes differed significantly with respect to the number of modules and the coexpression pattern within the modules. A total of 174 drought-responsive genes were selected from HKI1532, and their coexpression network revealed key correlations between different adaptive pathways, each cluster of the network representing a specific biological function. Transcription factors related to ABA-dependent stomatal closure, signalling, and phosphoprotein cascades work in concert to compensate for reduced photosynthesis. Under stress, water balance was maintained by coexpression of the genes involved in osmotic adjustments and transporter proteins. Metabolism was maintained by the coexpression of genes involved in cell wall modification and protein and lipid metabolism. The interaction of genes involved in crucial biological functions during stress was identified and the results will be useful in targeting important gene interactions to understand drought tolerance in greater detail.
SYNOPSISThe diagnostic yield of different electrophysiological criteria was examined to establish whether a peroneal palsy was due to compression of the nerve in the region of the capitulum fibulae. Slowing of sensory conduction along the segment of the nerve across the capitulum fibulae localized the lesion in 64% of 47 consecutive patients with a history indicating or suggesting compression of the nerve in the vicinity of the capitulum fibulae and there were no false positive findings in 18 patients whose peroneal palsy was not due to compression at the capitulum fibulae. In 20% of the patients with slowing along the segment across the capitulum, conduction velocity was normal when measured from the superior retinaculum to the popliteal fossa. Slowing along motor fibres (m. extensor digitorum brevis) localized the site of the lesion in one-third of the patients. Differences in amplitude and in split-up of the sensory responses recorded in the popliteal fossa as compared with those recorded distal to the capitulum fibulae were of limited diagnostic value because of many false positive findings among patients whose peroneal palsy was not due to compression of the nerve at the capitulum fibulae.
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