Thyroid eye disease associated with athyria.
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Adult↗
Biomedical subjects
N Gupta
Publications and source records attributed to N Gupta.
Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.
Neonates have a lower serum bicarbonate level than adults, which is caused by a lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption occurs in the proximal tubule, in which proton secretion is predominantly mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that there is a maturational increase in apical membrane rabbit proximal convoluted tubule Na+/H+ antiporter activity. However, in rat brush border membrane vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter activity was assayed as the proton secretory rate on luminal sodium removal. Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8 +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next examined whether the increase in Na+/H+ antiporter activity was associated with changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In summary, this study demonstrates that there is a maturational increase in rat apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush border membrane vesicle NHE3 protein abundance.
Aging↗
Hashimoto's thyroiditis: countrywide screening of goitrous healthy young girls in postiodization phase in India.
Countrywide salt iodization, to prevent nutritional iodine deficiency, has been achieved in India recently. The current study was planned to evaluate the prevalence of goiter and thyroid autoimmunity and assess thyroid functional status in a cohort of 6283 healthy schoolgirls from different parts of the country in the postiodization phase. Goitrous girls (n = 1810; 28% of subjects) were investigated for serum T4 and TSH, antithyroid microsomal antibody (TMA) and antithyroglobulin antibody (TGA), urinary iodine excretion, and cytomorphology by fine-needle aspiration cytology (FNAC). FNAC carried out successfully in 764 goitrous girls revealed juvenile autoimmune thyroiditis (JAT) in 58 (7.5%), which included Hashimoto's thyroiditis in 43 (5.6%) and focal lymphocytic thyroiditis in 15 (1.9%). TMA and TGA estimated in 722 goitrous girls detected significantly positive titers of TMA (> or =1:1600) and TGA (> or =1:160) in 52 (7.2%) and 4 (0.55%) girls, respectively. Only 29 (67.4%) girls with Hashimoto's thyroiditis were TMA positive. In patients with FNAC-proven JAT, overt clinical and biochemical hypothyroidism was seen in three (6.5%) and subclinical hypothyroidism in seven (15%). Subclinical hyperthyroidism was detected in 5.1% cases of JAT, and none had overt hyperthyroidism. No definite correlation was seen between urinary iodine excretion and thyroid autoimmunity.
Adolescent↗
Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.
The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.
Animals↗
Persistent presence of acid-fast bacilli in pulmonary tuberculosis : possible implications for developing countries.
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Antitubercular Agents↗
Current status of viral gene therapy for brain tumours.
Malignant glial tumours represent the majority of primary brain tumours. Despite the use of many adjunctive treatment strategies in addition to surgery, the prospect of cure or even long-term survival is poor. In the last decade, there has been an explosion of interest in the development of delivery systems that will allow the expression of exogenous genes in the CNS. For the most part, these systems are based upon modified viruses. To date, the greatest experience has been with retroviruses, herpes simplex virus 1 (HSV), adenovirus and adeno-associated virus (AAV). This review will outline the biology of these viral vectors, modifications permitting in vivo administration and their respective advantages and disadvantages for the treatment of malignant brain tumours. The present obstacles to gene therapy strategies will also be described. To date, no convincing clinical trial has emerged that provides objective proof of the superiority of gene therapy strategies as compared to conventional treatment.
Adenoviruses, Human↗
Decreased 3D-sound spatialization accuracy caused by speech bandwidth limitation over commodity audio components.
This paper studies the accuracy achievable in spatialized speech signals due to their limited bandwidth, in systems based on generic Head-Related Transfer Functions (HRTFs). The accuracy in the perception of sounds spatialized through HRTFs to emulate nine sound locations around the listener, at 0 elevation, are investigated. The tests contrast the localization accuracy for a speech segment and that for broadband noise, as perceived by two independent groups of 10 normal-hearing volunteers each. The sound localization perceived and reported by each subject is compared to the HRTF-emulated location, to define a localization error, in each case. The results are analyzed through a repeated measures, mixed-factorial design Analysis of Variance (ANOVA). The emulated source locations and the type of sounds are the independent variables, and the average perceived localization error for each case, the dependent variable. Since the spectrum of speech signals drive only sections of the complete HRTF frequency response for each location, the initial expectation is that they benefit less from the spectral-shaping process implemented by the HRTFs, thus resulting in a lower spatialization efficiency than the one for a full-spectrum noise signal. We study the measurement of these effects when 3D-sounds are delivered over commodity audio components, because of their widespread use in practical systems.
Adult↗
Issues related to the psychological aspects of recurrent abdominal pain.
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Abdominal Pain↗
The risk of injury and alcohol consumption.
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Alcohol Drinking↗
Tuberculous liver abscess.
Tuberculosis (TB) of liver is rare but may have a variety of presenting features similar to other more common conditions. A case of tuberculosis liver abscess with right sided pleural effusion is reported.
Aged↗
Purification & characterisation of haemolysin from Serratia marcescens B-91.
BACKGROUND & OBJECTIVES: Serratia marcescens an opportunistic human pathogen, is frequently encountered in a variety of debilitating diseases. Relatively little is known about its virulence traits though most clinical isolates secrete a distinct haemolysin which is considered as a useful marker for pathogenicity of Serratia. In this study purification and characterisation of S. marcescens B-91 haemolysin have been attempted. METHODS: S. marcescens B-91 haemolysin was purified to homogeneity from the growth medium using ammonium sulphate fractional precipitation and gel filtration through Sephadex G-75 column. Homogeneity was determined by gel electrophoresis and purified haemolysin was tested for its stability and other characteristics. RESULTS: The haemolysin was characterised to be a 45 kDa molecular weight protein on SDS-polyacrylamide gel electrophoresis. It was inactivated at 60-100 degrees C within 30 min, and on overnight treatment with 2 per cent formaldehyde. It was also susceptible to the action of pronase, protease and trypsin. INTERPRETATION & CONCLUSIONS: The results indicate that the fragile stability of S. marcescens haemolysin is dependent on the storage temperature. The purified haemolysin can be used for understanding the role of haemolysin in the pathogenesis of S. marcescens and also for evaluation of immunoprophylactic activity.
Electrophoresis, Polyacrylamide Gel↗
Accumulation of specific RNAs encoding transcriptional factors and stress response proteins against a background of severe depletion of cellular RNAs in cells infected with herpes simplex virus 1.
Herpes simplex virus 1 encodes several functions to preclude the shutoff of host response to infection, including degradation of mRNA immediately after infection. To determine whether any cellular mRNAs accumulate in infected cells against a background of severe loss of host RNA, we hybridized cDNAs derived from three different cell lines infected with wild type and a mutant virus to a DNA array containing probes for 588 human genes representing different functional groups. The results were that (i) infected cells accumulated at levels above those of mock-infected cells, a small number of transcripts representing transcriptional factors that could regulate gene expression both positively and negatively, and one stress response protein (GADD45), (ii) the amount and nature of the accumulated transcripts showed limited variability depending on the cell and virus, and (iii) at least some of the proteins encoded by the accumulated transcripts could benefit either the virus or the host.
Cell Line↗
Hydrogeologic modeling for permeable reactive barriers.
The permeable reactive barrier technology for in situ treatment of chlorinated solvents and other groundwater contaminants is becoming increasingly popular. Field scale implementation of this and other in situ technologies requires careful design based on the site-specific hydrogeology and contaminant plume characteristics. Groundwater flow modeling is an important tool in understanding the hydraulic behavior of the site and optimizing the reactive barrier design. A combination of groundwater flow modeling and particle tracking techniques was used to illustrate the effect of hydraulic conductivity of the aquifer and reactive media on key permeable barrier design parameters, such as the capture zone width, residence time, flow velocity, and discharge. Similar techniques were used to illustrate the modeling approach for design of different configurations of reactive barriers in homogeneous and heterogeneous settings.
Computer Simulation↗
Characterization of intracellular metabolites of axenic amastigotes of Leishmania donovani by 1H NMR spectroscopy.
The intracellular metabolites of long-term in vitro cultured axenic amastigotes of Leishmania donovani (strain Dd8) were determined and compared with those of promastigotes and intracellular amastigotes, employing proton NMR spectroscopy. The presence of two new metabolites, i.e. betaine and beta-hydroxybutyrate were reported. Betaine was detected in all the three stages being highest in the promastigotes while beta-hydroxybutyrate could be detected only in promastigotes and axenic amastigotes. Among other metabolites, succinate and valine were found in higher quantities in intracellular amastigotes and axenic amastigotes than in promastigotes. Acetoacetate was present only in axenic and intracellular amastigotes. The comparative metabolite profile of different parasite forms reveals that axenic amastigotes seem to represent an intermediate stage between promastigotes and intracellular amastigotes in spite of their strong resemblance to intracellular amastigotes in morphology, infectivity, biochemical studies and even in the manifestation of amastigote specific A2 protein.
3-Hydroxybutyric Acid↗
Construction of a recombinant live oral vaccine from a non-toxigenic strain of Vibrio cholerae O1 serotype inaba biotype E1 Tor and assessment of its reactogenicity and immunogenicity in the rabbit model.
The disease cholera is an important cause of mortality in many developing countries. Though it can be controlled through improved sanitation, this goal is not easily attainable in many countries. Development of an efficacious vaccine offers the best immediate solution. A new oral candidate vaccine has been constructed from a non-toxigenic strain of Vibrio cholerae E1 Tor, Inaba, which is not only devoid of the cholera toxin (CT) virulence cassette but also is completely non-reactogenic in rabbit ileal loop assay. The strain, however, had toxR and tcpA genes. Through a series of manipulations, the ctxB gene of V. cholerae, responsible for the production of the 'B' subunit of the cholera toxin (CTB) was introduced into the cryptic hemolysin locus of the strain. The resulting strain, named vaccine attempt 1.3 (VA1.3), was found to be able to produce copious amounts of CTB. In the RITARD model this strain was found to be non-reactogenic and provided full protection against the challenge doses of both V. cholerae O1, classical and E1 Tor. In the immunized rabbit it invoked significant levels of anti-bacterial and anti-toxin immunity.
Administration, Oral↗
Demonstration of cell-specific phosphorylation of LTC4 synthase.
PMA-induced leukotriene C4 synthase (LTC4S) phosphorylation was investigated over a period of 8 h in a monocytic cell line (THP-1). The level of LTC4S phosphorylation was increased 3-5 fold over a 4 h period decreasing to basal levels after 8 h. This phosphorylation event was found to be specific to THP-1 cells as there was a lack of LTC4S phosphorylation in both COS-7 and K-562 cells, and was also found to be dependent on the cellular confluency. In the presence of specific protein kinase C (PKC) inhibitors, a dose-dependent inhibition of the phosphorylation of LTC4S became evident, an effect not seen with PKA and tyrosine kinase inhibitors. This represents the first direct demonstration of LTC4S phosphorylation in whole cells.
Animals↗
Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene.
A T --> G mutation at position 8993 in human mitochondrial DNA is associated with the syndrome neuropathy, ataxia, and retinitis pigmentosa and with a maternally inherited form of Leigh's syndrome. The mutation substitutes an arginine for a leucine at amino acid position 156 in ATPase 6, a component of the F0 portion of the mitochondrial ATP synthase complex. Fibroblasts harboring high levels of the T8993G mutation have decreased ATP synthesis activity, but do not display any growth defect under standard culture conditions. Combining the notions that cells with respiratory chain defects grow poorly in medium containing galactose as the major carbon source, and that resistance to oligomycin, a mitochondrial inhibitor, is associated with mutations in the ATPase 6 gene in the same transmembrane domain where the T8993G amino acid substitution is located, we created selective culture conditions using galactose and oligomycin that elicited a pathological phenotype in T8993G cells and that allowed for the rapid selection of wild-type over T8993G mutant cells. We then generated cytoplasmic hybrid clones containing heteroplasmic levels of the T8993G mutation, and showed that selection in galactose-oligomycin caused a significant increase in the fraction of wild-type molecules (from 16 to 28%) in these cells.
Adenosine Triphosphatases↗
The SH2 domain-containing inositol 5'-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during FcgammaRIIb1-mediated inhibition of B cell receptor signaling.
Coligation of FcgammaRIIb1 with the B cell receptor (BCR) or FcepsilonRI on mast cells inhibits B cell or mast cell activation. Activity of the inositol phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide 3-kinase (PI3K) product phosphatidylinositol 3,4, 5-trisphosphate (PIP3) into phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation of FcgammaRIIb1 with BCR inhibits PIP3-dependent Btk (Bruton's tyrosine kinase) activation and the Btk-dependent generation of inositol trisphosphate that regulates sustained calcium influx. In this study, we provide evidence that coligation of FcgammaRIIb1 with BCR induces binding of PI3K to SHIP. This interaction is mediated by the binding of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only partially reduced during coligation of BCR with FcgammaRIIb1 despite a drastic reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent calcium signaling, activation of the serine/threonine kinase Akt was partially preserved during BCR and FcgammaRIIb1 coligation. The association of PI3K with SHIP may serve to activate PI3K and to regulate downstream events such as B cell activation-induced apoptosis.
3T3 Cells↗