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Biomedical subjects

S N Shah

Publications and source records attributed to S N Shah.

At least 19 recordsLinked to original sources
PubMed2001

Specific repression of beta-globin promoter activity by nuclear ferritin.

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult beta-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the beta-globin promoter at -153 to -148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress beta-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the beta-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant beta-globin promoter for the -150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the -150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human beta-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases.

Animals↗
PubMed2001

The post-prandial state and macrovascular disease: relevance to diabetes mellitus.

There is increasing evidence that the post-prandial state is an important contributing factor to the development of atherosclerosis. In non-diabetic subjects the atherosclerotic risk factors comprised in the categories of lipids, coagulation system and endothelial function may be adversely modified in the post-prandial phase. The generation of an oxidative stress may be the common pathway through which eating may induce these alterations. In diabetic patients these phenomena may be amplified by post-prandial hyperglycemia. There is a growing thought that diabetes is a cardiovascular disease.

Diabetes Mellitus, Type 2↗
PubMed2001

Intramedullary screw fixation of proximal fifth metatarsal fractures: a biomechanical study.

Intramedullary screw fixation is a popular technique for treatment of proximal fifth metatarsal fractures. The purpose of this study was to compare the fixation rigidity of a 5.5 mm partially threaded cannulated titanium screw, with presumed superior endosteal purchase, to a similar 4.5 mm screw. Acute fifth metatarsal fractures were simulated in cadavers, stabilized with intramedullary screws, and loaded to failure in three-point bending. The initial failure loads for the metatarsals fixed with 4.5 mm and 5.5 mm screws were not significantly different (332.4 N vs. 335.2 N, respectively), nor were the ultimate failure loads (849.8 N vs. 702.2 N, respectively). Based upon our results, maximizing screw diameter does not appear to be critical for fixation rigidity and may increase the risk of intraoperative or postoperative fracture.

Biomechanical Phenomena↗
PubMed2001

A benefit-based copay for prescription drugs: patient contribution based on total benefits, not drug acquisition cost.

Several managerial mechanisms have been used by managed care organizations to affect prescription drug utilization and related expenditures. Some efforts have focused on monitoring clinical conditions, drug use, and compliance, whereas other efforts have focused on consumer cost sharing and changing product-mix. Efforts focusing on improving quality of care by identifying untreated patients or by enhancing compliance can lead to appropriately increased drug costs, although perhaps with reduced overall medical expenditures. In contrast, the mechanisms implemented to constrain drug costs raise concerns regarding missed opportunities to enhance clinical outcomes, and the possibility of higher medical expenditures. Cost sharing plays a critical role in defining the pharmaceutical benefit. To balance the demands for access to pharmaceuticals with pressures to constrain costs, levels of cost sharing must be set in a manner that achieves appropriate clinical and financial outcomes. Modern multitier systems often base patient contributions on drug acquisition cost, and often do not consider medical necessity as a coverage criterion. Using an alternative approach, the benefit-based copay, patient contributions are based on the potential for clinical benefit, taking into consideration the patient's clinical condition. For any given drug, patients with a high potential benefit would have lower copays than patients with a low potential benefit. Implementation of such a system would provide a financial incentive for individuals to prioritize their out-of-pocket drug expenditures based on the value of their medications, not their price.

Cost Control↗
PubMed1999

Influence of microbial concentration on the rheology of non-Newtonian fermentation broths.

The objective of this study was to quantify the effect of fungal biomass concentration on the rheology of non-Newtonian fermentation systems. Batch fermentations of Penicillium chrysogenum were carried out with glucose as the sole carbon source. The flow behavior of the system was characterized at various fermentation times and was adequately described by the power-law model. The apparent viscosity of the fermentation broth was significantly affected by biomass concentrations in the fermenter. Fermentation broths containing 17.71 g/l biomass as dry weight were characterized by an apparent viscosity of 0.25 Pa s at a shear rate of 50 s-1. Microbial concentration also affected the power-law flow-behavior index and the consistency index. The value of the consistency index ranged from 0.002 Pa sn at a biomass concentration of 0.1 g/l to 6.14 Pa sn at a biomass concentration of 17.71 g/l. The flow-behavior index decreased from an initial value of 1 to a final value of 0.17. Simple empirical correlations have been proposed to quantify the dependence of the power-law parameters on fungal biomass concentration. Experimental data obtained in this study were accurately described by these correlations. The general applicability of these relationships was tested, using previously published rheological data on Aspergillus awamori and Aspergillus niger fermentation broths, and good agreement was seen between experimental data and the predictions from the empirical correlations.

Biomass↗
PubMed1999

Coronary artery disease in women: a silent killer.

Coronary Artery Disease (CAD) is the leading cause of death and disability among post-menopausal women. Contrary to popular belief, women are at a much greater risk for CAD than for breast cancer. For instance, a 50-year-old female faces a 46 percent risk of CAD and 31 percent risk of CAD mortality. In contrast, her probability of developing and dying from breast cancer is only 10 percent and 3 percent, respectively. In comparison to the other cardiovascular diseases such as mitral valve prolapse, peripartum cardiomyopathy, and eclempsia, CAD is most associated with mortality in women. In fact, one in three women die from CAD in this country.

Coronary Disease↗
PubMed1997

Insulin allergy.

Explore the source record for details and available documents.

Desensitization, Immunologic↗
PubMed1995

Arylsulfatase A and beta-galactosidase activities in leukocytes and lymphocytes from normal and psychiatric subjects. Effects of blood-processing delay and interleukin-2 stimulation.

Arylsulfatase A (ASA) and cerebroside-beta-galactosidase activities in leukocytes serve as a diagnostic tool for determining the presence of metachromatic leukodystrophy and globoid cell leukodystrophy, respectively. It has not been demonstrated whether a delay in blood processing and the presence of mixed cell types in different proportions in leukocytes affect the activities of the two enzymes in these cells. We have in the present study determined the specific activity in leukocytes and lymphocytes (T-cells) prepared from blood samples processed immediately after, 4, and 24 h after collection. In order to determine whether the enzyme activities in lymphocytes reflect expression of genetic trait, and not environmental or "state" influence, the activities of the two enzymes in interleukin 2-stimulated T-cells and resting T-cells were compared. A delay of up to 24 h in blood processing did not significantly change the specific activities of the two enzymes in both leukocytes and lymphocytes. The specific activity of ASA and beta-galactosidase in lymphocytes was 1.4-1.8 times that in leukocytes. The activities of the two enzymes in interleukin 2-stimulated T-cells did not differ from those in resting T-cells. These results indicate that blood-processing delay had no significant effects on ASA and beta-galactosidase activity. The data further indicate that the ASA and beta-galactosidase activity in interleukin 2-stimulated T-cells was not significantly different from resting lymphocytes from either normal or psychiatric subjects exposed to various medications. The activity levels in lymphocytes from psychiatric subjects thus reflect expression of genetic trait, rather than environmental or state influence.

Adult↗
PubMed1994

Cocaine exposure prebreeding to weaning: maternal and offspring effects.

In a model emphasizing prebreeding cocaine administration, rats exposed to cocaine (50 mg/kg) daily were compared to saline-injected and noninjected controls with respect to weight changes, food and water intake, maternal behavior, offspring weight, and activity. During the first 21 days cocaine-treated dams lost weight, while the control dams gained. Throughout gestation and the first 14 days of lactation all groups gained weight, but the cocaine-exposed dams never completely recovered from the initial anorectic effect. Except during the first week of exposure, cocaine dams ate and drank more than the normal controls and drank more than the saline group. During gestation there was no difference in food intake, although the cocaine dams continued to drink more than controls. During lactation there were no differences in food and water consumption across groups. However, the cocaine dams exhibited more nursing behavior. From birth to day 21, the offspring of cocaine-treated dams were smaller than those of either control group. By 51 days of age, group differences had disappeared. Cocaine-exposed pups and saline offspring tested at days 28 and 85 were more active than those of noninjected controls. The results indicate that administration of cocaine for a period prior to breeding and during gestation and lactation, a protocol which closely resembles human drug abuse patterns, is more devastating than the administration during gestation.

Aging↗