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Biomedical subjects

S L Turner

Publications and source records attributed to S L Turner.

At least 37 records · Page 2Linked to original sources
PubMed2000

Regulation of CDK7-carboxyl-terminal domain kinase activity by the tumor suppressor p16(INK4A) contributes to cell cycle regulation.

The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G(1) phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16(INK4A) inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G(1)/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16(INK4A) inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16(INK4A) to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16(INK4A) may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16(INK4A) thus may represent an alternative pathway for controlling cell cycle progression.

Amino Acid Sequence↗
PubMed2000

Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors.

PURPOSE: To investigate the side effects, determine the maximum-tolerated dose (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. PATIENTS AND METHODS: Patients with advanced solid tumors received S-1 bid for 28 days, followed by 1 week of rest. 5-FU pharmacokinetics were investigated after a single initial dose of S-1 during the first 24 hours and weekly thereafter. RESULTS: Twenty-eight patients received S-1 at the four consecutive dose levels of 25, 45, 35, and 40 mg/m(2). The MTD was initially found at 45 mg/m(2), with diarrhea as the dose-limiting toxicity (DLT). Diarrhea was also the DLT at the dose of 40 mg/m(2), which was the MTD for patients exposed to extensive prior chemotherapy. Other toxicities were generally mild. Two patients had a reduction of more than 50% in tumor dimension. Plasma pharmacokinetics of 5-FU were linear; at the highest S-1 dose level, 5-FU plasma peak concentrations reached 1 to 2 micromol/L, and the half-life of 5-FU was 3 to 4 hours. A statistically significant relationship was observed between the severity of diarrhea and pharmacokinetic parameters of 5-FU. CONCLUSION: The recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed patients is 40 mg/m(2) bid on 28 consecutive days, every 5 weeks. In heavily pretreated patients, the recommended dose is 35 mg/m(2) bid. Phase II trials are warranted in tumors known to be responsive to 5-FU treatment.

Administration, Oral↗
PubMed1999

Sexual dysfunction after radical radiation therapy for prostate cancer: a prospective evaluation.

OBJECTIVES: To determine the rate of loss of potency after radiation therapy (RT). METHODS: Two hundred ninety men with localized prostate cancer were evaluated prospectively before and after RT to the prostate alone for change in erectile function. Data were collected before treatment by way of a questionnaire using a simple three-tier potency scale and after RT by the clinician at each follow-up visit. RESULTS: At 12 months, 62% of men (90 of 146) who were potent before RT preserved their potency; at 24 months, this figure was 41%. Men who had "normal" potency before RT were statistically significantly more likely to remain potent after RT. CONCLUSIONS: We believe that detailed knowledge of potency rates before and after RT is important for current decision-making and for evaluating new treatment techniques.

Adult↗
PubMed1998

Prevention of dexamethasone-induced insulin resistance by metformin.

This study investigates the effect of the antidiabetic drug metformin on dexamethasone-induced hyperglycaemia and insulin resistance in mice. Normal mice were treated with dexamethasone (2.5 mg/kg/day p.o.) plus metformin (250 mg/kg/day p.o.) and pair-fed to those receiving dexamethasone alone. Metformin reduced the extent of dexamethasone-induced hyperglycaemia and decreased insulin resistance as indicated by an improved insulin-hypoglycaemia test. Metformin-treated mice also showed increased basal glucose uptake into isolated diaphragm (by 38%), soleus (by 19%) and deep (red) quadriceps (by 31%). Measurements in the quadriceps showed that the increase in glucose uptake occurred without increasing either the mRNA levels or total cellular membrane abundance of the GLUT1 or GLUT4 glucose transporter isoforms. Thus metformin can ameliorate dexamethasone-induced hyperglycaemia and insulin resistance in part by increasing glucose disposal into skeletal muscle. Since this was achieved in quadriceps muscle without increasing mRNA or total membrane abundance of GLUT1 or GLUT4, it is possible that metformin might influence the intrinsic activity of glucose transporters, as well as altering their intracellular translocation.

Animals↗
PubMed1998

The effectiveness of guided design on ethical decision making and moral reasoning among community nursing students.

This study evaluated the effectiveness of guided design as an instructional method in ethical decision making and moral reasoning among 145 community health nursing students. Changes in the process of ethical decision making and moral reasoning were measured using Ketefian's judgment About Nursing Decisions (JAND) one week after the intervention. Results indicated a significant difference in ethical decision-making scores after instruction, but no difference in moral reasoning. The one specific component--Taking professional initiatives--increased on both subscales.

Community Health Nursing↗
PubMed1998

A meaningful health assessment course for baccalaureate nursing students.

In response to the challenge of teaching health assessment to large groups of entry-level BSN students with minimal experience in the health professions and a faculty belief that theory and practice are best actualized with small groups, a new health assessment course was implemented. Based on a philosophy of student accountability and self-direction in learning, faculty willingness to try new teaching strategies, and using computer testing, a successful course was developed. Students rotated through specific small group clinical labs while preparing with textbooks, study questions, videotapes, and computer-assisted instruction. Evaluation methods based on case application and the use of computer testing technology were implemented for this course. The result was increased satisfaction for the faculty and the students with enhanced application experiences supportive of the clinical practice.

Curriculum↗
PubMed1997

Bladder movement during radiation therapy for bladder cancer: implications for treatment planning.

PURPOSE: To describe and quantify bladder movement during radical radiation therapy (RT). To attempt to identify factors that predict for excessive alterations in bladder position. To use the above information to assist in defining the "adequate" planning target volume margin. METHODS AND MATERIALS: Thirty patients with bladder cancer suitable for radical courses of RT were followed prospectively. Patients had an initial planning computerized tomography (CT) scan of the pelvis and three subsequent scans performed weekly during the treatment period. The following measurements were made on each scan in the midbladder slice: maximum anteroposterior (AP) and lateral bladder dimensions, AP rectal diameter, and the distance (margin) between the bladder walls (anterior, posterior, right, and left lateral) and the 95% isodose line. Various patient and tumor data, including bladder and bowel symptoms, were recorded to attempt correlation with bladder movement. RESULTS: Bladder size: the median bladder size (area) over all scans in all patients was 36.9 cm2 (range: 16.2 to 80.9 cm2). The change in bladder area across each sequence varied from 3.3 to 29.1 cm2 (7-55% change in area between scans). Patients with bladders of larger than the median size on the planning scan (despite emptying) were more likely to have alteration in size than those with small bladders, and this change was in the direction of contraction (p = 0.01). Bladder displacement: bladder wall movement of > 1.5 cm was defined as "significant." Eighteen of 30 patients (60%) demonstrated "significant" movement of at least one bladder wall relative to the original isodose plot. Movement resulting in margin reduction occurred in 10 patients (33%). Two patients required treatment replanning due to consistently altered bladder position. There was no pattern to displacement through RT, and all walls were at approximately equal risk of movement. Factors influencing bladder movement: posterior bladder wall movement appeared to relate to "marked" (>2 cm) rectal diameter change. There was a trend for patients with larger amounts of residual bladder tumor (greater than the median) to exhibit more bladder movement; 11 of 14 "moved" compared with 7 of 16 patients with less residual tumor. Other clinical factors including age, sex, body size, acute RT reaction, and tumor stage did not appear to relate to bladder movement. CONCLUSION: Bladder movement during RT is clinically relevant and is random with respect to both time and direction. We recommend, at least with respect to tumor-bearing regions of the bladder, that no less than a 2.0 cm margin should be allowed.

Aged↗
PubMed1997

Antihyperglycaemic effect of saccharin in diabetic ob/ob mice.

1. The effect of chronic saccharin (benzosulphimide) consumption on glucose homeostasis was examined in normal lean +/+ mice and genetically obese hyperglycaemic insulin-resistant ob/ob mice. 2. Consumption of a 5% (w/v) sodium saccharin solution for 7 weeks prevented the development of hyperglycaemia, improved glucose tolerance (area under curve decreased by 51%), reduced the extent of hyperinsulinaemia (by 21%), and reduced excessive weight gain (by 18%) in ob/ob mice. 3. Consumption of 5% (w/v) sodium saccharin temporarily decreased hyperphagia at the beginning of treatment, decreased hepatic glycogen content (by 47%), increased abdominal muscle glycogen content (by 82%), but did not significantly alter the hypoglycaemic response to exogenous insulin in ob/ob mice. 4. Consumption of a 1% (w/v) sodium saccharin solution did not prevent the development of hyperglycaemia in ob/ob mice. 5. Normal lean +/+ mice consuming 5% (w/v) sodium saccharin solution showed a marginal decrease (by 8%) in glycaemia, and glucose tolerance was improved (area under curve decreased by 30%) without a significant change in the insulin response to glucose or the hypoglycaemic effect of exogenous insulin. 6. These results suggest that chronic consumption of saccharin can defer the development of hyperglycaemia and improve glucose homeostasis in insulin-resistant ob/ob mice through a mechanism that is independent of insulin.

Animals↗
PubMed1997

The roles of herpes simplex virus in neuroscience.

Herpes simplex virus (HSV) has been a focus of research in many laboratories during the last 30-35 years, with the majority centered on the virus' replication, molecular biology and pathogenesis. Recently, HSV has begun to receive considerable attention in the field of neuroscience, where scientists have begun to use the virus as a tool or model for several areas of investigation. These areas include the construction and development of HSV-based vectors for gene therapy and the use of HSV as a neuronal tracer, as a model for demyelinating disease and to study interactions between the nervous, immune and endocrine systems. The goal of this paper is to review these different roles for HSV in the broad field of neuroscience.

Animals↗
PubMed1997

The influence of fashion magazines on the body image satisfaction of college women: an exploratory analysis.

This study examined the impact of exposure to fashion magazines on women's body image satisfaction. Participants were 39 undergraduate women, randomly assigned to two experimental conditions: half viewed fashion magazines prior to completing a body image satisfaction survey, and the remaining half, news magazines. Mean height and weight did not differ for the two groups. As hypothesized, women who viewed fashion magazines preferred to weigh less, were less satisfied with their bodies, were more frustrated about their weight, were more preoccupied with the desire to be thin, and were more afraid of getting fat than were their peers who viewed news magazines.

Adolescent↗
PubMed1996

Herpes simplex virus: a tool for neuroscientists.

Herpes viruses have received a great deal of attention due to their widespread and ubiquitous prevalence in the human population and to the diverse range of diseases caused as a result of an infection. During the last 20-25 years, many research laboratories have investigated the pathogenesis and molecular biology of these viruses; particularly herpes simplex virus (HSV). As a result of this research, HSV has begun to get the attention of neuroscientists. In fact, in the last few years there has been an explosion of research involving the use of HSV and related viruses as tools or model systems for different areas of neuroscience research. This brief review will describe several of these areas including demyelinating diseases, neuronal tracings, and genetic therapy.

Animals↗
PubMed1996

Radical external beam radiotherapy for 333 squamous carcinomas of the oral cavity--evaluation of late morbidity and a watch policy for the clinically negative neck.

BACKGROUND AND PURPOSE: The aims of this study were to examine local control/morbidity for all cases and a 'watch policy' for the node-negative neck. PATIENTS/METHODS: 333 patients with squamous cell carcinoma of the oral cavity were treated with a short radical radiotherapy regime to the primary site and involved lymph node groups at the Christie Hospital, Manchester, between 1980 and 1987. Only 10 of 278 node-negative patients received elective neck node irradiation. RESULTS: Actuarial cancer-free survival and local control rates at 5 years for the whole group were 55% and 61%, respectively. Control at the primary site was adversely related to increasing T-stage, node positivity and bone involvement at presentation. Osteonecrosis was seen in 14 (5.9%) of 237 cases without bone involvement at presentation. Taking all patients, late morbidity (non-healing soft tissue injury or bone necrosis) was seen in 45 patients (13.6%) at a median time of 21 months from treatment. The factors contributing to late morbidity were: (1) bone involvement at presentation, (2) synchronous MTX chemotherapy, (3) the contribution of scattered radiation from elective neck treatment, (4) increasing radiation dose, (5) increasing target volume for doses less than 55 Gy and (6) dental extractions. Eighty-four (31%) patients who were initially node-negative developed disease in the untreated neck during follow-up. Salvage neck dissections controlled neck disease in half of the node-only recurrences (21/42 cases). CONCLUSION: These results have influenced our treatment policy, with lowering of the primary tumour dose in some cases and addition of elective neck irradiation for T2-T4 No patients.

Antimetabolites, Antineoplastic↗
PubMed1996

Diversity of repC plasmid-replication sequences in Rhizobium leguminosarum.

Homologues of the plasmid replicator gene repC were detected and characterized in a sample of Rhizobium leguminosarum strains. Conserved PCR primers were designed from published sequences of repC; they amplified a fragment of about 750 bp from 39 out of 41 strains tested, and also from several Sinorhizobium strains, including S. meliloti. Restriction endonuclease digestion showed that the PCR product from individual strains, though uniform in size, was often heterogeneous in sequence. PCR products from 24 field isolates of R. leguminosarum from France, Germany and the UK were cloned and partially sequenced from both ends. Phylogenies constructed from the 5' and 3' ends (200 bp each) were largely congruent and demonstrated four clearly defined groups plus several unique strains. Published Agrobacterium repC sequences fall within the phylogeny of R. leguminosarum sequences, though not within any of the four groups. Specific pairs of PCR primers were designed for each of the four groups; 29 out of 41 R. leguminosarum strains gave a PCR product of the expected size with more than one group-specific primer pair. We hypothesize that the sequence groups correspond to incompatibility groups of Rhizobium plasmids.

Amino Acid Sequence↗
PubMed1995

The replicator region of the Rhizobium leguminosarum cryptic plasmid pRL8JI.

The replicator region of the cryptic plasmid pRL8JI from Rhizobium leguminosarum strain 3841 was cloned and sequenced. The recombinant plasmid (pYK3) was selected by function from a partial EcoRI library of total DNA cloned in pSUP202 and shows incompatibility with plasmid pRL8JI when conjugated into R. leguminosarum strains 3841 and its derivative 1062. The cloned insert (approximately 10.5 kb) comprises five EcoRI fragments none of which confers replicative stability when cloned individually. A single 5.0-kb BamHI fragment, that spans all five EcoRI fragments and confers replicative stability on pSUP202 in R. leguminosarum, has been sequenced. This replicator region shows organisational and sequence similarity to the replicator regions of the Agrobacterium plasmids pTiB6S3 and pRiA4b. It has three open reading frames (repA, repB, repC) and a conserved intergenic sequence.

Base Sequence↗
PubMed1995

Thyroid dysfunction following radiotherapy for head and neck cancer.

PURPOSE: To determine the frequency of hypothyroidism (both subclinical and clinical) following external beam radiotherapy to the whole of the thyroid gland in the treatment of squamous cell cancers of the head and neck. METHODS AND MATERIALS: One hundred and four patients who had completed radiotherapy 30 days to 5 years earlier (84 patients) or who were scheduled for radiotherapy (20 patients) had a single measurement of serum-free thyroxine and thyroid stimulating hormone levels between August 1991 and May 1992. RESULTS: None of the 20 patients assessed prior to treatment showed thyroid dysfunction. Twenty of 84 (23.8%) previously treated patients had subclinical (9.5%) or clinical (14.3%) hypothyroidism. By 5 years, up to 40% of patients may become hypothyroid. Thyroid underactivity was significantly more common in patients having both laryngectomy (including hemi-thyroidectomy) and radiotherapy compared to radiotherapy alone (p < 0.001). Hypothyroidism had not been suspected clinically in any patient tested. CONCLUSION: In view of the frequency and potential morbidity of this complication, thyroid function testing should become a routine part of posttreatment follow-up for these patients.

Female↗