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Biomedical subjects

Mukesh Sharma

Publications and source records attributed to Mukesh Sharma.

6 recordsLinked to original sources

Comprehensive evaluation of solution nuclear magnetic resonance spectroscopy sample preparation for helical integral membrane proteins.

The preparation of high quality samples is a critical challenge for the structural characterization of helical integral membrane proteins. Solving the structures of this diverse class of proteins by solution nuclear magnetic resonance spectroscopy (NMR) requires that well-resolved 2D 1H/15N chemical shift correlation spectra be obtained. Acquiring these spectra demands the production of samples with high levels of purity and excellent homogeneity throughout the sample. In addition, high yields of isotopically enriched protein and efficient purification protocols are required. We describe two robust sample preparation methods for preparing high quality, homogeneous samples of helical integral membrane proteins. These sample preparation protocols have been combined with screens for detergents and sample conditions leading to the efficient production of samples suitable for solution NMR spectroscopy. We have examined 18 helical integral membrane proteins, ranging in size from approximately 9 kDa to 29 kDa with 1-4 transmembrane helices, originating from a number of bacterial and viral genomes. 2D 1H/15N chemical shift correlation spectra acquired for each protein demonstrate well-resolved resonances, and >90% detection of the predicted resonances. These results indicate that with proper sample preparation, high quality solution NMR spectra of helical integral membrane proteins can be obtained greatly enhancing the probability for structural characterization of these important proteins.

Carbon Isotopes↗

A methodology for solid waste characterization based on diminishing marginal returns.

A methodology is developed for estimating the number of waste sorts for characterizing solid wastes into categories based on diminishing minimum incremental information. Convergence in the square of the coefficient of variation with successive waste sorts is used to indicate cost-efficient termination of sampling at substantially reduced numbers of sorts in comparison with existing methodologies. These findings indicate that the numbers of waste sorts beyond that determined using the proposed methodology do not add substantial marginal gains in information and/or reduction in the confidence interval of the estimate. The methodology is demonstrated using waste composition analyses from the Greater Vancouver Regional District where 22 waste sorts are examined. The proposed methodology is simple, and the number of waste sorts can be estimated with a hand-held calculator and utilized in the field.

Confidence Intervals↗

Dietary and inhalation intake of lead and estimation of blood lead levels in adults and children in Kanpur, India.

This research was initiated to study lead levels in various food items in the city of Kanpur, India, to assess the dietary intake of lead and to estimate blood lead (PbB) levels, a biomarker of lead toxicity. For this purpose, sampling of food products, laboratory analysis, and computational exercises were undertaken. Specifically, six food groups (leafy vegetables, nonleafy vegetables, fruits, pulses, cereals, and milk), drinking water, and lead air concentration were considered for estimating lead intake. Results indicated highest lead content in leafy vegetables followed by pulses. Fruits showed low lead content and drinking water lead levels were always within tolerable limits. It was estimated that average daily lead intake through diet was about 114 microg/day for adults and 50 microg/day in children; tolerable limit is 250 microg/day for adults and 90 microg/day for children. The estimated lead intakes were translated into the resultant PbB concentrations for children and adults using a physiologically-based pharmacokinetic (PBPK) model. Monte Carlo simulation of PbB level variations for adults showed that probability of exceeding the tolerable limit of PbB (i.e.,10 microg/dL) was 0.062 for the pre-unleaded and 0.000328 for the post-unleaded gasoline period. The probability of exceeding tolerable limits in PbB level was reduced by a factor of 189 in the post-unleaded scenario. The study also suggested that in spite of the introduction of unleaded gasoline, children continue to be at a high risk (probability of exceeding 10 microg/dL = 0.39) because of a high intake of lead per unit body weight.

Administration, Inhalation↗

Effects of particulate air pollution on the respiratory health of subjects who live in three areas in Kanpur, India.

In this study, the authors assessed the relationship between daily changes in respiratory health and particulate levels with diameters of (a) less than 10 microm (PM10) and (b) less than 2.5 microm (PM2.5) in Kanpur, India. The subjects (N = 91) were recruited from 3 areas in Kanpur: (1) Indian Institute of Technology (Kanpur), which was a relatively clean area; (b) Vikas Nagar, a typical commercial area; and (c) finally, the residential area of Juhilal Colony. All subjects resided near to air quality monitoring sites. Air quality and peak expiratory flow rate samplings were conducted for 39 d. Once during the sampling period, lung-function tests (i.e., forced expiratory volume in 1 s, forced vital capacity) were performed on each subject. Subjects who resided at the clean site performed at predicted (i.e., acceptable) values more often than did subjects who lived at the remaining 2 sites. Subjects who lived at all 3 sites demonstrated a substantial average deficit in baseline forced vital capacity and forced expiratory volume in 1 s values. The authors used a statistical model to estimate that an increase of 100 microg/m3 of the pollutant PM10 could reduce the mean peak expiratory flow rate of an individual by approximately 3.2 l/min.

Adult↗

Multiple myeloma presenting as primary non-secretory plasma cell leukemia.

Primary plasma cell leukemia is a rare manifestation of multiple myeloma, whose neoplastic hierarchy in the classification of malignant hematological disorders is not yet very clearly defined. Morphological and immunological criteria indicate that the cells are at end stage of B cell maturation pathway. This unusual disorder is diagnosed by the presence of more than 2 x 10(9) plasma cells per liter of peripheral blood or more than 20% of the leucocytes being plasma cells on differential count. This occurs either denovo or as a terminal event in patients with long standing multiple myeloma. A case report of a young male patient with primary plasma cell leukemia is presented.

Adult↗