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Biomedical subjects

S Green

Publications and source records attributed to S Green.

At least 217 records · Page 12Linked to original sources
PubMed1994

Y-intercept of the maximal work-duration relationship and anaerobic capacity in cyclists.

The degree to which the y-intercept (Y-int) of the linear regression of maximal work output on exercise duration represented anaerobic capacity was determined in ten well-trained male cyclists [peak oxygen uptake (VO2peak) = 69.8 (SD 4.2) ml.kg-1.min-1]. Each cyclist performed three exhausting cycle sessions on separate occasions; the mean exercise durations were 312, 243 and 141 s for the low (approximately 104% VO2peak), medium (approximately 108% VO2peak) and high (approximately 113% VO2peak) intensities respectively, and Y-int (kilojoules; joules per kilogram) was derived from the regression of work output on exercise duration. The muscle anaerobic adenosine 5'-triphosphate (ATP) yield (sigma ATP) and anaerobic capacity (AC) were estimated from changes in metabolites in the vastus lateralis muscle and blood lactate concentration during the high intensity cycling session. The activities of glycogen phosphorylase, phosphofructokinase and citrate synthase, as well as muscle buffer value (in vitro beta) were also determined. The Y-int (kilojoules) was positively correlated (P < or = 0.05) with AC (r = 0.73), sigma ATP (r = 0.70) and in vitro beta (r = 0.71); similar correlations (P < or = 0.05) were observed for Y-int (joules per kilogram). The Y-int was not correlated (P > 0.05) with any enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

A definition and systems view of anaerobic capacity.

The purpose of this paper is both to define terms used in exercise physiology, i.e. anaerobic capacity, anaerobic work capacity and anaerobic potential, and develop a systems perspective of anaerobic capacity. Philosophical argument is used to support the proposed definitions and systems view, which is an approach to assist in the universal acceptance of such terms amongst scientific investigators, coaches and athletes, and provide a focus on physiological mechanisms associated with anaerobic capacity which may be the subject of future investigation.

Anaerobiosis↗
PubMed1994

Phase II trial of piroxantrone in metastatic breast cancer. A Southwest Oncology Group study.

Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m2 intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m2. We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.

Adenocarcinoma↗
PubMed1994

Peroxisome proliferator-activated receptors: finding the orphan a home.

The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of fibrate hypolipidaemic drugs and non-genotoxic rodent hepatocarcinogens that are collectively termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl CoA oxidase, which is elevated about ten fold in the livers of treated rodents. Additional peroxisome proliferator responsive genes include other peroxisomal beta-oxidation enzymes and members of the cytochrome P450 IVA family. A peroxisome proliferator response element (PPRE), consisting of an almost perfect direct repeat of the sequence TGACCT spaced by a single base pair, has been identified in the upstream regulatory sequences of each of these genes. The retinoid X receptor (RXR) forms a heterodimer with PPAR and binds to the PPRE. Furthermore, the RXR ligand, 9-cis retinoic acid, enhances PPAR action. Retinoids may therefore modulate the action of peroxisome proliferators and PPAR may interfere with retinoid action, perhaps providing one mechanism to explain the toxicity of peroxisome proliferators. Interestingly, a variety of fatty acids can activate PPAR supporting the suggestion that fatty acids, or their acyl CoA derivatives, may be the natural ligands of PPAR and that the physiological role of PPAR is to regulate fatty acid homeostasis. Taken together, the discovery of PPAR has opened up new opportunities in understanding how lipid homeostasis is regulated, how the fibrate hypolipidaemic drugs may act and should lead to improvements in the assessment of human risk from peroxisome proliferators based upon a better understanding of their mechanism of action.

Acyl-CoA Oxidase↗
PubMed1994

Brain formation of oestrogen in the mouse: sex dimorphism in aromatase development.

Steroid sex hormones have an organizational role in gender-specific brain development. Aromatase, converting testosterone (T) to oestradiol-17 beta (E2), is a key enzyme in the brain and the regulation of this enzyme is likely to determine availability of E2 effective for neural differentiation. In rodents, oestrogens are formed very actively during male perinatal brain development. This paper reviews work on the sexual differentiation of the brain aromatase system in vitro. Embryonic day 15 mouse hypothalamic culture aromatase activity (AA: mean Vmax = 0.9 pmol/h/mg protein) is several times greater than in the adult, whereas apparent Km is similar for both (approximately 30-40 nM). Using microdissected brain areas and cultured cells of the mouse, sex differences in hypothalamic AA during both early embryonic and later perinatal development can be demonstrated, with higher E2 formation in the male than in the female. The sex differences are brain region-specific, since no differences between male and female are detectable in cultured cortical cells. AA quantitation and immunoreactive staining with an aromatase polyclonal antibody both identify neuronal rather than astroglial localizations of the enzyme. Kainic acid eliminates the gender difference in hypothalamic oestrogen formation indicating, furthermore, that this sex dimorphism is neuronal. Gender-specific aromatase regulation is regional in the brain. Oestrogen formation is specifically induced in cultured hypothalamic neurones of either sex by T, since androgen has no effect on cortical cells. Androgen is clearly involved in the growth of hypothalamic neurones containing aromatase. It appears that differentiation of the brain involves maturation of a gender-specific network of oestrogen-forming neurones.

Animals↗
PubMed1994

Sperm function and its manipulation for microassisted fertilization.

Comprehension of the intricate complexities of sperm function is clearly crucial to the success of attempts to manipulate it for the purposes of assisted conception. This is particularly important when considering various procedures for microassisted fertilization since these bypass critical physiological events that are mandatory for normal fertilization, to varying degrees. Methylxanthine derivatives such as pentoxifylline are useful agents for the management of oligoasthenozoospermic patients. This is particularly so for procedures such as SUZI where adequate motility of spermatozoa injected into the perivitelline space is crucial for fusion with the vitelline membrane to achieve fertilization. The generation of minute concentrations of reactive oxygen species in vitro may prove to be a valuable technique in this respect, in the light of recent evidence for their involvement in capacitation and hyperactivation. Induction of the acrosome reaction by non-invasive, non-toxic agents should markedly improve success rates for microassisted fertilization. Acrosin appears to play a central role in this and, therefore, it would seem prudent to monitor levels of acrosin activity in samples of spermatozoa used in assisted conception procedures. With respect to microassisted fertilization, the potential to select recently acrosome-reacted spermatozoa coated by activated acrosin promises to be a major improvement. Current methods employed for determination of the fertilization potential of spermatozoa are clearly inadequate (Polansky and Lamb, 1988; Aitken, 1990). In fact, the prevailing evidence suggests that no single parameter of sperm function reflects this potential (Zaneveld and Jeyendran, 1988). Therefore, we have both a scientific and a moral responsibility to investigate these processes further. Subsequently, we should be in a position to identify individual gametes with the potential for fertilization and so utilize procedures that result in maximal fertilization rates with minimal risk of polyploidy or abnormality.

Autoantibodies↗
PubMed1994

Tibial lead determination by 99Tcm radiopharmaceutical x-ray fluorescence.

The feasibility of measuring tibial lead concentration by x-ray fluorescence with an internal 99Tcm labelled bone-seeking radiopharmaceutical was investigated using phantoms containing known values of lead concentration and 99Tcm activity. The minimum detectable concentration (MDC) at two standard deviations based on the counts in the Kalpha1 peak of 10.9 microg Pb ml(-1) was estimated to correspond to an MDC for an individual within a range of approximately 8-15 microg Pb (g bone mineral)(-1) if the counts from all four K x-ray peaks were included. Due to its much greater dose compared to an external source, the MDC of this internal source technique would have to be reduced before it could be used for measurements of occupationally or environmentally exposed individuals other than as an adjunct for a patient undergoing a bone scan. Methods of achieving such a reduction include increasing the acquisition time and the number of HPGE detectors, and optimizing the design of their collimators.

Adult↗
PubMed1994

Carbohydrates and human appetite.

Experiments indicate that exposure to high-carbohydrate foods can give rise to a clear modulation of the expression of human appetite. The potency and time course of the effects of various carbohydrates on satiety vary with the amount consumed and the chemical structure. There is evidence that this biological effect can modulate the temporal profile of hunger and the eating pattern of meals and snacks. One important issue is the action of carbohydrate foods on satiation (within meals) and satiety (after meals). These effects can be compared with the effects of high-fat foods. The physiological mechanisms through which carbohydrates exert an action on appetite are not completely identified, although plasma glucose values are likely to play a role. The experimental evidence suggests that it is possible to design high-carbohydrate diets that provide good nutrition with adequate control over appetite and a beneficial effect on body weight.

Appetite↗
PubMed1994

Orthopaedic outpatient referral guidelines: experience in an English health district.

The suggestion that outpatient referral guidelines may improve patient care in orthopaedic surgery prompted this study in the South Tees Health District. In a postal questionnaire survey of all general practices (n = 48, response rate = 81%) 18 (46%) general practitioners (GPs) perceived guidelines to be helpful. Back pain in the young and middle aged was the most commonly mentioned subject. General practitioners wanted locally developed guidelines (78%), formulated with their participation mainly via the local medical committee (56%), to be distributed by post (89%) and at a special seminar (72%). Subsequent discussions in a multidisciplinary group led to three initiatives: a back pain clinic conducted by a physiotherapist or a trained nurse where all patients could be screened quickly, a policy of open access to physiotherapy for all GPs and special educational seminars on management of back pain. This case study provides valuable perspectives on outpatient referral guidelines in orthopaedic surgery in an English health district. The findings may apply equally to other subjects in other settings.

Adolescent↗
PubMed1994

Phase II trial of 5-fluorouracil and high-dose folinic acid as first- or second-line therapy for advanced breast cancer.

The use of leucovorin to modulate 5-fluorouracil (FUra)-mediated inhibition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of FUra. Based on the activity of this combination in previously untreated patients, we performed a study of FUra and high-dose leucovorin (HDFA) in patients with metastatic breast cancer and minimal prior chemotherapy. Patients were stratified by prior chemotherapy (or relapse within 12 months of completing adjuvant chemotherapy) versus no prior chemotherapy (or relapse at greater than 12 months since completion of adjuvant chemotherapy). FUra was given daily for 5 days at 370 mg/m2/day with HDFA, 500 mg/m2/day, beginning 24 hours before and continuing 12 hours beyond the first and last FUra doses, respectively. Two objective responses occurred among 21 patients in the pretreated group (10%; 95% confidence interval: 1-30%). Four of 36 eligible patients (11%) in the "no prior therapy group" had complete responses (95% confidence interval: 3-26%). The major toxicities were moderate leucopenia and mucositis. We conclude that FUra plus leucovorin has modest antitumor activity in metastatic breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Renal function and hyperfiltration capacity in lead smelter workers with high bone lead.

OBJECTIVE: The study was undertaken to assess whether the changes in urinary excretion of eicosanoids (a decrease of 6-keto-PGF1 alpha and PGF2 and an increase of thromboxane) previously found in lead (Pb) exposed workers may decrease the renal haemodynamic response to an acute oral protein load. METHODS: The renal haemodynamic response was estimated by determining the capacity of the kidney to increase the glomerular filtration rate (in terms of creatinine clearance) after an acute consumption of cooked red meat (400 g). A cross sectional study was carried out in 76 male Pb workers (age range 30 to 60 years) and 68 controls matched for age, sex, socioeconomic state, general environment (residence), and workshift characteristics. RESULTS: The Pb workers had been exposed to lead on average for 18 (range 6-36) years and showed a threefold higher body burden of Pb than the controls as estimated by in vivo measurements of tibial Pb concentration (Pb-T) (geometric mean 66 v 21 micrograms Pb/g bone mineral). The geometric mean concentrations of Pb in blood (Pb-B) and Pb in urine (Pb-U) were also significantly higher in the Pb group (Pb-B: 430 v 141 micrograms Pb/l; Pb-U: 40 v 7.5 micrograms Pb/g creatinine). These conditions of chronic exposure to Pb did not entail any significant changes in the concentration of blood borne and urinary markers of nephrotoxicity, such as urinary low and high molecular weight plasma derived proteins (beta 2-microglobulin, retinol binding protein, albumin, transferrin), urinary activities of N-acetyl-beta-D-glucosaminidase and kallikrein, and serum concentrations of creatinine, beta 2-microglobulin, urea, and uric acid. All participants also had normal baseline creatinine clearances (> 80 ml/min/1.73 m2) amounting on average to 115.5 in the controls v 121.3 ml/min/1.73 m2 in the Pb group. Both control and Pb exposed workers showed a significant increment in creatinine clearance (on average 15%) after oral protein load suggesting that the previously found changes in secretion of urinary eicosanoids apparently has no deleterious effect on renal haemodynamics in the examined Pb workers. CONCLUSIONS: The finding that both baseline and stimulated creatinine clearance rates were not only significantly higher in the Pb workers but also positively correlated with Pb-T, suggests that moderate exposure to Pb may be associated with a slight hyperfiltration state, which has been found to attenuate the age related decline in baseline creatinine clearance by a factor of two. Although the relevance of this effect for the worker's health is unknown, it can be concluded that adverse renal changes are unlikely to occur in most adult male Pb workers when their blood Pb concentration is regularly kept below 700 micrograms Pb/l. One should, however, be cautious in extra-polating this conclusion to the general population because of pre-employment screening of the Pb workers for the absence of renal risk factors.

Adult↗
PubMed1994

Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study.

PURPOSE: To compare chemohormonal therapy, chemotherapy alone, and hormonal therapy alone in postmenopausal patients with estrogen receptor (ER)-positive operable breast cancer and positive axillary nodes with respect to survival and disease-free survival (DFS). PATIENTS AND METHODS: Eight hundred ninety-two postmenopausal women with ER-positive, node-positive breast cancer were enrolled by the Southwest Oncology Group (SWOG) from July 1979 to March 1989 and 74 by the Eastern Cooperative Oncology Group (ECOG) between June 1987 and March 1989. Patients were stratified according to number of involved nodes and type of primary surgery and randomized to receive the following: (1) tamoxifen 10 mg twice daily by mouth for 1 year; (2) cyclophosphamide 60 mg/m2/d by mouth for 1 year, methotrexate 15 mg/m2 intravenously (IV) weekly for 1 year, fluorouracil (5-FU) 400 mg/m2 IV weekly for 1 year, vincristine .625 mg/m2 IV weekly for the first 10 weeks, and prednisone during weeks 1 to 10 with doses decreasing from 30 mg/m2 to 2.5 mg/m2 (CMFVP); or (3) the combination of tamoxifen and CMFVP. RESULTS: The median follow-up duration is 6.5 years, with a maximum of 12.8 years. Treatment arms are not significantly different with respect to either survival or DFS (log-rank, 2 df, P = .82 and .23, respectively). The 5-year survival rate is 77% for the tamoxifen arm, 78% for CMFVP, and 75% for the combination. No significant differences were observed in node or receptor level subsets. Severe or worse toxicity was experienced by 56% of patients on CMFVP and 61% on CMFVP plus tamoxifen, compared with 5% on tamoxifen alone. CONCLUSION: CMFVP chemotherapy, either alone or in combination with tamoxifen, has not been shown to be superior to tamoxifen alone in the treatment of postmenopausal women with node-positive, ER-positive, operable breast cancer.

Adult↗
PubMed1994

D-penicillamine metabolism in neurodegenerative diseases: an in vivo/in vitro sulphydryl methylation study.

1. D-Penicillamine (125 mg) was administered orally to control (healthy volunteers), Parkinson's and Motor Neurone Disease patients following an overnight fast. 2. Blood was collected at 08:00 h for the preparation of red blood cell membranes used in the in vitro S-methylation studies. Urine was collected from 08:00 to 16:00 h and analysed for D-penicillamine and its metabolites. 3. Metabolism occurred via S-methylation, N-acetylation and disulphide formation. Both the Parkinson's and Motor Neurone Disease patients excreted significantly higher median levels of S-methyl-D-penicillamine in the urine than the controls (177 and 209% more for the Parkinson's and Motor Neurone Disease patients respectively). 4. The in vitro and in vivo production of S-methyl-D-pencillamine was highly correlated in the control (rs = 0.936), Parkinson's (0.986) and Motor Neurone Disease (0.752) populations.

Adult↗
PubMed1994

Regulation of calmodulin gene expression by insulin is both transcriptional and post-transcriptional.

Previously we demonstrated that in streptozotocin-induced or spontaneously diabetic BB rats (BB-SDR), low-Km cyclic AMP (cAMP), phosphodiesterase (PDE), and calmodulin (CaM) are decreased. Isolated fat cells of diabetic animals synthesized less CaM and contained reduced levels of CaM transcripts (Solomon SS, Palazzolo MR, Green SA, Raghow R. Biochem Biophys Res Commun 1990; 168: 1007-12). Treatment of diabetic animals with insulin restores CaM transcripts to normal. RNA was extracted from isolated hepatocytes from BB-SDR rats in primary tissue culture treated with insulin (from 2.8 x 10(4) to 1.4 x 10(6) microU/ml) for 48 hours, was immobilized on nitrocellulose, and was sequentially hybridized with radiolabeled probes for CaM, actin, and tubulin. Insulin stimulates steady state levels of mRNA for calmodulin > actin > tubulin. Furthermore, decreased steady state levels of CaM mRNA in hepatocytes from diabetic animals are restored to normal levels with in vitro insulin incubation. Data from nuclear transcription run-on assays demonstrate that insulin stimulates transcription of mRNA CaM by 80%. In addition, we observed RNA degradation in the untreated diabetic but not insulin-treated liver. These data support transcriptional as well as post-transcriptional effects of insulin on CaM mRNA. We postulate that in uncontrolled diabetes, elevations in levels of cAMP in tissue result in part from decreased activity of the apparently co-regulated PDE and CaM and that PDE inactivation in diabetes results from both insulin insufficiency and CaM down-regulation.

Actins↗