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Biomedical subjects

C Parker

Publications and source records attributed to C Parker.

At least 109 records · Page 6Linked to original sources
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

The proto-oncogene c-myb mediates an intracellular calcium rise during the late G1 phase of the cell cycle.

The intracellular concentration of ionized calcium is involved in regulating mitosis. However, little is known about intracellular levels of calcium during G1. We have demonstrated in vascular smooth muscle cells a mid-G1 decrease in ionized calcium concentration followed by a 2-fold rise at the G1/S interface (44 nM +/- 0.6 nM versus 98 nM +/- 1.1 nM, p < 0.01). The elevation of intracellular calcium is preceded by an increase in c-myb mRNA levels and is abolished with antisense but not missense c-myb oligonucleotides. Furthermore, cells stably transfected with c-myb show a similar 2-fold augmentation in intracellular calcium concentrations, as compared with untransfected cells, which is also abolished by antisense c-myb oligonucleotides. The c-myb-induced rise in intracellular calcium is dependent upon the presence of extracellular calcium and is not suppressed by L type calcium channel blockers. We conclude that c-myb induces an elevation in intracellular calcium levels of vascular smooth muscle cells at the G1/S interface which provides a novel role for this proto-oncogene as well as a potentially important control point for cell cycle regulation.

Animals↗
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

Laparoscopic varicocele ligation.

A laparoscopic varicocele ligation was performed in 49 men with a clinically proven varicocele. Patients were treated predominantly on a day case or overnight basis with minimal post-operative morbidity. Identification of the testicular artery was aided by a laparoscopic Doppler probe in the majority of patients and preserved in 39 cases. The varicocele persisted in 7 patients, 4 of whom have subsequently had an inguinal exploration confirming a missed testicular vein as the source. In all 7 patients the artery was identified without the use of the Doppler probe, this being suggestive of misidentification of the vessels at laparoscopy. The complications included 4 wound infections, 1 scrotal haematoma and 1 vasal injury which necessitated an open vasovasostomy. Laparoscopic varicocele ligation is a simple and safe technique, causing minimal morbidity and enabling a rapid return to normal activity. The success rate can be improved by accurate identification of the testicular vessels with the use of a laparoscopic Doppler probe.

Adolescent↗
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

Notes: a suitable case for audit.

The increasing emphasis on management responsibilities and audit led us to investigate the state of surgical notes in our hospital. Twelve criteria were evaluated regarding information that should be contained in the notes and the absence of this important information was documented. Deficiencies were revealed in all criteria selected. Until hospital patients files are well kept and maintained, retrospective audit whether financial or medical will not be valid. A significant injection of resources is required to redress the situation. Hospitals which have not carried out detailed studies into the contents of their notes need to do so as a matter of urgency.

Humans↗
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

Progression of aortic stenosis. Role of age and concomitant coronary artery disease.

To determine the spontaneous progression of valvular aortic stenosis and to delineate clinical factors related to progression, a longitudinal study, including 49 patients (aged 16 to 81 years), was performed. All patients had auscultatory findings of aortic stenosis and multiple Doppler echocardiograms separated by at least 11 months. Rapid progression of aortic stenosis was defined as an increase of maximal instantaneous pressure gradient by > or = 10 mm Hg per year. During a mean follow-up period of 32 months (11 to 66 months), maximal pressure gradient rose from 38 +/- 15 to 60 +/- 20 mm Hg in the entire study population, resulting in a median increase of 7.2 mm Hg per year. In 21 patients (43 percent), an increase of > or = 10 mm Hg per year was found; in this subgroup with rapid progression, patients were older (64 vs 53 years, p < 0.01) and coronary artery disease was more prevalent (38 percent vs 7 percent, p = 0.01). We conclude that nearly half the patients with initially mild to moderate valvular aortic stenosis reveal a progression of > or = 10 mm Hg per year.

Adolescent↗
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↗