Biomedical subjects
Publications and source records attributed to S Kumar.
A different phase-separation process is capable of producing a composite system consisting of a very thin layer of liquid crystal in contact with a similarly thin layer of polymer. The morphology of the polymer depends on the composition of the prepolymer-liquid crystal mixture and the rate of polymerization. A simple one-dimensional theory is able to describe the essential features of this process.
This report presents a discussion of the wave number selection mechanism in the Faraday instability, which arises when standing waves form on the free surface of a liquid subject to vertical sinusoidal oscillation. The focus is on the case where the viscous effects are strong, i.e., when the wavelength is of the same order of magnitude as the boundary layer thickness at the free surface. We investigate the relationship between the Faraday instability and the Rayleigh-Taylor instability by performing linear stability calculations. In the deep water limit (wavelength << liquid depth), our results indicate that the preferred wave number in the Faraday instability is primarily determined through a Rayleigh-Taylor instability. In the case of shallow water (wavelength approximately liquid depth), the agreement between the Rayleigh-Taylor and Faraday wave numbers does not appear to be as good, probably due to the interaction between the oscillatory motion of the standing waves and the bottom boundary.
Whereas previously we have successfully utilized the folding funnels concept to rationalize binding mechanisms (Ma B, Kumar S, Tsai CJ, Nussinov R, 1999, Protein Eng 12:713-720) and to describe binding (Tsai CJ, Kumar S, Ma B, Nussinov R, 1999, Protein Sci 8:1181-1190), here we further extend the concept of folding funnels, illustrating its utility in explaining enzyme pathways, multimolecular associations, and allostery. This extension is based on the recognition that funnels are not stationary; rather, they are dynamic, depending on the physical or binding conditions (Tsai CJ, Ma B, Nussinov R, 1999, Proc Natl Acad Sci USA 96:9970-9972). Different binding states change the surrounding environment of proteins. The changed environment is in turn expressed in shifted energy landscapes, with different shapes and distributions of populations of conformers. Hence, the function of a protein and its properties are not only decided by the static folded three-dimensional structure; they are determined by the distribution of its conformational substates, and in particular, by the redistributions of the populations under different environments. That is, protein function derives from its dynamic energy landscape, caused by changes in its surroundings.
OBJECTIVE: Prognosis of patients with recurrent epithelial ovarian cancer (EOC) is generally poor. Cisplatin is the most effective drug. We used three cisplatin based chemotherapeutic (CT) regimens and retrospectively analyzed the data to determine the response rate, toxicity, survival and the impact of various prognostic factors on the outcome. PATIENTS AND METHODS: Between August, 1989 and September, 1997, 102 patients were diagnosed to have recurrent EOC. Sixty-five of 102 patients received CT every 3 weeks using cisplatin 75 mg/m2 i.v. day 1 plus cyclophosphamide 750 mg/m2 i.v. day 1 (CP, Group A, n = 29), cisplatin 75 mg/m2 i.v. day 1, plus adriamycin 40 mg/m2 i.v. day 1 and cyclophosphamide (CAP, Group B, n = 22) and paclitaxel 135 mg/m2 i.v. day 1 plus cisplatin 75 mg/m2 i.v. day 1 (TP, Group C, n = 14). Twelve patients received single agent CT and were not analyzed. Remaining 25 patients refused CT treatment and were followed for survival. RESULTS: The overall response rate (complete and partial) was 59.2% for patients receiving CP (Group A), 45% for CAP (Group B) and 76.9% for those receiving TP (Group C), p = ns. Response rate was significantly higher for patients with platinum sensitive disease compared to those with platinum resistant disease; 55.76 vs 39%, p < 0.007. CT was generally tolerated well; 2 patients died of CT toxicity, one each in Group A (CP) and C (TP), respectively. The median survival from the date of relapse for patients receiving chemotherapy was 15 months compared to 4 months for those who did not receive chemotherapy, p < 0.001. Chemotherapy responders had a significantly higher median survival than chemotherapy non-responders, 24 months vs 10 months, p < 0.01. The median overall survival was not significantly different in the 3 groups; Group A--15 months, Group B--12 months and 15 months in Group C, p = 0.738. On univariate analysis--time since last CT (< 6 months vs > 6 months, p < 0.037, response to previous CT, p < 0.0183, cisplatinum sensitivity vs resistance, p < 0.032, number of sites (< 2 vs > 2) of recurrence, p < 0.004 and response to salvage CT, p < 0.01 were associated with survival benefit. On multivariate analysis, 2 factors--platinum sensitivity and response to salvage CT attained significance. CONCLUSIONS: Our study confirms the benefit of platinum based chemotherapy in recurrent EOC. Patients with platinum sensitive disease, and those responding to salvage chemotherapy benefit most.
The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP1(19)) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP1(19) constructs elicited high levels of antibodies to MSP1(19) but only one construct, the 19-kDa fragment expressed as a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1(19)), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP1(19) in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.
The c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated c-Jun N-terminal protein kinase (SAPK). Here we show that nuclear c-Abl associates with MEK kinase 1 (MEKK-1), an upstream effector of the SEK1-->SAPK pathway, in the response of cells to genotoxic stress. The results demonstrate that the nuclear c-Abl binds to MEKK-1 and that c-Abl phosphorylates MEKK-1 in vitro and in vivo. Transient-transfection studies with wild-type and kinase-inactive c-Abl demonstrate c-Abl kinase-dependent activation of MEKK-1. Moreover, c-Abl activates MEKK-1 in vitro and in response to DNA damage. The results also demonstrate that c-Abl induces MEKK-1-mediated phosphorylation and activation of SEK1-SAPK in coupled kinase assays. These findings indicate that c-Abl functions upstream of MEKK-1-dependent activation of SAPK in the response to genotoxic stress.
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The aim of this case report is to highlight that risperidone may cause and ameliorate tardive dyskinesia. A 16 year old white women with a 12 month history of schizophrenia, developed buccolingual masticatory tardive dyskinesia after receiving risperidone 6 mg. She had received small dosages of typical antipsychotics before and during receiving risperidone for short periods. Recommencement of risperidone with 2 mg and increasing to 6 mg resulted in improvement in tardive dyskinesia and up until now she remains free of any abnormal involuntary movements.
We report two cases of unicornuate uterus with functioning rudimentary horn to highlight that Mullerian duct anomalies should be considered in the differential diagnosis of severe dysmenorrhoea even in normally menstruating girls.
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We present a novel technique for the estimation of global nonrigid motion of an object's boundary without using point correspondences. A complete description of the motion of an object's boundary involves specifying a displacement vector at each point of the boundary. Such a description provides a large amount of information, which needs to be processed further for study of the global characteristics of the deformation. Nonrigid motion can be studied hierarchically in terms of global nonrigid motion and point-by-point local nonrigid motion. The technique presented gives a method for estimating a global affine or polynomial transformation between two object boundaries. The novelty of the technique lies in the fact that it does not use any point correspondences. Our method uses hyperquadric models to model the data and estimate the global deformation. We show that affine or polynomial transformation between two datasets can be recovered from the hyperquadric parameters. The usefulness of the technique is twofold. First, it paves the way for viewing nonrigid motion hierarchically in terms of global and local motion. Second, it can be used as a front end to other motion analysis techniques that assume small motion. For instance, most nonrigid motion analysis algorithms make some assumptions on the type of nonrigid motion (conformal motion, small motion, etc.) that are not always satisfied in practice. When the motion between two datasets is large, our algorithm can be used to estimate the affine transformation (which includes scale and shear) or a polynomial transformation between the two datasets, which can then be used to warp the first dataset closer to the second so as to satisfy the small-motion assumption. We present experimental results with real and synthetic two- and three-dimensional data.
Type 2 diabetes mellitus is a common metabolic disorder that has become a major public health problem because of the long-term microvascular and macrovascular complications associated with it. Tight glycaemic control has been shown to prevent complications, but a number of studies have shown that many patients with Type 2 diabetes have sub-optimal control. Insulin resistance is a fundamental abnormality in Type 2 diabetes but there have not been drugs that are able to reverse this defect. Thiazolidinediones (TZD) may, therefore, represent a breakthrough in the management of Type 2 diabetes as it is the first class of oral agents for diabetes that act as an insulin action enhancer to reduce insulin resistance. This review will examine available data on the currently available TZDs and consider its place in the management of Type 2 diabetes.
Adipocytes contain large lipid droplets in their cytoplasm. When cultured, they float on top of the medium, clump together, and do not gain equal and sufficient access to the medium. Morphological changes cannot be observed and the majority of adipocytes undergo cell lysis within 72 h of isolation. We have used a ceiling culture method for human mature adipocytes which uses their buoyant property to allow them to adhere to a floating glass surface, where they remain viable for several weeks. Using confocal immunofluorescence microscopy we showed the cellular expression and subcellular localization of leptin in ceiling-cultured adipocytes. The secretion of leptin was increased from ceiling cultures following tumour necrosis factor-alpha treatment. Proliferation of mature human adipocytes in serum-containing medium was demonstrated by incorporation of bromodeoxyuridine, 2% of adipocytes showing positive incorporation after 4 h labelling. Proliferation was also evident from the budding of daughter cells. Apoptosis in the ceiling cultures was increased by 48 h serum deprivation (30-35 vs 10-15% in the control) and was assayed by propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling. Lipolysis, analysed by liquid scintillation counting, was increased by forskolin (10 microM for 90 min) and lipogenesis, shown by autoradiography, was stimulated by insulin (10 and 100 nM for 4 h). These findings indicate that ceiling-cultured adipocytes maintain adipocyte-specific functions and that ceiling culture, which overcomes the shortcomings of adipocyte suspension culture, can be used to study adipocyte cell biology.
The integration of transgenes into a plant host genome following Agrobacterium tumefaciens-mediated or direct transformation may occur as a single copy or in the form of tandem repeats. The latter has been associated with promoter methylation and silencing of transgenes. Thus, the early screening of such transgenic plants is desirable for ruling out future repeat-dependent transgene instability. We developed a simple PCR-based method in which primer pairs were specifically designed so that amplifications could only be obtained if the transgene was present in the form of multiple inserts in a transgenic line. The method was established using 35S-rolC transgenic aspen lines showing morphologically visible transgenic silencing. Later, it was possible to screen independent transgenic lines showing no visible marker gene expression. Furthermore, a method was developed in which positive PCR amplification was indicative of promoter methylation. The results were consistent and reproducible across different independent transgenic lines. The methods were quick, reliable, consistent and reproducible, and can be useful for routine screening of transgene silencing in lines derived from many different systems.
OBJECTIVE: There is a considerable imbalance of power in psychiatry that sits in favor of professionals. The abuse and discrimination of the mentally ill are not just restricted to the mental health system but may also exist in the primary care sector. This article aims to evaluate the effects of power imbalance on discrimination and abuse of people with mental illness by professionals. METHODS: A literature search was carried out on MEDLINE using the key words consumerism, client empowerment, abuse, and mental illness. Publications of two leading British consumer organizations: MIND and the Sainsbury Centre for Mental Health were hand searched. Relevant cross-references from the papers reviewed were consulted. Studies with information on the reasons for power imbalance and prevalence of discrimination and abuse of clients were critically reviewed. Explanations are offered as to why abuse and discrimination of clients by professionals may still occur despite the onset of the client empowerment movement. RESULTS AND DISCUSSION: The available evidence suggests that reasons for abuse of mental health clients fall under two broad categories: 1) direction from the imbalance of power and 2) those pertinent to the nature of physical or sexual abuse. Different grades of client empowerment and ways of strengthening it are described. CONCLUSIONS: There appears to be a link between power imbalance and abuse of clients with mental illness by professionals in all health care sectors. Client empowerment may help rectify the power imbalance. Prospective studies are required to establish whether client empowerment can reduce discrimination and abuse of clients and whether abuse is a consequence of power imbalance. Recommendations for future studies are made.