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Biomedical subjects

K Patel

Publications and source records attributed to K Patel.

At least 109 records · Page 6Linked to original sources
PubMed1999

Physicians for the 21st century. Challenges facing medical education in the United States.

Since the 1980s, the American medical educational system has come under attack for its failure to train and prepare physicians for the challenges created by the changing health care market. The medical schools have been criticized for producing too many specialists and for not providing sufficient training in ethics and moral reasoning, care of the terminally ill, health care economics, alternative medicine, and the role of spiritual and religious values in healing. This study attempts to ascertain the extent to which medical schools have responded to these criticisms by changing their curriculum. The study is based on a survey of deans of medical schools in the United States. The study finds that medical schools have indeed responded to some of the criticisms by incorporating training in ethics, communication, primary and preventive care, and care of the terminally ill in their curriculum. However, the study concludes that more changes are needed to train physicians for the 21st century.

Adult↗
PubMed1999

A molecular mechanism enabling continuous embryonic muscle growth - a balance between proliferation and differentiation.

Embryonic muscle growth requires a fine balance between proliferation and differentiation. In this study we have investigated how this balance is achieved during chick development. Removal of ectoderm from trunk somites results in the down-regulation of Pax-3 expression and cell division of myogenic precursors is halted. This initially leads to an up-regulation of MyoD expression and to a burst in terminal differentiation but further muscle growth is arrested. Locally applied bone morphogenetic protein-4 (BMP-4) to somites mimics the effect of the ectoderm and stimulates Pax-3 expression which eventually results in excessive muscle growth in somites. Surprisingly, BMP-4 up-regulates expression of noggin which encodes a BMP-4 antagonist. This suggests that the proliferation enhancing activity of BMP-4 can be limited via up-regulation of noggin and that myogenic cells differentiate, as an intrinsic property, when deprived of BMP-4 influence. In contrast to BMP-4, Sonic hedgehog (Shh) locally applied to somites arrests muscle growth by down-regulation of Pax-3 and immediate up-regulation of MyoD expression. Such premature muscle differentiation in somites at tongue and limb levels prevents myogenic migration and thus tongue and limb muscle are not formed. Therefore, precise limitation of differentiation, executed by proliferative and Pax-3 promoting signals, is indispensable for continuous embryonic muscle growth.

Animals↗
PubMed1998

Experimental induction of BMP-4 expression leads to apoptosis in the paraxial and lateral plate mesoderm.

In the avian embryo, epithelialization of the segmental plate and formation of an epithelial dermomyotome depend on signals from the neural tube and the ectoderm overlying the paraxial mesoderm. In this study, we report that ectoderm removal in combination with barrier insertion between the axial organs and the segmental plate leads to an induction of BMP-4 expression in the paraxial mesoderm. In the lateral plate, ectoderm removal alone leads to an increase of BMP-4 expression. Application of BMP-4 protein results in a lack of epithelialization of the paraxial mesoderm. In order to investigate whether the loss of epithelial structures after these manipulations can be attributed to a change in cell fate, a change in cell proliferation, or the induction of apoptosis, the paraxial mesoderm was tested for expression of Msx-2, BMP-2, BMP-4, and BMP-7. Moreover, BrdU and TUNEL staining were carried out. The inhibition of epithelialization after ectoderm removal alone and after segregation of the axial organs is accompanied neither by an increase in apoptosis nor by a reduction of the proliferation rate in the paraxial mesoderm. On the other hand, an ectopic BMP-4 expression in the paraxial mesoderm after ectoderm removal in combination with barrier insertion coincides with the occurrence of apoptotic cells and reduction of proliferation rate in this tissue. Increase of apoptosis and decrease in cell proliferation are observed in the paraxial and lateral plate mesoderm also after application of BMP-4 protein.

Animals↗
PubMed1998

Periapical cemental dysplasia: a case of misdiagnosis.

The correct diagnosis of pathological lesions of endodontic origin should allow for differentiation from those arising from other sources. A case of periapical cemental dysplasia (cementoma) is presented, whereby incorrect diagnosis resulted in not only inappropriate treatment, but an endodontic mishap and the superimposition of acute apical periodontitis in a previously disease-free site. This case report highlights the need for appropriate examination, simple special tests and diagnosis prior to management of lesions of questionable aetiology.

Adult↗
PubMed1998

Modulation of amyloid precursor protein processing by compounds with various mechanisms of action: detection by liquid phase electrochemiluminescent system.

beta-Amyloid peptide (A beta) is a major component of senile plaques formed in the brain of Alzheimer disease patients. We describe here a new method of quantitating A beta in biological material using liquid phase electrochemiluminescent system (LPECL). We used both enzyme-linked immunosorbent assay (ELISA) and LPECL methods to measure A beta and APPs alpha levels in conditioned medium of beta-amyloid precursor protein (APP)-transfected CHO cells treated with known modulators of APP processing, and in CSF and plasma of guinea pigs. Our results indicate that while maintaining the accuracy and sensitivity of ELISA, LPECL is a significantly taster and less labor-intensive method for measuring of A beta and APPs alpha levels in biological fluids.

Amyloid beta-Peptides↗
PubMed1998

Microbial inhibitory properties and stability of topotecan hydrochloride injection.

The viability of five microorganisms in topotecan 1 mg/mL (as the hydrochloride salt) in sterile water and the stability of the drug were studied. Duplicate portions of topotecan 1 mg/mL were inoculated with Escherichia coli. The process was repeated for Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. Samples were removed from each solution initially and after 6, 16, and 24 hours and 3, 7, 14, 21, and 28 days of incubation at 20-25 degrees C. To test stability, vials of reconstituted topotecan hydrochloride injection were stored at each of three temperatures--5, 25, and 30 degrees C--and other vials were used for time zero analysis. For each temperature, vials were removed at 1, 7, and 14 days and the remaining vials at 28 days for analysis by high-performance liquid chromatography and for visual and pH assessment. P. aeruginosa, S. aureus, and E. coli lost viability at 16 hours, 24 hours, and 28 days, respectively. C. albicans and A. niger did not lose viability, but their numbers did not grow. No differences in color or clarity were observed, and pH was constant. In all solutions, the topotecan concentration was > 98% of the initial concentration. Topotecan 1 mg/mL in sterile water stored at 20-25 degrees C for up t 28 days did not support growth of the five microorganisms studied; in solutions stored at 5, 25, or 30 degrees C for up to 28 days, topotecan 1 mg/mL remained stable.

Antineoplastic Agents↗
PubMed1998

Progenitor dispersal and the origin of early neuronal phenotypes in the chick embryo spinal cord.

Using DiI fluorescent dextrans, we have created fate maps of the neural plate and early neural tube describing the extent of progenitor cell dispersal and the spatial origin of morphologically distinct neuronal cell types along the dorsoventral axis of the developing chick spinal cord. Nonuniform dispersal and mixing of progenitors occur within the early neuroepithelium, with the degree of dispersal being determined by the initial position of the cells along the mediolateral axis of the neural plate. Dispersal is greatest in the midregions of the ventricular epithelium and decreases toward the dorsal and ventral midlines. Phenotypically diverse classes of neurons are born at specific dorsoventral locations in the neural tube. Motor neurons are the most ventral cell type generated followed, at progressively more dorsal positions, by distinct classes of interneurons. Several genes show dorsoventrally restricted patterns of expression within the neural tube and the fate maps were used to investigate the relationship between one of these genes, Pax3, and progenitor cell dispersal and fate. The results indicate that the dorsoventral pattern of Pax3 expression is not maintained by restrictions to cell mixing and are consistent with a role for this transcription factor in specifying the identity of neurons with contralateral descending axons.

Animals↗
PubMed1998

The importance of timing differentiation during limb muscle development.

BACKGROUND: Skeletal muscle of trunk, limbs and tongue develops from a small population of cells that originates from somites. Although promoters and inhibitors of muscle differentiation have been isolated, nothing is known about how the amplification of the muscle precursor pool is regulated; this amplification provides muscle mass during development. Furthermore, little is known about how cells accumulate in the pre-muscle masses in the limbs. We investigated the role of bone morphogenetic protein (BMPs) and Sonic hedgehog (Shh) during proliferation, differentiation and positioning of muscle. RESULTS: The proliferation of muscle precursors in limbs was linked to Pax-3 expression. Ectoderm removal downregulated Pax-3 expression, arrested proliferation and prematurely initiated muscle differentiation which exhausted the muscle precursor pool and prevented further muscle growth. BMP-2, BMP-4 and BMP-7 had a dose-dependent effect on pre-myogenic cells: low concentrations maintained a Pax-3-expressing proliferative population, substituting for ectoderm-derived proliferative signals and delaying differentiation, whereas high concentrations prevented muscle development, probably by inducing apoptosis. In the limb, Shh upregulated Bmp-2 and Bmp-7 expression which delayed muscle differentiation, upregulated Pax-3, amplified the muscle precursor population and stimulated excessive muscle growth. CONCLUSIONS: These data indicate that embryonic muscle growth requires muscle differentiation to be delayed. Muscle differentiation may occur through a default pathway after cells escape proliferative signals. Positioning of muscle is regulated by high concentrations of BMPs, thus a single type of signalling molecule can determine crucial steps in muscle development: when and where to proliferate, and when and where to differentiate.

Animals↗
PubMed1998

Analysis of 1.9 Mb of contiguous sequence from chromosome 4 of Arabidopsis thaliana.

The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Arabidopsis↗
PubMed1998

Distinct classes of chaperoned IL-6 in human blood: differential immunological and biological availability.

Transport of IL-6 in blood is fundamental to the biology of this cytokine. In the present study, IL-6 transport, immunological reactivity, and biological availability were investigated in blood from melanoma patients subjected to different active specific immunization regimens (an anti-idiotypic mAb immunization protocol (mAb-keyhole limpet hemocyanin (KLH)-Calmette-Guerin bacillus (BCG), an autologous anti-cancer vaccine protocol (AAAP), or both). Sera were subjected to Sephadex G-200 gel filtration chromatography, and the structure and biological activity of IL-6 complexes in the eluate fractions were probed using five IL-6 ELISAs and two bioassays. Sera from patients administered mAb-KLH+BCG followed by AAAP contained three distinct classes of IL-6 eluting at 30, 200, and 450 kDa, each with its characteristic ELISA reactivity and bioactivity: the 30- and 450-kDa complexes were bioactive in the B9 and Hep3B assays, but the 200-kDa complex was not. The 30- and 450-kDa IL-6 complexes were preferentially reactive in the 7IL6/5IL6 ELISA, the 200-kDa IL-6 complexes were preferentially reactive in the 4IL6/5IL6 ELISA, while the three commercial ELISAs (R&D, Endogen, and Genzyme) detected essentially only the 30-kDa IL-6. In contrast, 1) sera from AAAP patients contained biologically active 30- and 450-kDa IL-6 complexes, while 2) sera from mAb-KLH+BCG patients contained 200-kDa IL-6 complexes inactive in ex vivo bioassays. Both the 450- and 200-kDa complexes included soluble IL-6R, with the 200-kDa complexes additionally containing ligand-occupied anti-IL-6 and anti-soluble IL-6R IgG. The data indicate the existence of specific mechanisms that regulate the transport and function of IL-6 in vivo.

Antibodies, Neoplasm↗
PubMed1998

An analysis of the relationship between hydration and protein-DNA interactions.

Eleven protein-DNA crystal structures were analyzed to test the hypothesis that hydration sites predicted in the first hydration shell of DNA mark the positions where protein residues hydrogen-bond to DNA. For nine of those structures, protein atoms, which form hydrogen bonds to DNA bases, were found within 1.5 A of the predicted hydration positions in 86% of the interactions. The correspondence of the predicted hydration sites with the hydrogen-bonded protein side chains was significantly higher for bases inside the conserved DNA recognition sequences than outside those regions. In two CAP-DNA complexes, predicted base hydration sites correctly marked 71% (within 1.5 A) of protein atoms, which form hydrogen bonds to DNA bases. Phosphate hydration was compared to actual protein binding sites in one CAP-DNA complex with 78% marked contacts within 2.0 A. These data suggest that hydration sites mark the binding sites at protein-DNA interfaces.

Binding Sites↗
PubMed1998

Hydration of the phosphate group in double-helical DNA.

Water distributions around phosphate groups in 59 B-, A-, and Z-DNA crystal structures were analyzed. It is shown that the waters are concentrated in six hydration sites per phosphate and that the positions and occupancies of these sites are dependent on the conformation and type of nucleotide. The patterns of hydration that are characteristic of the backbone of the three DNA helical types can be attributed in part to the interactions of these hydration sites.

Binding Sites↗
PubMed1998

The provision of dental implants and a fixed prosthesis in the treatment of a patient with scleroderma: a clinical report.

This clinical report highlights some of the problems in providing a suitable prosthesis for a patient who suffers from systemic sclerosis. A conventional removable partial denture may not have been suitable because of the lack of denture bearing area, changing peripheral seal, and insufficient teeth to support and retain the denture. An implant-retained FPD overcame these difficulties. One would hope that, with regular maintenance and monitoring, quoted prosthesis success of 15 years can be achieved.

Chronic Disease↗
PubMed1998

Expression patterns of Notch1, Serrate1, Serrate2 and Delta1 in tissues of the developing chick limb.

Signalling via the receptor Notch, delivered by the ligands Delta and Serrate, plays a key role in many cell fate decisions in both Drosophila and vertebrate development (for review seeArtavanis-Tsakonas, S., Matsuno, K. and Fortini, M.E., 1995. Notch signalling. Science 268, 225-232; Lewis, J., 1996. Neurogenic genes and vertebrate neurogenesis. Curr. Opin. Neurobiol. 6, 3-10; Blair, S.S., 1997. Limb development: marginal fringe benefits. Curr Biol. 7, 686-690; Irvine, K.D. and Vogt, T.F., 1997. Dorsal-ventral signaling in limb development. Curr. Opin. Cell Biol. 9, 867-876). Recently vertebrate homologues of Notch (Notch1; Myat, A., Henrique, D., Ish-Horowicz, D. and Lewis, J., 1996. A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogeneis. Dev. Biol. 174, 233-247) and Serrate (Serrate1 and 2; Myat, A., Henrique, D., Ish-Horowicz, D. and Lewis, J., 1996. A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogeneis. Dev. Biol. 174, 233-247; Hayashi, H., Mochii, M., Kodama, R., Hamada, Y., Mizuno, N., Eguchi, G. and Tachi, C., 1996. Isolation of a novel chick homolog of Serrate and its coexpression with Notch-1 in chick development. Int. J. Dev. Biol. 40, 1089-96; Laufer, E., Dahn, R., Orozco, O.E., Yeo, C.Y., Pisenti, J., Henrique, D., Abbott, U., Fallon, J.F. and Tabin, C., 1996. Expression of Radical fringe in limb-bud ectoderm regulates apical ectodermal ridge formation. Nature 386, 366-373; Rodriguez-Esteban, C., Schwabe, J.W., De La Pena, J., Foys, B., Eshelman, B. and Izpisua-Belmonte, J.C., 1997. Radical fringe positions the apical ectodermal ridge at the dorsoventral boundary of the vertebrate limb. Nature 386, 360-366) were shown to be expressed in early chick limb mesenchyme and apical ridge. However, later expression patterns of these genes and of Delta 1 (Henrique, D. , Adam, J., Myat, A., Chitnis, A., Lewis, J. and Ish-Horowicz, D., 1995. Expression of a Delta homologue in prospective neurons in the chick. Nature 375, 787-790) in vertebrate limbs have not been documented. We have used whole mount in-situ hybridization to document expression patterns of Notch1, Serrate1, Serrate2 and Delta1 within the mesenchyme of the developing chick limb up to stage 31 of development. We show these genes are expressed, in different combinations, in the vasculature, the musculature and the tissues of the handplate.

Animals↗
PubMed1998

Follistatin.

Follistatin, a secreted protein is able to bind and neutralise the actions of many members of the Transforming Growth Factor-beta family of proteins. Follistatin was first implicated in the regulation of follicle-stimulating hormone secretion in the pituitary and subsequently in other regions of the adult body associated with reproductive functions. Recent work has shown that this protein is much more broadly distributed and may also play a significant role during embryogenesis. Gene targetting has shown that follistatin is essential for normal development and in its absence, mice die soon after birth with a range of defects including insufficient muscle development and skeletal abnormalities. A number of diseases have been identified thought to be caused by an over-production of members of the Transforming Growth Factor-beta family of proteins. Therefore it may be possible to use follistatin as a therapeutic agent in these disorders.

Animals↗
PubMed1998

Mammalian expression of transmembrane receptors for pharmaceutical applications.

Three mammalian expression systems suitable for expressing recombinant receptors have been described. Each is suited to a different aspect of the study of receptors and their behaviour. IRES-based vectors are ideal for creating stable mammalian cell lines suitable for screening receptors using a signalling readout. Unlike traditional vectors they result in almost 100% of cell lines generated expressing a particular receptor, thus increasing the efficiency of cell line generation and increasing the chance of higher expression-level cell lines being generated. They may also be utilized to express more than one protein of interest, for example it is possible to co-express a particular receptor with a particular signalling protein or trafficking protein from a single RNA, thus ensuring that both are expressed simultaneously in the same cell. The ecdysone-inducible expression system is ideal for studying receptor signalling and behaviour. It is possible to alter receptor expression levels in an identical cellular background thus making it possible to study phenomena such as constitutive receptor activity in the absence of agonist. The SFV expression system is ideal for expressing receptors at high levels of a mammalian cell. It is thus a good system for purifying receptors for structural analysis and for providing material for binding assays. All of the expression systems described above have been demonstrated to express seven-transmembrane receptors with the expected pharmacological and functional profile.

Animals↗
PubMed1998

The effect of rectally administered steroids on bone turnover: a comparative study.

BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.

Administration, Rectal↗