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V Patel

Publications and source records attributed to V Patel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cultural factors and international epidemiology.

The debate on the role of culture on psychiatric epidemiology has evolved considerably in the past two decades. There is now a general consensus that the integration of the universalist and culturally relativist approaches, and their methodologies, is required to generate a truly international psychiatric epidemiology. The large body of research investigating the influence of culture on the epidemiology of depression has produced a number of key findings: the clinical presentation of depression in all cultures is associated with multiple somatic symptoms of chronic duration; psychological symptoms, however, are important for diagnosis and can be easily elicited. The diagnostic differentiation between depression and anxiety in general health care settings is not clinically valid. Culturally appropriate terminology for depression can be identified and their use may improve levels of recognition and treatment compliance. It is also evident that culture is only one factor in the difference between, and within, human societies which has a bearing on the epidemiology of depression. Other factors, which may interact with culture, such as gender and income inequality, are major risk factors for depression. Future international research must focus on two themes: (i) intervention studies including cost-effectiveness outcomes; and (ii) research aiming to bridge the gap between regional public health priorities and the concern that psychiatrists have about depression.

Community Mental Health Services↗
PubMed2001

Stability after medial collateral ligament release in total knee arthroplasty.

Six knees from cadavers were tested for change in stability after release of the medial collateral ligament with posterior cruciate-retaining and substituting total knee replacements. Load deformation curves of the joint were recorded in full extension and 30 degrees, 60 degrees, and 90 degrees flexion under a 10 N-m varus and valgus torque, 1.5 N-m internal and external rotational torque, and a 35 N anterior and posterior force to test stability in each knee. The intact specimen and posterior cruciate ligament-retaining total joint replacement were tested for baseline comparisons. The superficial medial collateral ligament was released, followed by release of the posterior cruciate ligament. The knee then was converted to a posterior-stabilized implant. After medial collateral ligament release, valgus laxity was statistically significantly greater at 30 degrees, 60 degrees, and 90 degrees flexion after posterior cruciate ligament sacrifice than it was when the posterior cruciate ligament was retained. The posterior-stabilizing post added little to varus and valgus stability. Small, but significant, differences were seen in internal and external rotation before and after posterior cruciate ligament sacrifice. The posterior-stabilized total knee arthroplasty was even more rotationally constrained in full extension than the knee with intact medial collateral ligament and posterior cruciate ligament.

Arthroplasty, Replacement, Knee↗
PubMed2001

The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.

Protein-tyrosine phosphatases catalyze the hydrolysis of phosphate monoesters via a two-step mechanism involving a covalent phospho-enzyme intermediate. Biochemical and site-directed mutagenesis experiments show that the invariant Cys residue present in the PTPase signature motif (H/V)CX(5)R(S/T) (i.e., C215 in PTP1B) is absolutely required for activity. Mutation of the invariant Cys to Ser results in a catalytically inactive enzyme, which still is capable of binding substrates and inhibitors. Although it often is assumed that substrate-trapping mutants such as the C215S retain, in solution, the structural and binding properties of wild-type PTPases, significant differences have been found in the few studies that have addressed this issue, suggesting that the mutation may lead to structural/conformational alterations in or near the PTP1B binding site. Several crystal structures of apo-WT PTP1B, and of WT- and C215S-mutant PTP1B in complex with different ligands are available, but no structure of the apo-PTP1B C215S has ever been reported. In all previously reported structures, residues of the PTPase signature motif have an identical conformation, while residues of the WPD loop (a surface loop which includes the catalytic Asp) assume a different conformation in the presence or absence of ligand. These observations led to the hypothesis that the different spectroscopic and thermodynamic properties of the mutant protein may be the result of a different conformation for the WPD loop. We report here the structure of the apo-PTP1B C215S mutant, which reveals that, while the WPD loop is in the open conformation observed in the apo WT enzyme crystal structure, the residues of the PTPases signature motif are in a dramatically different conformation. These results provide a structural basis for the differences in spectroscopic properties and thermodynamic parameters in inhibitor binding observed for the wild-type and mutant enzymes.

Amino Acid Sequence↗
PubMed2001

New approaches to the understanding of the molecular basis of oral cancer.

Cancers of the oral cavity, salivary glands, larynx, and pharynx, collectively referred to as squamous cell carcinomas of the head and neck (HNSCC), are the sixth most common cancer among men in the developed world. The prognosis of HNSCC patients is still poor, which reflects the fact that although the risk factors for HNSCC are well-recognized, very little is known about the molecular mechanisms responsible for this malignancy. This review describes some of the current efforts and technological advances that have focused on the creation of a complete information infrastructure for genes expressed during squamous cell carcinogenesis. These include: the recently described HNSCC-specific chromosomal alterations (cCAP); the Head and Neck Cancer Genome Anatomy Project (HN-CGAP), whose goal is the systematic identification and cataloguing of known and novel genes expressed during tumor development; and the use of laser-capture microdissection (LCM), which is pivotal for the comprehensive molecular characterization of normal, pre-cancerous, and malignant cells by means of DNA-array technology. The latter provides the means for the analysis of expression patterns of thousands of genes simultaneously. The use of LCM for proteomics and DNA analysis is also included in this review. These revolutionary approaches are likely to have an unprecedented impact on cancer biology, and provide exciting opportunities to unravel the still-unknown mechanisms involved in squamous cell carcinogenesis. They are also expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of preneoplastic lesions, as well as novel targets for pharmacological intervention in this disease.

Carcinoma, Squamous Cell↗
PubMed2001

International representation in psychiatric literature: survey of six leading journals.

BACKGROUND: Despite the growing recognition of the global burden of psychiatric disease, there are questions about the strength of the evidence base from non-Western societies. AIMS: To compare the contribution of Euro-American countries and the rest of the world (RoW) to psychiatric literature. METHOD: Survey of the country of origin of papers submitted to and published in six leading psychiatric journals over a 3-year period (1996-1998). RESULTS: Only 6% of the literature is published from regions of the world that account for over 90% of global population. The three journals published in Europe had a significantly higher proportion of international articles when compared to the three American journals. Less than 1% of all published articles described mental health interventions in the ROW: Acceptance rates were significantly lower for papers submitted from the ROW: CONCLUSIONS: There is a gross under-representation of research from the ROW: This has implications for the development of a truly international psychiatry.

Bibliometrics↗
PubMed2001

Ethnic classification in primary dental care and dental health services research: time to pause for thought.

'Ethnicity' is an important concept in dental health services research and in enabling general dental practitioners to gain insight into their patients values and expectations. Since more health services research is being undertaken in primary dental care settings it is becoming an important issue for dental professionals and researchers in primary care to be aware of. Ethnicity is thought to be related to dental health inequalities and access and is often used as a stratifying variable in many dental studies. The meaning and use of the term however differs among researchers and among the public. It is clear that researchers and professionals need to pause for thought when considering what this often bandied about term actually means and the impact of different definitions. This is illustrated using examples from the authors' own research and published papers in the medical and dental literature. There is also much debate about whether ethnicity--however defined--is an important predictor of differences in dental health in itself or is merely a marker for other factors such as social deprivation or the impact of 'place' on dental health. While the jury on this debate is out we suggest guidelines on the reporting of ethnicity should be outlined in the dental literature--perhaps updating those published in 1996 in the British Medical Journal.

Cultural Characteristics↗
PubMed2001

Euglycemic clamp study in clozapine-induced diabetic ketoacidosis.

OBJECTIVE: To describe the fifth case of clozapine-induced diabetic ketoacidosis (DKA) with complete resolution of abnormal glucose metabolism after discontinuation of clozapine as assessed by oral glucose tolerance testing (OGTT) and the first to be serially studied with markers of pancreatic autoimmunity; to demonstrate insulin resistance using the euglycemic clamp study and reduced pancreatic insulin reserve using intravenous glucose tolerance testing (IVGTT) in clozapine-induced diabetes mellitus and DKA, when the OGTT was normal; and to systematically review the previously described cases of clozapine-induced diabetes mellitus and DKA. CASE SUMMARY: A 33-year-old white man without past or family history of diabetes mellitus presented with DKA after eight months of clozapine therapy (50 mg twice daily). After treatment of DKA and discontinuation of clozapine, glucose tolerance and concurrent serum insulin concentrations reverted to normal as measured by two OGTT performed 60 and 320 days after resolution of DKA. DISCUSSION: Antiislet-cell antibodies, antiglutamic acid decarboxylase antibodies, and human insulin antibody were negative on two separate occasions. Euglycemic clamp study demonstrated insulin resistance manifested by a glucose disposal rate of approximately 55% of mean normal values. IVGTT demonstrated a low rate of glucose disappearance (KG = 0.95) and diminished first-phase insulin response when OGTT was normal, indicating impairment in insulin sensitivity and reduction in beta cell function 323 days after discontinuance of clozapine. This adverse reaction is considered probable according to the Naranjo probability scale. CONCLUSIONS: The occurrence of cases of DKA and new or worsening diabetes mellitus in patients using clozapine suggests a causal relationship. We hypothesize that the mechanism by which clozapine may produce glucose intolerance may require a preexisting latent defect in insulin secretion and insulin action. With the administration of clozapine, some of these patients may develop worsening insulin resistance and may fail to mount an appropriate compensatory beta cell insulin secretion for the degree of insulin resistance. As a consequence, hyperglycemia develops and its persistence results in glucose toxicity, further suppressing beta cell insulin secretion. Such combined defects in insulin secretion and sensitivity are known to be synergistic, leading to the development of abnormal glucose tolerance, which can be clinically manifested as a spectrum ranging from impaired glucose tolerance through severe hyperglycemia to DKA. Patients being started on clozapine should be carefully followed for the development or worsening of diabetes mellitus, regardless of the dose of the drug.

Adult↗
PubMed2001

Sharable computer-based clinical practice guidelines: rationale, obstacles, approaches, and prospects.

Clinical practice guideline automation at the point of care is of growing interest, yet most guidelines are authored in unstructured narrative form. Computer-based execution depends on a formal structured representation, and also faces a number of other challenges at all stages of the guideline lifecycle: modeling, authoring, dissemination, implementation, and update. This is because of the multiplicity of conceptual models, authoring tools, authoring approaches, intended applications, implementation platforms, and local interface requirements and operational constraints. Complexity and time required for development and structure are also huge obstacles. These factors argue for convergence on a common shared model for representation that can be the basis of dissemination. A common model would facilitate direct interpretation or mapping to multiple implementation environments. GLIF (GuideLine Interchange Format) is a formal representation model for guidelines, created by the InterMed Collaboratory as a proposed basis for a shared representation. GLIF currently addresses the process of authoring and dissemination; the InterMed team's major focus now is on tools to facilitate these tasks and the mapping to clinical information system environments. Because of limitations in what can be done by a single team with finite resources, however, and the variety of additional perspectives that need to be accommodated, the InterMed team has determined that further development of a shared representation would be best served as an open process in which the world community is engaged. Under the auspices of the HL7 Decision Support Technical Committee, a GLIF Special Interest Group has been established, which is intended to be a forum for collaborative refinement and extension of a standard representation that can support the needs of the guideline lifecycle. Significant areas for future work will need to include demonstrations of effective means for incorporating guide-lines at point of care, reconciliation of functional requirements of different models and identification of those most important for supporting practical implementation, im-proved means for authoring and management of complexity, and methods for automatically analyzing and validating syntax, semantics, and logical consistency of guidelines.

Artificial Intelligence↗
PubMed2000

Universal distribution of transparencies in highly conductive Nb/AlO(x)/Nb junctions.

We report the observation of the universal distribution of transparencies, predicted by Schep and Bauer [Phys. Rev. Lett. 78, 3015 (1997)] for dirty sharp interfaces, in uniform Nb/AlO(x)/Nb junctions with high specific conductance (10(8) ohm(-1) cm(-2)). Experiments used the BCS density of states in superconducting niobium for transparency distribution probing. Experimental results for both the dc I-V curves at magnetic-field-suppressed supercurrent and the Josephson critical current in zero magnetic field coincide remarkably well with calculations based on the multimode theory of multiple Andreev reflections and the Schep-Bauer distribution.

Journal Article↗
PubMed2000

Induction of apoptosis in head-and-neck squamous carcinoma cells by gamma-irradiation and bleomycin is p53-independent.

We have examined the ability of gamma-irradiation and bleomycin to induce apoptosis in a model system consisting of cell lines derived from naturally occurring human head-and-neck squamous-cell carcinomas with contrasting p53 status and expression levels of pro- and anti-apoptotic molecules. Following exposure to gamma-irradiation (20 Gy) or bleomycin (3.5 microM) for 0 to 96 hr, cells expressing either transcriptionally inactive mutant p53 (HN6) or a truncated p53 molecule (HN19) underwent apoptosis, as assessed by fluorescence-activated cell sorting and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, in contrast to cells that express wild-type p53 (HN30), suggesting that apoptosis induced by these agents occurs by p53-independent mechanisms. Apoptosis in HN6 and HN19 cells was preceded by a G(2)/M cell-cycle block, as analyzed by DNA content and BrdU staining. In contrast, HN30 cells remained blocked in both G(1) and G(2)/M and failed to re-enter the cell cycle. Levels of Bcl-2 were elevated in 3 of 10 cell lines, and only marginal differences were observed for Bcl-x(L). Pro-apoptotic proteins bax and Bcl-x(S) were detectable in normal keratinocytes and 4 tumor cell lines. Bax-delta (16 kDa) was highly represented in normal keratinocytes, and levels of bak were variable between cell lines. Elevated expression of Bcl-2 failed to protect HN19 cells from either gamma-irradiation or bleomycin-induced apoptosis. Our data support the existence of p53- and Bcl-2-independent pathways regulating apoptosis in keratinocytes and suggest that efficacy of either radiotherapy or bleomycin treatment for oral squamous-cell neoplasms may not, therefore, be influenced solely by endogenous p53 status.

Antibiotics, Antineoplastic↗
PubMed2000

What makes a good dentist and do recent trainees make the grade? The views of vocational trainers.

OBJECTIVE: The aim of this paper is to examine the factors that vocational trainers regard as important in a 'good' dentist and to assess whether they think recent graduates were achieving these factors. DESIGN: The study was based on a statistical analysis of returns from a postal questionnaire. SETTING: Postal questionnaires were sent to all vocational advisors in England who then sent them on to a number of their vocational trainers. MATERIALS AND METHODS: The questionnaire was analysed using various statistical techniques including factor analysis. Analysis was undertaken to determine whether student or trainer characteristics influenced the trainer's responses. RESULTS: The vocational trainers judged that the group of skills that contribute to technical ability are the most important component in making a 'good' dentist. However, the most important single skill is communication with patients, closely followed by diagnostic skills and communication with the dental team. The areas where trainees are most likely to fall short in terms of actual as compared to desired performance are in areas of technical ability. CONCLUSION: Overall, recent trainees scored rather well when compared with an idealised good dentist. However, it is clear that more evaluation of vocational training is needed. Recent studies, including this one have looked at several different aspects of vocational training. However, the time seems ripe for a full-scale prospective evaluation.

Attitude of Health Personnel↗
PubMed2000

The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha.

The elucidation of the molecular mechanisms governing the transition from a nonangiogenic to an angiogenic phenotype is central for understanding and controlling malignancies. Viral oncogenes represent powerful tools for disclosing transforming mechanisms, and they may also afford the possibility of investigating the relationship between transforming pathways and angiogenesis. In this regard, we have recently observed that a constitutively active G protein-coupled receptor (GPCR) encoded by the Kaposi's sarcoma-associated herpes virus (KSHV)/human herpes virus 8 is oncogenic and stimulates angiogenesis by increasing the secretion of vascular endothelial growth factor (VEGF), which is a key angiogenic stimulator and a critical mitogen for the development of Kaposi's sarcoma. Here we show that the KSHV GPCR enhances the expression of VEGF by stimulating the activity of the transcription factor hypoxia-inducible factor (HIF)-1alpha, which activates transcription from a hypoxia response element within the 5'-flanking region of the VEGF promoter. Stimulation of HIF-1alpha by the KSHV GPCR involves the phosphorylation of its regulatory/inhibitory domain by the p38 and mitogen-activated protein kinase (MAPK) signaling pathways, thereby enhancing its transcriptional activity. Moreover, specific inhibitors of the p38 (SKF86002) and MAPK (PD98059) pathways are able to inhibit the activation of the transactivating activity of HIF-1alpha induced by the KSHV GPCR, as well as the VEGF expression and secretion in cells overexpressing this receptor. These findings suggest that the KSHV GPCR oncogene subverts convergent physiological pathways leading to angiogenesis and provide the first insight into a mechanism whereby growth factors and oncogenes acting upstream from MAPK, as well as inflammatory cytokines and cellular stresses that activate p38, can interact with the hypoxia-dependent machinery of angiogenesis. These results may also help to identify novel targets for the development of antiangiogenic therapies aimed at the treatment of Kaposi's sarcoma and other neoplastic diseases.

3T3 Cells↗
PubMed2000

Quantum superposition of distinct macroscopic states

In 1935, Schrodinger attempted to demonstrate the limitations of quantum mechanics using a thought experiment in which a cat is put in a quantum superposition of alive and dead states. The idea remained an academic curiosity until the 1980s when it was proposed that, under suitable conditions, a macroscopic object with many microscopic degrees of freedom could behave quantum mechanically, provided that it was sufficiently decoupled from its environment. Although much progress has been made in demonstrating the macroscopic quantum behaviour of various systems such as superconductors, nanoscale magnets, laser-cooled trapped ions, photons in a microwave cavity and C60 molecules, there has been no experimental demonstration of a quantum superposition of truly macroscopically distinct states. Here we present experimental evidence that a superconducting quantum interference device (SQUID) can be put into a superposition of two magnetic-flux states: one corresponding to a few microamperes of current flowing clockwise, the other corresponding to the same amount of current flowing anticlockwise.

Journal Article↗
PubMed2000

Distinct pattern of expression of differentiation and growth-related genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays.

Although risk factors for squamous cell carcinomas of the head and neck (HNSCC) are well recognized, very little is known about the molecular mechanisms responsible for this malignancy. Furthermore, the ability to investigate gene expression profiles at different stages of tumor progression is usually limited by the remarkable heterogeneity of these neoplastic lesions. Here, we show the successful use of laser capture microdissection (LCM) to procure specific cell populations. The 5000 cells from representative sets of HNSCC and their matching normal tissues are sufficient to extract RNA of high integrity for the synthesis of labeled amplified cDNA probes which can then be hybridized to these membranes arrayed with known human cancer-related cDNAs. Furthermore, when compared to normal tissues, we demonstrate a consistent decrease in expression of differentiation markers such as cytokeratins, and an increase in the expression of a number of signal transducing and cell cycle regulatory molecules, as well as growth and angiogenic factors and tissue degrading proteases. Unexpectedly, we also found that most HNSCC overexpress members of the wnt and notch growth and differentiation regulatory system, thus suggesting that the wnt and notch pathways may contribute in squamous cell carcinogenesis. This experimental approach may facilitate the identification candidate markers for the early detection of preneoplastic lesions, as well as novel targets for pharmacological intervention in this disease.

Carcinoma, Squamous Cell↗
PubMed2000

A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of Th2 cells.

Although exogeneous "danger" signals such as LPS can activate APC to produce a Th1 response, the nature of events initiating a Th2 response is controversial. We now show that pathogen-derived products have the capacity to induce bone marrow-derived dendritic cell cultures to acquire a phenotype that promotes the differentiation of naive CD4+ T cells toward either a Th1 or Th2 phenotype. Thus, LPS-matured dendritic cells (DC1) promote a Th1 response (increased generation of IFN-gamma and reduced production of IL-4) by Ag-stimulated CD4+ T cells from the DO.11.10 transgenic mouse expressing a TCR specific for an OVA peptide (OVA323-339). In contrast, a phosphorylcholine-containing glycoprotein, ES-62, secreted by the filarial nematode, Acanthocheilonema viteae, which generates a Th2 Ab response in vivo, is found to induce the maturation of dendritic cells (DC2) with the capacity to induce Th2 responses (increased IL-4 and decreased IFN-gamma). In addition, we show that the switch to either Th1 or Th2 responses is not effected by differential regulation through CD80 or CD86 and that a Th2 response is achieved in the presence of IL-12.

Animals↗
PubMed2000

Gene expression profiles in squamous cell carcinomas of the oral cavity: use of laser capture microdissection for the construction and analysis of stage-specific cDNA libraries.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer among men in the developed world affecting the oral cavity, salivary glands, larynx and pharynx. Utilizing tissue from patients with HNSCC, we sought to systematically identify and catalog genes expressed in HNSCC progression. Here, we demonstrate the successful use of laser capture microdissection for procuring pure populations of cells from patient tissue sets comprised of oral squamous cell carcinomas (OSCCs) and matching normal tissue. From the estimated 5000 cells procured for each sample, we were able to extract total RNA (14.7-18.6 ng) of sufficient quality to transcribe GAPDH by reverse transcriptase-polymerase chain reaction (RT-PCR). The RNA was used for the synthesis of blunt-ended, double-strand complementary DNAs (cDNAs) by oligo (dT)-mediated reverse transcription, followed by addition of linkers. Primers specific for these linkers with uracil deglycosylase-compatible ends were used to amplify these cDNAs by PCR and the product was subcloned into the pAMP10 cloning vector. Ninety-six clones from each of six libraries were randomly sequenced and results indicated that 76-96% of the inserts represent either anonymous expressed sequence tags (ESTs) (25-48%), known genes (9-29%) or novel sequences (27-51%), respectively, with very little redundancy. These results demonstrate that high quality, representative cDNA libraries can be generated from microdissected OSCC tissue. Furthermore, these finding suggest the existence of at least 132 novel genes expressed in our cDNA libraries, which may have a role in the pathogenesis of HNSCC, and may represent novel markers for early detection as well as targets for pharmacological intervention in this disease.

Aged↗
PubMed2000

How experts' adaptations to representative task demands account for the expertise effect in memory recall: comment on Vicente and Wang (1998).

K. A. Ericsson and W. Kintsch's (1995) theoretical framework of long-term working memory (LTWM) accounts for how experts acquire encoding and retrieval mechanisms to adapt to real-time demands of working memory during representative interactions with their natural environments. The transfer of the same LTWM mechanisms is shown to account for the expertise effect in unrepresentative "contrived" memory tests. Therefore, K. J. Vicente and J. H. Wang's (1998) critique of the generalizability of the LTWM framework is rejected. Their proposed refutation of LTWM accounts is found to be based on misrepresented facts. The process-based framework of LTWM is shown to be superior to their product theory because it can explain interactions of the expertise effect in "contrived" recall under several testing conditions differing in presentation rate, instructions, and memory procedures.

Adaptation, Psychological↗