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Biomedical subjects

A Chakraborty

Publications and source records attributed to A Chakraborty.

At least 73 records · Page 4Linked to original sources
PubMed1998

Vanadium toxicology--an assessment of general health, haematological aspects and energy response in an Indian catfish Clarias batrachus (Linn).

The pervasive occurrence of vanadium in nature and its use in various industrial processes has increased its inputs in the environment. This has prompted us to elucidate the impact of vanadium on aquatic environment, the primary body for industrial effluent discharge. The energy response of the fish, Clarias batrachus, its haematological status including haemoglobin (Hb), haematocrit (Ht), leutocrit (Lt), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) etc. And overall general health conditions have been observed to be significantly hampered leading to deleterious alterations in the general metabolism of the fish following long term exposure to vanadate. The increase in muscle and tissue lactic acid (2-12 fold) in association with decrease in pyruvic acid (72% in muscle; 26% in liver) reflect a shift towards an anaerobic metabolism of the fish. We conclude that vanadium could be toxic for the fish in question under long term exposure at the doses under observation (2-10 mg L-1).

Anaerobiosis↗
PubMed1998

Pharmacokinetics and leukocyte responses of recombinant human interleukin-10.

PURPOSE: To study the pharmacokinetics and ex vivo leukocyte responses of recombinant human IL-10 (rHuIL-10) following single s.c. and i.v. dosing. METHODS: A randomized two-way cross-over study was undertaken in 17 healthy volunteers in which rHuIL-10 was administered as 25 microg/kg s.c. and i.v. doses. Blood samples were collected for 48 hr after dosing to determine serum IL-10 concentrations. Inhibitory activity of IL-10 on ex vivo production of inflammatory cytokines (TNF-alpha and IL-1beta) by LPS-treated peripheral blood cells were measured over 96 hr. RESULTS: A physiologically-relevant modeling approach was developed to determine the pharmacokinetics for two routes of administration (s.c. and i.v.). The i.v. dose showed polyexponential disposition with CL of 65 mL/kg/hr, Vss of 70 mL/kg, and t1/2 of 1.94 hr. Absolute bioavailability averaged 42% for s.c. dosing which produced lower but sustained concentrations. Substantial and prolonged suppression of TNF-alpha and IL-1beta production was achieved during IL-10 treatment. The Hill Function was used to account for the joint concentration-dependent immunosuppressive action of rHuIL-10 after both i.v. and s.c. doses. The IC50 values were about 0.03 ng/ml and Imax values were about 0.85 for both TNF-alpha and IL-1beta suppression. The degree of change as well as the duration of leukocyte response was greater after s.c. administration than after i.v. administration. CONCLUSION: rHuIL-10 shows favorable PKPD characteristics especially by the s.c. route of administration which produced prolonged suppression of cytokine production (ex vivo) which may be applicable in various immune-related disorders.

Cross-Over Studies↗
PubMed1998

Stat3 and G-CSF-induced myeloid differentiation.

Granulocyte colony-stimulating factor (G-CSF) is the cytokine critical for directing neutrophilic granulocyte differentiation. Early G-CSF signaling events in myeloid cells involves activation of STATs, proteins that serve the dual function of signal transduction and activation of transcription, especially the activation of Stat3. A dominant-negative mutant construct of Stat3 inhibited G-CSF-mediated neutrophilic differentiation indicating that Stat3 is a essential component for driving the G-CSF-mediated differentiation program in myeloid cells. Three isoforms of Stat3 have been identified, alpha(p92), beta(p83) and gamma(p72) each derived from a single gene. Stat3alpha is the predominant isoform expressed in most cells. Stat3beta is derived from Stat3alpha by alternative RNA splicing. Stat3gamma is derived from Stat3alpha by limited proteolysis. Mapping of Stat3alpha and Stat3beta activation in M1 murine myeloid leukemia cells revealed that their optimal activation required G-CSFR constructs containing both Y704 and Y744. These amino acid residues has previously been demonstrated to be essential for G-CSF-induced differentiation in this cells. Phosphopeptide affinity and phosphopeptide inhibition studies indicate that Stat3alpha and Stat3beta are recruited to the G-CSF receptor complex through their interaction with the receptor at phosphotyrosines Y704 and Y744. Y744 is followed at the +3 position by Cys (C). This sequence YXXC, represents a novel motif implicated in the recruitment and activation of Stat3alpha, Stat3beta and Stat3gamma by the hG-CSFR. Structurally, Stat3alpha, Stat3beta and Stat3gamma differ from each other in their C-terminal transactivation domain. In the beta isoform, the Stat3alpha transactivation domain is replaced by 7 amino acid residues which enable Stat3beta to interact with c-Jun. In the gamma isoform, the Stat3alpha transactivation domain is removed by limited proteolysis creating a dominant negative isoform. In immature human myeloid cells capable of differentiating into neutrophils in response to G-CSF, G-CSF did not activate Stat3alpha; rather. it activated predominantly Stat3beta. These findings combined with recent reports linking Stat3alpha with proliferation and transformation suggest that the beta isoform of Stat3 may be more critical for G-CSF-mediated differentiation. Activation of Stat3gamma occurred predominantly in terminally differentiated neutrophils suggesting that it may be part of a controlled proteolytic mechanism modulating pro-proliferative protein(s) in mature myeloid cells.

Bone Marrow Cells↗
PubMed1998

Primary cutaneous cryptococcosis in an immune competent patient.

A 50-year-old female developed a swelling in the epigastrium which later ruptured to form a sinus. A diagnosis of primary cutaneous cryptococcosis was made with the help of histopathology and microbiological studies. Treatment with amphotericin-B and 5-flucytosine gave a good therapeutic response and the sinus healed within 2 months.

Antifungal Agents↗
PubMed1997

Reactivation of denatured proteins by domain V of bacterial 23S rRNA.

In vitro transcripts containing domain V of the 23S rRNA of Escherichia coli and Bacillus subtilis can reactivate denatured proteins almost as efficiently as the total 23S rRNA. Here we show that almost the full length of domain V is required for reactivation of denatured pig muscle lactate dehydrogenase and pig heart cytoplasmic malate dehydrogenase: the central loop of this domain alone is not enough for this purpose. The antibiotic chloramphenicol, which binds to domain V of 23S rRNA, can inhibit reactivation of these proteins completely. Activity is eliminated by EDTA at a concentration of <1 mM, even in the presence of 4 mM MgCl2, suggesting that the three-dimensional conformation of the RNA should be maintained for this activity.

Animals↗
PubMed1997

Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells.

Previous reports have shown that fresh tissues and cell lines from patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress transforming growth factor alpha (TGF-alpha) and its receptor, the epidermal growth factor receptor (EGFR) at both the mRNA and protein levels. Protein localization studies confirm that TGF-alpha and EGFR are produced by the same epithelial cells in tissues from head and neck cancer patients further supporting an autocrine growth pathway. Using three strategies, we examined the hypothesis that downmodulation of EGFR would reduce the proliferation of SCCHN cells. We targeted EGFR mRNA using antisense oligonucleotides and the mature EGFR protein at two sites, the ligand-binding domain and the kinase domain, and determined the effects of this targeting on SCCHN proliferation. Treatment of several SCCHN cell lines with a pair of antisense oligodeoxynucleotides directed against the translation start site and first intron-exon splice junction of the human EGFR gene resulted in decreased EGFR protein production and inhibited growth by 86% compared to a 13% reduction in cells treated with sense oligonucleotides (P=0.03). Growth inhibition was specific for carcinoma cells since the same EGFR antisense oligonucleotides had no effect on the proliferation of normal mucosa cells harvested from non-cancer patients. Two monoclonal antibodies which block ligand binding to EGFR (MAbs 425 and 528) inhibited the growth of several SCCHN cell lines by up to 97% which suggests that EGFR is participating in an autocrine pathway in SCCHN that is, at least in part, external. An EGFR-specific tyrosine kinase inhibitor (PD 153035) was found to inhibit EGFR phosphorylation in SCCHN cell lines and to reduce growth by 68% although it had no effect on the growth rate of normal mucosal epithelial cells. These experiments indicate that EGFR gene expression and function is critical for SCCHN cell growth but not for growth of normal mucosa cells and therefore may serve as a tumor-specific target for preventive and therapeutic strategies in head and neck cancer.

Aged↗
PubMed1997

Viral infection. II. Hemin induces overexpression of p67 as it partially prevents appearance of an active p67-deglycosylase in baculovirus-infected insect cells.

The roles of p67-deglycosylase (p67-DG) in the regulation of protein synthesis in baculovirus-infected insect cells were studied. Like vaccinia viral infection, baculovirus infection of insect cells also induced the appearance of a p67-DG. However, p67-DG activity could not be detected because these cells do not contain a detectable level of p67. The baculovirus expression vector system (BEVS), however, promotes significant expression of cloned p67-cDNA. The expression of p67 was significantly enhanced by the addition of hemin to the growth medium. Maximum enhancement was observed at 5 microM hemin. Data suggest that hemin prevents the activation of latent p67-DG inside the cell and does not have any effect on p67 gene transcription. To gain a better understanding of the mechanism of p67-DG activation and hemin stimulation of p67 synthesis, we have now purified p67-DG from baculovirus-infected insect cells. We prepared antibodies against this protein. These antibodies reacted with a 105-kDa protein in cell extracts from the uninfected insect cells (Sf9), KRC-7, and L929 (animal cells). In addition, these antibodies reacted with an additional 60-kDa protein in the cell extracts of baculovirus-infected Sf9 cells and vaccinia virus-infected KRC-7 and L929 cells. Data are also presented to show that the antibodies against p67-DG reacted more efficiently (40%) with the 60-kDa protein in both hemin-deficient reticulocyte lysate and hemin-deficient baculovirus-infected cells. We suggest that hemin prevents the conversion of an inactive p67-DG into an active form possibly by covalent modification such as protein phosphorylation or protein glycosylation. The active form is more efficiently recognized by the p67-DG antibodies since these antibodies were prepared against the active form of p67-DG.

Acetylglucosaminidase↗
PubMed1996

Granulocyte colony-stimulating factor activation of Stat3 alpha and Stat3 beta in immature normal and leukemic human myeloid cells.

Granulocyte colony-stimulating factor (G-CSF) is the cytokine critical for directing neutrophilic granulocyte differentiation. Acute myelogenous leukemia (AML) cells, which frequently arise from this lineage, respond aberrantly to G-CSF by proliferating without differentiating. The basis for this abnormal responses is unknown. In the present study, we investigated whether G-CSF signaling in immature normal and leukemic human myeloid cells diverges at the level of activation of signal transducers and activators of transcription (STAT) proteins. We compared the profile of STAT proteins activated in G-CSF-stimulated immature normal and leukemic human myeloid cells. G-CSF activated Stat3 alpha in all AML cell lines examined except HL60 and in three of six uncultured AML patient samples. In normal human CD34+ bone marrow cells and HL60 cells, both reported to differentiate in response to G-CSF, G-CSF did not activate Stat3 alpha; rather, it activated only an 83 kD form of Stat3 that proved to be the human homologue of a short form of Stat3, Stat3 beta. Because the transcriptional activity of Stat3 beta is distinct from Stat3 alpha, these results suggest that the balance of the two Stat3 isoforms in myeloid cells may influence the cellular pattern of gene activation and consequently the ability of these cells to differentiate in response to G-CSF.

Acute Disease↗
PubMed1996

Prolactin response of NK cells, but not of LAK cells, is deficient in patients with carcinoma of oral cavity and during aging.

The regulatory role of prolactin (Prl) on peripheral blood natural killer (NK) and lymphokine-activated killer (LAK) cell activities was studied in young (mean age, 40 years) and elderly (mean age, 68 years) healthy men and patients with carcinoma of the oral cavity (oral cancer). The peripheral blood NK cells, but not the LAK cells, were found to be depressed in oral cancer patients compared with age-matched healthy men. However, age-associated deficiency in both NK and LAK cell activity was observed in healthy men and cancer patients. Prl produced dose-dependent inhibition (1, 10, 100 or 250 ng/ml) or stimulation (25-50 ng/ml) of resting NK cells in young groups of healthy men and cancer patients. In elderly groups less or no response of the NK cells to low doses of Prl (1-10 ng/ml) was evident. The NK cells of young and elderly healthy men were stimulated by human recombinant Interleukin-2 (rIL-2) (100 U/ml), and Prl (1-25O ng/ml) inhibited these cells. In oral cancer patients an altered response to low doses of Prl (1-5O ng/ ml) was observed in IL-2-stimulated NK cells, which also revealed malignancy- associated loss of IL-2 response. In contrast, there was no malignancy or age-associated change in Prl response of the LAK cells. Treatment of peripheral blood lymphocytes of both healthy men and oral cancer patients for 5 days with Prl (50 ng/ml) in the ++presence of low concentration of serum generated LAK cells.

Adult↗
PubMed1996

Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a model for studying the melanocyte response to and recovery from cytotoxic drug damage in situ.

Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to postdihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.

Animals↗
PubMed1996

Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague--Dawley rats.

The vitamin D-endocrine system has mostly been studied for its role in calcium and phosphorus metabolism and its possible role as an antioxidant has been neglected. This study attempts to elucidate the antioxidative properties of the prohormone with respect to vitamin E, a membrane antioxidant. Results herein show that D3 treatment brought about similar reduction in the extent of lipid peroxidation and induction in superoxide dismutase (SOD) activity, as with vitamin E supplementation. While selenium dependent glutathione peroxidase (Sedep. GPx) activity reflected no change with vitamin D3 treatment, total GPx activity was more significantly influenced by vitamin D3 than by vitamin E. The glutathione (GSH) content in the experimental rats also reflected similar changes. Vitamin E supplementation caused 8.57% increase in glutathione reductase (GR) activity, while vitamin D3 decreased the concerned enzymes activity by 11.11%. Vitamin D3 treatment also caused 25% increase in glucose 6-phosphate dehydrogenase (G6PD) activity. These data thus suggest that vitamin D3 may function as an antioxidant in the liver in vivo and illustrate an effectiveness higher than that observed with vitamin E supplementation.

Animals↗
PubMed1995

Granulocyte colony-stimulating factor rapidly activates a distinct STAT-like protein in normal myeloid cells.

Binding of granulocyte colony-stimulating factor (G-CSF) to normal myeloid cells activates the protein tyrosine kinases Lyn and Syk and results in the immediate early upregulation of G-CSF receptor (R) mRNA. In our studies of the signaling pathways activated by G-CSF that are coupled to proliferation and differentiation of myeloid cells, we examined whether G-CSF activated a latent transcription factor belonging to the STAT protein family. Electrophoretic mobility shift assays (EMSAs) of nuclear extracts from G-CSF-stimulated human myeloid cells showed the rapid activation of a DNA-binding protein that bound to the high-affinity serum-inducible element (hSIE) and migrated with mobility similar to serum inducible factor (SIF)-A (Stat3 homodimer). The G-CSF-stimulated SIF-A complex (G-SIF-A) did not bind to duplex oligonucleotides used to purify and characterize other Stat proteins (Stat1-6). In addition, antibodies raised against Stat1-6 failed to supershift the G-SIF-A complex or interfere with its formation. Based on its binding to the hSIE and lack of antigenic cross-reactivity with other known STAT proteins that bind to this element, it is likely that G-SIF-A is composed of a distinct member of the STAT protein family. EMSAs of whole-cell extracts prepared from cell lines containing full-length and truncated mutants of the G-CSFR showed that activation of G-SIF-A did not correlate with proliferation; rather, optimal activation requires the distal half of the cytosolic domain of the G-CSFR that is essential for differentiation. Activation of G-SIF-A, therefore, may be an early G-CSFR-coupled event that is critical for myeloid maturation.

B-Lymphocytes↗
PubMed1995

Proopiomelanocortin, corticotropin releasing hormone and corticotropin releasing hormone receptor genes are expressed in human skin.

Evidence is provided that human skin, the largest body organ exposed to multiple stressors, expresses proopiomelanocortin (POMC), corticotropin releasing hormone (CRH) and CRH-receptor (CRHR) genes in vivo. In vitro studies show that POMC and CRHR mRNAs are transcribed in melanocytes, cells derived from the neural crest, and in keratinocytes, cells derived from the ectoderm. CRH mRNA is transcribed in cultured melanocytes but not in keratinocytes. It is proposed that an equivalent of the 'hypothalamus-pituitary axis' composed of the CRH-CRHR-POMC loop is conserved in mammalian skin.

Base Sequence↗
PubMed1995

Carbazole alkaloid with antimicrobial activity from Clausena heptaphylla.

A new carbazole alkaloid designated as clausenal was isolated from the leaves of Clausena heptaphylla and its structure established as 1,8-dimethoxy-3-formylcarbazole from physical, chemical and synthetic evidence. The alkaloid was found to be active against both Gram-positive and Gram-negative bacteria, and fungi.

Alkaloids↗
PubMed1995

Clausenol and clausenine--two carbazole alkaloids from Clausena anisata.

Two new carbazole alkaloids, designated as clausenol and clausenine, were isolated from an alcoholic extract of the stem bark of Clausena anisata. Their structures were established as 1-hydroxy-6-methoxy-3-methylcarbazole and 1,6-dimethoxy-3-methyl carbazole, respectively, from physical and chemical evidence and synthesis. Clausenol was found to be active against Gram-positive and Gram-negative bacteria and fungi.

Anti-Bacterial Agents↗
PubMed1995

Direct detection and characterization of rotavirus into subgroups by dot blot hybridization and correlation with 'long' and 'short' electropherotypes.

BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) and polyacrylamide gel electrophoresis (PAGE) of viral RNA are well-established methods for detection of rotavirus in stool samples. Dot-blot hybridization has also been found to be a sensitive and specific technique for detection and characterization of rotaviruses. OBJECTIVES: To compare the performance of dot blot hybridization with ELISA and PAGE for detection of rotavirus in stool samples. To assess the use of dot blot hybridization for characterization of rotaviruses into subgroups. STUDY DESIGN: Stool samples were collected from 214 children presenting to the hospital with acute diarrhoea. These were assayed for rotavirus by ELISA and PAGE. Dot-blot hybridization was done with full length cloned radiolabelled c-DNA probes of gene segment 6 of SA-11 (subgroup I) and Wa (subgroup II) rotaviruses. RESULTS: Out of 214 stool samples 134 were found to be positive for rotavirus by one of the three methods. Among these 134 positive specimens 114 were positive by dot blot hybridization, this included 18 specimens which were positive only by dot blot assay. One-hundred-and-twelve of these 114 specimens could be subgrouped. Fifteen of these were classified as subgroup I, 97 as subgroup II and two had a dual subgroup specificity. Three subgroup 1 strains had a 'long' RNA pattern, whereas one subgroup II strain had a 'short' RNA pattern which has not been reported earlier for human rotaviruses. CONCLUSION: Dot blot hybridization as described here is a sensitive and specific assay for detection and subgrouping of rotaviruses. However, as there is a considerable genomic diversity among rotaviruses, the panel should include probes from all the genotypes of gene segment 6.

Journal Article↗