Immunosenescence of human NK cells: effects on tumor target recognition, lethal hit and interferon sensitivity.

Previous results from this laboratory have shown the preservation of non-MHC-restricted, constitutive oncolytic activity of human peripheral blood NK cells in the elderly as assessed by the chromium release assay which quantitates the lytic endpoint at the cell population level. We have now addressed this senescence-related change at single-cell level using 101 blood samples. Both the efficiency of the initial tumor target binding step i.e., recognition of K562, the NK-sensitive erythroleukemia cell line, as well as the ability of NK cells to deliver lethal hit are highly conserved during healthy aging. In fact, the elderly exhibit a statistically significant, moderately higher frequency of active killers among circulating lymphocytes. Analyzed in another way, a majority of "high NK responders" were found to be older donors, while none in the "low NK responders" group were > 70 years old. Gamma interferon, a gene product as well as an autocrine activator of NK cells, is effective in converting non-lytic "pre-NK" cells to active killers at single-cell level. This in vitro cytokine sensitivity of NK cells is unaltered during immune senescence. The intactness of the NK cell's capacity to be modulated may be vital in both tumor resistance and host viral defenses of aged humans.     

<Emphasis Type="Italic">Rhizobium</Emphasis> Mutant Deficient in Mineral Phosphate Solubilization Activity Shows Reduced Nodulation and Plant Growth in Green Gram

The aim of the present study was to understand the mineral phosphate solubilization (MPS) in Rhizobium sp. MR-54 (MPS⁺) by using forward genetic approach and its effect on nodulation as well as nitrogen accumulation on green gram. Tn5 mutants (MPS^?) were generated from the MPS⁺ strain by Tn5 mutagenesis. Screening 1,603 colonies of MR-54::Tn5 resulted in identification of those mutants which failed to show any solubilization zone up to 72 h after incubation on Tri-calcium phosphate medium (TCP). pH drops and Pi release were highly correlated up to 15 days after incubation in TCP broth. Gluconic acid was detected in the culture supernatants of MPS⁺ isolates through thin layer chromatography indicating the presence of direct oxidation pathway in MR-54 strain. Detailed characterization of mutants was carried out for related properties like colony morphology, Pi release and pH change in TCP broth, organic acid production, surface characteristics and plant growth promoting ability etc. Mutants deficient in MPS showed reduced nodulation and nitrogen accumulation in green gram under green house conditions in leonard jar apparatus over the wild strain indicating the MPS by Rhizobium being involved in nodulation, nitrogen accumulation and plant growth.     

A 4-year retrospective study of mandibular fractures in a South Indian city

The medical records of 238 patients treated for mandibular fractures at Sri Ramachandra Dental College and Hospital, India, over a period of 4 years were reviewed. Of the total 238 patients with mandibular fractures, 81% were males, and 19% were females. The majority of the patients were 21 to 30 years of age. Road traffic accidents, especially people traveling on motorcycles, accounted for 73% of all patients, with a high prevalence during the month of September and on Saturdays. The most common area of fracture was in the parasymphysis region (35.2%) followed by the condyle region (22.6%).     

Exposure and toxicity of green tea polyphenols in fasted and non-fasted dogs

Standardized green tea extract was evaluated for exposure and toxicity in Beagle dogs following oral dosing by capsules. The main component (−)-epigallocatechin gallate (EGCG) accounted for 56–72% of the material. A 9-month chronic study (0, 200, 500, and 1000 mg/kg/day) was done in fasted dogs to take advantage of the reported improved catechin bioavailability with fasting. Extensive morbidity, mortality, and pathology of many major organs led to its early termination at 6.5 months and prevented identification of the toxicity mechanisms. A follow-up 13-week study examined the exposure to and toxicity of the extract. In general, toxicities were less severe than in the chronic study during the same interval. Dosing in a fed state resulted in considerably lower and less variable exposure than found under fasted conditions. Toxicity was less frequent and of lesser severity with lower exposure but limited sample size and large variability prevented reaching that definitive conclusion. Differences in mortality and morbidity between the preliminary terminated chronic and follow-up subchronic studies with the same dose of the same drug lot and similar exposure were not fully resolved as there may be other as yet unclear confounding factors.     

Mining of Blast Resistance Gene,Pi2 and Its Novel Allelic Variant from Landraces of Rice from Karnataka

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Rice blast is one of the important fungal diseases of rice, caused by Magnaporthe oryzae. Rice blast can be...     

Screening mammography after breast cancer treatment: patterns in community practice

SummaryBackground Guidelines for screening women post-breast cancer treatment are generally lacking. This study was conducted to review the literature on guidelines for this population and to evaluate whether there is a common practice in the community for following these women.Methods The literature was reviewed for presence of published or inferred guidelines. Data were then used from the Carolina Mammography Registry (CMR) to see if patterns exist in community practice. For the years 1995–1999, 3081 women with a new diagnosis of unilateral breast cancer and a post-treatment screening mammogram in CMR were included. Recommendations for initial mammographic examination and intervals of subsequent mammograms post-treatment were described and tested for patterns of follow-up time.Results The only evidence-based guidelines found for post-treatment mammographic examinations were from the American Society of Clinical Oncology. They recommend 6 month follow-up initially followed by 12 month follow-up if findings remain stable. Among the 3081 women included in the study, 17.4% were recommended to return at 6 months post-treatment following their initial mammogram. Of the women who had at least three post-cancer mammograms (1592/3081), 82.6% were recommended for 12 month intervals at all three visits; only 2.1% of women were recommended for 6 month intervals at all three visits.Conclusions This study found that most community-based radiologists included in our study recommend following women at 12 month intervals post-treatment. Whether this 12 month screening interval is optimal for detecting recurrent cancers is not known and should be the focus of future research.     

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.     

Relevance of miR-21 in HIV and non-HIV-related lymphomas

The critical role of microRNAs (miRNAs) in cell differentiation, homeostasis and cancer development has been extensively discussed in recent publications. The microRNAs with RISC enzyme complex allow it to find its complementary sequence, which is usually located in the 3′-untranslated region (UTR) of the target messenger RNA (mRNA). This is followed by inhibition of protein translation or promotion, resulting in degradation of the target gene. miR-21 has been mapped at chromosome 17q23.2, where it overlaps with the protein coding gene vacuole membrane protein 1 (VMP1), a human homologue of rat vacuole membrane protein. Recent evidence indicates that miR-21 plays a vital role in tumour cell proliferation, apoptosis and invasion. The inhibition of miR-21 may induce cell cycle arrest and increased chemosensitivity to anticancer agents, providing evidence that miR-21 functions as an oncogene in human cancer. Increased expression levels of miR-21 were observed in tumours arising from diverse tissue types. This also includes tumours of haematological origin, such as chronic lymphatic leukaemia, diffuse large B cell lymphomas (DLBCLs), acute myeloid leukaemia and Hodgkin lymphomas. Recently, it has been shown that high levels of B cell activation were induced by miR-21 in circulating B cells and are seen in HIV-infected individual. Notably, miR-21 is overexpressed in activated B cells, suggesting its assistance in maintaining B cell hyperactivation, which plays a pivotal role in HIV-infected cells. Therefore, miR-21 can be considered as a powerful biomarker in HIV-related lymphomas. The number of studies related to the role of miR-21 in HIV-related lymphomas is sparse; therefore, this mini review highlights the recent publications related to clinical impact and significance of miR-21, specifically in HIV- and non-HIV-related lymphomas.