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Biomedical subjects

A Sengupta

Publications and source records attributed to A Sengupta.

At least 55 records · Page 3Linked to original sources
PubMed1999

Characterisation of the binding of digitoxin and acetyldigitoxin to human serum albumin by high-performance affinity chromatography.

Zonal elution and high-performance affinity chromatography were used to examine interactions of the drugs digitoxin and acetyldigitoxin with the protein human serum albumin (HSA). This was done by injecting small amounts of digitoxin and acetyldigitoxin onto an immobilized HSA column in the presence of mobile phases that contained various concentrations of digitoxin, acetyldigitoxin or other solutes as competing agents. A fixed concentration of beta-cyclodextrin was also present in the mobile phase as a solubilising agent. It was found that digitoxin and acetyldigitoxin each had strong interactions at a single common binding site on HSA, but with slightly different equilibrium constants for this region. Neither compound showed any competition with warfarin or L-tryptophan, which were used as probes for binding at the warfarin-azapropazone and indole-benzodiazepine sites of HSA. These results confirmed the presence of a separate binding region on HSA for digitoxin-related compounds.

Acetyldigitoxins↗
PubMed1999

Percutaneous transluminal coronary angioplasty in the elderly: epidemiology, clinical risk factors, and in-hospital outcomes. The Northern New England Cardiovascular Disease Study Group.

OBJECTIVES: To explore the relation between older age and clinical presentation, procedural success, and in-hospital outcomes among a large unselected population undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Although more elderly patients are receiving PTCA, studies of post-PTCA outcomes among the elderly have been limited by small numbers and exclusive selection criteria. METHODS: Data were collected as a part of a prospective registry of all percutaneous coronary interventions performed in Maine, New Hampshire, and from 1 institution in Massachusetts between October 1989 and December 1993. Comparisons across 4 age groups, (<60, 60 to 69, 70 to 79, and 80 years and above) were performed using chi-square tests, the Mantel-Haenzsel test for trend, and logistic regression. RESULTS: Twelve thousand one hundred seventy-two hospitalizations for PTCA were performed with 507 of them (4%) in persons at least 80 years old. Octogenarians were more likely to be women, have multivessel disease, high-grade stenoses, and complex lesions but were less likely to have hypercholesterolemia, a history of smoking, or have undergone a previous PTCA. In the elderly, PTCAs were more often performed urgently and for unstable syndromes compared with younger age groups. Advancing age is strongly associated with in-hospital death, and among the oldest old with an increased risk of postprocedural myocardial infarction. Despite differing presentation and procedural priority, angiographic success and subsequent bypass surgery did not vary by age. CONCLUSIONS: With the increasing age of the population at large as well as that segment at risk for cardiac revascularization, information about age-associated risks of the procedure, especially the substantially higher risk of death in octogenarians, will be critical for both physicians and patients considering PTCA.

Age Factors↗
PubMed1999

Difficulties in estimating age using root dentine translucency in human teeth of varying antiquity.

Estimation of age at death is an essential part of reconstructing information from skeletal material. This becomes more difficult after development has ceased and following taphonomic alteration in archaeological material. Most biological markers of age do not record the chronological age (calendar age), but the biological or physiological age of the individual. Of the age-related changes in the mature dentition of modern samples, the extent of root dentine translucency (RDT) has been shown to correlate closely with chronological age. A protocol for measurement of RDT was established and applied to modern and archaeological teeth of known age (Spitalfields sample). Percentage length of RDT in sectioned teeth was found to correlate well with chronological age in the modern sample but not in the archaeological sample. The majority of the archaeological sample was affected by a morphological change creating a "chalky" appearance to the dentine. Removal of the obviously affected teeth did not improve the correlation coefficients to any useful degree. "Chalky" dentine appeared, under the light microscope, to be composed of large fenestrations, islands of mineralized tissue and masses of filiform structures that appeared to be following the path of the dentinal tubules in their invasion of the peripheral dentine. The filiform structures are consistent in their appearance with a previously reported tunnelling mycelium and impart such an effect on RDT that it cannot readily be used for age estimation in affected teeth.

Adult↗
PubMed1999

The effects of dental wear on third molar eruption and on the curve of Spee in human archaeological dentitions.

The abrasiveness of food is a key determinant in the rate of physiological attrition (dental wear) in humans. With increasing food processing through time, the rate of physiological dental wear in human teeth has decreased markedly. Many consider such wear to be beneficial to oral health and that insufficient wear may result in impaction of the third molars. If enhanced extraoral food processing provides an evolutionary advantage, then it is possible that agenesis of the redundant third molar may follow. One of the aims here was to examine impaction and agenesis of the third molars in four populations of varying antiquity and hence varying dental-wear rates. Paradoxically, whilst there is a decrease in the rate of dental wear with modernity, there is also an increasing prevalence of advanced dental wear due to prolongation of the lifespan of the human dentition. As the effect of dental wear on the curve of Spee was unknown, a second aim was to examine it in an archaeological population with a high rate of dental wear. The results showed an increase in non-eruption and impaction of the third molars with modernity, but did not demonstrate a significant increase in the rate of agenesis. The time period over which impaction and agenesis could be discerned was of the order of 600 years and this may not be sufficient to observe adaptive changes at the genetic level in humans. In molar teeth there was no clear indication of maintenance of the curve of Spee with dental wear. This has potential implications on the design of prostheses for the worn dentition.

Adult↗
PubMed1999

The anti-carcinogenic role of lycopene, abundantly present in tomato.

Among the many carotenoids present in nature, lycopene has been of special interest and has received attention in recent times due to its suggestive association in reducing risk for cancer at many sites including breast, prostate and pancreas. Several studies have attempted to determine the bioactive levels of this carotenoid in human tissues and the influence of plant food and cancer on carotenoid levels. Experimental studies have also implicated the protective role of lycopene during carcinogenesis. These observations should justify further exploration and evaluation of the biological function of lycopene alone or in combination with other chemical compounds present in tomato fruit for their use in cancer prevention.

Animals↗
PubMed1998

Studies of protein binding to nonpolar solutes by using zonal elution and high-performance affinity chromatography: interactions of cis- and trans-clomiphene with human serum albumin in the presence of beta-cyclodextrin.

High-performance affinity chromatography and zonal elution studies were used to examine the binding that takes place between the drug clomiphene and the protein human serum albumin (HSA). Equations were derived to describe the behavior of zonal elution experiments in which a solubilizing agent is present in the mobile phase to aid in the dissolution of a competing agent or injected analyte. These equations were then used to determine the association equilibrium constants for the clomiphene/HSA system, with beta-cyclodextrin being used as a complexation agent to improve the water solubility of cis- and trans-clomiphene without affecting the nature of their binding to HSA. It was found in these studies that both cis- and trans-clomiphene have 1:1 interactions at a common binding region on HSA (association constants at pH 7.4 and 37 degrees C: cis, 7.5 x 10(6) M-1; trans, 1.3 x 10(6) M-1). Further competition experiments between cis- or trans-clomiphene and various site-selective probes indicated that the clomiphene-binding region is the same as the proposed tamoxifen site of HSA. The approach and equations used within this report are general ones that can be applied to zonal elution studies of other solute-ligand systems in which one or more of the test components have limited solubility in the desired mobile phase.

Chromatography, Affinity↗
PubMed1998

Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules.

The paired helical filaments (PHFs) found in Alzheimer's disease (AD) brains are composed primarily of the microtubule-associated protein tau. PHF-tau is in a hyperphosphorylated state and is unable to promote microtubule assembly. We investigated whether the inhibition of tau binding to microtubules is increased when tau is phosphorylated by different kinases in combination with GSK-3. We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. From these observations we estimate that the phosphorylation of Thr 231, Ser 235, and Ser 262 contributes approximately 26, approximately 9, and approximately 33%, respectively, of the overall inhibition of tau binding to microtubules. Together, our results indicate that the binding of tau to microtubules is controlled by the phosphorylation of several sites, among which are Thr 231, Ser 235, and Ser 262.

Amino Acid Sequence↗
PubMed1998

Ortner's syndrome revisited.

Hoarseness of voice due to paralysis of the left recurrent laryngeal nerve caused by a dilated left atrium in mitral stenosis as discussed by Ortner, is a subject of controversy. Different authors have cited different mechanisms as explanation. A variety of cardiac problems such as primary pulmonary hypertension, ischaemic heart disease, various congenital heart disorders can all lead to paralysis of the left recurrent laryngeal nerve. Most authors believe that pressure in the pulmonary artery causes the nerve compression. In Papua New Guinea cor pulmonale and rheumatic heart disease are the commonest cardiac disorders seen. Ortner's syndrome is a rarity and has never been reported from here before. Here three different case reports are presented with mitral stenosis, primary pulmonary hypertension and combined mitral stenosis and regurgitation and the pathogenesis of hoarseness is discussed.

Adolescent↗
PubMed1998

CGRP upregulation in dorsal root ganglia and ileal mucosa during Clostridium difficile toxin A-induced enteritis.

We have previously reported that pretreatment of rats with capsaicin (an agent that ablates sensory neurons) or CP-96345 (a substance P receptor antagonist) dramatically inhibits fluid secretion and intestinal inflammation in ileal loops exposed to Clostridium difficile toxin A. The aim of this study was to determine whether calcitonin gene-related peptide (CGRP), a neuropeptide also found in sensory afferent neurons, participates in the enterotoxic effects of toxin A. Administration of toxin A was also found to increase CGRP content in dorsal root ganglia and ileal mucosa 60 min after toxin exposure. Furthermore, immunohistochemical studies demonstrated increased neuronal staining for CGRP 2 h after toxin A treatment. Pretreatment of rats with CGRP-(8-37), a specific CGRP antagonist, before instillation of toxin A into ileal loops significantly inhibited toxin-mediated fluid secretion (by 48%), mannitol permeability (by 83%), and histological damage. We conclude that CGRP, like substance P, contributes to the secretory and inflammatory effects of toxin A via increased production of this peptide from intestinal nerves, including primary sensory afferent neurons.

Animals↗
PubMed1998

An experimental study to evaluate the technological limitations in the understanding of the haemodynamic change in pre-eclampsia.

BACKGROUND: Conventional indices could not define the pathogenesis of pre-eclampsia and its predictability. It has also not been possible to record these indices from the local uteroplacental system where the pathology lies. OBJECTIVE: To investigate the limitations of the currently available blood pressure-flow measuring indices and techniques commonly used in pregnancy.METHOD: Blood pressure and velocity profiles were obtained under various pathophysiological conditions for pregnant and non-pregnant animals and human subjects. The data were analysed using both conventional and computer-based spectral methods. RESULTS: Continuous monitoring of blood pressure and velocity together with their spectral analysis appeared to be a useful sensitive indicator in pregnancy beyond the commonly available conventional analytical method. In high-resistance flow such as in hypertension and in pre-eclampsia, the power amplitude was relatively low at low frequency. Power amplitude remained high at low frequency in normal low-resistance state of pregnancy. CONCLUSION: The results suggest the need to develop a highly sensitive instrumentation whereby any minute variation in mean arterial pressure that is of clinical significance can be measured. Alternatively, analytical advancement, such as use of power spectrum analysers, might prove to be useful and sensitive. Variability of heart rate is an important determinant of the underlying pathophysiology in pregnancy. It is concluded that the heart rate of pre-eclamptics and hypertensives has to increase in order to maintain a constant organic blood flow whereas in normal pregnancy bloow flow can rise even without an incrase in heart rate. Future research should be directed towards blood flow mapping, power spectral analysis and image processing of the blood pressure-flow profile obtained from local and systemic compartments under different pathophysiological conditions of pregnancy.

Journal Article↗
PubMed1997

Results of directional coronary atherectomy in Northern New England. Northern New England Cardiovascular Disease Study Group.

The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.

Aged↗
PubMed1997

Predictors of mortality from kidney cancer in 332,547 men screened for the Multiple Risk Factor Intervention Trial.

BACKGROUND: The authors examined predictors of mortality from kidney cancer in 332,547 men who were screened as part of the Multiple Risk Factor Intervention Trial. METHODS: The vital status of each member of this cohort was ascertained through 1990. Death certificates were obtained from state health departments and coded by a trained nosologist. Three hundred ninety-eight deaths due to kidney cancer occurred among the cohort of 332,547 men after an average of 16 years of follow-up. The authors used the Cox proportional hazards model to study the joint associations of age, race, income, blood pressure, cigarette smoking, and use of medication for diabetes with risk of death from kidney cancer. RESULTS: The authors observed independent associations with age, cigarette smoking status (relative risk [RR] = 2.02; 95% confidence interval [CI], 1.65-2.48), and systolic blood pressure (relative risk [RR] = 1.12 for systolic blood pressure level 10 millimeters of mercury higher; 95% CI, 1.06-1.18). The authors obtained similar results when deaths that occurred during the first 5 years were excluded. CONCLUSIONS: These findings add to the increasing body of evidence that cigarette smoking and blood pressure level are modifiable risk factors for kidney cancer in men.

Adult↗
PubMed1997

Understanding utero-placental blood flow in normal and hypertensive pregnancy through a mathematical model.

Normal development of utero-placental circulation is crucial not only for the survival and growth of the fetus in utero, but also for maternal well-being. Any disturbance or abnormality may reflect underlying pathology. Geometric conversion of a pre-pregnant spiral vessel into a divergent low-resistance vessel is believed to be responsible for the increased utero-placental blood flow in normal pregnancy. Known biomedical investigative techniques have failed to explain many such underlying haemodynamic changes taking place in the utero-placental system. Therefore, proper understanding of the system using a mathematical model has been found to be useful. The physiological fluid dynamic study is the first in this branch of physiology. Abnormal pressure gradient, axial velocity, volume flow and shear rate are obtained for various slowly changing geometries such as, tapering, divergence, local constrictions and sinusoidal tube for low Womersley parameters. The model can explain many enhanced patho-physiological changes, such as persistence or the appearance of local constriction in the utero-placental vessels. Such pathological changes are considered to be responsible for very high utero-placental resistance, leading to blood flow insufficiency in pre-eclampsia or intra-uterine growth retardations. It is believed that these changes may be caused by low shear rate on the pre-existing deranged or abnormal endothelium. Furthermore, this derangement is caused by an abnormal proliferation of either spiral vessels or the invading non-villous trophoblasts. Doppler flow study can explain and validate some of the theoretically derived flow velocity results. The study opens up a new area of research into utero-placental physiological fluid dynamics.

Computer Simulation↗
PubMed1997

Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylation of human tau by cdk5.

Tau protein from Alzheimer disease (AD) brain is hyperphosphorylated by both proline-dependent protein kinases (PDPKs) and non-PDPKs. It is presently unclear how PDPKs and non-PDPKs interact in tau hyperphosphorylation. Previously we have shown that non-PDPKs can positively modulate the activity of a PDPK (GSK-3) in tau phosphorylation (Singh et al. (1995) FEBS Lett. 358, 267-272). In this study we have investigated whether (A) non-PDPKs can also modulate the activity of the PDPK, cdk5, (B) a PDPK can modulate the activities of another PDPK, as well as non-PDPKs. We found that, like GSK-3, the activity of cdk5 is stimulated if tau were first prephosphorylated by any of several non-PDPKs (A-kinase, C-kinase, CK-1, CaM-kinase II). Prephosphorylation of tau by cdk5 stimulated both the rate and extent of a subsequent phosphorylation catalyzed by GSK-3. Under these conditions thr 231 phosphorylation was especially enhanced (9-fold). No significant stimulation of phosphorylation was observed when the order of these kinases was reversed (i.e. GSK-3 followed by cdk5). By contrast, prephosphorylation of tau by cdk5 served to inhibit subsequent phosphorylation catalyzed by C-kinase and CK-1, but not by A-kinase or CaM-kinase II. Our results suggest that in tau hyperphosphorylation in AD brain, cdk5-catalyzed phosphorylation may serve to upregulate the activity of GSK-3 and down-regulate the activities of C-kinase and CK-1.

Alzheimer Disease↗
PubMed1997

Nitric oxide and gallbladder motility in prairie dogs.

In this study we evaluated the role of nitric oxide (NO) on gallbladder motility in the normal prairie dog by 1) immunohistochemistry, 2) an enzymatic assay for NO synthase (NOS), and 3) an in vivo model to measure whole gallbladder tone and contractility. NOS was localized to gallbladder mucosal cells by NADPH-diaphorase and polyclonal antibodies to a constitutive brain NOS. Gallbladder mucosal homogenates demonstrated total NOS activity in the range of 578 +/- 115 pmol x mg protein(-1) x 30 min(-1). Blockade of NOS activity in vivo using N(omega)-nitro-L-arginine methyl ester resulted in an up to 80% increase in gallbladder tone from basal. A 40% increase in tone was seen with methylene blue, suggesting that tone was maintained by both NO activation of guanylate cyclase and possibly direct effects on Ca2+ channels. An exogenous nitrosothiol, S-nitroso-N-acetyl-cysteine, abolished cholecystokinin (CCK) octapeptide and bethanechol-stimulated gallbladder contraction. We conclude that the prairie dog gallbladder contains constitutive NOS and synthesizes NO, which is important for the maintenance of basal gallbladder tone and is an inhibitor of the contractile response of the gallbladder to agonists such as CCK and bethanechol.

Animals↗
PubMed1996

Cigarette smoking as a predictor of death from prostate cancer in 348,874 men screened for the Multiple Risk Factor Intervention Trial.

The association of cigarette smoking and mortality from prostate cancer was evaluated in 348,874 black and white men who were screened as part of the Multiple Risk Factor Intervention Trial (MRFIT). Current smoking status was assessed, serum cholesterol was measured, and demographics were recorded at screening; however, no information was collected on history of smoking, prostate screening, or diet. The vital status of each member of this cohort was ascertained through 1990. Death certificates were obtained from state health departments and coded by a trained nosologist. A total of 826 deaths due to prostate cancer occurred over an average of 16 years follow-up. The proportional hazards model was used to study the joint association of age, race, income, cigarette smoking, serum cholesterol level, and use of medication for diabetes mellitus on risk of death from prostate cancer. Statistically significant associations were observed with age (p < 0.01), cigarette smoking status (relative risk (RR) = 1.31, p < 0.01), black race (RR = 2.70, p < 0.01), and serum cholesterol (RR = 1.02 for 10 mg/dl higher cholesterol level, p < 0.05). Similar results were obtained when deaths that occurred during the first 5 years were excluded. Among cigarette smokers, there was some evidence of a dose-response relation (p = 0.20). The relative risk for those who reported that they smoked 1-25 cigarettes per day compared with nonsmokers was 1.21 (p = 0.04); the relative risk for those who reported smoking > or = 26 cigarettes per day compared with nonsmokers was 1.45 (p = 0.0003). These findings add to the limited evidence that cigarette smoking may be a risk factor for prostate cancer.

Adult↗
PubMed1996

Blood pressure in minorities screened for the Multiple Risk Factor Intervention Trial (MRFIT).

THE AUTHORS PRESENT DATA FROM 361, 662 MEN ages 35 to 57, screened from 1973 to 1976 for possible participation in the Multiple Risk Factor Intervention Trial (MRFIT). Volunteers identified themselves as "white," "black," "Oriental," "Spanish American," "American Indian," or "other." They also noted if they were taking medication for diabetes. A trained technician measured blood pressure after participants had rested for 5 minutes, using the fifth Korotkoff sound to define diastolic pressure and averaging the second and third of three readings. Differences among the groups included the following: blacks had consistently higher systolic and diastolic blood pressure (SBP and DBP) than other groups; Orientals had slightly lower pressure than other nonblack groups; American Indians had somewhat higher pressure than other nonblack groups at ages 35 to 44 but lower at ages 45 to 54; Hispanics in Miami and Davis, California, had significantly higher SBP and DBP than whites in the same area; Orientals in California had significantly higher DBP (but not SBP) than whites in California.

Adult↗