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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,333 records · Page 74Linked to original sources

Expression and antigenicity of Plasmodium falciparum major merozoite surface protein (MSP1(19)) variants secreted from Saccharomyces cerevisiae.

Four antigenic variants of the 19-kDa carboxy terminal fragment of Plasmodium falciparum merozoite surface protein, MSP1 (MSP1(19)), were expressed in Saccharomyces cerevisiae as a histidine-tagged, secreted polypeptides (rMSP1(19)s). Structural analysis of the rMSP1(19)s indicated that a single amino acid change (E to Q) in the first EGF-like domain of the yeast-secreted rMSP1(19) proteins caused a significant change in their disulfide bond-dependent conformation. The antigenicity of the rMSP1(19)s were qualitatively and quantitatively analyzed by direct and competitive binding ELISAs. The data indicate that conserved and variant B cell determinants of MSP1(19), as well as epitopes that are known targets of protective antibodies, were recreated authentically in the rMSP1(19)s. Secretion of histidine-tagged rMSP1(19)s using the expression system described may be an efficient and effective means of producing a properly folded immunogen for a human vaccine against the blood stages of P. falciparum.

Amino Acid Sequence↗

Effects of plasminogen and interleukin-1 beta on bone resorption in vitro.

Inflammatory bone resorption, a characteristic feature of periodontal disease and rheumatoid arthritis, appears to be mediated by interleukin-1 beta (IL-1 beta). IL-1 beta has been shown to stimulate a wide range of proteolytic enzymes, including collagenases and plasminogen activators, in particular chondrocytes, synovial cells, and isolated osteoblasts. In this study, we have examined the hypothesis that IL-1 beta may stimulate bone loss by inducing the activity of plasminogen activators (PAs) in bone cultures. The latter would convert plasminogen to plasmin, which in turn can activate precursor procollagenase to collagenase. Active collagenase would then break down the bone collagen matrix. In the present study, release of 45Ca from fetal rat long bones in culture was studied in the presence of plasminogen and IL-1 beta. Plasminogen and IL-1 beta separately enhance resorption of fetal rat long bones in vitro. When plasminogen and IL-1 beta are added together at suboptimal levels, mainly additive effects are observed. The presence of heat-inactivated serum does not alter these results. These data tend to indicate that IL-1 beta is stimulating bone resorption through both PA-dependent and PA-independent pathways.

Animals↗

Natural history of aortoarteritis: an angiographic study in 26 survivors.

The natural history of aortoarteritis was angiographically studied in 26 surviving patients (19 female; 7 male). The interval between the initial and current angiographic study was 38-228 months (mean -84.46 months). All patients underwent panaortography during both studies and one patient also underwent pulmonary angiography. The lesions were extensive involving the ascending, arch and the descending thoracic and/or the abdominal aorta (Type III) in 15 patients; localized to the arch alone (Type I) in five patients and to the descending thoracic and/or abdominal aorta in five patients (Type II). Pulmonary angiography in the solitary patient with clinical features of pulmonary hypertension showed occlusion of the lower lobe branch of the right pulmonary artery. The lesions were occlusive in 19 patients, aneurysmal in one patient and mixed in six patients. While four patients developed fresh lesions in the follow-up period, two showed progression of existing lesions and one revealed partial thrombosis of an aneurysm. Persistently elevated erythrocytic sedimentation rate (> 40 mm) was identified as a reliable indicator for activity of inflammatory process and disease progression. The stable nature of the lesions in 20 out of 26 patients in this study indicates a non-progressive course in the healed stage of aortoarteritis and suggests a conservative approach to the management of this disease in all patients except those with severe, life-threatening manifestations.

Adolescent↗

Results of radical radiotherapy in carcinoma of the uterine cervix stage I-III.

A retrospective analysis is described of 271 diagnosed cases of carcinoma of the uterine cervix who were treated with radical radiotherapy between January 1987 and July 1988 at the Institute Rotary Cancer Hospital. The mean age at presentation was 49 years and 89% of the tumours were FIGO Stage II and III. The median duration of follow-up was 60 months. The early cases were treated with two intracavitary insertions of 34 Gy each to point A with a Selectron LDR intracavitary system, followed by 36 Gy external radiotherapy to the parametrium. Late stage disease was treated with 50 Gy of external radiotherapy, followed by a single intracavitary insertion of 30 Gy to point A. To compensate for the higher dose rate of the Selectron (180 cGy/h) a dose reduction factor of 15% was applied over the intracavitary dose. There were 2.5% and 4.7% of late Grade III bladder and bowel complications, respectively, requiring surgical intervention. There was no relationship between haemoglobin level at diagnosis and the development of late complications. The actuarial 5-year survivals were 65%, 63% and 35% for Stages I, II and III disease, respectively. This study from the Indian subcontinent shows the effectiveness of radiotherapy in Stages I, II and III carcinoma of the uterine cervix, with acceptable morbidity rates.

Actuarial Analysis↗

Bacteriophage typing in Salmonella bareilly.

A total of 675 strains of Salmonella bareilly received from different parts of India and France during 1959-92 were phage typed using six bacteriophages. Overall typability achieved was 90.8% with 23 distinct phage types excluding a group of untypable strains. Phage types have been defined in octal code. Simpson's coefficient was applied for diversity index having a value of 0.839. This system was found to be reproducible, stable and epidemiologically useful.

Animals↗

The accuracy of magnitude production of submaximal precision and power grips and gross motor efforts.

The objective of the study was to measure maximal and subjectively graded submaximal efforts in a pinch grip, power grip, and stoop life activity, subsequently to study the relationship of these efforts across activities and time, and furthermore to determine the reliability of effort perception of activities in different grades of operation. Ten normal male university students with mean age of 22.2 years, mean height of 175.3 cm, and mean weight of 71.4 kg volunteered for the study. All subjects were required to exert their maximal efforts, 80%, 60%, 40%, and 20% (of the maximal) effort in pinching, gripping and stoop lifting for three trials in a random order on four different days. The subjects were tested at the same time of the day on a Monday, Wednesday, Friday of one week, and Friday of the next week. While the activity and perception had significant main effects (p < 0.001) the trial was significant only for average strength (p < 0.04). There was a significant two-way interaction between activity and perception; all other interactions were not significant. There was a systematic bias in perception at all graded contractions except at 40% level of effort. The perceived 60% and 80% of maximal voluntary contractions (MVC) were lower and 20% was higher than their respective objective values based on MVC (p < 0.01). At 40% effort there was no statistical difference between perceived and objective strength effort in all three activities. The reliability of perception was similar for precision, power, or gross activity.

Adult↗

Lumbosacral compression in maximal lifting efforts in sagittal plane with varying mechanical disadvantage in isometric and isokinetic modes.

Nine normal male subjects (mean age 28.2 years and mean weight 72.6 kg) performed 20 standardized maximal effort lifting tasks. They were asked to perform stoop and squat lifts at half, three-quarters and full individual horizontal reach distances in mid-sagittal plane in isometric and isokinetic modes (fixed velocity 60 cm/s). Both stoop and squat lifts were initiated at the floor level and terminated at the individual's knuckle height keeping the horizontal distance constant throughout the lift. The isometric stoop lifts were performed with hip at 60 degrees and 90 degrees of flexion with hands at preselected reach distances. The isometric squat lifts were performed with knees at 90 degrees and 135 degrees of flexion with hands at similarly preselected reach distances. The force was measured using a Static Dynamic Strength Tester with load cell (SM 1000). The postures were recorded using a two-dimensional Peak Performance System with an event synchronizing unit. The load cell was sampled at 60 Hz and the video filming was done at 60 frames per second. The force and postural data were fed to a biomechanical model (Cheng and Kumar 1991) to extract external moment and lumbosacral compression. The strengths generated in different conditions were significantly different (p < 0.01). The strength variation ranged by up to 73% whereas the lumbosacral compression varied by only up to 15%. A high level of lumbosacral compression was maintained in all conditions.

Adult↗

Modification of the expression of adenosine 3',5'-cyclic monophosphate-induced differentiated functions in neuroblastoma cells by beta-carotene and D-alpha-tocopheryl succinate.

OBJECTIVE: The role of beta-carotene and vitamin E in modifying the effect of cell differentiating agent has not been studied. This study has investigated the effects of beta-carotene and d-alpha-tocopheryl succinate (alpha-TS) on adenosine 3',5'-cyclic monophosphate (cAMP) induced differentiated functions in murine neuroblastoma cells (NBP2) in culture. METHODS: Prostaglandin E1 (PGE1), a stimulator of adenylate cyclase, and 4-(3-butoxy-4-methoxy-benzyl)-2-imidazolidinone (R020-1724), an inhibitor of cyclic nucleotide phosphodiesterase, were used to induce differentiation in NB cells. RESULTS: Both beta-carotene and alpha-TS markedly enhanced the level of morphologic differentiation (neurite formation) induced by both PGE1 and R020-1724. However, beta-carotene and alpha-TS by themselves were ineffective. These vitamins increased tyrosine hydroxylase (TH) activity. However, beta-carotene did not significantly affect PGE1- and R020-1724-stimulated rise in TH activity. alpha-TS at a higher concentration inhibited PGE1- and R020-1724-stimulated increase in TH activity. None of the above treatments affected basal choline acetyltransferase (ChAT) activity. beta-carotene and alpha-TS caused a transient increase in cAMP level, and they also enhanced the effect of PGE1 and R020-1724 on cAMP level in a transient manner. CONCLUSION: These results suggest that beta-carotene and alpha-TS modify the effects of cAMP stimulating agents on differentiation of NB cells in culture.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Molecular dynamics simulations suggest that the Eco RI kink is an example of molecular strain.

The energy surface in the vicinity of the "Eco RI kink" was investigated by conducting both in vacuo molecular dynamics simulations as well as a simulation with explicit solvent. The in vacuo simulations used the "all atom" AMBER 3.0 force field with a distant dependent dielectric function and "hydrated" counter ions while the simulation with explicit solvent used the AMBER 4.0 force field, fully charged phosphates and counter ions and a dielectric constant of 1.0. The thrust of the simulations was to discriminate between two models of the energy surface of the deformed DNA as found in the recognition complex with Eco RI endonuclease. In the intrinsic model, the kinked DNA is a local minimum of the energy surface intrinsic to the DNA itself while in the strained model there is no significant energy barrier separating kinked and regular B-DNA. The two models have significant implications for theories of indirect recognition of DNA based on sequence-dependent deformability. The simulations suggest that the Eco RI-kinked structure is an example of molecular strain because it is not near a minimum of any of the potential energy functions examined. The simulations leave the question of an energy barrier somewhat open and raise the possibility that the Eco RI kink is at (or near) a point of dynamic instability of the energy surface (either a true maximum or a saddle point).

Base Sequence↗

In situ-forming gels for ophthalmic drug delivery.

Poor bioavailability of ophthalmic solutions caused by dilution and drainage from the eye can be overcome by using in situ-forming ophthalmic drug delivery systems prepared from polymers that exhibit reversible phase transitions. Joshi et al. (1), have demonstrated that aqueous compositions that reversibly gel in response to simultaneous variations in at least two physical parameters, such as temperature, pH, and ionic strength, can be formed by appropriate combinations of macromolecular polymers which exhibit reversible gelation properties. In the present study, the rheological characterization of such a system, prepared by a combination of Carbopol (C) and methyl cellulose (MC), was carried out at two different pH (4.0 and 7.4) and temperatures (25 and 37 degrees C) by rotational cone and plate viscometry. The shear stress (tau) vs. shear rate (D) flow curves of the aqueous polymer solutions indicated a pseudoplastic behavior, with a yield point. An increase in pH from 4.0 to 7.4, or temperature from 25 to 37 degrees C, resulted in an increase in viscosity (eta), tau, and yield point, the magnitude of changes being highest when both the parameters were altered simultaneously. An increase in concentration of either C or MC, or an increase in MC molecular weight results in an increase in eta, tau, and yield point. Among the compositions studied, a solution containing 1.5% MC 0.3% C was found to have low eta, and formed a strong gel under simulated physiological conditions. Such a system can be formulated as drug containing liquid suitable for administration by instillation into the eye, which upon exposure to physiological conditions will shift to the gel (semi-solid) phase, thus increasing the precorneal residence time of the delivery system and enhancing ocular bioavailability.

Acrylic Resins↗

Plasma cell myeloma in patients who are HIV-positive.

This report describes the occurrence of plasma cell neoplasia in three young HIV-positive males. Two patients presented with massive ascites. On cytologic examination of the fluid, many immature plasma cells were noted. Genotyping of fluid demonstrated clonal rearrangement of immunoglobulin heavy and kappa light chain genes in both cases. Postmortem examination on one of these revealed neoplastic plasmacellular infiltrate in various organs, including the bone marrow. The third case presented with a hemorrhagic, rapidly enlarging gingival mass with a histologic appearance of an undifferentiated neoplasm. Immunoperoxidase studies revealed positive staining only for epithelial membrane antigen. On flow cytometry, the neoplastic cells did not mark with leukocyte common antigen or any of the B- or T-cell markers. Cytoplasmic kappa light chain restriction, as well as genotypic studies, confirmed the diagnosis of anaplastic plasmacytoma. In two cases a clonal population was detected using a probe to the terminal repeat region of the Epstein-Barr virus. These results suggest that plasma cell malignancy is another AIDS-associated neoplasm. Its occurrence in this group of patients is not only coincidental.

Adult↗

MEGA: Molecular Evolutionary Genetics Analysis software for microcomputers.

A computer program package called MEGA has been developed for estimating evolutionary distances, reconstructing phylogenetic trees and computing basic statistical quantities from molecular data. It is written in C++ and is intended to be used on IBM and IBM-compatible personal computers. In this program, various methods for estimating evolutionary distances from nucleotide and amino acid sequence data, three different methods of phylogenetic inference (UPGMA, neighbor-joining and maximum parsimony) and two statistical tests of topological differences are included. For the maximum parsimony method, new algorithms of branch-and-bound and heuristic searches are implemented. In addition, MEGA computes statistical quantities such as nucleotide and amino acid frequencies, transition/transversion biases, codon frequencies (codon usage tables), and the number of variable sites in specified segments in nucleotide and amino acid sequences. Advanced on-screen sequence data and phylogenetic-tree editors facilitate publication-quality outputs with a wide range of printers. Integrated and interactive designs, on-line context-sensitive helps, and a text-file editor make MEGA easy to use.

Algorithms↗

Expression of peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase enzyme and its mRNA in peroxisome proliferator-induced liver tumors.

We have examined ciprofibrate and dehydroepiandrosterone (DHEA)-induced hepatic lesions for the peroxisomal beta-oxidation system enzyme peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) and its mRNA using SDS-polyacrylamide gel electrophoresis, antibodies and cDNA probe. All 12 neoplastic nodules and nine hepatocellular carcinomas (HCCs) that were analyzed for PBE mRNA by in situ hybridization showed an intense signal comparable to the adjacent non-neoplastic liver. SDS-polyacrylamide gel electrophoresis of postnuclear fractions of six HCC and adjacent liver tissue showed a marked increase in an 80 kDa polypeptide. Immunoblot and Northern blot analysis showed a marked increase in PBE enzyme and PBE mRNA respectively in HCC and adjacent non-neoplastic liver tissue. In control livers (animals not treated with peroxisome proliferators), the levels of PBE enzyme and mRNA were very low or undetectable. The results of this study clearly indicate that peroxisome proliferator (PP)-induced liver lesions express peroxisomal enzymes to the same extent as adjacent liver and that these enzymes are not useful markers for identification of PP-induced lesions.

3-Hydroxyacyl CoA Dehydrogenases↗

Using vehicle-mounted nets for studying activity of Arabian sand flies (Diptera: Psychodidae).

Vehicle-mounted nets were used on 15 nights in northern Oman to collect 2,216 sand flies. The composition of the catch was compared with that of 100 sticky traps, which were used twice a month over a 15-mo period to collect 3,099 sand flies. Sticky trap catches showed no obvious seasonal change in abundance. The vehicle nets collected up to 260 flies per night, with a mean of 148. This compared with the catch of the 100 sticky traps, which had an overall mean of 115 flies per night. The vehicle nets collected seven species of sand flies (four Phlebotomus and three Sergentomyia). Phlebotomus alexandri Sinton, the presumed vector of visceral leishmaniasis in Oman, made up 29% of the catch. In contrast, the sticky traps collected mainly Sergentomyia spp., and P. alexandri was only 4% of the catch. Overall, catch of both methods had a sex ratio of 1:1, but both collected a higher proportion of female P. alexandri. The vehicle nets collected only a few blood-fed flies, the greatest number being 33 P. alexandri (8% of the females for this species). However, some females were collected at each stage of the gonotrophic cycle; the smallest number was in stage II. All the flies developing eggs beyond stage II had had a blood meal, so that there was no sign of autogeny in these species. Ten percent of the females were parous. The vehicle-mounted net placed on the side of the vehicle at 0.3 to 1.8 m above the ground caught a greater number of Sergentomyia clydei Sinton than an identical net mounted on top of the vehicle at 1.8 to 2.8 m, in which the rest of the species, including P. alexandri, mainly were caught.

Animals↗