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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 199 records · Page 11Linked to original sources
PubMed1995

General dental practitioner referral patterns for minor oral surgery.

A questionnaire was sent to all general dental practitioners within Grampian region investigating the frequency of referral to hospital of medically fit patients for minor oral surgery. This was compared with their general dental practice experience and previous hospital employment. A 91.8% (n = 135) response rate was achieved. The responses indicated that practitioners refer if they believe specialist treatment is required, but less experienced practitioners were more likely to refer in the belief that general anaesthesia was necessary for treatment. A patient's request was a rare cause of referral, particularly with the more experienced practitioners. Referrals for the patient to avoid paying National Health Service (NHS) charges were rare, as were referrals due to lack of equipment. Inappropriate NHS fees for minor oral surgery treatment was a cause of referral by one third of practitioners.

Age Factors↗
PubMed1994

The role of protein kinase C in arachidonic acid release and prostaglandin E production from CHO cells transfected with EGF receptors.

Arachidonic acid release and prostaglandin production are stimulated by both phorbol esters and growth factors in various cell types. Whereas phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal transduction. We investigated the involvement of protein kinase C in the pathway of arachidonic acid metabolism by CHO cells transfected with full-length EGF receptor (CHOwt). Two isoforms of protein kinase C were identified in CHOwt cells, alpha and zeta. On downregulation, the parallel loss of phorbol ester-stimulated arachidonic acid release and the alpha-isoform suggests a possible involvement of this isoform in phospholipase A2 activation in these cells. In addition, we propose that the zeta-isoform may be separately involved in prostaglandin production as residual phorbol ester-stimulation of PGE production occurs in downregulated cells where PKC zeta is the sole remaining isoform. EGF stimulation of arachidonic acid release, as a measure of phospholipase A2 activation, and subsequent prostaglandin production are unaffected by inhibition of protein kinase C in CHOwt cells. Indeed one such inhibitor, staurosporine, augmented the EGF effect. These results suggest that PKC is not required for EGF activation of phospholipase A2 in these cells.

Alkaloids↗
PubMed1994

Insulin receptor autophosphorylation and exogenous substrate phosphorylation: role of receptor C-terminus and effects of mild reduction.

A mutant insulin receptor lacking the final 69 amino acids of the beta-subunit (delta 69) was used to examine the role of the receptor C-terminal domain in kinase activation. With increasing deletion of the C-terminus from 43 to 69 amino acids we show that exogenous peptide kinase activity is lost before autokinase activity. Despite this, phosphorylation of an in vivo insulin receptor substrate, IRS-1, and insulin bioeffects are similar to wild-type. In addition, with the exception of insulin-stimulated peptide phosphorylation, the reductant glutathione modified kinase activity in a similar manner for both wild-type and mutant delta 69 receptors. These results suggest that conformational changes proposed to occur within the receptor C-terminus upon insulin binding may not be necessary for kinase activation under a variety of conditions.

Amino Acid Sequence↗
PubMed1994

GLUT-2 gene transfer into insulinoma cells confers both low and high affinity glucose-stimulated insulin release. Relationship to glucokinase activity.

The rat insulinoma cell line RIN 1046-38 loses glucose-stimulated insulin secretion as a function of time in culture. We found that the loss of glucose sensing in these cells was correlated with the loss of expression of GLUT-2 and glucokinase. Stable transfection of RIN cells with a plasmid containing the GLUT-2 cDNA conferred glucose-stimulated insulin release in intermediate but not high passage cells, with the near-maximal 3-fold increase occurring at 50 microM glucose. GLUT-2 expressing cells also exhibited a larger response to the combination of 5 mM glucose + 1 microM forskolin than untransfected cells (7.9 versus 1.6-2.7-fold, respectively). GLUT-2 expressing intermediate passage, but not high passage, RIN cells exhibited a 4-fold increase in glucokinase enzymatic activity relative to nonexpressing controls. Glucokinase activity was also increased by transfer of the GLUT-2 gene into intermediate passage RIN cells via recombinant adenovirus. Preincubation of GLUT-2 expressing intermediate passage RIN cells with 2-deoxyglucose to inhibit low Km hexokinases resulted in a glucose-stimulated insulin secretion response that was shifted toward the physiologic range. These studies indicate that GLUT-2 expression confers both a high and low affinity glucose-stimulated insulin secretion response to intermediate passage RIN cells.

3-O-Methylglucose↗
PubMed1994

Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs.

Bacterial mutS and mutL mutations confer large increases in recombination between sequences that are divergent by several percent at the nucleotide level, an effect attributed to a role for products of these genes in control of recombination fidelity. Since MutS and MutL are proteins involved in the earliest steps of mismatch repair, including mismatch recognition by MutS, we have tested the possibility that they may affect strand exchange in response to occurrence of mispairs within the recombination heteroduplex. We show that MutS abolishes RecA-catalyzed strand transfer between fd and M13 bacteriophage DNAs, which vary by 3% at the nucleotide level, but is without effect on M13-M13 or fd-fd exchange. Although MutL alone has no effect on M13-fd heteroduplex formation, the protein dramatically enhances the inhibition of strand transfer mediated by MutS. Analysis of strand-transfer intermediates that accumulate in the presence of MutS and MutL indicates that the proteins block branch migration, presumably in response to occurrence of mispairs within newly formed heteroduplex.

Adenosine Triphosphatases↗
PubMed1994

Sequencing 5-methylcytosine residues in genomic DNA.

To analyse the biological role of 5-methylation of cytosine residues in DNA requires precise and efficient methods for detecting individual 5-methylcytosines (5-MeCs) in genomic DNA. The methods developed over the past decade rely on either differential enzymatic or chemical cleavage of DNA, or more recently on differential sensitivity to chemical conversion of one base to another. The most commonly used methods for studying the methylation profile of DNA, including the bisulphite base-conversion method, are reviewed.

5-Methylcytosine↗
PubMed1994

Effect of interferon gamma and tumour necrosis factor alpha on sensitivity to cisplatin in ovarian carcinoma cell lines.

This study aimed to investigate whether the biological response modifiers (BRM) interferon gamma (IFN gamma) and tumour necrosis factor alpha (TNF alpha) could enhance the cytotoxic action of cisplatin on ovarian tumour cells in vitro. The sensitivity of four cell lines (OAW42, GG, JAM and PE01) to drugs and drug combinations was tested by a radiolabelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each of the BRM. When IFN gamma was used in combination with cisplatin, a significant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines but diminished the toxicity of cisplatin in one cell line. A purely additive effect of the agents may explain the enhanced toxicity of cisplatin in some of these cases. However, in one cell line at least (PEO1), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may provide better antitumour regimen than cisplatin alone in some patients with ovarian cancer, but the response is likely to be heterogeneous between patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Male fertility after VAPEC-B chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma.

Semen analysis was performed in 14 men a median of 13.5 months after completion of VAPEC-B chemotherapy for Hodgkin's disease or non-Hodgkin's lymphoma. Semen from 12 patients contained motile spermatozoa, and in nine cases the count was > 20 million ml-1. One patient was azoospermic (VAPEC-B followed by pelvic radiotherapy) and another had a count of 21 million ml-1 but sperm were non-motile. These findings suggest that, in the majority of cases, VAPEC-B chemotherapy does not cause permanent damage to the male germinal epithelium. A more detailed study of gonadal function in males and females before and after treatment with VAPEC-B for Hodgkin's disease is currently in progress.

Adolescent↗
PubMed1994

Clean-up of lead in household carpet and floor dust.

Methods to remove lead-containing dust were tested on carpets from homes of children with high blood lead and on new carpets artificially contaminated in the laboratory. The household carpets could not be cleaned effectively by repetitive vacuuming with HEPA-filtered cleaners. The lead concentration in the removed dust remained about the same from the initial cleaning (1 min/m2) to the final cleaning (total cleaning time of 10 min/m2). The lead loading on the surface of the carpets often increased during cleaning because vacuuming brought lead from deeper in the carpet to the surface. Over 95% of the total dust was removed from bare wooden floors by dry vacuuming (5 min/m2). For linoleum, more than 75% was removed by vacuuming for 5 min/m2. However, little was removed in vacuuming after the initial two minutes and about 20% was removed in a final wet-washing step. HEPA-vacuuming of the laboratory-contaminated carpets revealed that two of the commercially available vacuum cleaners tested were essentially equivalent and each removed significantly more dust than a third vacuum during a total cleaning time of 10 min/m2. Cleaning for 6 min/m2 was necessary to remove more than 70% of the embedded dust by the two more efficient vacuums. Cleaning efficiencies were about the same for short pile and sculptured carpets. It was concluded that it may be more practical to replace rather than clean carpets. HEPA-vacuum cleaning of carpets was shown to increase lead dust on the surface under some conditions.

Dust↗
PubMed1994

Comparison of Tc-99m MAG3 and Tc-99m DTPA scintigraphy in neonates.

Tc-99m MAG3 scans were obtained in two neonates in whom previous Tc-99m DTPA scans had been interpreted as showing possible obstruction. In both patients, Tc-99m MAG3 provided superior diagnostic images and allowed obstruction to be excluded. The favorable dosimetry of MAG3, coupled with the fact that its clearance is two to three times higher than that of DTPA, makes MAG3 an excellent radiopharmaceutical for pediatric patients, particularly in those patients with impaired renal function and possible obstruction.

Female↗
PubMed1994

Effect of interferon-gamma and TNF-alpha on MUC1 mucin expression in ovarian carcinoma cell lines.

In view of the potential uses of cell surface tumour associated antigens in novel anticancer treatment, a study was designed to investigate whether the biological response modifiers interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) could effect the expression of an epitope on the tumour associated MUC1 epithelial mucin. Four ovarian carcinoma cell lines showing high (OAW42 and GG) and low (JAM and PE01) basal expression of MUC1 were treated with 10-1000 U/mL of IFN-gamma or TNF-alpha for one or five days. Changes in MUC1 expression in cells exposed to IFN-gamma or TNF-alpha were monitored using an ELISA technique with the monoclonal antibody BC2 which reacts with a core protein epitope on the MUC1 mucin, and then corrected for the number of viable cells present. TNF-alpha had little effect on MUC1 expression, but one or five days exposure to IFN-gamma significantly increased MUC1 expression (p < 0.01) in all cell lines including the two cell lines that initially showed little or no expression.

Antigens, Neoplasm↗
PubMed1994

Health data collection and verification in a collaborative model: development of a position paper on cardiac catheterization laboratories by the Rocky Mountain Heart Consortium.

The framework of cooperation and collaboration enabled a unique voluntary organization of health care providers and consumers to develop and publish a position paper regarding the utilization of cardiac catheterization laboratories in the state of Colorado. The collection and analysis of valid, consistent, and comparable administrative health data provided the basis for recommendations regarding current utilization of cardiac catheterization laboratories, assessment of need by geographic area, and development of criteria for the establishment of additional laboratories. The article describes the methodology used to collect and analyze health data on a statewide basis, the issues of data reliability and validity that resulted, and the process of public release of such data.

Cardiac Catheterization↗
PubMed1994

An in vitro characterization of cefditoren, a new oral cephalosporin.

Cefditoren (ME 1206) is a new cephalosporin available for oral administration as the pivaloyloxymethyl ester (ME 1207). The effect of medium formulation. pH, cation concentration and inoculum on the in vitro activity of cefditoren was investigated prior to determining its comparative antibacterial potency against a wide range of clinical bacterial isolates, its bactericidal activity against susceptible strains and the duration of its post-antibiotic effect (PAE). Cefditoren was shown to possess a broad-spectrum of cidal antibacterial activity against both Gram-positive and Gram-negative species with stability to many beta-lactamases of clinical importance. Its activity against Gram-positive species was similar to augmentin and cefuroxime, but superior to that of cefaclor and cefixime, while its beta-lactamase stability was similar to that of cefixime and ceftazidine, characterizing it as a third generation cephalosporin. Investigation of the effect of laboratory variables on the in vitro activity of cefditoren indicates that it will present no special problems when tested in the clinical setting against bacterial pathogens. PAE of 0.9 h, or greater, for Staphylococcus spp, Streptococcus pneumoniae and Moraxella catarrhalis may support the use of an extended dose-interval when cefditoren is used for the treatment of respiratory tract infections.

Bacteria↗
PubMed1994

Increased blood pressure variability during 24h blood pressure monitoring as an early sign of autonomic dysfunction in non-insulin-dependent diabetics.

To evaluate the presence of early autonomic dysfunction in non-insulin-dependent diabetics we examined 24h control of blood pressure (1/4 hourly readings day and 1/2 hourly at night, using TM 2420) in 20 non-insulin-dependent diabetics, controlled only on diet or oral hypoglycaemics and 20 age/sex/BP matched non-diabetics selected from a random population survey. The two groups were aged 52 +/- 9 years and 53 +/- 8 years, respectively. Both groups included normotensives and mild hypertensives in equal numbers but none was on antihypertensive treatment. The groups were well matched for daytime systolic blood pressure (SBP; 132.2 +/- 11.4 vs. 131.2 +/- 10.3) and diastolic blood pressure (DBP; 82.1 +/- 8.3 vs. 81.1 +/- 7.0). The diabetics had a significantly greater heart rate (HR) both during the day (79.6 +/- 9.5 vs. 72.3 +/- 8.8: P = 0.015) and during sleep (67.7 +/- 6.8 vs. 62.5 +/- 8.9). There was increased BP variability in the diabetics during the day (standard deviation of SBP; 16.9 +/- 6.2 vs. 13.3 +/- 4.7: P < 0.05) but the difference for DBP variability was not significant. The day-night difference for SBP, DBP, HR and HR variability was the same in both groups. We conclude that in these patients there was evidence for an alteration in BP variability (which may reflect baroreflex insensitivity) at a stage where there was no alteration in day-night rhythms of BP or HR. The increased HR both at day and night may also reflect baroreflex dysfunction and/or sympathovagal imbalance.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗