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Biomedical subjects

S Balachandran

Publications and source records attributed to S Balachandran.

At least 19 recordsLinked to original sources

Ultrasonic enhancement of the supercritical extraction from ginger.

This work examines the concurrent use of power ultrasound during the extraction of pungent compounds from a typical herb (ginger) with supercritical CO(2). A power ultrasonic transducer with an operating frequency of 20 kHz is connected to an extraction vessel and the extraction of gingerols from freeze-dried ginger particles (4-8 mm) is monitored. In the presence of ultrasound, we find that both the extraction rate and the yield increase. The higher extraction rate is attributed to disruption of the cell structures and an increase in the accessibility of the solvent to the internal particle structure, which enhances the intra-particle diffusivity. While cavitation would readily account for such enhancement in ambient processes, the absence of phase boundaries should exclude such phenomena above the critical point. Possible alternate mechanisms for the cell structure damage are discussed.

Aluminum↗

Profile of PAHs in the diesel vehicle exhaust in Delhi.

A preliminary study to determine the profile of PAHs in the exhaust of diesel vehicles plying on Delhi roads was conducted. Two different types of diesel vehicles (buses and trucks) with different age groups were selected for sampling purpose. The concentration of Total PAHs (sigma12 PAHs) was found to be 50.76 +/- 6.62 and 57.72 +/- 4.15 mg/g in the exhaust of buses and trucks, respectively. The levels of PAHs were found to be high in trucks as compared to that of buses. The total PAHs concentration in the present study was found to be higher as compared to other studies. Such a high concentration could be attributed to different parameters like the age of the vehicles, driving conditions, the fuel quality and the emission standards.

Air Pollutants↗

Profile of PAH in the exhaust of gasoline driven vehicles in Delhi.

A preliminary study to determine the profile of PAHs in the exhaust of gasoline vehicles in Delhi was conducted. Three different types of vehicles (cars, autorickshaws and scooters) were selected with different age groups for sampling purpose. The concentration of Total PAHs (Sigma12PAHs) was found to be 27.27 +/- 2.27, 28.61 +/- 3.70 and 29.81 +/- 3.57 mg/g in the exhaust of cars, auto- rickshaws (three wheelers) and two wheelers, respectively. The levels of PAHs were found to be high in scooter exhaust as compared to that of cars and autorickshaws. The total PAHs concentration in the present study was found to be higher as compared to other studies. Such a high concentration could be attributed to different parameters like the age of the vehicles, driving conditions, the fuel quality and the emission standards.

Air Pollutants↗

Histamine release during adult cardiopulmonary bypass.

Histamine, an inflammatory mediator in its own right, may also be a marker for a more widespread systemic inflammatory process. In this study we have examined variations in plasma histamine concentrations produced during the course of cardiac surgery involving cardiopulmonary bypass, the relationship between these variations and intra-operative events. By assays of serum tryptase and CD-63 expression we have also attempted to identify the source of histamine. Histamine concentrations that were significantly raised from baseline level were demonstrated. These were elevated from the time of aortic cross-clamping and continued to be raised for 24 h postoperatively (p < 0.00625). This was associated with an increase in CD-63 expression (p < 0.025) (but not an increase in tryptase concentration) following aortic cross-clamping and protamine administration, suggesting that basophils are the source of histamine. 41% of patients had arrhythmias in the post bypass period. The rise in histamine levels was not related to the incidence of cardiac arrhythmias.

Adult↗

Scoliosis in cystic fibrosis: is it idiopathic?

STUDY DESIGN: This is a retrospective study of all the patients registered with the Yorkshire Regional Cystic Fibrosis unit from 1982 to 1997. Of the 316 patients, there were 184 adults (age 17 years and above) and 132 children (age 0-6 years). OBJECTIVES: This study was aimed at determining the prevalence of scoliosis in people with cystic fibrosis and describes the characteristics and progression of scoliosis in these patients and highlights predictive factors, which account for high prevalence of scoliosis in this condition. SUMMARY OF THE BACKGROUND DATA: Two previous North American studies (1978 and 1982) have indicated a high prevalence of scoliosis in patients with cystic fibrosis. METHODS: The patients were divided into 3 groups based on their chronologic age as on January 1998. Chest, abdomen, and whole spine radiographs were studied for the presence of any spinal deformity, and measurements were made using the Oxford Cobbmeter (Oxford Metrics). The extent, apex, and the side of the curves were described. The disease-specific scores, ie, Chrispin-Norman score (score for radiologic severity of lung disease) and Shwachman score (score for general condition), were noted from the patient follow-up database maintained by the Regional Cystic Fibrosis Unit. Multiple linear regression analysis was used to study the correlation between Cobb angle and the previously mentioned scores. RESULTS: In the 4- to 16-year age group, the prevalence of scoliosis was 15.6%, which is 20 times the prevalence in 15,793 school children with a similar age and sex distribution from the same geographic area. The majority of curves were single-thoracic, apical around T6-T8 with no side predilection. In the adult population (above 16 years), the prevalence was 9.8%, which is higher than that of the general population. These curves were thoracic, apical around T7-T8, and approximately two thirds of them were right-sided. Infantile curves are described for the first time in our study; these tend to be nonprogressive, right-sided, upper thoracic curves. CONCLUSION: Our study shows a high prevalence of scoliosis in people with cystic fibrosis. These are benign short midthoracic curves, apical between T6-T8 with no side predilection.

Adolescent↗

Spatial and temporal variation of heavy metals in atmospheric aerosol of Delhi.

The levels of Suspended Particulate Matter (SPM) and heavy metals viz. Pb, Cd, Cr, Ni and Fe were measured. Aerosol samples from four different locations in Delhi were collected by High-volume samplers for a period of one year from July 1997 June 1998. Metal concentration was determined by Atomic Absorption Spectrometry. The annual average concentration of SPM in Delhi was found to be 416.34 +/- 223 microg m(-3). The atmospheric aerosol samples were highly enriched with elements viz. Pb and Cd, which originate from various human activities like transportation and industrial processes. Principal Component Analysis (PCA) showed vehicular traffic and industrial emission as the major contributors of metals. The annual average concentration of Pb did not exceed the national standard of 0.75 microg m(-3).

Aerosols↗

Anaesthesia for cardioversion: a comparison of sevoflurane and propofol.

This study compared the induction time, haemodynamic changes, recovery characteristics and patient satisfaction for sevoflurane and propofol when used as the main anaesthetic agents for cardioversion. Sixty-one unpremedicated patients scheduled for elective cardioversion were anaesthetised with either inhaled sevoflurane 8% or an intravenous propofol target-controlled infusion set at 6 microg.ml(-1). There was no significant difference in induction time between the two groups: mean (SD) = 90.1(40) s in the sevoflurane group vs. 83.7(35) s in the propofol group. Mean (SD) time to recovery was significantly shorter in the sevoflurane group than in the propofol group: 318 (127) s vs.738 (355) s, respectively, p < 0.001. At recovery, the patients in the propofol group had significantly lower systolic and diastolic blood pressures than those in the sevoflurane group, p < 0.001. The incidence of complications was low in both groups, with similar patient satisfaction expressed after the procedure. We conclude that sevoflurane is a suitable choice for anaesthesia for cardioversion and may provide greater haemodynamic stability than a target-controlled infusion of propofol.

Adult↗

Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR.

We report here the isolation and characterization of two proteins, NFAR-1 and -2, which were isolated through their ability to interact with the dsRNA-dependent protein kinase, PKR. The NFAR proteins, of 90 and 110 kDa, are derived from a single gene through alternative splicing and are evolutionarily conserved nuclear phosphoproteins that interact with double-stranded RNA. Both NFAR-1 and -2 are phosphorylated by PKR, reciprocally co-immunoprecipitate with PKR, and colocalize with the kinase in a diffuse nuclear pattern within the cell. Transfection studies indicate that the NFARs regulate gene expression at the level of transcription, probably during the processing of pre-mRNAs, an activity that was increased in fibroblasts lacking PKR. Subsequent functional analyses indicated that amino acids important for NFAR's activity were localized to the C terminus of the protein, a region that was found to specifically interact with FUS and SMN, proteins also known as regulators of RNA processing. Accordingly, both NFARs were found to associate with both pre-mRNAs and spliced mRNAs in post-transcriptional studies, similar to the known splicing factor ASF/SF-2. Collectively, our data indicate that the NFARs may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription and possibly contribute to host defense-related mechanisms in the cell.

Alternative Splicing↗

Analyzing the mechanisms of interferon-induced apoptosis using CrmA and hepatitis C virus NS5A.

The dsRNA-dependent protein kinase, PKR, is a key component of interferon (IFN)-mediated anti-viral action and is frequently inhibited by many viruses following infection of the cell. Recently, we have demonstrated that IFN and PKR can sensitize cells to apoptosis predominantly through the FADD/caspase-8 pathway (S. Balachandran, P. C. Roberts, T. Kipperman, K. N. Bhalla, R. W. Compans, D. R. Archer, and G. N. Barber. (2000b) J. Virol. 74, 1513-1523). Given these findings, it is thus plausible that rather than specifically target IFN-inducible genes such as PKR, viruses could also subvert the mechanisms of IFN action, in part, at locations that could block the apoptotic cascade. To explore this possibility, we analyzed whether the poxvirus caspase-8 inhibitor, CrmA, was able to inhibit IFN or PKR/dsRNA-mediated apoptosis. Our findings indicated that CrmA could indeed inhibit apoptosis induced by both viral infection and dsRNA without blocking PKR activity or inhibiting IFN signaling. In contrast HCV-encoded NS5A, a putative inhibitor of PKR, did not appear to inhibit cell death mediated by a number of apoptotic stimuli, including IFN, TRAIL, and etoposide. Our data imply that viral-encoded inhibitors of apoptosis, such as CrmA, can block the innate arms of the immune response, including IFN-mediated apoptosis, and therefore potentially constitute an alternative family of inhibitors of IFN action in the cell.

Adaptor Proteins, Signal Transducing↗

Occurrence of acid rain over Delhi.

Precipitation samples were collected as wet-fall only and primarily on event basis in Delhi during the monsoon period of 1995. Concentrations of major anions (SO4(2-), NO3- and Cl-) and cations (Ca2+, Mg2+, Na+ and K+) were determined. The pH of the rain water was found to be more than 5.6, showing alkalinity during the early phase of monsoon, but during the late phase of monsoon pH tendency was towards acidity due to lack of proper neutralization of acidic ions. Neutralization is not only due to the local process but also due to the pre-monsoon 'Andhi' which brings Suspended Particulate Matter (SPM) containing Ca2+, Mg2+, Na+ and K+ as well as the local emission of NH3. In the late monsoon the concentration of cations gets reduced because of heavy rainfall and relatively unfavourable condition for their transport from the adjoining areas, whereas the anion concentrations remain unchanged owing to their continuous emission.

Acid Rain↗

Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, Ras, or myc function and involves the induction of apoptosis.

We have recently shown that vesicular stomatitis virus (VSV) exhibits potent oncolytic activity both in vitro and in vivo (S. Balachandran and G. N. Barber, IUBMB Life 50:135-138, 2000). In this study, we further demonstrated, in vivo, the efficacy of VSV antitumor action by showing that tumors that are defective in p53 function or transformed with myc or activated ras are also susceptible to viral cytolysis. The mechanism of viral oncolytic activity involved the induction of multiple caspase-dependent apoptotic pathways was effective in the absence of any significant cytotoxic T-lymphocyte response, and occurred despite normal PKR activity and eIF2alpha phosphorylation. In addition, VSV caused significant inhibition of tumor growth when administered intravenously in immunocompetent hosts. Our data indicate that VSV shows significant promise as an effective oncolytic agent against a wide variety of malignant diseases that harbor a diversity of genetic defects.

3T3 Cells↗

Particle size distribution and its elemental composition in the ambient air of Delhi.

This study examines the chemical composition of PM10, the thoracic fraction of the atmospheric particulate matter. An eight-stage Anderson impactor is used to separate the PM10 from other fractions with different aerodynamic behaviour at three different area representative sites in Delhi from February to May 1998. PM10 particulate are subdivided into two fractions, coarse (> 2.1-10 microns) and fine (< 2.1 microns). The concentrations of major heavy metals such as Pb, Zn, Cd, Ni, and Fe are determined by atomic absorption spectrophotometer. The average concentration of coarse fraction of PM10 is found to be 68.3 +/- 17 micrograms/m3 while the fine fraction of PM10 is 71.3 +/- 15 micrograms/m3 for Delhi. Metal concentration (except Fe) in fine fraction exceeds by a factor of up to 6, as compared to that in the coarse fraction. In order to identify the major sources of fine and coarse fraction of PM10, principle component analysis (PCA) was undertaken and three major sources were identified, namely vehicular emissions, industrial emission, and soil resuspension.

Air Movements↗

Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to viral infection.

The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play an important role in interferon's (IFN's) response to viral infection. Here, we demonstrate that mice lacking PKR are predisposed to lethal intranasal infection by the usually innocuous vesicular stomatitis virus, and also display increased susceptibility to influenza virus infection. Our data indicate that in normal cells, PKR primarily prevents virus replication by inhibiting the translation of viral mRNAs through phosphorylation of eIF2alpha, while concomitantly assisting in the production of autocrine IFN and the establishment of an antiviral state. These results show that PKR is an essential component of innate immunity that acts early in host defense prior to the onset of IFN counteraction and the acquired immune response.

Animals↗

Vesicular stomatitis virus (VSV) therapy of tumors.

Vesicular stomatitis virus (VSV) is an essentially nonpathogenic negative-stranded RNA virus, the replication of which is extremely sensitive to the antiviral effects of interferon (IFN). We demonstrate here that VSV selectively induces the cytolysis of numerous transformed human cell lines in vitro, with all the morphological characteristics of apoptotic cell death. Importantly, VSV can also potently inhibit the growth of p53-null C6 glioblastoma tumors in vivo without infecting and replicating in normal tissue. With our previous findings demonstrating that primary cells containing the double-stranded RNA-activated protein kinase PKR and a functional IFN system are not permissive to VSV replication, these results suggest that signaling by IFN may be defective in many malignancies. Thus VSV might be useful in novel therapeutic strategies for targeting neoplastic disease.

Animals↗

Alpha/beta interferons potentiate virus-induced apoptosis through activation of the FADD/Caspase-8 death signaling pathway.

Interferon (IFN) mediates its antiviral effects by inducing a number of responsive genes, including the double-stranded RNA (dsRNA)-dependent protein kinase, PKR. Here we report that inducible overexpression of functional PKR in murine fibroblasts sensitized cells to apoptosis induced by influenza virus, while in contrast, cells expressing a dominant-negative variant of PKR were completely resistant. We determined that the mechanism of influenza virus-induced apoptosis involved death signaling through FADD/caspase-8 activation, while other viruses such as vesicular stomatitis virus (VSV) and Sindbis virus (SNV) did not significantly provoke PKR-mediated apoptosis but did induce cytolysis of fibroblasts via activation of caspase-9. Significantly, treatment with IFN-alpha/beta greatly sensitized the fibroblasts to FADD-dependent apoptosis in response to dsRNA treatment or influenza virus infection but completely protected the cells against VSV and SNV replication in the absence of any cellular destruction. The mechanism by which IFN increases the cells' susceptibility to lysis by dsRNA or certain virus infection is by priming cells to FADD-dependent apoptosis, possibly by regulating the activity of the death-induced signaling complex (DISC). Conversely, IFN is also able to prevent the replication of viruses such as VSV that avoid triggering FADD-mediated DISC activity, by noncytopathic mechanisms, thus preventing destruction of the cell.

Adaptor Proteins, Signal Transducing↗

The IRF-3 transcription factor mediates Sendai virus-induced apoptosis.

Virus infection of target cells can result in different biological outcomes: lytic infection, cellular transformation, or cell death by apoptosis. Cells respond to virus infection by the activation of specific transcription factors involved in cytokine gene regulation and cell growth control. The ubiquitously expressed interferon regulatory factor 3 (IRF-3) transcription factor is directly activated following virus infection through posttranslational modification. Phosphorylation of specific C-terminal serine residues results in IRF-3 dimerization, nuclear translocation, and activation of DNA-binding and transactivation potential. Once activated, IRF-3 transcriptionally up regulates alpha/beta interferon genes, the chemokine RANTES, and potentially other genes that inhibit viral infection. We previously generated constitutively active [IRF-3(5D)] and dominant negative (IRF-3 DeltaN) forms of IRF-3 that control target gene expression. In an effort to characterize the growth regulatory properties of IRF-3, we observed that IRF-3 is a mediator of paramyxovirus-induced apoptosis. Expression of the constitutively active form of IRF-3 is toxic, preventing the establishment of stably transfected cells. By using a tetracycline-inducible system, we show that induction of IRF-3(5D) alone is sufficient to induce apoptosis in human embryonic kidney 293 and human Jurkat T cells as measured by DNA laddering, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay, and analysis of DNA content by flow cytometry. Wild-type IRF-3 expression augments paramyxovirus-induced apoptosis, while expression of IRF-3 DeltaN blocks virus-induced apoptosis. In addition, we demonstrate an important role of caspases 8, 9, and 3 in IRF-3-induced apoptosis. These results suggest that IRF-3, in addition to potently activating cytokine genes, regulates apoptotic signalling following virus infection.

Apoptosis↗