Biomedical subjects

J Mukherjee

Publications and source records attributed to J Mukherjee.

At least 19 recordsLinked to original sources

PubMed2007

Algorithms and heuristics for efficient medical information display in PDA.

Accessing medical information in mobile devices such as PDAs and mobile phones is becoming widespread. Since these devices do not have the same rendering capabilities as of desktop computers, it is necessary for medical information to be fragmented for proper presentation on these types of devices. In this paper, we propose an architecture for displaying medical information in PDA. In the proposed system, a server extracts the information, categorizes the information in order of its relevance for diagnosis, and dynamically generates a hierarchical view of the relevant information based on certain medical domain knowledge. Displaying image and graphics data in PDA poses several challenges. The proposed system supports an image visualization tool, which interactively displays an image or a portion of an image in user's PDA. This visualization tools increases the resource utilization of PDA by offloading a part of the computation to the server. A suitable caching scheme is incorporated for optimum utilization of communication channel bandwidth.

Algorithms↗

PubMed2006

Determinants of discontinuation of initial highly active antiretroviral therapy regimens in a US HIV-infected patient cohort.

OBJECTIVES: Optimization of initial highly active antiretroviral therapy (HAART) for complete viral suppression and better tolerability is paramount for the prognosis of HIV-infected patients. Observational studies provide a better means than clinical trials of studying the determinants of discontinuation in actual practice. METHODS: A longitudinal cohort of US HIV-positive patients who initiated HAART for the first time from 1996 to 2003 were included in the analysis. Stratified Cox proportional hazards models, considering time-updated viral load and CD4 count data, were developed for analyzing time to first discontinuation. RESULTS: A total of 3414 antiretroviral-naive HAART patients were identified. In a median follow-up period of 211 days (mean 324 days), 628 patients (18.4%) reportedly discontinued the HAART regimen because of drug toxicity, 456 (13.4%) because of non-compliance, and 257 (7.5%) because of treatment failure. In addition to the recorded reasons for discontinuation, black ethnicity [relative risk (RR) 1.28, 95% confidence interval (CI) 1.13-1.45], current smoking (RR 1.33, CI 1.18-1.50), high pill burden (RR 1.44, CI 1.22-1.70), and recent viral control (RR 0.63, CI 0.56-0.70) were all predictive of discontinuation. Only high pill burden (>15 pills/day), which is considered to be a surrogate for treatment regimen complexity, and the most recent poor viral control (HIV RNA) were found to be consistently associated with a higher likelihood of discontinuation. CONCLUSIONS: Risk factors other than physician- or patient-reported reasons play a role in discontinuation of initial HAART regimens. Identification of these risk factors and simplification of treatment regimens in those at high risk for discontinuation appear to be necessary in order to maximize the effectiveness of HAART regimens.

Adult↗

PubMed2005

Functional imaging of a large demyelinating lesion.

PURPOSE: To determine the metabolic characterization of a large solitary demyelinating lesion. METHODS: Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) studies with 2-deoxy-2-[F-18]fluoro-d-glucose (FDG), carbon-11-methionine (methionine) and carbon-11-choline (choline) were done on the demyelinating lesion. RESULTS: The demyelinating lesion exhibited a low glucose uptake, prominent methionine uptake and a minimal choline uptake on the PET studies. MRS data revealed an increased choline to creatine (cho/cr) ratio and a decreased N-acetyl-aspartate to creatine (NAA/cr) ratio, which demonstrated a return to near normal ratios on follow-up study. CONCLUSION: The report summarizes the metabolic characteristics of a demyelinating plaque.

Adult↗

PubMed2004

Studies on the production and purification of an antimicrobial compound and taxonomy of the producer isolated from the marine environment of the Sundarbans.

A microorganism isolated from the Sundarbans region of the Bay of Bengal, India, showed potent antimicrobial activity against gram-positive and gram-negative bacteria, molds, yeast and several multiple-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The isolate grew in the presence of 20% (w/v) NaCl, antibiotic production being maximum with 5% (w/v) NaCl in the production medium. Natural seawater stimulated antibiotic biosynthesis. The absence of catabolite repression during the synthesis of the antimicrobial substance was demonstrated by the utilization of glucose by this isolate. The 16S rRNA gene of this aerobic, gram-positive, mycelium- and spore-forming microorganism was amplified, and molecular phylogenetic analysis of the DNA sequence showed less than 93% similarity with its closest relative, indicating differentiation at the genus level. The highly stable, active principle was purified by butyl acetate extraction and silica-gel chromatography and a single compound was found to posses the broad-spectrum activity. Molecular characterization showed that the active compound is a lipid. Bioreactor studies demonstrated that antibiotic production is strongly dependent on the scale of operation and there is a definite relation between the dissolved oxygen concentration, medium pH, glucose utilization, cell differentiation and antibiotic production. Maximum production in 30 h could be obtained by regulation of the medium pH in the alkaline range by a combination of controlled addition of NaOH, regulation of the air supply and changes in the reactor configuration. Considering all of the above evidences and based on comparison with the current literature, a novel antimicrobial appears to have been isolated.

Anti-Bacterial Agents↗

PubMed2004

Documentation of immune profile of microglia through cell surface marker study in glioma model primed by a novel cell surface glycopeptide T11TS/SLFA-3.

STATEMENT OF THE PROBLEM: The sheep erythrocyte membrane glycoprotein T11TS/SLFA-3 can form a ligand-receptor complex with CD2 present on immunocyte and exert stimuli for activation and proliferation. Regression of brain tumor with the application of T11TS indicates the probable role of microglia, the chief immunomodulatory cell within the brain compartment. In the present study microglial activation and immunophenotypic modulation were assessed in T11TS treated brain tumor-bearing animal models. Rat glioma models induced by chemical carcinogen ENU were treated with three consecutive doses of T11TS. Microglial cells from brain were isolated and assessed through E-rosette formation, SEM and FACS for CD2, MHC class II, CD25, and CD4. The preliminary indication of presence of CD2 on microglia through E-rosette formation was confirmed by SEM and FACS. MHC class II and CD2 single and double positive subpopulations exist, and their expression is also modulated in different doses of T11TS. A general trend of highest receptor saturation and microglial activation, measured through the activation marker CD25 and CD4 expression, was observed in 2nd dose of T11TS administration, which was then dampened via a complex immune feedback mechanism in the 3rd dose.

Alkylating Agents↗

PubMed2004

A comparative analysis of immunorestoration and recovery with conventional and immunotherapeutic protocols in canine generalized demodicosis: a newer insight of immunotherapeutic efficacy of T11TS.

Demodex canis is a natural inhabiting mite of canine skin. Immunological disorder or genetic disorder induces the Demodex population to proliferate vigorously resulting in generalized demodicosis with consequent chronic immunosuppression. Signs of generalized demodicosis include alopecia, crysting, erythema, secondary pyoderma etc. Amitraz, an acaricide, is used conventionally for the treatment of generalized demodicosis. In many instances, the disease relapses due to the residual immunosuppression. The need of an immunorestorative therapy has been urged in generalized demodicosis. Two immunorestorative drugs, namely, Immuplus, a herbal drug, and T11TS, a sheep erythrocyte surface glycoprotein, has been used in two separate groups of dogs having generalized demodicosis and receiving Amitraz treatment. It was observed that though Amitraz treated group responded to the therapy showing increased E-rosettes and nonspecific cytotoxic efficacy of T-lymphocytes and decrease in phagocytic potential of macrophages, the groups treated with the immunotherapeutics like Immuplus and T11TS, responded better. However, the group treated with T11TS showed best recovery. These results emphasize the need for an immunorestorative therapy in generalized demodicosis and provide data in favor of T11TS as a better immunomodulator in comparison to Immuplus.

Animals↗

PubMed2004

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy.

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Adult↗

PubMed2001

Application of oxygen vectors to Claviceps purpurea cultivation.

The application of a two-phase fermentation system for the production of ergot peptide alkaloids by Claviceps purpurea is described. Perfluorocarbons (PFC) are used as oxygen vectors in Claviceps fermentation for the first time. In shake-flask cultivations, the inclusion of PFC in the medium brings about a five-fold increase in the total alkaloid production and a six-fold increase in the pharmaceutically important component, ergotamine. This rise cannot be correlated with the concentration of the added PFC and it is thought that the enhancement is due to a combination of factors, including the influence of PFC. Other oxygen vectors, such as several hydrocarbons, prove to be poor oxygen carriers in our study. Cultivations with PFC in a bioreactor are reproducible, the maximum total alkaloid and ergotamine production being attained on the 11th and 9th days, respectively. The relatively lower increase in the total alkaloid production in the bioreactor as compared to the shake-flasks is attributed to the unequal oxygen availability in the reactor. Processes with PFC offer the operational advantage of a five-fold reduction in aeration rate.

Alkaloids↗

PubMed2001

Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride.

We have used the high-affinity dopamine D-2 receptor radioligand, 18F-fallypride for evaluating receptor occupancy by the antipsychotic drugs, clozapine, risperidone, and haloperidol in rodents and nonhuman primates. In rodents, clozapine (0.1 mg/kg to 100 mg/kg) competed with 18F-fallypride at all the doses administered. At doses over 40 mg/kg, clozapine was able to displace all the administered 18F-fallypride. A pseudobiphasic profile of receptor occupancy by clozapine was observed. This behavior was compared with such other neuroleptics as risperidone and haloperidol that exhibited over 90% receptor occupancy at doses over 0.1 mg/kg and did not exhibit a biphasic nature. Dopamine D-2 receptor occupancy in the monkeys was studied using positron emission tomography (PET) after acute subcutaneous doses of the various drugs. At therapeutically relevant doses, clozapine, risperidone, and haloperidol were able to compete significantly with the binding of 18F-fallypride in all brain regions in rhesus monkeys, and our analyses indicate that these drugs (clozapine, risperidone, and haloperidol) do not discriminate between the striatal (caudate and putamen) and the extrastriatal (thalamus and cortical regions) dopamine receptors. The following extent of D-2 receptor occupancies were measured in the monkey brain using PET: clozapine approximately 70% (dose of 9.7 mg/kg), risperidone approximately 75% (0.05 mg/kg), and haloperidol approximately 90% (0.05 mg/kg).

Animals↗

PubMed2001

Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs.

Acquired Immunodeficiency Syndrome↗

PubMed2000

In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist (11)C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate.

The in vitro autoradiographic binding characteristics as well as in vivo imaging characteristics of a dopamine D2 receptor agonist, (R, S)-2-(N-propyl-N-1'-(11)C-propyl)amino-5-hydroxytetralin ((11)C-5-OH-DPAT), were studied. In (3)H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC(50) = 2.5 nM. In vitro autoradiographs in rat brain slices with (11)C-5-OH-DPAT revealed selective binding to the dopaminergic regions in the striata which was displaceable by sulpiride. Varying concentrations of dopamine displaced this selective binding of (11)C-5-OH-DPAT to the striata in rat brain slices. This selective binding to the striata was also removed in the presence of the GTP analog, 5'-guanylylimidodiphosphate, indicative of the binding of (11)C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of (11)C-5-OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of (11)C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2000

Quantitation of striatal and extrastriatal D-2 dopamine receptors using PET imaging of [(18)F]fallypride in nonhuman primates.

[(18)F]Fallypride is a highly selective, high-affinity dopamine D-2 receptor ligand. The high affinity, K(D) = 30 pM, makes it a suitable candidate for visualizing both striatal and extrastriatal binding in the brain. In this work, dynamic PET studies of two macaque monkeys were acquired along with arterial plasma samples. Compartmental analysis and Logan plots were used to analyze the striatum, thalamus, frontal, and temporal cortices and to validate a reference region of analysis which yields a distribution volume ratio (DVR). The cerebellum was used as the reference region. The results indicate that all methods of analysis are in close agreement over all the analyzed regions in the brain. The average DVRs for the two monkeys was found to be: caudate = 26, putamen = 29, thalamus = 3.8, frontal ctx = 1.7, and temporal ctx = 1.7 on a high-resolution PET scanner. It was found that a scan time of 2 h is needed to accurately estimate the DVR for all regions of the brain. The striatal regions require the longest to linearize and are the most sensitive to variations in the average tissue-to-plasma efflux constant, k(2). For the extrastriatal regions, the effect of the k(2) term on DVR calculation is negligible. Repeatability measurements for all regions were found to be within 10% using the DVR parameter.

Animals↗

PubMed2000

Progress and prospects of ergot alkaloid research.

Ergot alkaloids, produced by the plant parasitic fungi Claviceps purpurea are important pharmaceuticals. The chemistry, biosynthesis, bioconversions, physiological controls, and biochemistry have been extensively reviewed by earlier authors. We present here the research done on the organic synthesis of the ergot alkaloids during the past two decades. Our aim is to apply this knowledge to the synthesis of novel synthons and thus obtain new molecules by directed biosynthesis. The synthesis of clavine alkaloids, lysergic acid derivatives, the use of tryptophan as the starting material, the chemistry of 1,3,4,5-tetrahydrobenzo[cd]indoles, and the structure activity relationships for ergot alkaloids have been discussed. Recent advances in the molecular biology and enzymology of the fungus are also mentioned. Application of oxygen vectors and mathematical modeling in the large scale production of the alkaloids are also discussed. Finally, the review gives an overview of the use of modern analytical methods such as capillary electrophoresis and two-dimensional fluorescence spectroscopy.

Animals↗

PubMed2000

Studies on nutritional and oxygen requirements for production of L-asparaginase by Enterobacter aerogenes.

The carbon and nitrogen sources most suitable for L-asparaginase production by Enterobacter aerogenes were selected and their concentrations optimized in shake-flask cultures. Sodium citrate (1.0%) and diammonium hydrogen phosphate (0.16%) proved to be the best sources of carbon and nitrogen, respectively. Nitrogen catabolite repression of enzyme formation was absent in this bacterium. Cultivation in a reactor showed that the dissolved oxygen level is the limiting factor for L-asparaginase production by E. aerogenes. Glucose was found to be a repressor of enzyme synthesis. Asparagine was absent intracellularly when the L-asparaginase level was high. An increase in the extracellular alanine level when the dissolved oxygen remained low indicated a shift from aerobic to fermentative metabolism.

Aerobiosis↗

PubMed2000

Urease as a virulence factor in experimental cryptococcosis.

Urease catalyzes the hydrolysis of urea to ammonia and carbamate and has been found to be an important pathogenic factor for certain bacteria. Cryptococcus neoformans is a significant human pathogenic fungus that produces large amounts of urease; thus we wanted to investigate the importance of urease in the pathogenesis of cryptococcosis. We cloned and sequenced the genomic locus containing the single-copy C. neoformans urease gene (URE1) and used this to disrupt the native URE1 in the serotype A strain H99. The ure1 mutant strains were found to have in vitro growth characteristics, phenoloxidase activity, and capsule size similar to those of the wild type. Comparison of a ure1 mutant with H99 after intracisternal inoculation into corticosteroid-treated rabbits revealed no significant differences in colony counts recovered from the cerebrospinal fluid. However, when these two strains were compared in both the murine intravenous and inhalational infection models, there were significant differences in survival. Mice infected with a ure1 strain lived longer than mice infected with H99 in both models. The ure1 strain was restored to urease positivity by complementation with URE1, and two resulting transformants were significantly more pathogenic than the ure1 strain. Our results suggest that urease activity is involved in the pathogenesis of cryptococcosis but that the importance may be species and/or infection site specific.

Animals↗

PubMed1999

Monoamine oxidase A inhibition by fluoxetine: an in vitro and in vivo study.

Monoamine oxidase A (MAO-A) inhibition was investigated both in vitro and in vivo in rat brains by using the radioligand, 18F-fluoroclorgyline (N-[3-(2',4'-dichlorophenoxy)-2-18F-fluoropropyl]-N-methylpropa rgylamine). In vitro binding affinities of six compounds, clorgyline, Ro 41-1049, deprenyl, fluoxetine, norfluoxetine and citalopram, were studied. Fluoxetine and norfluoxetine showed in vitro affinities of 36.5 and 68 microM for MAO-A, respectively. Fluoxetine and norfluoxetine also significantly inhibited (more than 20%) the binding of the radioligand in vivo while citalopram and deprenyl showed very poor affinities in vitro for MAO-A and had no effect in vivo. The in vivo effects of the various drugs were directly comparable to their in vitro affinities for binding to MAO-A as seen in the correlation plot of percent control in vivo binding of 18F-fluoroclorgyline and binding affinity, -log IC50 (R2 = 0.979). An acute dose of 20 mg/kg of fluoxetine inhibited binding of 18F-fluoroclorgyline by more than 20%, while lower doses had some significant effects. These results provide evidence on the in vitro and in vivo inhibition of monoamine oxidase A by fluoxetine.

Animals↗

PubMed1999

Two-state mixed renewal processes for chronic disease.

We develop a model based on a two-state mixed renewal process and propose its use for modelling disease activity in studies of chronic conditions. We specify Weibull forms for the conditional transition intensities to allow for time trends, and bivariate frailties to accommodate subject-to-subject variability in the disease process. Extensions of this model are considered for stratified analyses in which strata are defined by the number of past exacerbations. Data from a motivating study of chronic bronchitis are analysed to illustrate the methodology.

Anti-Infective Agents↗

PubMed1999

A simple method for the isolation and purification of L-asparaginase from Enterobacter aerogenes.

L-Asparaginase from Enterobacter aerogenes was purified by a simple method involving sonication of the crude cell mass, gel filtration with Sephacryl S-100 as the separating material, followed by ultrafiltration. Recent methods involve complex purification procedures of 5-6 steps. The isolation process resulted in 10-fold purification of the enzyme with a specific activity of 55 IU/mg protein and recovery of 54%. The purity was tested by capillary electrophoresis, used for the first time for documenting the purification of L-asparaginase. The choice of the column material was critical in the purification process.

Asparaginase↗