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Biomedical subjects

S K Das

Publications and source records attributed to S K Das.

At least 73 records · Page 4Linked to original sources

Photochemical behavior of xanthophylls in the recombinant photosystem II antenna complex, CP26.

The steady state absorption and fluorescence spectroscopic properties of the xanthophylls, violaxanthin, zeaxanthin, and lutein, and the efficiencies of singlet energy transfer from the individual xanthophylls to chlorophyll have been investigated in recombinant CP26 protein overexpressed in Escherichia coli and then refolded in vitro with purified pigments. Also, the effect of the different xanthophylls on the extents of static and dynamic quenching of chlorophyll fluorescence has been investigated. Absorption, fluorescence, and fluorescence excitation demonstrate that the efficiency of light harvesting from the xanthophylls to chlorophyll a is relatively high and insensitive to the particular xanthophyll that is present. A small effect of the different xanthophylls is observed on the extent of quenching of Chl fluorescence. The data provide the precise wavelengths of the absorption and fluorescence features of the bound pigments in the highly congested spectral profiles from these light-harvesting complexes. This information is important in assessing the mechanisms by which higher plants dissipate excess energy in light-harvesting proteins.

Chlorophyll↗

Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors.

The implantation of a blastocyst into a receptive uterus is associated with a series of events, namely the attachment reaction followed by decidualization of the stroma. Previous studies established that the gene encoding heparin-binding EGF-like growth factor (HB-EGF) is expressed in the luminal epithelium solely at the site of blastocyst apposition preceding the attachment reaction. We report here the expression during implantation of 21 genes encoding other signaling proteins, including those belonging to the Bone morphogenetic protein (BMP), fibroblast growth factor (FGF), WNT, and Hedgehog (HH) pathways. We find that the attachment reaction is associated with a localized stromal induction of genes encoding BMP-2, FGF-2, and WNT-4. Despite efforts by many investigators, a simple in vitro model of implantation is not yet available to study either the hierarchy of the events triggered in the uterus by the embryo or the function of individual signaling proteins. We have therefore approached these questions by introducing beads loaded with purified factors into the receptive uterus. We show that beads soaked in HB-EGF or insulin-like growth factor-1 (IGF-1), but not other proteins, induce many of the same discrete local responses elicited by the blastocyst, including increased localized vascular permeability, decidualization, and expression of Bmp2 at the sites of the beads. By contrast, the expression domains of Indian hedgehog (Ihh), patched, and noggin become restricted as decidualization proceeds. Significantly, beads containing BMP-2 do not themselves elicit an implantation response but affect the spacing of implantation sites induced by blastocysts cotransferred with the beads.

Animals↗

VCAM-1 activates phosphatidylinositol 3-kinase and induces p120Cbl phosphorylation in human airway smooth muscle cells.

VCAM-1 is a member of the Ig superfamily of receptors the expression of which is up-regulated on human airway smooth muscle (ASM) cells following stimulation with inflammatory mediators. The function of these receptors in adhesion is well known, but there is growing recognition that they also possess "outside-in" signaling functions, such as cytoskeletal reorganization, calcium mobilization, and cytokine release. The present study examined the activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase (PI3K) in ASM cells following VCAM-1 engagement. VCAM-1 ligation activated extracellular signal-regulated kinase 2 and resulted in increased expression of cyclin D1, yet there was neither p27(kip1) degradation nor an increase in smooth muscle cell DNA synthesis. VCAM-1 ligation, however, augmented the proliferative response to submitogenic concentrations of epidermal growth factor. VCAM-1 engagement also stimulated a rapid increase in PI3K activity. This was associated with phosphorylation of the adapter protein p120(Cbl) and an increase in Cbl-associated PI3K activity. These studies suggest that VCAM-1 is linked to multiple signaling pathways in human ASM cells and may function to augment growth factor-induced responses.

Cell Division↗

Correlation of expression of cyclooxygenase-2, vascular endothelial growth factor, and peroxisome proliferator-activated receptor delta with head and neck squamous cell carcinoma.

Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2. These isoforms are encoded by separate genes and demonstrate cell-specific expression and regulation. Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is activated by prostacyclin. Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up-regulated in various tumors. Vascular endothelial growth factor has been shown to interact with COX-derived prostaglandins in angiogenesis. To better understand the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we examined the differential expression of the COX1, COX2, VEGF, and PPARdelta genes in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX-1, COX-2, VEGF, and PPARdelta messenger RNAs (mRNAs) by in situ hybridization. COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization. Immunohistochemistry was used to analyze for COX-2 and PPARdelta proteins. Results showed focal areas of accumulation for COX-2, VEGF, and PPARdelta but not COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2 mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in development and/or progression of HNSCCA. In addition, PPARdelta may be a receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role for selective COX-2 inhibitors in the treatment of these lesions.

Blotting, Northern↗

Testing the stress-vulnerability hypothesis in ICD-10-diagnosed acute and transient psychotic disorders.

OBJECTIVE: To examine if family-history-positive (FHP) vis-à-vis family-history-negative (FHN) probands with ICD-10-diagnosed acute and transient psychotic disorders (ATPD) differ significantly with respect to number of life events and cumulative stress score prior to the onset of ATPD. METHOD: Forty probands with ICD-10-based clinical diagnosis of acute and transient psychotic disorders were studied with respect to: (a) history of psychiatric disorders in first-degree relatives, and (b) antecedent life events and cumulative stress. The FHP and FHN probands were compared on the latter variables using Mann-Whitney U-test. RESULTS: FHP probands reported significantly less number of total life events compared to FHN probands (P = 0.006). Similarly, FHP probands had significantly less stress score than FHN probands (P = 0.002). There were no significant demographic or clinical differences between the two groups. CONCLUSION: The findings support the stress-vulnerability hypothesis in the aetiology of ATPD.

Acute Disease↗

A review on the origin and spread of deleterious mutants of the beta-globin gene in Indian populations.

Deleterious mutations of the human beta-globin gene are responsible for beta-thalassaemia and other haemoglobinopathies, which are the most common genetic diseases in Indian populations. A highly heterogeneous distribution of those mutations is observed in India and certain mutations are restricted to some extent to particular groups only. The reasons behind the geographical clustering and origin of the mutations in India is a highly debated issue and the evidence is conflicting. Our present article aims at tracing the origin of the deleterious beta-globin mutation and evaluates the role of different evolutionary forces responsible for the spread and present distribution of those mutations in Indian populations, using data from molecular biology and statistical methods. Mutations are generated essentially randomly, but "hot-spot" sites for mutation are reported for the beta-globin gene cluster, indicating sequence dependency of mutation. A single origin of a deleterious beta-globin mutation, followed by recombination (in a hot spot region) and/or interallelic gene conversion (within beta-globin gene) through time is the most plausible hypothesis to explain the association of those mutations with multiple haplotype backgrounds and frameworks. It is suggested that India is the place of origin of HbE and HbD mutations and that they dispersed to other parts of the would by migration. HbS mutants present in Indian populations are not of Middle East origin but rather a fresh mutation is the probable explanation for the prevalence among tribal groups. beta-thalassaemia represents a heterogeneous group of mutant alleles in India. Five common and twelve rare mutations have been reported in variable frequencies among different Indian populations. Gene flow of those mutant alleles from different populations of the world by political, military and commercial interactions possibly accounts for the heterogenous nature of beta-thalassaemia among Indians. A multiple allelic polymorphic system of the beta-globin gene exists in different populations. Dynamic interaction of the mutant alleles in the presence of different selective forces including falciparum malaria and biosocial patterns of Indian populations is discussed in order to explain the variable distribution and maintenance of those mutant alleles.

Biological Evolution↗

Effects of a cereal rich in soluble fiber on body composition and dietary compliance during consumption of a hypocaloric diet.

OBJECTIVES: To investigate the effects of oats, a cereal rich in soluble fiber, on body composition changes and dietary compliance during consumption of a weight loss diet. METHODS: Subjects were 41 healthy men and women aged 18 to 78 years. Weight maintenance energy requirements were established over two weeks during consumption of a control diet with low soluble fiber content. Subjects then consumed a hypocaloric diet for six weeks, either consuming a low soluble fiber control diet or a diet containing 45 g/1000 kcal rolled oats, a whole grain cereal rich in soluble fiber (mean energy deficit -895+/-18 kcal/day relative to weight maintenance energy requirements). Changes in body fat and fat-free mass were determined by underwater weighing, and dietary compliance was assessed using the urinary osmolar excretion rate technique. In a final phase of the study, subjects ate ad libitum for six months, and changes in body weight and composition were monitored. RESULTS: There was no significant effect of the oat-containing diet on body weight or composition changes during the hypocaloric regimen or in the subsequent ad libitum period. In addition, fecal energy excretion was not significantly different between groups. However, there were non-significant trends indicating reduced hunger in the oat group compared to controls (frequency of hunger 2.5+/-0.5 vs. 3.6+/-0.4, P=0.1). In addition, fewer oat subjects were non-compliant (four versus seven subjects dropped out or had urinary osmolar excretions greater than 130% of values predicted from dietary intake), but again the difference was not significant. CONCLUSIONS: These results suggest that use of a cereal rich in soluble fiber in a closely monitored hypocaloric feeding regimen does not improve weight loss or dietary compliance. Further studies are needed to examine the possibility that cereals containing soluble fiber may have effects on hunger and dietary compliance that could be important in less tightly controlled protocols than the one described here.

Adult↗

An oat-containing hypocaloric diet reduces systolic blood pressure and improves lipid profile beyond effects of weight loss in men and women.

Hypertension, dyslipidemia and overweight contribute substantially to cardiovascular disease risk. One of the most effective methods for improving high blood pressure and lipid profiles is loss of excess weight. Other recommendations for reducing cardiovascular risk include changes in dietary micronutrient, macronutrient and fiber intakes. To better define a diet for reduction in cardiovascular risk, 43 adults (body mass index 26.4 +/- 3.3, range 20.5-33.9 kg/m(2)) participated in an 8-wk study to determine the effects of two diets on weight, blood pressure, lipids and insulin sensitivity. For 2 wk, weight was maintained and all subjects consumed a control diet. For the next 6 wk, subjects consumed one of two hypocaloric diets (maintenance energy minus 4.2 MJ/d): the control diet (n = 21) or a diet containing oats [45 g/(4.2 MJ dietary energy. d), n = 22]. There was no significant difference between groups in changes in weight loss (control -4.0 +/- 1.1 kg, oats -3.9 +/- 1.6 kg, P = 0.8). The oats diet resulted in greater decreases in mean systolic blood pressure (oats -6 +/- 7 mm Hg, control -1 +/- 10 mm Hg, P = 0.026), whereas diastolic blood pressure change did not differ between the two groups (oats -4 +/- 6 mm Hg, control -3 +/- 5 mm Hg, P = 0.8). The oat diet resulted in significantly greater decreases in total cholesterol (oats -0.87 +/- 0.47 mmol/L, control -0.34 +/- 0.5 mmol/L, P = 0.003) and LDL cholesterol (oats -0.6 +/- 0.41 mmol/L, control -0.2 +/- 0.41mmol/L, P = 0.008). In summary, a hypocaloric diet containing oats consumed over 6 wk resulted in greater improvements in systolic blood pressure and lipid profile than did a hypocaloric diet without oats.

Adult↗

An underfeeding study in healthy men and women provides further evidence of impaired regulation of energy expenditure in old age.

The effect of aging on energy regulation remains controversial. We compared the effects of underfeeding on changes in energy expenditure and respiratory quotient in young normal weight men and women [YNW, age 25.7 +/- 3.2 y(SD), body mass index (BMI) 23.1 +/- 1.6 kg/m(2)], young overweight men and women (YOW, age 26.1 +/- 3.5 y, BMI 27.7 +/- 2.1 kg/m(2)) and older (OLD) men and women (age 68.4 +/- 3.3 y, BMI 27.4 +/- 3.4 kg/m(2)). The thermic effect of feeding (TEF) during weight maintenance, and changes in resting energy expenditure (REE) and respiratory quotient were determined in response to undereating by an average 3.75 MJ/d for 6 wk. In addition, body composition was measured. No significant differences among the groups were observed in TEF, fasting and postprandial respiratory quotient, or the change in fasting respiratory quotient with underfeeding. However, REE adjusted for fat-free mass and fat mass was significantly lower in OLD subjects compared with YNW and YOW subjects (P < 0.05). In addition, the REE response to weight change was significantly attenuated in the OLD subjects (P = 0.023). These data suggest that the responsiveness of energy expenditure to negative energy balance is attenuated in old age, and provide further support for the hypothesis that mechanisms of energy regulation are broadly disregulated in old age.

Adult↗

Expression of heparin/heparan sulfate interacting protein/ribosomal protein l29 during the estrous cycle and early pregnancy in the mouse.

Using a variety of approaches, we have examined the expression of the heparin/heparan sulfate (Hp/HS) interacting protein/ribosomal protein L29 (HIP/RPL29) in mouse uteri during the estrous cycle and early pregnancy. HIP/RPL29 selectively binds heparin and HS and may promote HS-dependent embryo adhesion. HIP/RPL29 was prominently expressed in both luminal and glandular epithelia under almost all conditions, including the phase of embryo attachment. In contrast, differences were noted in HIP/RPL29 expression in the stromal compartment both during the estrous cycle and during early pregnancy. Most notably, HIP/RPL29 accumulated in decidua, where it displayed a pattern complementary to that of pericellular deposition of the HS proteoglycan, perlecan. HIP/RPL29 protein was detected in implanted embryos at both initial and later stages of implantation; however, embryonic HIP/RPL29 mRNA accumulation was more pronounced at later stages (Day 7.5 postcoitum). In situ hybridization revealed similar spatial changes for HIP/RPL29 mRNA during these different physiological states. Whereas differences in the spatial pattern of HIP/RPL29 protein and mRNA expression were demonstrable, little change was detected in the level of HIP/RPL29 mRNA or protein in total endometrial extracts. Mouse blastocysts attached, but did not outgrow, on surfaces coated with recombinant murine HIP/RPL29. Surprisingly, soluble glycosaminoglycans including heparin, low molecular weight heparin, or chondroitin sulfate were not able to inhibit embryo attachment to HIP/RPL29-coated surfaces. These latter observations indicate that embryonic cell surface components other than HS proteoglycans can promote binding to HIP/RPL29 expressed by uterine cells.

Animals↗

Three-dimensional tumor perfusion reconstruction using fractal interpolation functions.

It has been shown that the perfusion of blood in tumor tissue can be approximated using the relative perfusion index determined from dynamic contrast-enhanced magnetic resonance imaging (DE-MRI) of the tumor blood pool. Also, it was concluded in a previous report that the blood perfusion in a two-dimensional (2-D) tumor vessel network has a fractal structure and that the evolution of the perfusion front can be characterized using invasion percolation. In this paper, the three-dimensional (3-D) tumor perfusion is reconstructed from the 2-D slices using the method of fractal interpolation functions (FIF), i.e., the piecewise self-affine fractal interpolation model (PSAFIM) and the piecewise hidden variable fractal interpolation model (PHVFIM). The fractal models are compared to classical interpolation techniques (linear, spline, polynomial) by means of determining the 2-D fractal dimension of the reconstructed slices. Using FIFs instead of classical interpolation techniques better conserves the fractal-like structure of the perfusion data. Among the two FIF methods, PHVFIM conserves the 3-D fractality better due to the cross correlation that exists between the data in the 2-D slices and the data along the reconstructed direction. The 3-D structures resulting from PHVFIM have a fractal dimension within 3%-5% of the one reported in literature for 3-D percolation. It is, thus, concluded that the reconstructed 3-D perfusion has a percolation-like scaling. As the perfusion term from bio-heat equation is possibly better described by reconstruction via fractal interpolation, a more suitable computation of the temperature field induced during hyperthermia treatments is expected.

Animals↗

Discretizing large traceable vessels and using DE-MRI perfusion maps yields numerical temperature contours that match the MR noninvasive measurements.

The success of hyperthermia treatments is dependent on thermal dose distribution. However, the three-dimensional temperature distribution remains largely unknown. Without this knowledge, the relationship between thermal dose and outcome is noisy, and therapy cannot be optimized. Accurate computations of thermal distribution can contribute to an optimized therapy. The hyperthermia modeling group in the Department of Radiotherapy, University Medical Center Utrecht devised a Discrete Vasculature [Kotte et al., Phys. Med. Biol. 41, 865-884 (1996)] model that accounts for the presence of vessel trees in the computational domain. The vessel tree geometry is tracked using magnetic resonance (MR) angiograms to a minimum diameter between 0.6 and 1 mm. However, smaller vessels (0.2-0.6 mm) are known to account for significant heat transfer. The hyperthermia group at Duke University Medical Center has proposed using perfusion maps derived from dynamic-enhanced magnetic resonance imaging to account for the tissue perfusion heterogeneity [Craciunescu et al., Int. J. Hyperthermia 17, 221-239 (2001)]. In addition, techniques for noninvasive temperature measurements have been devised to measure temperatures in vivo [Samulski et al., Int. J. Hypertherminal, 819-829 (1992)]. In this work, a patient with high-grade sarcoma has been retrospectively modeled to determine the temperature distribution achieved during a hyperthermia treatment. Available for this model were MR depicted geometry, angiograms, perfusion maps, as necessary for accurate thermal modeling, as well as MR thermometry data for validation purposes. The vasculature assembly through modifiable potential program [Van Leeuwen et al., IEEE Trans. Biomed. Eng. 45, 596-604 (1998)] was used in order to incorporate the traceable large vessels. Temperature simulations were made using different approaches to describe perfusion. The simulated cases were the bioheat equation with constant perfusion rates per tissue type, perfusion maps alone, tracked vessel tree and perfusion maps, and generated vessel tree. The results were compared with MR thermometry data for a single patient data set, concluding that a combination between large traceable vessels and perfusion map yields the best results for this particular patient. The technique has to be repeated on several patients, first with the same type of malignancy, and after that, on patients having malignancies at other different sites.

Algorithms↗

Heparin-binding EGF-like growth factor modulation by antiprogestin and CG in the baboon (Papio anubis).

The objectives of this study were to determine whether antiprogestin therapy or the infusion of human CG to mimic blastocyst transit in the baboon alters heparin-binding EGF-like growth factor expression during the window of implantation. During the menstrual cycle, heparin-binding EGF-like growth factor protein accumulation in the glandular epithelium was low in the proliferative phase and increased to maximal expression on d 5 and 10 postovulation. Stromal cells accumulated high levels of heparin-binding EGF-like growth factor in the proliferative phase, which decreased by d 5 postovulation. These transitional changes in both cell types were delayed when cycling baboons were treated with the antiprogestin ZK 137.316 during the luteal phase. The treatment with human CG had no effect on expression of heparin-binding EGF-like growth factor when compared with cycling baboons on d 10 postovulation and was comparable with that observed on d 18 and 22 of pregnancy. However, the superimposition of the antiprogestin with the human CG treatment also decreased expression in the epithelial cells. In summary, heparin-binding EGF-like growth factor accumulation in the epithelial glands is under the influence of progesterone and does not seem to be influenced by the paracrine secretion of trophoblast CG.

Animals↗

Adult tissue angiogenesis: evidence for negative regulation by estrogen in the uterus.

Increased uterine vascular permeability and angiogenesis are two major events of embryo implantation and placentation during pregnancy. These latter processes require coordinated, uterine-specific interactions between progesterone (P4) and estrogen (E) signaling. Although roles of these steroids have long been suspected, definitive functions of E and/or P4 in uterine angiogenesis still remain elusive. We have therefore exploited the availability of reporter and mutant mice to explore the regulation of angiogenesis in response to steroid hormonal changes in vivo. We present here molecular, genetic, physiological, and pharmacological evidence that E and P4 have different effects in vivo: E promotes uterine vascular permeability but profoundly inhibits angiogenesis, whereas P4 stimulates angiogenesis with little effect on vascular permeability. These effects of E and P4 are mediated by differential spatiotemporal expression of proangiogenic factors in the uterus.

Animals↗

Nail unit matrix transplantation: a plastic surgeon's approach.

The growth of the nail is primarily from the nail bed and mostly from the germinal matrix component, and to some extent from the sterile matrix as well. The purpose of this article is to describe the approach and technique of a composite nail, nail bed, hyponychium, and perionychium transplant when the total nail and nail bed need reconstruction. A case is presented when a nail bed junctional nevus is excised and reconstruction with nail unit matrix transplantation and the result is shown.

Child↗

Molecular characterization of hereditary persistence of foetal haemoglobin mutation by restriction fragment length polymorphism mapping.

Characterization of hereditary persistence of foetal haemoglobin (HPFH) mutation in a family from West Bengal, India, was carried out by analysing the structure of the 5'-Ggamma-Agamma-psibeta-delta-beta-3' globin gene region by using the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. The HPFH in this family was due to a deletion in the beta-globin gene cluster spanning at least from the Hin cII/5' psibeta to the Hin fI/3' beta RFLP site. This work indicates the importance of RFLP-PCR technique in characterization of the HPFH mutation.

Adolescent↗

Arterial waves in humans during peripheral vascular surgery.

The purpose of this study was to investigate the effect of aortic clamping on arterial waves during peripheral vascular surgery. We measured pressure and velocity simultaneously in the ascending aorta, in ten patients (70+/-5 years) with aortic-iliac disease intra-operatively. Pressure was measured using a catheter tip manometer, and velocity was measured using Doppler ultrasound. Data were collected before aortic clamping, during aortic clamping and after unclamping. Hydraulic work in the aortic root was calculated from the measured data, the reflected waves were determined by wave-intensity analysis and wave speed was determined by the PU-loop (pressure-velocity-loop) method; a new technique based on the 'water-hammer' equation. The wave speed is approx. 32% (P<0.05) higher during clamping than before clamping. Although the peak intensity of the reflected wave does not alter with clamping, it arrives 30 ms (P<0.05) earlier and its duration is 25% (P<0.05) longer than before clamping. During clamping, left ventricule (LV) hydraulic systolic work and the energy carried by the reflected wave increased by 27% (P<0.05) and 20% (P<0.05) respectively, compared with before clamping. The higher wave speed during clamping explains the earlier arrival of the reflected waves suggesting an increase in the afterload, since the LV has to overcome earlier reflected compression waves. The longer duration of the reflected wave during clamping is associated with an increase in the total energy carried by the wave, which causes an increase in hydraulic work. Increased hydraulic work during clamping may increase LV oxygen consumption, provoke myocardial ischaemia and hence contribute to the intra-operative impairment of LV function known in patients with peripheral vascular disease.

Aged↗