Multilocational Evaluation of Some Selected Chickpea Nodulation Variants in India

High- (HN) and low-nodulating (LN) selections from each of the two cultivars ICC 4948 and ZCC 5003 developed at ZCRISAT Asia Center, were evaluated in seven experiments in five diffaent agroecological pones in India, The objectives of this multilouzrional experiment were to validate nodulation uzpacities of the selections in difftent environments, and to determine if the high-nodulating seleaions were indeed high yielding. Two nonnodulczting selections were included as refweaces to assess N, fixed by the different selections wing the N difference method. Relative differences for nodule number and nodule mass between the HN and LN selections within a cultivcrr were consistent across Locations and years. The HN selections genendly yielded higher (range 4-41 % in ICC 5003 HN and 4-1 06% in ZCC 4948 HN) than the LN versions of the same cultiuar, but the differences wme significant (P < 0.05) only in two of the seven experiment

Vaccination against nonmutated neoantigens induced in recurrent and future tumors

Vaccination of patients against neoantigens expressed in concurrent tumors, recurrent tumors, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP downregulation-induced antigens was more effective than vaccination against mutation-derived neoantigens, was devoid of measurable toxicity, and inhibited the growth of concurrent and future tumors in models of recurrence and premalignant disease. Human CD8(+) T cells stimulated with TAP(low) dendritic cells elicited a polyclonal T-cell response that recognized tumor cells with experimentally reduced TAP expression. Vaccination against TAP downregulation-induced antigens overcomes the main limitations of vaccinating against mostly unique tumor-resident neoantigens and could represent a simpler vaccination strategy that will be applicable to most patients with cancer.Experimental cancer immunology and therap

Familial adenomatous polyposis is associated with a marked decrease in alkaline sphingomyelinase activity: a key factor to the unrestrained cell proliferation?

The hydrolysis of sphingomyelin generates key molecules regulating cell growth and inducing apoptosis. Data from animal cancer models support an inhibitory role for this pathway in the malignant transformation of the colonic mucosa. In the intestinal tract, a sphingomyelinase with an optimum alkaline pH has been identified. We recently found that the activity of alkaline sphingomyelinase is significantly decreased in colorectal adenocarcinomas, indicating a potential anticarcinogenic role of this enzyme. To further examine whether the reduction of sphingomyelinase is present already in the premalignant state of neoplastic transformation, we measured sphingomyelinase activities in patients with familial adenomatous polyposis (FAP) and in sporadic colorectal tubulovillous adenomas. Tissue samples were taken from adenomas and surrounding macroscopically normal mucosa from 11 FAP patients operated with ileorectal anastomosis, from three FAP patients with intact colon, from 13 patients with sporadic colorectal adenomas and from 12 controls. Activities of acid, neutral and alkaline sphingomyelinase were measured together with alkaline phosphatase. In FAP adenoma tissue, alkaline sphingomyelinase activity was reduced by 90% compared to controls (P < 0.0001), acid sphingomyelinase by 66% (P < 0.01) and neutral sphingomyelinase by 54% (P < 0.05). Similar reductions were found in the surrounding mucosa. In sporadic adenoma tissue, only alkaline sphingomyelinase was reduced significantly, by 57% (P < 0.05). Alkaline phosphatase was not changed in FAP adenomas, but decreased in the sporadic adenomas. We conclude that the markedly reduced levels of alkaline sphingomyelinase activities in FAP adenomas and in the surrounding mucosa may be a pathogenic factor that can lead to unrestrained cell proliferation and neoplastic transformation. © 1999 Cancer Research Campaig

Risk factors for myocardial infarction among low socioeconomic status South Indian population

<p>Abstract</p> <p>Background</p> <p>As longevity increases, cases of myocardial infarction (MI) are likely to be more. Cardiovascular disease (CVD) is a major global health problem reaching epidemic proportions in the Indian subcontinent, also among low socio-economic status (SES) and thin individuals.</p> <p>Objectives</p> <p>The present study was undertaken to elicit risk factors for MI among low SES Southern Indians and to find out its association with body mass index (BMI).</p> <p>Materials and methods</p> <p>A case-control study of patients with MI matched against healthy control subjects was carried out in a tertiary care teaching hospital. Standard methods were followed to elicit risk factors and BMI. Chi-square and Fishers exact test for categorical versus categorical, to show relationship with risk factors were analyzed.</p> <p>Results</p> <p>A total of 949 patients (male (M) = 692 and post menopausal female (F) = 257) and 611 age and sex matched healthy controls were included. In our study, BMI was below 23 in 48.2% of patients and below 21 in 22.5%. The risk of developing MI was significantly more in males (odds ratio (OR) = 3.3, 95% confidence interval (C.I.) = 2.69-4.13), among females with post-menopausal duration (PMD) of more than or equal to 3 years (OR = 9.27, 95% C.I. = 6.36-13.50) and in those with BMI less than 23 with one or other risk factors (P = 0.002, OR = 1.38, 95% C.I. = 1.13-1.70).</p> <p>Conclusion</p> <p>BMI cannot be considered as a lone independent risk factor, as the study population had low BMI but had one or more modifiable risk factors. It would be advisable to keep BMI at least 21 kg/m²for screening program. Health education on life style modification and programs to diagnose and control diabetes and hypertension have to be initiated at community level in order to reduce the occurrence.</p

Diagnostic strategy and timing of intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study

AbstractBackgroundThe optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis is subject to debate. We performed a survey on these topics amongst a group of international expert pancreatologists.MethodsAn online survey including case vignettes was sent to 118 international pancreatologists. We evaluated the use and timing of fine needle aspiration (FNA), antibiotics, catheter drainage and (minimally invasive) necrosectomy.ResultsThe response rate was 74% (N = 87). None of the respondents use FNA routinely, 85% selectively and 15% never. Most respondents (87%) use a step-up approach in patients with infected necrosis. Walled-off necrosis (WON) is considered a prerequisite for endoscopic drainage and percutaneous drainage by 66% and 12%, respectively. After diagnosing infected necrosis, 55% routinely postpone invasive interventions, whereas 45% proceed immediately to intervention. Lack of consensus about timing of intervention was apparent on day 14 with proven infected necrosis (58% intervention vs. 42% non-invasive) as well as on day 20 with only clinically suspected infected necrosis (59% intervention vs. 41% non-invasive).DiscussionThe step-up approach is the preferred treatment strategy in infected necrotizing pancreatitis amongst expert pancreatologists. There is no uniformity regarding the use of FNA and timing of intervention in the first 2–3 weeks of infected necrotizing pancreatitis

Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004