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Biomedical subjects

C Parker

Publications and source records attributed to C Parker.

At least 19 recordsLinked to original sources
PubMed1995

Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources.

OBJECTIVE: To compare the efficacy of mannose-terminated glucocerbrosidase prepared from natural (alglucerase; Ceredase, Genzyme Corp., Cambridge, Massachusetts) and recombinant (imiglucerase; Cerezyme, Genzyme Corp.) sources in treating type 1 Gaucher disease. DESIGN: Double-blind, randomized, parallel trial. SETTING: University medical center and clinical research hospital. PATIENTS: 15 patients (4 children and 11 adults) randomly assigned to receive Ceredase and 15 patients (3 children and 12 adults) assigned to receive Cerezyme. INTERVENTION: Ceredase and Cerezyme were infused every 2 weeks for 9 months at a dose of 60 U/kg body weight. OUTCOME MEASURES: Hemoglobin levels, platelet counts, and serum acid phosphatase and angiotensin-converting enzyme activities were monitored every 2 weeks during the trial. Hepatic and splenic volumes were assessed at the time of randomization and after 6 and 9 months of enzyme infusion. Formation of IgG antibodies to Ceredase or Cerezyme was monitored every 3 months by radioimmunoprecipitation assay. RESULTS: No significant differences were found in the rate or extent of improvement in hemoglobin levels, platelet counts, serum acid phosphatase or angiotensin-converting enzyme activities, or hepatic or splenic volumes between either treatment group. The incidence of IgG antibody formation was greater in the Ceredase group (40%) than in the Cerezyme group (20%). No major immunologic adverse events occurred in either group. CONCLUSIONS: Our study shows the therapeutic similarity of Ceredase and Cerezyme. Cerezyme has the advantage of being theoretically unlimited in supply and free of potential pathogenic contaminants.

Adolescent↗
PubMed1995

Cortical bone perfusion in plated fractured sheep tibiae.

The limited contact dynamic compression plate and partial contact plate were designed to decrease contact with cortical bone in an attempt to decrease cortical ischemia, remodeling, and eventual porosis under the plate after use of standard dynamic compression plates. This study quantified cortical bone blood flow beneath the plate with these three different designs in a sheep tibia fracture model. In 18 skeletally immature sheep, the right tibia was fractured and then was internally fixed with an interfragmentary screw and a dynamic compression plate, limited contact dynamic compression plate, or partial contact plate. At 12 weeks, cortical bone perfusion was assessed with laser Doppler flowmetry in nine areas beneath the plate. The baseline (before fracture) cortical bone cell flux averaged 100 +/- 60 mV. After fracture, this decreased to 60 +/- 48 mV (p < 0.0003); immediately after plating, the perfusion averaged 29 +/- 25 mV (p < 0.01). Cortical bone perfusion then increased to 106 +/- 52, 165 +/- 71, and 163 +/- 71 mV at 2, 6, and 12 weeks after fracture (p < 0.001 for all when compared with values after plating). No significant differences in cortical perfusion were seen between the types of plate. Cortical porosity under the plate was assessed with digital density analysis of microradiographs of this region. No significant difference was seen between the types of plate in this analysis or in biomechanical and disulphine blue perfusion analysis. Thus, no significant advantage was seen for the new plate designs used in this model. This lack of advantage may be a result of the immature animals used in the study, the protocol for blood flow measurement, the invasive periosteal stripping employed to create the fracture, or all three. However, as advantages with the new plate designs have been seen in other studies, this area warrants further investigation.

Analysis of Variance↗
PubMed1995

Characterization of the Zymomonas mobilis glucose facilitator gene product (glf) in recombinant Escherichia coli: examination of transport mechanism, kinetics and the role of glucokinase in glucose transport.

Zymomonas mobilis is known to transport glucose by a facilitated diffusion process. A putative glucose facilitator gene (glf), closely related to a large family of glucose transporters, is located in a cluster of genes that code for enzymes of glucose metabolism. The Z. mobilis glf gene is able to complement glucose transport in an Escherichia coli strain that is defective in native glucose transport and glucokinase. In this study, the recombinant E. coli was shown to be capable of influx counterflow when preloaded with glucose and had an apparent Km for glucose of approximately 1.1-2.9 mM, consistent with the function of Glf as a low-affinity glucose facilitator. The ability of glucokinase mutants expressing glf to transport glucose made it clear that glucokinase activity was not required for Glf-dependent glucose transport. The possibility that glucokinase can interact with Glf to improve the affinity for glucose was not supported since expression of the Z. mobilis glucokinase gene, in addition to glf, did not affect the Km of Glf for glucose in recombinant E. coli. The inability of various sugars to compete with glucose during glucose transport by recombinant E. coli expressing glf indicated that Glf is specific for glucose. While the results of fructose transport assays did not completely rule out the possibility of very low affinity for fructose, the apparent specificity of Glf for glucose makes it possible that Z. mobilis utilizes a different transporter(s) for fructose.

Bacterial Proteins↗
PubMed1995

Alterations in cell-cell communication in human papillomavirus type 16 (HPV16) transformed rat myoblasts.

A reduction of gap-junctional intercellular communication (GJIC) often accompanies neoplastic transformation. The present work demonstrates that transformation by the oncogenic human DNA virus, human papilloma virus 16(HPV16), also reduces GJIC between L6 rat myoblasts. HPVs are associated with anogenital cancers, the incidence of which is increasing in HIV positive patients of both sexes. Using videofluorescence imaging of Fura-2 loaded cells a lack of GJIC between transformed HPV16-L6 cells was first indicated by uncoordinated brief [Ca2+]i spikes in clusters of DMSO-treated HPV16-L6 cells instead of the synchronous, sustained [Ca2+]i surges in clusters of DMSO-treated L6 cells. Reduced GJIC between HPV16-L6 cells was demonstrated directly by a much reduced transfer of lucifer yellow dye from HPV16-L6 cells, which had been loaded with the dye through electroporation with an EPIZAP II in situ electroporator, to neighbouring nonelectroporated HPV16-L6 cells. One reason for this reduced GJIC between HPV16-L6 cells could have been their dramatically enhanced activity of membrane-associated PKC which is known to phosphorylate connexins and down-regulate gap junctions. However, the main reason was the viral-induced inhibition of the expression of a major gap junction component, Cx43 (Connexin 43), in the transformed myoblasts.

Animals↗
PubMed1994

Induction of 18A2/mts1 gene expression and its effects on metastasis and cell cycle control.

The metastasis associated 18A2/mtsI gene was inserted into the mammalian expression vector pMAMneo placing it under the control of the dexamethasone-inducible MMTV promoter. The construct was transfected into dexamethasone receptor negative F1 and receptor positive F10 cells of the B16 murine melanoma. The transferred gene was switched on in two transfectant clones of F10, by exposure to 10(-6) M dexamethasone, but not in clones of the receptor negative F1 line. One of the F10 transfectant clones (F10-192/10) was characterized further. A 13.5-fold increase in 18A2/mts1 transcripts was found in this clone upon exposure to dexamethasone. There was also a seven-fold increase in lung colonization in an experimental metastasis assay, together with increased expression of depolymerized tubulin and enhanced detection of p53 protein. The number of cells in the S phase increased by 2.5-fold following dexamethasone treatment of the clone. These data suggest a direct involvement of the 18A2/mts1 gene in lung colonization by the tumor cells. The 18A2/mts1 protein promotes tubulin depolymerization, sequesters the p53 phosphoprotein, and induces the cells to enter the S phase, but the relevance of these in the metastatic process remains to be elucidated.

Animals↗
PubMed1994

Metastasis-associated mts1 gene expression correlates with increased p53 detection in the B16 murine melanoma.

MTS1 is a metastasis-associated gene highly expressed in high-metastasis tumors. Here we show that the expression of the suppressor gene p53 protein correlates with mts1 expression. In murine melanoma B16-F1 cells, alpha-melanocyte-stimulating hormone up-regulated mts1 and increased p53 positivity in immunohistochemical tests. In B16-ML8 cells, retinoic acid reduced mts1 expression together with a reduction of p53 positivity. The variation of p53 in association with mts1 gene expression suggests that the mts1 product might interact with and stabilize p53. Taxol-induced aneuploidy increased the proportion of G0G1 phase cells, increased p53 positivity, and down-regulated mts1. This suggests that mts1 transcription may have been negatively regulated, possibly on account of the stabilization of microtubules by taxol. We postulate that the control of G1-S transition by p53 could be due to p53 sequestration by mts1, leading to microtubule depolymerization and signaling entry, into the S phase. Thus, a coordinated function of mts1 and p53 may be involved not only in uncontrolled growth but also in cytoskeletal depolymerization that could lead to cancer invasion.

Calcium-Binding Proteins↗
PubMed1994

Metastasis-associated mts1 gene expression is down-regulated by heat shock in variant cell lines of the B16 murine melanoma.

Tumour cells are more heat sensitive than corresponding normal cells but the reasons for this are poorly understood. Here we report that induction of heat shock proteins was associated with a down-regulation of the metastasis associated mts1 gene in BL6-B16 murine melanoma cells, and the heat-resistant HTG variant of the BL6 line. Melanocyte stimulating hormone, which does not affect B16 cell proliferation but upregulates mts1 expression, only marginally enhanced heat shock protein expression in F1 cells as determined by immunohistochemical methods. Retinoic acid, which inhibits cell proliferation and down-regulates the mts1 gene, reduced heat shock protein expression in the ML8-B16 variant line. This suggests that the changes in the heat shock protein expression reported here may be cell proliferation related. Heat shock proteins are known to stabilize microtubules, whereas mts1 has been implicated in their depolymerization. Taxol, which stabilizes microtubules and arrests cells at the G1 phase of the cell cycle, down-regulated mts1 gene expression in both F1 and ML8 lines. Taxol also reduced heat shock protein expression in ML8 cells. These data suggest opposing functions of heat shock proteins and the mts1 gene in microtubule polymerization, and may provide a rationale for the use of hyperthermia as a treatment for tumours.

Animals↗
PubMed1994

Overexpression of the 18A2/mts1 gene and down-regulation of the TIMP-2 gene in invasive human glioma cell lines in vitro.

Invasion of the reconstituted extracellular matrix composite, Matrigel, by eight human glioma-derived cell lines and human fetal brain cells was assessed in vitro using 8 microns polycarbonate filters in a modified Boyden migration chamber. With the exception of one low grade glioma derived cell line, all lines studied proved to be invasive while normal fetal brain cells failed to invade. This invasive potential was independent of the histological grade of the tumour from which the cell lines originated. In addition, the expression of the metastasis-associated gene 18A2/mts1 as well as the tissue inhibitor of metalloproteinases-2 (TIMP-2) was analysed in each of the glioma-derived cell lines. The 18A2/mts1 was expressed in all the cells studied with the exception of fetal brain cells and the low grade non-invasive glioma derived IPRK-7 cell line. The 18A2/mts1 related genes coding for the S100 subfamily of calcium binding proteins were found to be differentially and overexpressed in invasive cell lines. TIMP-2 was expressed only in non-invasive cell lines. These results suggest that the 18A2/mts1 and TIMP-2 genes could play an important role in the invasive behaviour of human glioma cells in vitro.

Blotting, Northern↗
PubMed1993

Nonaffinity purification of recombinant gp120 for use in AIDS vaccine development.

The gene encoding the major envelope glycoprotein of the HIV-SF2 isolate was engineered for the secretion of recombinant gp120 (rgp120SF2) from permanent Chinese hamster ovary (CHO) cell lines. Cellular production methods were scaled up and a method for purification of the secreted glycoprotein was devised. Mild purification conditions were selected in order to preserve the native structure of the protein. rgp120SF2 exhibits a molecular weight of 120 kDa in reduced or nonreduced SDS gels; thus the polypeptide chain is intact. Deglycosylated rgp120SF2 has the predicted molecular weight of the polypeptide backbone, 54 kDa. Gel-filtration HPLC in a nondenaturing buffer at neutral pH yields a molecular weight estimate of approximately 120 kDa. Purified rgp120 closely resembles authentic viral gp120 by several physical, chemical, and immunochemical tests. rgp120SF2 reacts strongly with human HIV-positive sera, monoclonal antibodies reactive with HIV-SF2 and HIV-MN viral envelope, and a human virus-neutralizing monoclonal antibody that maps to a conserved discontinuous epitope on HIV-1 gp120. Purified rgp120SF2 forms a 1:1 molecular complex with soluble recombinant human CD4 (rCD4) receptor, as demonstrated by gel-filtration HPLC; binding is high affinity (Kd approximately 2 x 10(-9) M).

AIDS Vaccines↗
PubMed1993

The Ca2+ channel blocker verapamil enhances melanogenesis without altering metastatic potential in the B16 murine melanoma.

The relationship between the processes of melanogenesis and metastasis were investigated using metastatic variants of the B16 murine melanoma. alpha-Melanocyte stimulating hormone (MSH) enhanced lung colonization by the low metastasis variant F1 as well as inducing melanogenesis. The Ca2+ channel blocker verapamil had no effect on lung colonization by the F1 and ML8 variants but markedly enhanced melanogenesis in both these cell lines. We previously showed that the expression of the dominant metastasis associated gene mts1 was up-regulated by MSH but down-regulated by verapamil. These findings may demonstrate that the processes of melanogenesis and metastasis can be uncoupled at both genetic and phenotypic levels, and that the mechanisms involved in the regulation of metastatic behaviour and melanogenesis are different.

Animals↗
PubMed1993

Continuous flow resectoscopes. Are the theory and design wrong?

The optical design of rod-lens telescopes has now reached a zenith. The only way of improving the resectoscope is to investigate the ergonomics and flow dynamics. We present a comparative analysis of the flow mechanics of continuous flow resectoscopes. The morphology, flow characteristics and irrigating potential (washout gradient) of several instruments were examined. It was found that when used with balanced continuous flow (inflow and outflow balanced), all of the endoscopes had poor visibility compared with unbalanced continuous flow (inflow > outflow). Possible changes in the design of the instruments are discussed.

Endoscopes↗
PubMed1993

Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group.

BACKGROUND: High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma. Although effective, they may cause systemic side effects. Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses. METHODS: Fluticasone propionate, 1.5 mg per day, was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate. The study was multicentre, double blind and of a parallel design. For the first three months patients attended the clinic every four weeks and completed daily diary cards. For the next nine months they were only seen at three monthly intervals in the clinic. RESULTS: During the first three months diary card peak expiratory flow (PEF) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate (difference in morning PEF 15 l/min (95% CI 6 to 25)), and these differences were apparent at the end of the first week. The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8% compared with those receiving beclomethasone dipropionate. No significant differences between the two groups were observed in morning plasma cortisol levels, urinary free cortisol levels, or response to synthetic ACTH stimulation. In addition, both the rates of withdrawal and of adverse events were low, and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate. CONCLUSIONS: This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate, with no increase in systemic or other side effects.

Administration, Topical↗
PubMed1993

Transient preservation of photoreceptors on the flanks of argon laser lesions in the RCS rat.

In the RCS rat there is a progressive degeneration of the photoreceptors which starts at two to three weeks after birth. We have demonstrated that there is prolonged survival of photoreceptors on the flanks of argon laser lesions made at post-natal day 23, just as degeneration begins. The cells in the outer nuclear layer retained a relatively normal appearance on the flanks of the lesions for the first two weeks and there was a very low percentage of pyknotic cells. By one month some cell loss occurred but much less than in non-irradiated regions where very few cells remained. At two months after lesion there were still elevated numbers on the flanks but only 2-3 rows of cells remained. The prolonged survival correlated with disruption to the pigment epithelial layer, increased migration of phagocytic cells into the outer segment/debris layer and a reduction in thickness of the debris layer at late stages. The mechanisms of this effect are unknown however laser lesions provide a well controlled and reproducible situation in which to study these mechanisms.

Animals↗
PubMed1992

Co-expression of sulfonylurea receptors and KATP channels in hamster insulinoma tumor (HIT) cells. Evidence for direct association of the receptor with the channel.

Cell membranes isolated from hamster insulinoma (HIT T15) cells at passages 65-74 contain high and low affinity receptors for a sulfonylurea derivative, 5-[125I]iodo,2-hydroxyglyburide (KD values of approximately 7 nM and 16 microM). Between passages 75 and 85, the estimated B(max) for the high affinity receptor decreases approximately 10-fold from approximately 1.6 to 0.16 pmol/mg membrane protein. By contrast, the density of low affinity binding sites, 800-1000 pmol/mg, is unaltered. The drop in high affinity receptors is paralleled by a decrease in the density of KATP channels assessed using patch-clamp and 86Rb(+)-efflux techniques. These results strongly support the idea that the high affinity sulfonylurea receptor is an integral part of the KATP channel.

ATP-Binding Cassette Transporters↗