Biomedical subjects

M Srivastava

Publications and source records attributed to M Srivastava.

At least 19 recordsLinked to original sources

PubMed2006

ARK, the Apaf-1 related killer in Drosophila, requires diverse domains for its apoptotic activity.

In mammals and Drosophila, apoptotic caspases are under positive control of the CED-4-like proteins Apaf-1 and ARK, respectively. In an EMS-mutagenesis screen, we isolated 33 ark mutants as recessive suppressors of hid-induced apoptosis. The ark mutants are loss-of-function alleles characterized by reduced developmental apoptosis. Using the phenotypic series of these alleles, we identified helical domain I in the nucleotide oligomerization domain as critical for ARK's apoptotic activity. Interestingly, the WD40 region may also have an unanticipated positive requirement for the apoptotic activity of ARK. Considering structural information, we discuss the roles of these domains for assembly and activity of the ARK apoptosome, and propose that the WD40 region is anti-apoptotic in the absence of apoptotic signals, and pro-apoptotic in the presence of such signals. Furthermore, a defined null allele reveals that ark is required for most, but not all apoptosis suggesting the existence of an ARK-independent apoptotic pathway.

Alleles↗

PubMed2005

A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage.

AIM: Due of paucity of studies on stress ulcer prophylaxis in intracerebral hemorrhage (ICH), we have evaluated the usefulness of ranitidine and sucralfate in preventing gastric hemorrhage (GH) in patients with ICH. SUBJECTS AND METHODS: In a hospital-based randomized placebo-controlled study, patients with CT-proven ICH within 7 days of ictus were randomized into ranitidine 50 mg i.v. eight hourly, sucralfate 1 g six hourly and placebo groups. Patients were conservatively managed. Primary endpoint was occurrence of GH within 15 days of ictus and secondary endpoint 1-month mortality. RESULTS: The mean age of the patients was 57.2 (range 25-90) years and 40 were females. There were 45 patients in ranitidine, 49 in sucralfate and 47 in placebo group. Demographic, clinical and radiological features were not significantly different in 3 groups. GH occurred in 11 (23.4%) patients in placebo, 5 (11.1%) in ranitidine and 7 (14.3%) in sucralfate group, which was not significant. Only one female had GH. There were 13 (27.7%) deaths in placebo, 5 (11.1%) in ranitidine and 12 (24.5%) in sucralfate group. Pneumonia occurred in placebo group in 5 (10.6%), ranitidine in 2 (4.4%) and sucralfate in 5 (10.2%) patients, which was not significantly different. CONCLUSION: Ranitidine and sucralfate do not seem to significantly prevent GH or reduce 1-month mortality.

Adult↗

PubMed2005

Letrozole for brain and scalp metastases from breast cancer--a case report.

Brain metastases from breast cancer have a poor prognosis. There have been reports of patients with breast cancer and brain metastases responding well to tamoxifen therapy. We report a very unusual case of intact breast carcinoma with brain as well as scalp metastasis responding well to letrozole (aromatase inhibitor) therapy for a prolonged period of time.

Aromatase Inhibitors↗

PubMed2005

Prognostic predictors of thalamic hemorrhage.

BACKGROUND AND OBJECTIVE: There is no study evaluating the role of clinical, evoked potential and radiological parameters in the prognosis of thalamic hemorrhage employing multivariate logistic regression analysis, thus we aimed to evaluate the role of these parameters in predicting the 3 month outcome following thalamic hemorrhage. SETTING: Tertiary care referral teaching hospital. METHODS: Fifty-three patients with CT proven thalamic hematoma were evaluated. Conscious level was assessed using the Glasgow Coma Score (GCS), severity of stroke by the Canadian Neurological Scale (CNS), while muscle tone, tendon reflexes and power were also recorded. Hematoma size and type, and evidence of ventricular extension were obtained from the CT scan. Hematomas were classified as (A) thalamic with postero-lateral extension or (B) thalamic without postero-lateral extension. Central motor conduction to upper limb and median somatosensory evoked potentials (SEP) were recorded. Outcome was defined at 3 months on the basis of the Barthel Index (BI) with good being a BI of 12 or greater and poor a BI of less than 12. Best predictors of outcome were evaluated by single variable logistic regression analysis followed by multivariate logistic regression. RESULTS: Age ranged between 35 and 85 years; 18 were women. Mean GCS was 10.4 and CNS was 3.9. Thirty-one patients had type A hematomas and 22 type B. The hematoma was small in 5, medium in 35 and large in 13 patients. Ventricular extension was present in 34 patients. Motor evoked potentials were unrecordable in 36 and central motor conduction time was prolonged in 8 patients. Median SEP was unrecordable in 37 and N9-N20 conduction time was prolonged in 2 patients. At 3 months, 8 patients had died, 24 had good and 21 had poor outcome. On univariate logistic regression analysis diabetes mellitus, GCS, pupillary asymmetry, CNS score, type and size of hematoma and motor and somatosensory evoked potentials were significant in relation to outcome. On multivariate logistic regression analysis, the best predictors of outcome at 3 months were the type of hematoma and CNS score. CONCLUSION: CNS score and CT appearance of hematoma are the best predictors of 3 month outcome following thalamic hemorrhage. The proposed model for outcome assessment is simple and easy to apply and could have wide clinical application.

Adult↗

PubMed2005

Prognosis of conservatively treated patients with Pott's paraplegia: logistic regression analysis.

OBJECTIVE: To evaluate the prognostic significance of various clinical, radiological, and neurophysiological findings in conservatively treated patients with Pott's paraplegia, using multiple regression analysis. METHODS: The study included 43 patients with Pott's paraplegia, managed conservatively. The diagnosis of Pott's spine was based on clinical, magnetic resonance imaging, and computed tomography or ultrasound guided aspiration biopsy. All patients were examined clinically, and motor evoked potentials (MEPs) to lower limbs and tibial somatosensory evoked potentials (SEP) were recorded. Outcome at six months was defined as good or poor. For evaluating predictors of outcome, 15 clinical, investigative, and evoked potential variables were analysed, using multiple logistic regression analysis. RESULTS: The age range of the patients was 16-70 years, and 22 were female. Mild spasticity with hyperreflexia only was seen in 13 patients. In the remaining, weakness was severe in eight, and moderate and mild in 11 patients each. Twenty patients had loss of joint position sensation. MEP and SEP were abnormal in 19 and 18 patients, respectively. On multiple regression analysis, the best model predicting six month outcome included power, paraplegia score, SEP, and MEP. CONCLUSION: Patients with Pott's paraplegia are likely to recover completely by six months if they have mild weakness, lower paraplegia score and normal SEPs and MEPs.

Adolescent↗

PubMed2004

Observation of a narrow charm-strange meson D(+)(sJ)(2632)-->D(+)(s)eta and D(0)K(+).

We report the first observation of a charm-strange meson D(+)(sJ)(2632) at a mass of 2632.5+/-1.7 MeV/c(2) in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, D(+)(s)eta and D0K+. In the D(+)(s)eta decay mode we observe a peak with 101 events over a combinatoric background of 54.9 events at a mass of 2635.4+/-3.3 MeV/c(2). There is a corresponding peak of 21 events over a background of 6.9 at 2631.5+/-2.0 MeV/c(2) in the decay mode D0K+. The decay width of this state is <17 MeV/c(2) at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(D(+)(s)eta) is 0.14+/-0.06. The mechanism that keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the D(+)(s)eta decay mode.

Journal Article↗

PubMed2004

Annexin 7 mobilizes calcium from endoplasmic reticulum stores in brain.

Mobilization of intracellular calcium from inositol-1,4,5-triphosphate (IP3)-sensitive endoplasmic reticulum (ER) stores plays a prominent role in brain function. Mice heterozygous for the annexin A7 (Anx7) gene have a profound reduction in IP3 receptor function in pancreatic islets along with defective insulin secretion. We examined IP3-sensitive calcium pools in the brains of Anx7 (+/-) mice by utilizing ATP/Mg(2+)-dependent (45)Ca(2+) uptake into brain membrane preparations and tissue sections. Although the Anx7 (+/-) mouse brain displayed similar levels of IP3 binding sites and thapsigargin-sensitive (45)Ca(2+) uptake as that seen in wild-type mouse brain, the Anx7 (+/-) mouse brain Ca(2+) pools showed markedly reduced sensitivity to IP3. A potent and saturable Ca(2+)-releasing effect of recombinant ANX7 protein was demonstrated in mouse and rat brain membrane preparations, which was additive with that of IP3. We propose that ANX7 mobilizes Ca(2+) from an endoplasmic reticulum-like pool, which can be recruited to enhance IP3-mediated Ca(2+) release.

Animals↗

PubMed2004

Properties of an immobilized lipase of Bacillus coagulans BTS-1.

Lipase (EC 3.1.1.3) is a tri-acylglycerol ester hydrolase, catalysing the hydrolysis of tri-, di-, and mono-acylglycerols to glycerol and fatty acids. To study the effect of adsorption of a lipase obtained from Bacillus coagulans BTS-1, its lipase was immobilized on native and activated (alkylated) matrices, i.e. silica and celite. The effect of pH, temperature, detergents, substrates, alcohols, organic solvent etc. on the stability of the immobilized enzyme was evaluated. The gluteraldahyde or formaldehyde (at 1% and 2% concentration, v/v) activated matrix was exposed to the Tris buffered lipase. The enzyme was adsorbed/entrapped more rapidly on to the activated silica than on the activated celite. The immobilized lipase showed optimal activity at 50 degrees C following one-hour incubation. The lipase was specifically more hydrolytic to the medium C-length ester (p-nitro phenyl caprylate than p-nitro phenyl laurate). The immobilization/entrapment enhanced the stability of the lipase at a relatively higher temperature (50 degrees C) and also promoted enzyme activity at an acidic pH (pH 5.5). Moreover, the immobilized lipase was quite resistant to the denaturing effect of SDS.

Bacillus↗

PubMed2002

First observation of the doubly charmed baryon Xi(+)(cc).

We observe a signal for the doubly charmed baryon Xi(+)(cc) in the charged decay mode Xi(+)(cc)-->Lambda(+)(c)K-pi(+) in data from SELEX, the charm hadroproduction experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1+/-0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is 3519+/-1 MeV/c(2). The Gaussian mass width of this state is 3 MeV/c(2), consistent with resolution; its lifetime is less than 33 fs at 90% confidence.

Journal Article↗

PubMed2002

Modulation of radiation-induced changes in the xanthine oxidoreductase system in the livers of mice by its inhibitors.

The xanthine oxidoreductase (XOD) system, which consists of xanthine dehydrogenase (XDH) and xanthine oxidase (XO), is one of the major sources of free radicals in biological systems. The XOD system is present predominantly in the normal tissues as XDH. In damaged tissues, XDH is converted into XO, the form that generates free radicals. Therefore, the XO form of the XOD system is expected to be found mainly in radiolytically damaged tissue. In this case, XO may catalyze the generation of free radicals and potentiate the effect of radiation. Inhibition of the XOD system is likely to attenuate the detrimental effects of ionizing radiation. We have examined this possibility using allopurinol and folic acid, which are known inhibitors of the XOD system. Swiss albino mice (7-8 weeks old) were given single doses of allopurinol and folic acid (12.5-50 mg/kg) intraperitoneally and irradiated with different doses of gamma radiation at a dose rate of 0.023 Gy/s. The XO and XDH activities as well as peroxidative damage and lactate dehydrogenase (LDH) were determined in the liver. An enhancement of the activity of XO and a simultaneous decrease in the activity of XDH were observed at doses above 3 Gy. The decrease in the ratio XDH/XO and the unchanged total activity (XDH + XO) suggested the conversion of XDH into XO. The enhanced activity of XO may potentiate radiation damage. The increased levels of peroxidative damage and the specific activity of LDH in the livers of irradiated mice supported this possibility. Allopurinol and folic acid inhibited the activities of XDH and XO, decreased their ratio (XDH/XO), and lowered the levels of peroxidative damage and the specific activity of LDH. These results suggested that allopurinol and folic acid have the ability to inhibit the radiation-induced changes in the activities of XDH and XO and to attenuate the detrimental effect of this conversion, as is evident from the diminished levels of peroxidative damage and the decreased activity of LDH.

Allopurinol↗

PubMed2001

Precision measurements of the lambda(+)(c) and D0 lifetimes.

We report new precision measurements of the lifetimes of the Lambda(+)(c) and D0 from SELEX, the charm hadroproduction experiment at Fermilab. Based upon 1630 Lambda(+)(c) and 10 210 D0 decays we observe lifetimes of tau[Lambda(+)(c)] = 198.1+/-7.0+/-5.6 fs and tau[D0] = 407.9+/-6.0+/-4.3 fs.

Journal Article↗

PubMed2001

ANX7, a candidate tumor suppressor gene for prostate cancer.

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.

Annexin A7↗

PubMed2001

Lipoxygenase-5 is overexpressed in prostate adenocarcinoma.

BACKGROUND: Epidemiologic studies suggest that populations that consume large amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic acid and its precursor, linoleic acid, are major ingredients of animal fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by either the cyclooxygenase pathway or the lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer, and are now believed to play important roles in tumor promotion, progression, and metastasis. Studying these pathways in specimens from patients with prostate carcinoma, the authors recently demonstrated the overexpression of cyclooxygenase-2 in prostate adenocarcinoma. In the current study, the authors report the overexpression of lipoxygenase-5 (5-LO) in samples from patients with prostate adenocarcinoma. METHODS: Employing 22 pair-matched benign and malignant tissue samples that were obtained from the same patients with prostate carcinoma, the expression of 5-LO was determined using reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and by measuring the levels of 5-hydroxyeicosatetraenoic acid (5-HETE) by radioimmunoassay. RESULTS: The mean level of 5-LO mRNA was six-fold greater (P < 0.001) in malignant tissue compared with benign tissue. The immunoblot analysis demonstrated that, compared with benign tissue, 5-LO protein was overexpressed in 16 of 22 samples examined and was 2.6 fold greater (P < 0.001) in malignant tissue. Immunohistochemical studies further verified 5-LO up-regulation in malignant tissue that was not present in benign tissue. The levels of 5-HETE, which is a metabolic product of arachidonic acid, was found to be 2.2-fold greater (P < 0.001) in malignant tumor tissue compared with benign tissue. CONCLUSIONS: To the authors' knowledge, this is the first in vivo study showing overexpression of 5-LO in patients with prostate carcinoma. This study suggests that inhibitors of arachidonic acid pathway in general and selective 5-LO inhibitors in particular may be useful for prevention or therapy in patients with prostate carcinoma.

Adenocarcinoma↗

PubMed2001

Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis.

Photodynamic therapy (PDT), a promising treatment modality, is an oxidative stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its therapeutic efficacy. Although studies suggest the involvement of multiple pathways, the triggering event(s) responsible for PDT-mediated apoptotic response is(are) not clear. To investigate the role of Bcl-2 in PDT-mediated apoptosis, we employed Bcl-2-antisense and -overexpression approaches in two cell types differing in their responses toward PDT apoptosis. In the first approach, we treated radiation-induced fibrosarcoma (RIF 1) cells, which are resistant to silicon phthalocyanine (Pc 4)-PDT apoptosis, with Bcl-2-antisense oligonucleotide. This treatment resulted in sensitization of RIF 1 cells to PDT-mediated apoptosis as demonstrated by i) cleavage of poly(ADP-ribose) polymerase, ii) DNA ladder formation, iii) terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and iv) DEVDase activity. This treatment also resulted in oligonucleotide concentration-dependent decrease in cell viability and down-regulation of Bcl-2 protein with a concomitant increase in apoptosis. However, the level of Bax, a pro-apoptotic member of Bcl-2 family, remained unaltered. In the second approach, an overexpression of Bcl-2 in PDT apoptosis-sensitive human epidermoid carcinoma (A431) cells resulted in enhanced apoptosis and up-regulation of Bax following PDT. In both the approaches, the increased Bax/Bcl-2 ratio was associated with an increased apoptotic response of PDT. Our data also demonstrated that PDT results in modulation of other Bcl-2 family members in a way that the overall ratio of pro-apoptotic and anti-apoptotic member proteins favors apoptosis.

Apoptosis↗

PubMed2001

Nucleolin stimulates viral internal ribosome entry site-mediated translation.

Previous results from our laboratory have identified a small (60 nt) RNA from the yeast S. cerevisiae that specifically inhibits internal ribosome entry site (IRES)-mediated translation programmed by poliovirus (PV) and hepatitis C virus (HCV) 5'-untranslated region (5'UTR). The yeast inhibitor RNA (called IRNA) was found to efficiently compete with viral 5'UTR for binding of several cellular polypeptides that presumably play important roles in IRES-mediated translation. One such IRNA (and 5'UTR)-binding protein has previously been identified as the La autoantigen. In this report, we have identified a 110-kDa IRNA-binding protein (which also interacts with viral 5'UTR) as nucleolin, a nucleolar RNA binding protein that was previously shown to translocate into the cytoplasm following infection of cells with poliovirus. We demonstrate that nucleolin (called C23) stimulates viral IRES-mediated translation both in vitro and in vivo. We also show that nucleolin mutants containing the carboxy-terminal RNA binding domains but lacking the amino terminal domain inhibit IRES-mediated translation in vitro. The translation inhibitory activity of these mutants correlates with their ability to bind the 5'UTR sequence. These results suggest a role of nucleolin/C23 in viral IRES-mediated translation.

5' Untranslated Regions↗

PubMed2001

Reactive pocket epithelium in untreated chronic periodontal disease: possible derivation from developmental remnants of the enamel organ and root sheath.

The pathological lining epithelium of destructive periodontitis was studied by analysis of the expression of intermediate filament proteins in biopsies of untreated advanced periodontitis. The cytokeratin (CK) pair 8/18 characteristic of simple epithelia was expressed consistently in a distribution pattern confined to the reactive pocket epithelium. The pattern of CK8/18 expression was complex with two broad presentations evident. In two-thirds of the advanced disease biopsies, the entire pathological lining epithelium was strongly reactive for both CK8 and CK18. In the remainder, the more superficial lining epithelium was mixed with foci of reactive and unreactive cells, with the deeper epithelium uniformly reactive. Only occasional highly localised reactivity for the simple keratins (CK8/18) was found in the lining epithelia of biopsies from minimally inflamed periodontal tissues. The pathological lining epithelium of advanced periodontitis was further characterised by the co-expression in basal layers of CK14, and of CK13 but not CK4, which are characteristic of suprabasal layers of stratified squamous epithelia. Cytokeratin 17, a marker of high turnover and migrating epithelial cells was extremely variable with no clear association between expression pattern and location of the epithelium ordisease status. There was no reactivity for CK10/11 typical of cornifying cells nor of vimentin, the characteristic intermediate filament of mesenchymal cells. The intermediate filament protein profile of the reactive lining epithelium was indistinguishable from the reactive epithelium present in three of five biopsies of periapical granulomas containing hyperplastic epithelium from activation of the developmental remnants of Hertwig's sheath, known as the cell rests of Malassez. The data reported are compatible with a contribution by remnants of developmental epithelium, including the reduced enamel epithelium and the cell rests of Malassez, to the reactive lining epithelium of the subgingival pocket in the pathogenesis of chronic periodontitis.

Adult↗

PubMed2001

Elevated serum hepatocyte growth factor in children and young adults with inflammatory bowel disease.

BACKGROUND: Elevated serum levels of several potent angiogenesis factors, including vascular endothelial growth factor and basic fibroblast growth factor have been described in children with active inflammatory bowel disease. Angiogenesis-promoting cytokines may promote inflammation by increasing vascular permeability but also mediate tissue repair by activating fibroblasts. Hepatocyte growth factor (HGF) is another angiogenesis-promoting cytokine that is increased in colon cancer tissues. We therefore evaluated serum HGF levels in individuals with Crohn disease and ulcerative colitis. METHODS: Serum samples were obtained from 60 patients with Crohn disease, 31 with ulcerative colitis, and 38 controls with functional abdominal pain and other gastrointestinal illnesses. Disease activity for Crohn disease patients was determined using the pediatric Crohn disease activity index, and for ulcerative colitis patients using the Kozarek score. The HGF levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum HGF levels were significantly ( P < 0.001) higher for Crohn disease patients (1439 +/- 84 pg/mL) and ulcerative colitis patients (1384 +/- 107 pg/mL) than for control patients (807 +/- 50 pg/mL). Serum HGF levels also rose with increasing disease activity in individuals with both Crohn disease and ulcerative colitis. CONCLUSION: Serum HGF is elevated in children and young adults who have Crohn disease or ulcerative colitis. Levels of serum HGF correlate directly with disease activity. The raised serum HGF suggests that HGF may mediate angiogenesis and vascular permeability in the mucosa of children with inflammatory bowel disease. Alternatively, the raised serum HGF may be an epiphenomenon of inflammation.

Adolescent↗

PubMed2001

ANX7 as a bio-marker in prostate and breast cancer progression.

The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.

Animals↗