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Biomedical subjects

D G Clark

Publications and source records attributed to D G Clark.

At least 19 recordsLinked to original sources

Effect of pollination and exogenous ethylene on accumulation of ETR1 homologue transcripts during flower petal abscission in geranium (Pelargonium x hortorum L.H. Bailey).

We have isolated two cDNAs from geranium, PhETR1 and PhETR2. The deduced amino acid sequences of PhETR1 anti PhETR2 share 78% and 79% identity with ETR1 from Arabidopsis thaliana respectively. These genes are members of a multigene family and are expressed at moderate levels in leaves, pedicels, sepals, pistils and petals, and at very low levels in roots. PhETR1 and PhETR2 mRNAs are expressed in geranium florets long before they are receptive to pollination and transcript levels remain constant throughout floral development. Message levels of PhETR1 and PhETR2 in pistils and receptacles are unaffected by self-pollination or treatment with 1 micro/l ethylene that induces petal abscission. Our results indicate that the amount of PhETR1 and PHETR2 mRNA is not indicative of the level of sensitivity of geranium florets to ethylene.

Amino Acid Sequence↗

Hypersexuality and hemiballism due to subthalamic infarction.

OBJECTIVE: A 70-year-old right-handed man presented with a subthalamic infarction followed by persistent hypersexuality and hemiballism. A lacunar infarction 1 cm in diameter was observed on magnetic resonance imaging. We hypothesized that metabolic abnormalities would be detected in cortical areas related to his neurobehavioral symptoms. BACKGROUND: Statistical validation of the regional metabolic changes that may relate to neuropsychiatric symptoms has been elusive. Relating metabolic changes to neuropsychiatric symptoms is especially important in unique neurobehavioral cases. METHOD: Quantitative fluorodeoxyglucose positron emission tomography was obtained for a single-subject comparison with scans from 60 healthy subjects. RESULTS: Substantial glucose hypometabolism (p <0.001, uncorrected; [df = 56]) was identified in the subthalamic nucleus at the site of the lacunar infarction. Hypermetabolism (p <0.01) was identified within the basal forebrain and temporal lobes, anterior cingulate and medial prefrontal cortices (areas previously associated with hypersexuality), and striatum (p <0.001) ipsilateral to the stroke (areas known to relate to hemiballism). CONCLUSIONS: Single-subject statistical parametric mapping may improve our understanding of unique neurobehavioral cases.

Aged↗

Resting metabolic rate, body composition and aerobic fitness comparisons between active and sedentary 54-71 year old males.

OBJECTIVE: To test the hypothesis that 55-70 y old male longterm exercisers (LE) have higher resting metabolic rates (RMR) than longterm nonexercisers (LNE). DESIGN: A power analysis demonstrated that this cross-sectional study required 12 subjects per group to detect a 10% RMR difference (kJ x kg FFM(-1) x d(-1)) between the LE and LNE (power = 0.8;alpha = 0.05). SUBJECTS: Twelve LE (X +/- s.d.; 63.5+/-3.4 y; 1.75+/-0.06 m; 69.01+/-8.24 kg; 20.4+/-4.9 %BF) and 12 LNE (63.6+/-5.6 y; 1.72+/-0.07 m; 79.44 12.4 kg; 29.6 4.4 %BF) were recruited from advertisements placed in a newspaper and on university and community noticeboards. INTERVENTIONS: Measurements were conducted for: RMR using the Douglas bag technique; body composition via a four compartment model which is based on determination of body density, total body water and bone mineral mass; and aerobic fitness using a submaximal work test on a cycle ergometer. RESULTS: The LE (93.00+/-7.16 kJ x kg(-1) x d(-1)) registered a significantly greater (P = 0.04) RMR than the LNE (84.70+/-11.23 kJ x kg(-1) x d(-1)) when energy expenditure was expressed relative to body mass, but this difference disappeared (P = 0.55) when the data were corrected for the non-zero intercept of the graph of RMR (MJ/d) against body mass. ANCOVA with FFM as the covariate also indicated that the RMR (MJ/d) difference between the groups was not statistically significant (P = 0.28). The adjusted means for the LE and LNE were 6.39 and 6.62 MJ/d, respectively. CONCLUSIONS: There are no RMR (MJ/d) differences between LE and LNE 54-71 y old males when statistical control is exerted for the effect of FFM and the higher value of the former group for RMR normalised to body mass disappears when this ratio is corrected for statistical bias.

Aged↗

Root formation in ethylene-insensitive plants.

Experiments with ethylene-insensitive tomato (Lycopersicon esculentum) and petunia (Petunia x hybrida) plants were conducted to determine if normal or adventitious root formation is affected by ethylene insensitivity. Ethylene-insensitive Never ripe (NR) tomato plants produced more below-ground root mass but fewer above-ground adventitious roots than wild-type Pearson plants. Applied auxin (indole-3-butyric acid) increased adventitious root formation on vegetative stem cuttings of wild-type plants but had little or no effect on rooting of NR plants. Reduced adventitious root formation was also observed in ethylene-insensitive transgenic petunia plants. Applied 1-aminocyclopropane-1-carboxylic acid increased adventitious root formation on vegetative stem cuttings from NR and wild-type plants, but NR cuttings produced fewer adventitious roots than wild-type cuttings. These data suggest that the promotive effect of auxin on adventitious rooting is influenced by ethylene responsiveness. Seedling root growth of tomato in response to mechanical impedance was also influenced by ethylene sensitivity. Ninety-six percent of wild-type seedlings germinated and grown on sand for 7 d grew normal roots into the medium, whereas 47% of NR seedlings displayed elongated tap-roots, shortened hypocotyls, and did not penetrate the medium. These data indicate that ethylene has a critical role in various responses of roots to environmental stimuli.

Ethylenes↗

Energy metabolism in sedentary and active 49- to 70-yr-old women.

This study examined differences between long-term exercising (LE) and long-term nonexercising (LNE) women [n = 24; age 56.4 +/- 6.2 (SD) yr] for resting metabolic rate (RMR) and energy expenditure in the free-living state by using doubly labeled water (DLW). There was a statistically significant difference (P = 0.0002) between the 12 LE (94.85 +/- 8.44 kJ . kg-1 . day-1) and 12 LNE (81.16 +/- 6.62 kJ . kg-1 . day-1) for RMR, but this difference was only marginally significant (P = 0.06) when the data (MJ/day) were subjected to an analysis of covariance with fat-free mass as the covariate. The DLW data indicated that the eight most active LE (12.99 +/- 3.58 MJ/day) expended significantly (P = 0.01) more energy than did the eight least active LNE (9.30 +/- 1.15 MJ/day). Energy expenditures ranged from 7.64 to 18.15 MJ/day, but there was no difference (P = 0.96) between the LE and LNE in energy expenditure during activity that was not designed to either improve or maintain fitness. These cross-sectional data on 49- to 70-yr-old women therefore suggest that 1) aerobic-type training results in a greater RMR per unit of body mass and also when statistical control is exerted for the effect of the metabolically active fat-free mass, 2) there is a large range in the energy intake necessary to maintain energy balance, and 3) aerobic training does not result in a compensatory reduction in energy expenditure during the remainder of the day.

Aged↗

Effect of pollination on accumulation of ACC synthase and ACC oxidase transcripts, ethylene production and flower petal abscission in geranium (Pelargonium x hortorum L.H. Bailey).

Self-pollination of diploid zonal geranium (Pelargonium x hortorum L.H. Bailey) florets leads to a dramatic rise in ethylene production, followed by abscission within 4 h. Neither wounding of the stigma, pollination with tetraploid pollen, nor heat-killed self pollen could elicit as much ethylene production and petal abscission as self-pollination. A cDNA sharing sequence identity with ACC synthase (GACS2) and three different cDNAs sharing sequence identity with ACC oxidase (GACO1, GACO2, GACO3) were isolated from geranium pistils. Transcripts hybridizing with these probes increased slightly in response to self-pollination, but the degree of accumulation in response to various treatments did not correlate with ethylene production. When calculated on a per-plant-part basis, transcripts hybridizing with GACS2 were equally distributed among the stigma+style, sterile ovary, and ovary tissues, but transcripts hybridizing with the three ACC oxidase clones were differentially distributed. All transcripts were differentially expressed among the other tissues of the plant, with GACO1 being the most widely distributed. Ethylene production in geranium pistils was not autocatalytic. Propylene failed to induce ethylene production and ethylene did not induce the accumulation of ACC synthase or ACC oxidase transcripts. ACC accumulated in the stigma and style, and to a smaller extent in the sterile ovary, after pollination. These data support a model of pollination-induced ethylene production by post-transcriptional regulation of ethylene biosynthetic gene expression.

Amino Acid Oxidoreductases↗

A dominant mutant receptor from Arabidopsis confers ethylene insensitivity in heterologous plants.

Ethylene (C2H4) is a gaseous hormone that affects many aspects of plant growth and development. Ethylene perception requires specific receptors and a signal transduction pathway to coordinate downstream responses. The etr1-1 gene of Arabidopsis encodes a mutated receptor that confers dominant ethylene insensitivity. Evidence is presented here that etr1-1 also causes significant delays in fruit ripening, flower sensecence; and flower abscission when expressed in tomato and petunia plants. The ability of etr1-1 to function in heterologous plants suggests that this pathway of hormone recognition and response is highly conserved and can be manipulated.

Amino Acid Sequence↗

Relationship between maximum aerobic power and resting metabolic rate in young adult women.

The literature is inconclusive as to the chronic effect of aerobic exercise on resting metabolic rate (RMR), and furthermore there is a scarcity of data on young women. Thirty-four young women exhibiting a wide range of aerobic fitness [maximum aerobic power (VO2max) = 32.3-64.8 ml.kg-1.min-1] were accordingly measured for RMR by the Douglas bag method, treadmill VO2max, and fat-free mass (FFM) by using Siri's three-compartment model. The interclass correlation (n = 34) between RMR (kJ/h) and VO2max (ml.kg-1.min-1) was significant (r = 0.39, P < 0.05). However, this relationship lost statistical significance when RMR was indexed to FFM and when partial correlation analysis was used to control for FFM differences. Furthermore, multiple linear-regression analysis indicated that only FFM emerged as a significant predictor of RMR (kJ/h). When high- (n = 12) and low-fitness (n = 12) groups were extracted from the cohort on the basis of VO2max scores, independent t-tests revealed significant between-group differences (P < 0.05) for RMR (kJ.kg-1.h-1) and VO2max (ml.kg-1.min-1) but not for RMR (kJ/h), RMR (kJ.kg FFM-1.h-1), and FFM. Analysis of covariance of RMR (kJ/h) with FFM as the covariate also showed no significant difference (P = 0.56) between high- and low-fitness groups. Thus the results suggest that 1) FFM accounts for most of the differences in RMR between subjects of varying VO2max values and 2) the RMR per unit of FFM in young healthy women is unrelated to VO2max.

Adult↗

The contribution of glucose cycling to the maintenance of steady-state levels of lactate by hepatocytes during glycolysis and gluconeogenesis.

When hepatocytes from fasted rats were incubated with 10 mM glucose, there was a linear accumulation of lactate and pyruvate for about 80 min after which steady-state concentrations of these metabolites became established. The rate of glycolysis, determined with [6-3H]glucose, was constant over the entire incubation period and was 50% greater than that calculated from carbon balance studies. This suggests that one-third of the glycolytic products formed were recycled to glucose. To enable study of the factors associated with the generation and maintenance of the lactate steady state and to measure accurately the carbon balance, incubations were performed using supraphysiological concentrations of glucose (20-80 mM). Under these conditions the initial rate of lactate accumulation and its concentration at steady state were shown to be dependent on the concentration of extracellular glucose. Rates of glycolysis were also measured using 40 mM [6-3H]glucose and [U-14C]glucose added alone, or in combination with a steady-state lactate concentration (3 mM). There was no effect on the rate of glycolysis determine with [6-3H]glucose, even when lactate was present in the medium. The difference in rates between measurements with the two isotopes reflect the apparent degree of glucose recycling which in the absence and presence of added lactate increased from 0.26 to 0.54 mumol C3 equivalents min-1.g-1 respectively. Identical studies employing [U-14C]lactate showed that glucose and CO2 were the major products of lactate metabolism under steady-state conditions and that the formation of lactate from [U-14C]glucose exactly balanced the rate of lactate removal as a result of oxidation and gluconeogenesis. These studies provide evidence for the concomitant operation of glycolysis and gluconeogenesis, even in the presence of high glucose concentrations. They also demonstrate that lactate steady states are achieved not by the cessation of glycolysis but rather by the removal of lactate and pyruvate at a rate equal to that of their production.

Animals↗

Differences in substrate metabolism between self-perceived 'large-eating' and 'small-eating' women.

OBJECTIVE: To compare different aspects of intermediary metabolism in self perceived 'small-eating' females and self-perceived near normal weight 'large-eating' females and relate the data to those reported for Pima Indians who have the world's highest prevalence of non-insulin dependent diabetes mellitus and obesity. DESIGN: Make repeat measurements of rates of oxygen consumption, carbon dioxide production and blood metabolites in 'large-' and 'small-eating' females at rest, during different activities and after ingestion of a standardised liquid meal. SUBJECTS: Nine self perceived, 'large-eating' females and nine self perceived 'small-eating' females. MEASUREMENTS: Resting metabolic rates (RMR), respiratory quotient (RQ) values and plasma insulin, glucagon insulin-like growth factor (IGF-1), dehydroepiandrosterone sulphate (DHEA-SO4) and glucose. RESULTS: RMR (adjusted for FFM) averaged 3891 +/- 93 J/min in the 'small-eaters' and 3375 +/- 107 J/min in the 'large-eaters' for ten consecutive measurements conducted at 30 min intervals during the control period for the measurement of the thermic effect of food. Over this period the average RQ for the 'small-eating' women (0.81) was significantly greater than that of the 'large-eating' women (0.78). The two groups responded similarly to an oral glucose tolerance test but the concentration of DHEA-SO4 in plasma was 35% higher in the 'small-eaters'. CONCLUSION: The 'small-eating' women may have a greater risk of weight gain but they counteract this tendency by maintaining high activity levels.

Adult↗

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes.

We have studied the inhibitory action of long- and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-3H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 mumol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 mumol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle.

Animals↗

US-guided automated large-core breast biopsy.

To evaluate the efficacy of ultrasound (US)-guided automated large-core percutaneous needle breast biopsy, biopsy of 181 ultrasonographically suspicious breast lesions was performed by using a long-throw biopsy gun and 14-gauge needles with continuous US guidance. A "freehand" technique with either 5.0- or 7.5-MHz linear-array transducers was used. Needle core diagnoses were compared with surgical diagnoses in the 49 lesions subsequently surgically excised. The remaining 132 cases were followed for 12-36 months. Agreement between needle-core and surgical diagnoses in the 49 lesions was 100%. This group included 34 cancers (28 infiltrating ductal, two mucinous, one mixed infiltrating ductal and lobular, and one each of intraductal, infiltrating lobular, and tubular carcinoma). To date, no cancers have been found in the other 132 cases. The procedure time averaged 20 minutes, and no complications occurred. With an accuracy approaching that of excisional biopsy, US-guided needle core biopsy provides an alternative to surgery.

Biopsy, Needle↗

No differences in rates of energy expenditure between post-obese women and their matched, lean controls.

Rates of energy expenditure at rest, during different daily activities and following a standardized liquid meal were compared in eight post-obese women, with a mean weight loss of 21.5 kg (range 14.1 to 33.3 kg) and eight controls who had never been overweight. Age, height, body mass index, fat-free mass and average daily energy intake were similar for both experimental groups. Resting metabolic rate averaged 23.04 cal/min/kg FFM (s.e.m. 1.14) in the post-obese and 22.70 cal/min/kg FFM (s.e.m. 0.64) in the controls on their first visit to the laboratory. Metabolic rates in the two groups rose in parallel as energy expenditure was increased by sitting, standing and walking at three different speeds (2.4, 3.9 and 5.4 km/h). At the highest walking speed energy expenditure averaged 95.30 cal/min/kg FFM (s.e.m. 4.18) in the post-obese and 93.42 cal/min/kg FFM (s.e.m. 2.97) in the control women. Comparisons of postprandial thermogenesis revealed no significant differences between the two groups. The results of the present study do not support the thesis that rates of energy expenditure, whether at rest, during different activities, or after eating, are reduced in post-obese women.

Adult↗

Muscle metabolism during 30, 60 and 90 s of maximal cycling on an air-braked ergometer.

This study examined the anaerobic and aerobic contributions to muscle metabolism during high intensity short duration exercise. Six males [mean (SD): age 25.0 (6.0) years, height 179.0 (8.2) cm, mass 70.01 (7.42) kg, VO2max 4.63 (0.53) l.min-1, body fat 12.7 (2.3)%] performed three counterbalanced treatments of 30, 60 and 90 s of maximal cycling on an air-braked ergometer. All treatments were also performed on days when biopsies were not taken from the vastus lateralis muscle and cannulae not inserted into a forearm vein to ascertain whether these procedures adversely affected performance. The mean results can be summarised as follows: (Table: see text). The muscle lactate and O2 deficit data suggested that 60 and 90 s were more appropriate durations than 30 s for assessing the anaerobic capacity on an air-braked cycle ergometer. The mean power outputs also indicated that the invasive procedures did not adversely affect performance [corrected].

Adenosine Triphosphate↗

The international validation of a fixed-dose procedure as an alternative to the classical LD50 test.

In an international study involving 33 laboratories in 11 countries, the acute oral toxicity to the rat of 20 substances and preparations was evaluated using a fixed-dose procedure and the results compared with those obtained for the test materials using the classical LD50 test. The study has shown that the fixed-dose approach to acute oral toxicity testing: (1) produces consistent results that are not substantially affected by inter-laboratory variations; (2) provides adequate information for risk assessment purposes on signs of toxicity, including their nature, time to onset, duration and outcome; (3) uses fewer animals than the current internationally agreed OECD procedure (Guideline 401-revised); (4) subjects animals to less pain and distress than the classical LD50 test and causes less compound-related mortality; and (5) enables substances and preparations to be ranked according to the EEC classification system on the basis of their acute oral toxicity, such ranking being compatible with that allocated by the results of classical LD50 studies.

Administration, Oral↗

Physical fitness and all-cause mortality. A prospective study of healthy men and women.

We studied physical fitness and risk of all-cause and cause-specific mortality in 10,224 men and 3120 women who were given a preventive medical examination. Physical fitness was measured by a maximal treadmill exercise test. Average follow-up was slightly more than 8 years, for a total of 110,482 person-years of observation. There were 240 deaths in men and 43 deaths in women. Age-adjusted all-cause mortality rates declined across physical fitness quintiles from 64.0 per 10,000 person-years in the least-fit men to 18.6 per 10,000 person-years in the most-fit men (slope, -4.5). Corresponding values for women were 39.5 per 10,000 person-years to 8.5 per 10,000 person-years (slope, -5.5). These trends remained after statistical adjustment for age, smoking habit, cholesterol level, systolic blood pressure, fasting blood glucose level, parental history of coronary heart disease, and follow-up interval. Lower mortality rates in higher fitness categories also were seen for cardiovascular disease and cancer of combined sites. Attributable risk estimates for all-cause mortality indicated that low physical fitness was an important risk factor in both men and women. Higher levels of physical fitness appear to delay all-cause mortality primarily due to lowered rates of cardiovascular disease and cancer.

Adult↗

Pelvic exenteration for recurrent or persistent gynecologic malignancies: a 10-year review of the Memorial Sloan-Kettering Cancer Center experience (1972-1981).

From January 1, 1972 to December 31, 1981, sixty-five patients underwent pelvic exenteration as treatment for recurrent or persistent gynecologic malignancy at Memorial Sloan-Kettering Cancer Center. Cervical carcinoma was the disease most commonly treated by exenteration. The operative mortality of 9.2% represents an improvement over previous reports from this institution. After routine use of prophylactic minidose heparin, no cases of thrombophlebitis or pulmonary embolus occurred postoperatively. A 5-year survival rate of 23% warrants continued use of exenteration in carefully selected patients. The significant mortality and morbidity associated with pelvic exenteration preclude its use as a palliative procedure.

Female↗

Inhalation toxicity of high flash aromatic naphtha.

A petroleum distillate--a high aromatic naphtha--consisting of a 50/50 blended mixture of equivalent products. SHELLSOL A* and SOLVESSO 100**, containing C9 isomers (75 percent) particularly trimethyl benzenes, was examined for systemic toxicity in rats by inhalation exposure. A preliminary 13-week inhalation study with SHELLSOL A had resulted in liver and kidney weight increases in female rats at the high (7400 mg/m3) and medium (3700 mg/m3) exposure levels, and a low grade anaemia in females at all exposure levels (7400, 3700 and 1800 mg/m3). The follow-up 12-month inhalation study in rats described here used atmosphere generated from the SHELLSOL A/SOLVESSO 100 blend of 1800, 900 and 450 mg/m3. Initial reduction in body weight gain occurred in both male and female rats at the higher exposures. Various statistically significant haematological changes were transiently seen in males up to six months, but were not considered biologically significant. High exposure male liver and kidney weights were increased at 6 and 12 months but, in the absence of histopathological changes, were considered to be physiological adaptive responses. No treatment-related histopathological abnormalities were found. It is concluded that chronic exposure to this high aromatic naphtha is without systemic toxicity in rats under the conditions of these studies.

Administration, Intranasal↗