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Biomedical subjects

T Chandra

Publications and source records attributed to T Chandra.

At least 19 recordsLinked to original sources
PubMed2005

Molecular interactions of the type 1 human immunodeficiency virus transregulatory protein Tat with N-methyl-d-aspartate receptor subunits.

We investigated the effect of type 1 human immunodeficiency virus (HIV-1) regulatory protein Tat on N-methyl-d-aspartate (NMDA) receptors expressed in Xenopus oocytes by voltage-clamp recording and its role in NMDA-mediated neurotoxicity using cultured rat hippocampal neurons. Tat (0.01-1muM) potentiated NMDA-induced currents of recombinant NMDA receptors. However, in the presence of Zn(2+), the potentiating effect of Tat was much more pronounced, indicating an additional Zn(2+)-related effect on NMDA receptors. Consistently, Tat potentiated currents of the particularly Zn(2+)-sensitive NR1/NR2A NMDA receptor with a higher efficacy, whereas currents from a Zn(2+)-insensitive mutant were only marginally augmented. In addition, chemical-modified Tat, deficient for metal binding, did not reverse Zn(2+)-mediated inhibition of NMDA responses, demonstrating that Tat disinhibits NMDA receptors from Zn(2+)-mediated antagonism by complexing the cation. We therefore investigated the interplay of Tat and Zn(2+) in NMDA-mediated neurotoxicity using cultures of rat hippocampal neurons. Zn(2+) exhibited a prominent rescuing effect when added together with the excitotoxicant NMDA, which could be reverted by the Zn(2+)-chelator tricine. Similar to tricine, Tat enhanced NMDA-mediated neurotoxicity in the presence of neuroprotective Zn(2+) concentrations. Double-staining with antibodies against Tat and the NR1 subunit of the NMDA receptor revealed partial colocalization of the immunoreactivities in membrane patches of hippocampal neurons, supporting the idea of a direct interplay between Tat and glutamatergic transmission. We therefore propose that release of Zn(2+)-mediated inhibition of NMDA receptors by HIV-1 Tat contributes to the neurotoxic effect of glutamate and may participate in the pathogenesis of AIDS-associated dementia.

Animals↗
PubMed2003

MRI features of tuberculosis of peripheral joints.

The aim of this article is to present the magnetic resonance imaging (MRI) features of peripheral tubercular arthritis. The clinical presentation of peripheral tubercular arthritis is variable and simulates other chronic inflammatory arthritic disorders. MRI is a highly sensitive technique which demonstrates fine anatomical details and identifies the early changes of arthritis, which are not visible on radiographs. The MRI features of tubercular arthritis include synovitis, effusion, central and peripheral erosions, active and chronic pannus, abscess, bone chips and hypo-intense synovium. These imaging features in an appropriate clinical setting may help in the diagnosis of tubercular arthritis. Early diagnosis and treatment can effectively eliminate the long-term morbidity of joints affected by tuberculosis.

Abscess↗
PubMed2002

Inhibition of collagen glycation and crosslinking in vitro by methanolic extracts of Finger millet (Eleusine coracana) and Kodo millet (Paspalum scrobiculatum).

The present investigation was carried out to study the effects of methanolic extracts of Finger millet (Eleusine coracana) and Kodo millet (Paspalum scrobiculatum) on glycation and crosslinking of collagen. Tail tendons obtained from rats weighing 200-225 g were incubated with glucose (50 mM) and 3 mg of extracts of the above millets in methanol under physiological conditions of temperature and pH for 10 days. Early glycation was estimated by phenol-sulfuric acid method and the crosslinking was assessed by pepsin digestion, cyanogen bromide peptide map and viscosity measurements. Tendon collagen incubated with glucose (50 mM) showed 65% solubility on pepsin treatment; poor resolution of bands in the cyanogen bromide peptide map, and intrinsic viscosity of 0.84 dl/g. The collagen incubated with Finger millet and Kodo millet extracts inhibited glycation; 89% and 92% solubility in pepsin; good resolution of bands in the cyanogen bromide peptide map and intrinsic viscosity of 0.46 and 0.58 dl/g respectively. The study implicates the potential usefulness of the above millets in protection against glycation and crosslinking of collagen.

Journal Article↗
PubMed2002

Giant-cell tumors of the patella.

This study describes the clinical, radiographic, and histopathologic features, and discusses the management options of 11 cases of benign giant-cell tumors of the patella seen over 20 years. Fine needle aspiration cytology was a useful preoperative diagnostic tool. Ptellectomy and reconstruction of the extensor apparatus is the favored treatment option with curettage and bone grafting restricted to selected localized lesions.

Adolescent↗
PubMed2001

Macrocyclic metalloenediynes of Cu(II) and Zn(II): a thermal reactivity comparison.

The syntheses of tetradentate enediyne macrocycles with 24 (tact1:1)-, 26 (tact1:2)-, and 28 (tact2:2)-membered rings are described, along with their thermal reactivities and those of the corresponding Cu(II) (Cu(tact1:1), Cu(tact1:2)) and Zn(II) (Zn(tact1:1), Zn(tact1:2)) complexes. These enediyne macrocyclic ligands are not benzannulated and thus exhibit thermal Bergman cyclization temperatures near 200 degrees C by differential scanning calorimetry (DSC). Moreover, the synthetic route allows incorporation of additional carbon atoms into the macrocycles which increases their conformational flexibilities and lowers their Bergman cyclization temperatures. Specifically, as the size of the macrocycle increases, the temperatures at which these compounds undergo Bergman cyclization decrease by approximately 5 degrees C per additional carbon atom, leading to an overall decrease across the series of 19 degrees C. Incorporation of Cu(II) and Zn(II) into these macrocycles further reduces their cyclization temperatures relative to those of the free ligands. More uniquely, for Cu(tact1:1) and Zn(tact1:1), the observed cyclization temperatures vary by 27 degrees C with the Zn(II) complex lying to higher temperature (Cu(tact1:1) = 121 degrees C, (Zn(tact1:1) = 148 degrees C). As the macrocycle size is increased, the decrease in the Bergman cyclization temperatures observed for the free ligands does not systematically hold for the Cu(II) and Zn(II) derivatives. Rather, the Cu(II) complex exhibits the expected 9 degrees C decrease in the cyclization temperature (Cu(tact1:2) = 112 degrees C), whereas the temperature for the Zn(II) analogue increases by 15 degrees C (Zn(tact1:2) = 163 degrees C). From the X-ray crystal structure of the free ligand and the geometric structural preferences of the electronic configurations of Cu(II) and Zn(II), the higher cyclization temperatures for the Zn(II) complex with the larger ring size can be explained by a distortion of the macrocycle toward a more tetrahedral metal center geometry.

Chemical Phenomena↗
PubMed2001

HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program.

HES6 is a novel member of the family of basic helix-loop-helix mammalian homologues of Drosophila Hairy and Enhancer of split. We have analyzed the biochemical and functional roles of HES6 in myoblasts. HES6 interacted with the corepressor transducin-like Enhancer of split 1 in yeast and mammalian cells through its WRPW COOH-terminal motif. HES6 repressed transcription from an N box-containing template and also when tethered to DNA through the GAL4 DNA binding domain. On N box-containing promoters, HES6 cooperated with HES1 to achieve maximal repression. An HES6-VP16 activation domain fusion protein activated the N box-containing reporter, confirming that HES6 bound the N box in muscle cells. The expression of HES6 was induced when myoblasts fused to become differentiated myotubes. Constitutive expression of HES6 in myoblasts inhibited expression of MyoR, a repressor of myogenesis, and induced differentiation, as evidenced by fusion into myotubes and expression of the muscle marker myosin heavy chain. Reciprocally, blocking endogenous HES6 function by using a WRPW-deleted dominant negative HES6 mutant led to increased expression of MyoR and completely blocked the muscle development program. Our results show that HES6 is an important regulator of myogenesis and suggest that MyoR is a target for HES6-dependent transcriptional repression.

Active Transport, Cell Nucleus↗
PubMed2001

Bronchial, alveolar, and vascular-induced anaphylaxis and irritant-induced cardiovascular and pulmonary responses.

We examine the respiratory, bronchomotor, cardiac, and vascular responses to histamine and ragweed allergen delivered to the bronchi or alveoli compartments and the potential role of sensory nerves and reflexes mediating the histamine-induced responses. The masses of aerosols deposited in the bronchi and alveoli were quantitated using radioaerosol techniques. Activation of sensory nerves and/or histamine-induced mediator release were characterized by depositing nedocromil sodium aerosol prior to histamine challenge. The histamine-induced responses due to vagosympathetic transmission were determined by performing bilateral vagotomy. Both histamine and ragweed increased respiratory rate, ventilation, and bronchomotor tone whether deposited in the bronchial or alveolar regions. However, these responses were not elicited when histamine was administered intravenously. Precipitous allergen-induced decreases in heart rate and systolic and diastolic pressure were maximal 72 sec following ragweed deposition in alveolar regions of the lungs. Increases in respiratory rate were mediated via the vagus whether delivered to the bronchi, alveoli, or vasculature. Histamine-induced increases in respiratory rate and bronchomotor tone were attenuated by nedocromil. When histamine was delivered to the alveolar regions, increases in lung resistance appeared to be mediated primarily via the vagus and when delivered to the bronchial airways primarily by its action on smooth muscle or local reflexes. Histamine-induced hypotension and bradycardia appear to be mediated by the direct action of histamine on the cardiovascular system rather than through a vagally mediated reflex.

Allergens↗
PubMed2001

Immunohistochemical localization of transferrin in human breast cancer tissue.

The present study was planned to detect the iron binding protein, transferrin (TR) in paraffin sections of the human breast tumors. The distribution of transferrin has been studied in 153 cases (63 benign lesions and 90 malignant tumors). The extent of staining reaction was determined by semiquantitative grading (weak, moderate and consistent). Positivity rate for transferrin was higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%) with significant p value (P = .0001) for both the groups. The intensity was variable in both the groups, being more intense in the malignant tumors. Tumors with higher grade of malignancy presented consistent positive staining along with the lymph nodes involved. The extent of immunoreactivity revealed a significant positive correlation with axillary lymph node status. However, no significant correlation was found with the age of the patients. Thus the study of transferrin in breast tumors besides being of prognostic significance helps in the further management of malignant lesions of the breast.

Biomarkers, Tumor↗
PubMed2000

Disappearance of intramolecular stacking due to one-atom movement or increment of a 'propylene linker' in pyrazolo[3,4-d]pyrimidine-based flexible models.

In the crystal structures of 4,6-dimethylthio-1-[3-(4, 6-dimethylthio-2H-pyrazolo[3, 4-d]pyrimidin-2-yl)propyl]-1H-pyrazolo[3,4-d]pyrimidine, C(17)H(20)N(8)S(4), and 1-[4-(4-methoxy-6-methylthio-1H-pyrazolo[3, 4-d]pyrimidin-1-yl)butyl]-5-methyl-6-methylthio-4, 5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one, C(18)H(22)N(8)O(2)S(2), only intermolecular stacking due to aromatic pi-pi interactions between pyrazolo[3,4-d]pyrimidinerings is present.

Journal Article↗
PubMed2000

Immunohistochemical localization of transferrin in human breast cancer tissue.

The present study was planned to detect the iron binding protein, transferrin (TR) in paraffin sections of the human breast tumors. The distribution of transferrin has been studied in 153 cases (63 benign lesions and 90 malignant tumors). The extent of staining reaction was determined by semiquantitative grading (weak, moderate and consistent). Positivity rate for transferrin was higher (92.2%) in malignant tumors as compared to benign breast lesions (28.5%) with significant p value (p = 0.0001) for both the groups. The intensity was variable in both the groups, being more intense in the malignant tumors. Tumors with higher grade of malignancy presented consistent positive staining along with the lymph nodes involved. The extent of immunoreactivity revealed a significant positive correlation with axillary lymph node status. However, no significant correlation was found with the age of the patients. Thus the study of transferrin in breast tumors besides being of prognostic significance helps in the further management of malignant lesions of the breast.

Breast↗
PubMed1998

Cytopathology and AgNOR counts in fine-needle aspiration cytology smears of thyroid lesions.

The object of the present work is to study the cytomorphological features and the value of silver colloidal staining method in distinguishing the non-neoplastic, benign, and malignant neoplasm in fine-needle aspiration cytology (FNAC) smears of thyroid nodules. One hundred forty histologically confirmed aspirated samples of thyroid lesions were studied and classified cytologically. These smears were stained for AgNOR counts. The number and location of AgNOR dots as well as clusters in nuclei were studied by two different observers independently. Lower AgNOR counts were recorded in cases of thyroiditis (1.375 +/- 0.414), whereas follicular carcinoma had a higher number of AgNOR counts (5.04 +/- 0.52). The clusters of AgNOR dots were centrally located in colloid goitre, but no cluster arrangement was observed in cases of carcinomas. Increased nuclear size, nucleoli, and chromocentres were helpful in the diagnosis of follicular carcinoma. AgNOR counting cannot be reliably used on an individual case basis to differentiate adenoma from carcinoma. Therefore, AgNOR study in thyroid lesions can be used as an additional diagnostic method with cytomorphological features to differentiate benign and malignant follicular neoplasms.

Adenoma↗
PubMed1998

Statistical significance of AgNOR counts in FNAC smears and corresponding histopathological sections.

The object of the present study was to determine the statistical significance of AgNOR counts in fine needle aspiration cytology (FNAC) smears and corresponding paraffin sections by using an one step silver colloidal staining method. Ninety five cases (31 benign and 64 malignant) were taken and a correlation between smears and sections was studied by two different observers. The total number of mean (SD) AgNOR counts was significantly higher in FNAC smears in benign (3.081 +/- .753) and malignant (7.101 +/- 1.544) neoplasms in comparison to paraffin sections in the same group of cases. FNAC smears had a cut off point 4 with proliferation index 1% in benign tumors and 97.5% in malignant tumors. Sections had an overlapping of AgNOR counts (5-7) with proliferation index 3.8 and 82% for benign and malignant groups respectively. The difference in the coefficient of variations was 3% in benign group and 2% in malignant group in FNAC smears while sections had 6 and 8% difference in the coefficient of variations. Smears present a superior staining and accurate number of AgNOR dots in nucleus as compared to paraffin sections. Therefore the results suggest that AgNOR technique can be successfully used in FNAC smears in comparison to paraffin sections to differentiate benign and malignant tumors in routine laboratory diagnosis.

Biopsy, Needle↗
PubMed1995

Diagnostic relevance of silver stained nucleolar organizer region (AgNORs) in benign and malignant breast lesions.

The present study is planned to assess the diagnostic relevance of silver stained nucleolar organizer regions (NORs) in discriminating benign from malignant lesions of the breast and to ascertain the interobserver variability in the enumeration of AgNOR counts. Forty four specimens of benign and malignant breast tissues were studied and mean number of silver stained nucleolar organizer regions (MNORA) have been counted in paraffin sections. Malignant lesions have a higher number of MNORA than benign lesions. These results also showed correlation between the AgNOR counts and size of the tumor, axillary lymph node status and age of the patient. Our results also indicate a close agreement between the two observers with limits of agreement. However, AgNOR counts are of little diagnostic importance since a broad zone of overlap exists between benign and malignant breast diseases despite significant higher mean counts in malignant lesions. AgNOR sequence could perhaps be of use to differentiate those two histological indistinguishable lesions. The tumor size and axillary lymph node involvement suggested to its prognostic significance also. Interobserver agreement further suggests the utility of AgNOR counts as diagnostic or prognostic discriminants in breast malignancies.

Breast Diseases↗
PubMed1995

Antiallergic activity of alkyl substituted pyrazolo[3, 4-d]pyrimidine (compound 88-765).

Compound 88-765 (4-amino-6-methylthio-1-(2', 2'-diethoxyethyl)-1 H-pyrazolo[3, 4-d]pyrimidine) has shown potent antiallergic activity in experimental models. The compound inhibited the passive cutaneous anaphylaxis (PCA) reaction in rats in dose-dependent manner (5-100 mg/kg, po) by 47 to 87%. In mice it inhibited PCA by 78% at 50 mg/kg, po. It also inhibited mast cell degranulation of normal and passively sensitised rats induced by compound 48/80 and egg albumin, respectively. These effects of Compound 88-765 were comparable with that of disodium cromoglycate (DSCG). The results suggest that compound 88-765 possesses potent antiallergic activity.

Animals↗
PubMed1994

Stationary and nonstationary correlation-frequency analysis of heterodyne mode laser light scattering: magnitude and periodicity of canine tracheal ciliary beat frequency in vivo.

Stationary and nonstationary correlation-frequency analysis of heterodyne laser light scattering were utilized to make automated, on-line, objective measurements of tracheal ciliary beat frequency (CBF) in intact, anesthetized canines. The stationary correlation-frequency analysis laser light-scattering technique was used to assess the magnitude of the CBF stimulatory responses induced by aerosolized 10(-5) M fenoterol (sympathomimetic), and 10(-8) M and 10(-6) M methacholine (parasympathomimetic) delivered to the whole lungs of eight barbiturate-anesthetized beagles. The nonstationary correlation-frequency analysis laser light-scattering technique was used to measure the effect on tracheal CBF of increasing the cytosolic calcium ion concentration with a calcium ionophore, A23187. Aerosolized A23187 was delivered to the isolated tracheal lumens of eight beagle dogs in cumulative doses ranging from 10(-9)M to 10(-6) M. Administration of the ionophore synchronized the CBF with a period of 5.3 min. Dose dependencies were observed in both the time to the peak CBF stimulation and the magnitude of the stimulatory response. The magnitude of CBF stimulation was inhibited by prior administration of aerosolized nifedipine (2 mg/ml), a voltage-operated calcium channel blocker. The A23187-induced modulation period of tracheal CBF, was unchanged by nifedipine. These are the first data to demonstrate that the magnitude and periodicity of CBF are two independent coupled processes. The cooperativity of these two processes could be determined in the effectiveness of mucociliary transport.

Algorithms↗
PubMed1992

A pore transport model for pulmonary alveolar epithelium.

Hydrodynamic heteropore flow models for transport of solutes across alveolar epithelial tissue have been developed. A two-size cylindrical pore model and a similar parallel-plate model were formulated, tested and used to predict effective pore sizes from literature data on transport in bullfrog, canine and rat lungs. The best fit equivalent pore-size estimates were obtained using a modified, nonlinear least squares procedure, with alveolar surface area to volume ratio (S/V) and small-pore area fraction of total pore area as parameters. Small-pore and large-pore width estimates of 4 nm (84% of total flow area) and 10 nm, respectively, with an average deviation of 20% from experimentally derived permeabilities were obtained from the bullfrog alveolar epithelium parallel-plate pore model (13 solutes, diameters 0.3 to 2.8 nm). The equivalent cylindrical pore model diameter estimates were 5 nm and 10 nm, with small-pore area fraction and percentage deviations similar to the parallel-plate model estimates. Eighty-eight percent of the bulk water driven by a sucrose osmotic gradient was predicted to be transported through the small pores. The rat alveolus parallel-plate pore model (6 solutes) yielded small-pore and large-pore widths of 0.4 nm and 50 nm, respectively. Clearance rate-constant data for dextran macromolecules (3,000 to 250,000 Daltons), using a single parallel-plate pore model, resulted in a pore width estimate of 98 nm for canine alveoli with an average deviation of the predicted rate constants of 18% from literature experimental values. In all cases tested, the parallel-plate pore model predicted lower small-pore size estimates than did the cylindrical pore model, and both models had appreciably smaller percentage deviations from experimental data than previous models.

Animals↗