Comparison of ATP-dependent calcium transport and calcium-activated ATPase activities of cardiac sarcoplasmic reticulum and sarcolemma from rats of various ages

Age-associated decline in the Ca2+ pump function of cardiac sarcoplasmic reticulum (SR), and increase in the Ca2+ pump activity of sarcolemma (SL) were suggested by my previous study which compared the ATP-energized in vitro Ca2+ transport activities of these membranes from young (3-4-month-old) and aged (24-25-month-old) rat myocardium (Biochim. Biophys. Acta, 678 (1981) 442-459). In the present study, ATP-dependent Ca2+ transport and Ca2+ sensitive ATPase activities of SR and SL derived from the myocardium of rats aged 3 (young), 6 (young adult), 12 (adult), 18 (aging) and 24 (aged) months were determined so as to further characterize age-related changes in the Ca2+ transport function of these membranes. The rates of ATP-dependent Ca2+ accumulation by SR from 3- and 6-month-old rats were virtually similar whereas the rates of Ca2+ accumulation by this membrane from 12-, 18- and 24-month-old rats were significantly lower when compared to 3- or 6-month-old rats; the magnitude of this age-related decline amounted to approx. 18, 45 and 50%, respectively, for SR from 12-, 18- and 24-month-old animals. In contrast to the above findings with SR, SL from 18- and 24-month-old rats displayed substantially higher rates (approx. 45 and 80% increase, respectively, at 18 and 24 months of age) of ATP-dependent Ca2+ accumulation than SL preparations from 3-, 6- and 12-month-old rats; no significant age-related difference was evident between the latter three age groups. The divergent age-related changes in the Ca2+ accumulating activities of SR and SL were seen at varying Ca2+ concentrations (0.54-25.2 microM). With either membrane, kinetic analysis showed that the velocity of Ca2+ transport, but not the apparent affinity of the transport system for Ca2+ underwent age-related changes. The Ca2+-stimulated ATPase activities of SR and SL were not altered significantly with increasing age from 3 to 24 months. Comparison of the 'combined Ca2+ transport activity' of SR and SL from rats of various ages showed a significant overall age-related decline in the rates of Ca2+ transport via the ATP-driven membrane Ca2+ pumps; this decrement in membrane function was moderate at 12 months of age (approx. 16%) and became pronounced with advancing age thereafter (approx. 35 and 38%, respectively, at 18 and 24 months of age). Similar progressive age-related decline was observed in the ATP-dependent Ca2+ sequestering activity of cardiac homogenates.(ABSTRACT TRUNCATED AT 400 WORDS)     

ProKinO: A Unified Resource for Mining the Cancer Kinome

Protein kinases represent a large and diverse family of evolutionarily related proteins that are abnormally regulated in human cancers. Although genome sequencing studies have revealed thousands of variants in protein kinases, translating “big” genomic data into biological knowledge remains a challenge. Here, we describe an ontological framework for integrating and conceptualizing diverse forms of information related to kinase activation and regulatory mechanisms in a machine readable, human understandable form. We demonstrate the utility of this framework in analyzing the cancer kinome, and in generating testable hypotheses for experimental studies. Through the iterative process of aggregate ontology querying, hypothesis generation and experimental validation, we identify a novel mutational hotspot in the αC‐β4 loop of the kinase domain and demonstrate the functional impact of the identified variants in epidermal growth factor receptor (EGFR) constitutive activity and inhibitor sensitivity. We provide a unified resource for the kinase and cancer community, ProKinO, housed at http://vulcan.cs.uga.edu/prokino .     

Single-Center Comparison of Overall Survival and Toxicities in Patients with Infiltrative Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization or Drug-Eluting Embolic Transarterial Chemoembolization

Purpose

To compare overall survival and toxicities after yttrium-90 (⁹⁰Y) radioembolization and chemoembolization with drug-eluting embolics (DEE) in patients with infiltrative hepatocellular carcinoma (HCC).

Laparoscopic Colonic Resection for Rectosigmoid Colonic Tumours: A Retrospective Analysis and Comparison with Open Resection

Laparoscopic approach for treatment of colorectal malignancy is gaining acceptance gradually; however the benefits of laparoscopic surgery in colonic and rectal tumours is still open to debate. This study aims at a retrospective analysis of operative and short term outcome of patients with rectosigmoid tumours. A retrospective analysis of operative, postoperative and short-term outcome of 62 patients who underwent laparoscopic colorectal resection for cancer of rectosigmoid region were compared with a same number of parameters-matched patients who underwent open colorectal resection. Blood transfusion requirement was significantly more in the open group compared to the laparoscopy group (38.7% versus 6.4%, p = 0.001). ICU stay was less in the laparoscopy group (p = <0.05) and they were started on oral liquid diet earlier (p = 0.013). The number of the lymph nodes retrieved, positive distal margin and radial involvement were similar in both groups. The hospital stay was significantly shorter in laparoscopy group (8.4 versus 13.8 days, p < 0.05). Radical operation for rectosigmoid tumors is technically feasible with laparoscopic surgery. Laparoscopic approach is associated with less blood loss, transfusion and significantly less ICU stay. Laparoscopic group recovers early and needs less hospital stay     

Gastric carcinoma after peptic ulcer surgery

Gastric carcinoma following surgery for benign peptic ulcer disease is being increasingly reported. The authors have reviewed their experience at Saint Francis Hospital and Medical Center and Mount Sinai Hospital from 1970 to 1980 and found 319 cases of gastric carcinoma, 16 of whom had undergone previous surgical procedures for peptic ulcer disease, with an incidence of 5 per cent of gastric stump carcinoma. The average time interval for the development of gastric stump carcinoma was 17.4 years, ranging from 5 to 49 years. The average survival after the diagnosis was 4.6 months, making the prognosis uniformly poor, probably due to delayed diagnosis. Treatment modalities consisted of major and minor surgical procedures, medical therapy, and no treatment in some instances. It is recommended that all patients who undergo operations for peptic ulcers have careful long-term follow-up. Vague gastrointestinal symptoms occurring in these patients, especially 10 years or more after surgery, require endoscopy and biopsies of the gastric stump to exclude gastric stump carcinoma.     

Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts.

Increased lung collagen and increased collagen synthesis by lung fibroblasts is well recognized in pulmonary fibrosis. gamma-Interferon has been shown to inhibit collagen synthesis by fibroblasts. To understand its effect on lung fibroblasts we compared how this lymphokine affects the growth and collagen synthesis of normal and fibrotic human lung fibroblasts. The results showed that gamma-IFN inhibited DNA synthesis in all fibroblast strains examined. Both collagen production and type 1 mRNA levels were reduced in three normal and two fibrotic cell strains exposed to gamma-IFN, while they were not affected in one strain from fibrotic lung. Even though an occasional cell was unaffected by the gamma-IFN, collagen mRNA level was reduced in most cells and it remained reduced for 48 h after removing the gamma-IFN. These results show that gamma-IFN inhibits the growth of fibroblast cultures derived from normal and fibrotic human lungs and suppresses collagen synthesis in most of these cells.     

Antioxidant and Antimicrobial Potential of Natural Colouring Pigment Derived from Bixa orellana L. Seed Aril

Natural colourants with bio-potential are of great commercial demands as we are moving away from the hazardous and toxic chemical dyes. Bixa orellana L. a representative of Bixaceae is rich in bixin and nor-bixin pigments which could be explored for various applications. In the present study, extraction and characterization of bixin and its associated pigment from the aril of the B. orellana L. seeds were performed using various spectroscopic techniques. Spectroscopic analysis and Gas chromatographic profiling of the pigment were performed to understand the present pigments. Toxicity was evaluated through in silico method. The major component, bixin and nor-bixin were proved to be non-toxic, non-carcinogenic and non-mutagenic through in silico methods. The pigment was found to be a potent antioxidant as well as bactericidal against opportunistic bacteria. It was found that bixin extract was a potential antioxidant and bactericidal agent. Hence it could be used for imparting bactericidal potential for cellulosic materials like papers or textiles in biomedical applications.

     

Therapeutic plasma exchange for exogenous insulin antibody syndrome in combined variable immunodeficiency: a case report

A 32-year-old male with type I diabetes presented with profound hypoglycemia due to exogenous insulin antibody syndrome in the setting of newly-diagnosed common variable immunodeficiency. Immunomodulatory therapy was not initially effective, but after the initiation of plasma exchange hypoglycemia resolved, and glucose lability improved.     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.