Biomedical subjects

S Chakravarty

Publications and source records attributed to S Chakravarty.

At least 19 recordsLinked to original sources

PubMed2006

Electrically injected quantum-dot photonic crystal microcavity light sources.

The design, fabrication, and characterization of an electrically injected quantum-dot photonic crystal microcavity light source are described. The optical gain in the GaAs/AlGaAs-based device is provided by self-organized InGaAs quantum dots with ground-state room-temperature emission at 1.1 microm. The carriers are injected directly into the photonic crystal microcavity, which contains approximately 50 dots, avoiding surface state recombination in the photonic crystal pattern. The spectral characteristics of a single-defect photonic crystal microcavity show a single 2 nm broad microcavity resonance. The output power is of the order of a few tens of nanowatts.

Journal Article↗

PubMed2006

Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo.

Inhibition of p38 kinase blocks the production of tumor-promoting factors in the multiple myeloma (MM) bone marrow microenvironment. Proteasome inhibitors MG132 and bortezomib have been shown to have direct cytotoxic effects on MM cells. We show that a selective inhibitor of p38alpha, SCIO-469, enhances the ability of MG132 and bortezomib to induce the apoptosis of MM cells. Previously, we showed that p38 inhibition with SCIO-469 enhances MM cytotoxicity of bortezomib by inhibiting the transient expression and phosphorylation of Hsp27, a downstream target of p38. Here we show that continued treatment of MM cells with bortezomib leads to a SCIO-469-enhanced downregulation of Hsp27 and to increased MM apoptosis. Furthermore, we show that p38 inhibition enhances the bortezomib-induced MM apoptosis by upregulation of p53 and downregulation of Bcl-X(L) and Mcl-1. In a mouse xenograft plasmacytoma model of MM, we found that inhibiting p38 augments the effects of bortezomib in decreasing MM tumor growth in vivo. Thus, in addition to its role in suppressing an activated MM microenvironment, co-treatment with a p38 inhibitor, such as SCIO-469, may enhance the cytotoxicity of bortezomib by modulating pro-apoptotic and anti-apoptotic factors in MM cells, suggesting great potential for co-therapy.

Administration, Oral↗

PubMed2005

Ion detection with photonic crystal microcavities.

We have experimentally demonstrated a cation and anion sensor by using short linear photonic crystal microcavities with an embedded quantum dot active region. The photonic crystal microcavity covered with an ion-selective polymer forms a submicrometer optical detection system sensitive to small changes of perchlorate anion (ClO4(-)) and calcium cation (Ca2+) concentrations.

Journal Article↗

PubMed2005

Metal contents in the groundwater of Sahebgunj district, Jharkhand, India, with special reference to arsenic.

A detailed study has been presented on groundwater metal contents of Sahebgunj district in the state of Jharkhand, India with special reference to arsenic. Both tubewell and well waters have been studied separately with greater emphasis on tubewell waters. Groundwaters of all the nine blocks of Sahebgunj district have been surveyed for iron, manganese, calcium, magnesium, copper and zinc in addition to arsenic. Normal distribution statistic, exploratory data analysis and robust Z-score analysis have been employed to find out the distribution pattern, localisation of data, outliers and other related information. Groundwaters of three blocks of Sahebgunj, namely, Sahebgunj, Rajmahal and Udhawa have been found to be alarmingly contaminated with arsenic present at or above 10 ppb. Arsenic distribution patterns in these blocks are highly asymmetric in nature with the common feature of increasing width from first to fourth quartile. A very broad fourth quartile in each case represents a long asymmetric tail on the right of the median. Tubewell waters of at least two more blocks require regular monitoring to identify the outbreak of arsenic at the onset. Groundwaters of Sahebgunj district in general contain high iron and manganese. It is by and large soft in nature. Well waters have been found to be better with regard to arsenic but iron and manganese contents do not vary significantly. Normal distribution analysis (NDA), box and whisker (BW) plot and Z-score analysis together can provide a reasonably complete statistical picture of metal contents in Sahebgunj district groundwaters.

Arsenic↗

PubMed2005

A study on arsenic adsorption on polymetallic sea nodule in aqueous medium.

A detailed study on As(III) and As(V) adsorption on polymetallic sea nodule in aqueous medium has been reported. Elemental composition of sea nodule comprises primarily, iron, manganese and silicon with trace quantities of aluminium, copper, cobalt and nickel. As(V) adsorption on sea nodule is dependent on pH while As(III) is insensitive to it. Adsorption data broadly follow Langmuir isotherm. Kinetic data follow a pseudo-second-order model for both As(III) and As(V). Arsenic loading on sea nodule is dependent on initial arsenic concentration. Optimum As(III) loading is 0.74 mg/g at 0.34 mg/L and for As(V) it is 0.74 mg/g at 0.78mg/L. As(III) adsorption is broadly independent of ionic environment. Except for PO(4)(3-), As(III) adsorption is not influenced by anions but cations influence it significantly. As(V) adsorption, on the other hand, is influenced by anions and not by cations. Experimental evidence indicates an inner sphere complex for As(III) and partial inner and partial outer sphere complex for As(V). Both As(III) and As(V) adsorptions are marked with very little desorption in the pH range of 2-10. Sea nodule can speciate As(III) and As(V) in groundwater at or above pH 6. Sea nodule was successfully tested as an adsorbent for the removal of arsenic from six contaminated groundwater samples of West Bengal, India, containing arsenic in the range 0.04-0.18mg/L.

Adsorption↗

PubMed2004

Evaluation and standardisation of a simple HG-AAS method for rapid speciation of As(III) and As(V) in some contaminated groundwater samples of West Bengal, India.

A simple HG-AAS technique has been evaluated and standardised for rapid speciation of As(III) and As(V) in a number of contaminated groundwater samples of West Bengal, India. Citric acid has been used for selective hydride formation of As(III). The sensitivity of the evaluated HG-AAS method is 7.91 mg(-1)l, standard deviation, 0.001 and detection limit, 0.4 microg l(-1). As(III) sensitivity remains constant in the sample pH range of 2.3-10.6. Concomitant mineral matrix of the water samples did not interfere with arsenic determination. Eight out of ten groundwater samples analysed for As(IlI)and As(V) contain more As(III), which lies in the range of 54-350 ppb. As(III) estimation in drinking water along with total arsenic should be invoked as a policy for a realistic risk assessment of the contaminated water.

Arsenic↗

PubMed2004

Peripheral and central p38 MAPK mediates capsaicin-induced hyperalgesia.

The stress-activated mitogen-activated protein kinase (MAPK) p38 is emerging as an important mediator of pain. The present study examined the possible involvement of peripheral and spinal p38 MAPK in capsaicin-induced thermal hyperalgesia. Topical capsaicin produced phosphorylation of p38 MAPK in the skin from the affected hindpaw as well as the corresponding lumbar spinal cord in a time dependent manner. Topical capsaicin produced robust C-fiber mediated thermal hyperalgesia that was inhibited by systemic, local peripheral, or central intrathecal pre-treatment with the p38 MAPK inhibitor, SD-282. Intraperitoneal SD-282 (10-60 mg/kg) significantly and dose-dependently attenuated capsaicin-induced C-fiber mediated thermal hyperalgesia. Similarly, 0.1-5mg/kg subcutaneous SD-282 in the hindpaw dose-dependently attenuated capsaicin-induced thermal hyperalgesia. Intrathecal administration of 1microg SD-282 was also anti-hyperalgesic in this model. Functionally, SD-282 decreased capsaicin-induced release of calcitonin gene related peptide in an in vitro skin release assay, consistent with a role for p38 MAPK in peripheral nerve function. These results suggest that p38 MAPK plays a role in the development of hyperalgesic states, exerting effects both centrally in the spinal cord and peripherally in sensory C fibers.

Animals↗

PubMed2002

Removal of arsenic from groundwater using low cost ferruginous manganese ore.

A low cost ferruginous manganese ore (FMO) has been studied for the removal of arsenic from groundwater. The major mineral phases present in the FMO are pyrolusite and goethite. The studied FMO can adsorb both AS(III) and As(V) without any pre-treatment, adsorption of As(III) being stronger than that of As(V). Both As(II) and As(V) are adsorbed by the FMO in the pH range of 2-8. Once adsorbed, arsenic does not get desorbed even on varying the pH in the range of 2-8. Presence of bivalent cations, namely, Ni2+, Co2+ Mg2+ enhances the adsorption capability of the FMO. The FMO has been successfully used for the removal of arsenic from six real groundwater samples containing arsenic in the range of 0.04-0.18 ppm. Arsenic removals are almost 100% in all the cases. The cost of the FMO is about 50-56 US$ per metric tonne.

Adsorption↗

PubMed2002

Intracerebroventricular but not intravenous interleukin-1beta induces widespread vascular-mediated leukocyte infiltration and immune signal mRNA expression followed by brain-wide glial activation.

Interleukin-1beta (IL-1beta) is a pro-inflammatory cytokine that appears in brain and cerebrospinal fluid following peripheral immune challenges and central infections or injury. We examined the consequences of i.c.v. infusion of IL-1beta on mRNA expression of several immune markers and on recruitment of peripheral leukocytes. Awake rats were infused with IL-1beta (100 ng/rat) into the lateral ventricle, and 0.5, 2, 4, 8, 12, or 24 h later, animals were killed and their fresh-frozen brains processed for in situ hybridization and immunohistochemistry. Widespread vascular expression of inhibitory factor kappa(B)alpha (Ikappa(B)alpha, marker of nuclear factor kappa(B)alpha transcriptional activity) and inducible cyclooxygenase (COX-2) mRNAs at 0.5-2 h was credited to movement of IL-1beta along ventricular, subarachnoid, and perivascular pathways to target endothelia that express type 1 IL-1 receptor mRNA. Induction of monocyte chemoattractant protein-1 mRNA and intercellular adhesion molecule-1 (ICAM-1) immunostaining on endothelia began at 0.5-2 h. Leukocytes (neutrophils and monocytes, recognized by morphology and CD45 and ED1 immunostaining) appeared in meninges and blood vessels at 2-4 h and diffusely penetrated the parenchyma at 8-24 h. The leukocytes strongly expressed IL-1beta and inducible nitric oxide synthase mRNAs. Beginning at 4-12 h, astrocytes (glial acidic fibrillary protein mRNA and protein and c-fos mRNA) and microglia (ionized calcium-binding adaptor molecule 1 mRNA and protein) showed widespread activation. Other rats received i.v. IL-1beta (6 microg/kg). Their brains showed induction of Ikappa(B)alpha and COX-2 mRNAs in the vasculature at 2 h but none of the other sequelae. In summary, our data indicate that IL-1beta in the cerebrospinal fluid reaches its target receptors on the endothelia via perivascular volume transmission, up-regulates ICAM-1, and triggers a targeted leukocyte emigration and widespread glial activation stimulated perhaps by pro-inflammatory molecules expressed by leukocytes. The dramatic difference between i.c.v. and i.v. routes of administration underscores the potency of IL-1beta within the brain to dynamically affect the cellular trafficking component of 'immune privilege'.

Animals↗

PubMed2001

Female odors lead to rapid activation of mitogen-activated protein kinase (MAPK) in neurons of the vomeronasal system.

Pheromonal mediation of reproductive function proceeds along a neuroanatomical pathway that connects the vomeronasal organ (VNO) at the periphery with downstream target-sites in the amygdala and hypothalamus. The MAPK pathway is a prominent cascade linking receptor activation to induction of effectors such as c-Fos. We addressed the question: Does a specific pheromone stimulus lead to activation (phosphorylation, P) of MAPK in the VN system of the male mouse? Phosphorylation of MAPK in the VN system was evaluated 15-30 min and 1.5-2 h after exposure to female odors, using immunocytochemical techniques. A rapid and transient cytoplasmic expression of PMAPK was noted in the VNO with a unique distribution of the expressing neurons in columns extending over the entire basal to apical axis. A rapid and sustained expression was noted in most amygdaloid and hypothalamic VN target-sites and also in a few amygdaloid and hypothalamic sites outside the traditional VN system. The extent of expression and the subcellular compartmentalization (nucleus, cytoplasm, processes) of PMAPK were region-dependent. Of the VN target-sites, the accessory olfactory bulb (AOB) stood out in the lack of expression of PMAPK, in the high expression of the MAPK enzyme itself and in the massive of expression of c-Fos. This expression profile implicates another pathway(s) in mediating VNO signaling to the AOB. Our results are the first to demonstrate the use of PMAPK to trace functional pathways. Based on the wide cellular and intracellular expression of phosphorylated MAPK in the VN system, we propose that the MAPK pathway plays an important role in mediating female pheromone signaling in the male mouse.

Amygdala↗

PubMed2001

Inhibition of the mitogen activated protein kinase, p38 alpha, prevents proinflammatory cytokine induction by human adherent mononuclear leukocytes in response to lipid loading.

Macrophage infiltration, inflammatory processes and oxidatively modified low density lipoprotein (LDL) are known contributing factors in the formation of the atherosclerotic plaque. To determine whether a direct link might exist between these factors, we examined the effect of oxidized LDL upon proinflammatory cytokine production in adherent human peripheral blood mononuclear leukocytes. Oxidized LDL, as well as a combination of cholesterol and 25-hydroxycholesterol, induced tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1 beta) mRNA as measured by quantitative real time PCR, by a maximum of two- to fourfold following a 24-h incubation. Analysis of cell culture supernatants revealed a concomitant stimulation of TNFalpha and IL-1 beta secreted protein as determined by ELISA. Treatment of human peripheral blood mononuclear leukocytes with oxidized LDL or the combination of cholesterol and 25-hydroxycholesterol caused activation of p38 alpha as determined by the ability of immunoprecipitated p38 to phosphorylate an ATF-2 fusion protein, a surrogate substrate of p38 alpha. VK-19911 (Pyridine, 4-[4-(4-fluorophenyl)-1-(4-piperidinyl)-1H-imidazol-5-yl]-dihydrochloride), a specific inhibitor of p38 alpha, prevented the induction of TNFalpha and IL-1 beta by oxidized LDL in a dose-dependent manner. Activated p38 alpha is known to be involved in the stabilization of cyclooxygenase-2 mRNA in response to stimuli such as lipopolysaccharide; however, in the setting of oxidized LDL-induced p38 alpha activation, COX-2 mRNA levels were not affected. Taken together, the data imply a potential role for p38 alpha activation in lipid-associated inflammatory processes.

Activating Transcription Factor 2↗

PubMed2001

Effect of nitrofurazone on the reproductive organs in adult male mice.

AIM: To study the effect of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone), a derivative of nitrofuran, on male reproductive organs of Parkes (P) strain mice. METHODS: Mice were given nitrofurazone orally at a dose of 64 mg/kg body weight per day, for 10 and 20 days, and were killed 24 h and/or 56 days after the last treatment. Histological appearance of testis, motility and number of spermatozoa in cauda epididymidis, and biochemical indices in epididymis and seminal vesicle were evaluated. RESULTS: Histologically, testis showed marked regressive changes in the seminiferous tubules in mice treated with nitrofurazone. Ten days after treatment, there was much depletion of germ cells in the seminiferous tubules, and the germinal epithelium was lined mainly with Sertoli cells, spermatogonia, spermatocytes, and a few round spermatids; intraepithelial vacuoles and multinucleated giant cells were also observed in tubules. By 20 days, regressive changes in the seminiferous tubules were further pronounced, and pachytene spermatocytes were the most advanced germ cells noticed in the tubules. In severe cases, the tubules were lined with a thin layer of Sertoli cells and spermatogonia. The treatment also caused marked reductions in the motility and number of spermatozoa in the cauda epididymidis, in weight and the level of fructose in the seminal vesicle, and in sialic acid level in the epididymis. Fifty six days after drug withdrawal, the alterations induced in the reproductive organs returned to control levels. CONCLUSION: Our results suggest that nitrofurazone treatment in P mice induces marked alterations in the male reproductive organs, and that the alterations are reversible following cessation of treatment.

Analysis of Variance↗

PubMed2001

Acquisition and analysis of repeating patterns in time-oriented clinical data.

OBJECTIVES: (1) Creation of an expressive language for specification of temporal patterns in clinical domains, (2) Development of a graphical knowledge-acquisition tool allowing expert physicians to define meaningful domain-specific patterns, (3) Implementation of an interpreter capable of detecting such patterns in clinical databases, and (4) Evaluation of the tools in the domains of diabetes and oncology. METHODS: We describe a constraint-based language, named CAPSUL, for specification of temporal patterns. We implemented a knowledge-acquisition tool and a temporal-pattern interpreter within Résumé, a larger temporal-abstraction architecture. We evaluated the knowledge-acquisition process with the help of domain experts. In collaboration with the Rush Presbyterian/St. Luke's Medical Center, we analyzed data of bone-marrow transplantation patients. The expert compared the detected patterns to a manual inspection of the data, with the help of an experimental information-visualization tool we are developing in a related project. RESULTS: The CAPSUL language was expressive enough during the knowledge-acquisition process to capture almost all of the patterns that the experts found useful. The patterns detected in the data by the pattern interpreter were all verified as correct. Completeness (whether all correct patterns were found) was difficult to assess, due to the size of the database. CONCLUSIONS: The CAPSUL language enables medical experts to express temporal patterns involving multiple levels of abstraction of clinical data. The ability to reuse both domain-patterns and abstract constraints seems highly useful. The Résumé interpreter, augmented by the CAPSUL semantics, finds the complex patterns within a clinical time-oriented database in a sound fashion.

Algorithms↗

PubMed2000

Protein stabilization through phage display.

RNase S consists of two proteolytic fragments of RNase A, residues 1-20 (S20) and residues 21-124 (S pro). A 15-mer peptide (S15p) with high affinity for S pro was selected from a phage display library. Peptide residues that are buried in the structure of the wild type complex are conserved in S15p though there are several changes at other positions. Isothermal titration calorimetry studies show that the affinity of S15p is comparable to that of the wild type peptide at 25 degrees C. However, the magnitudes of DeltaH(o) and DeltaC(p) are lower for S15p, suggesting that the thermal stability of the complex is enhanced. In agreement with this prediction, at pH 6, the T(m) of the S15p complex was found to be 10 degrees C higher than that of the wild type complex. This suggests that for proteins where fragment complementation systems exist, phage display can be used to find mutations that increase protein thermal stability.

Amino Acid Sequence↗

PubMed2000

Elucidation of determinants of protein stability through genome sequence analysis.

Sequences of putative soluble proteins from complete genomes of eight thermophiles and 12 mesophiles were analyzed to gain insight into determinants of protein thermostability. The predator algorithm was used to assign secondary structures to each protein sequence. Based on simple statistical tests, a set of stabilizing factors was identified. These include reduced protein size, increases in number of residues involved in hydrogen bonding, beta-strand content and helix stabilization through ion pairs. There are also significant increases in the relative amounts of charged and hydrophobic beta-branched amino acids and decreases in uncharged polar amino acids in proteins from thermophiles relative to mesophilic organisms. Factors such as the relative proportion of residues in loops, proline and glycine content and helix capping do not appear to be important.

Amino Acids↗

PubMed2000

Fragile X (fmr1) mRNA expression is differentially regulated in two adult models of activity-dependent gene expression.

We sought to determine whether the fragile X mental retardation gene fmr1 is regulated in long-term potentiation (LTP) and electroconvulsive shock (ECS). In situ hybridization of fmr1 mRNA in hippocampus of rats given LTP in vivo showed no change in fmr1 mRNA levels relative to control. However, ECS induced a selective increase in fmr1 mRNA expression in the dentate gyrus (DG) granule cell layer at 6 h post-ECS. The ECS paradigm may unmask relevant activity-dependent regulatory mechanisms that modulate fmr1 gene transcription in vivo.

Analysis of Variance↗

PubMed2000

Histologic changes in the mouse testis after bilateral vasectomy.

AIM: To study the effect of vasectomy on histological appearance of the testis. METHODS: Parkes strain mice were used as the animal model; they were bilaterally vasectomized (Vx) or sham-operated (So) and killed at intervals of 4, 6, 9, and 12 months after the operation. Testes were excised from 5 Vx and 5 So mice at each interval and processed for histological examination. RESULTS: Testes of So mice showed normal histological features. By contrast, marked alterations were observed in the seminiferous tubules in testes of Vx mice, except in those killed 4 months after the operation. The seminiferous epithelium in the tubules was only 2-3 layers thick and showed much depletion of germ cells; in severe cases, the epithelium consisted of only a thin layer of Sertoli cells, spermatogonia and a few spermatocytes. Exfoliation of germ cells, occurrence of multinucleated giant cells and vacuolated appearance of the epithelium were of common features in the tubules. Furthermore, lumen of the rete testis in Vx mice was greatly dilated and showed accumulation of spermatozoa with immature germ cells; in mice vasectomized for 6-12 months, several macrophages ingesting spermatozoa were often observed in the lumen of the rete testis. Spermatic granuloma was also sometimes noticed in corpus or in cauda regions of the epididymis in mice vasectomized for 6-12 months. CONCLUSION: We suggest that consequences of vasectomy should be thoroughly understood in order to make this method rather more popular as a reversible method of male contraception.

Animals↗

PubMed1999

Characterization of the Taxol binding site on the microtubule. Identification of Arg(282) in beta-tubulin as the site of photoincorporation of a 7-benzophenone analogue of Taxol.

Photoaffinity labeling methods have allowed a definition of the sites of interaction between Taxol and its cellular target, the microtubule, specifically beta-tubulin. Our previous studies have indicated that [(3)H]3'-(p-azidobenzamido)Taxol photolabels the N-terminal 31 amino acids of beta-tubulin (Rao, S., Krauss, N. E., Heerding, J. M., Swindell, C. S., Ringel, I., Orr, G. A., and Horwitz, S. B. (1994) J. Biol. Chem. 269, 3132-3134) and [(3)H]2-(m-azidobenzoyl)Taxol photolabels a peptide containing amino acid residues 217-233 of beta-tubulin (Rao, S., Orr, G. A., Chaudhary, A. G., Kingston, D. G. I., and Horwitz, S. B. (1995) J. Biol. Chem. 270, 20235-20238). The site of photoincorporation of a third photoaffinity analogue of Taxol, [(3)H]7-(benzoyldihydrocinnamoyl) Taxol, has been determined. This analogue stabilizes microtubules polymerized in the presence of GTP, but in contrast to Taxol, does not by itself enhance the polymerization of tubulin to its polymer form. CNBr digestion of [(3)H]7-(benzoyldihydrocinnamoyl)Taxol-labeled tubulin, with further arginine-specific cleavage by clostripain resulted in the isolation of a peptide containing amino acid residues 277-293. Amino acid sequence analysis indicated that the photoaffinity analogue cross-links to Arg(282) in beta-tubulin. Advances made by electron crystallography in understanding the structure of the tubulin dimer have allowed us to visualize the three sites of photoincorporation by molecular modeling. There is good agreement between the binding site of Taxol in beta-tubulin as determined by photoaffinity labeling and electron crystallography.

Animals↗