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Biomedical subjects

L Clarke

Publications and source records attributed to L Clarke.

At least 91 records · Page 5Linked to original sources
PubMed1997

Conflict, consistency and fulfillment revisited: approaches to modelling the person.

The issue of consistency in human personality is reviewed. Attention is given to personality both as a fixed entity and as something mediated by situational factors. Mischel's reinvention of the person-situation debate is noted as well as the seminal contributions of Allport, Eysenck and the 'forgotten figure' of Henry Murray. The discussion is resolved largely in favour of 'the whole person' in psychology but not before central issues of conflict, consistency and fulfillment are accounted for. In particular, the manner by which an evolving 'scientific' psychology chooses to ignore person psychology is seen to be pertinent. The topic is especially relevant to those psychiatric practitioners who espouse a whole person or 'fulfillment psychology' in their practice. However, the overall intention is to reintroduce material that extends the usual humanistic confines of the discussion.

Cognitive Behavioral Therapy↗
PubMed1997

Influence of maternal bodyweight on size, conformation and survival of newborn lambs.

Although body condition score was not significantly different between light (<55 kg, n = 6) and heavy (> or =60 kg, n = 7) ewes at mating, it declined between Day 30 and Day 90 of gestation in light but not heavy ewes, and remained lower up to term. All ewes bore twins, delivered near term (Days 144-146) by Caesarean section. One lamb was immediately placed into a warm (30 degrees C; WD) and its twin into a cool (15 degrees C; CD) ambient temperature, and tissues were sampled at 0.5 h or 6 h. All CD lambs born to light ewes exhibited hypothermia and/or respiratory failure and did not survive longer than 30 min; these symptoms were not observed in their WD twins or any lamb born to heavy ewes. Total lamb birth weight, placental weight and fetal cotyledonary weight were lower with light than with heavy ewes. Lambs born to light ewes had less perirenal adipose tissue and smaller liver, heart, kidneys, brain, adrenals and thyroid, although their heart, brain and pancreas represented a larger proportion of total bodyweight; pancreas weight was similar to that in lambs born to heavy ewes. Hence, maternal bodyweight critically influences placental weight and lamb size and survival after birth.

Animals↗
PubMed1997

Maternal manipulation of brown adipose tissue and liver development in the ovine fetus during late gestation.

We examined the effect of maternal chronic cold exposure, induced by winter-shearing ewes 4 weeks before their predicted lambing date, on brown adipose tissue (BAT) and liver development in lambs. Fetuses were sampled from under-fed (60% of energy requirements for maintenance and pregnancy of an unshorn ewe) shorn or unshorn ewes at 126, 140 and 145 d of gestation. Lambs were sampled from ewes within 2 h of birth. Throughout gestation fetal body, BAT and liver weights were similar in shorn and unshorn groups. The level of GDP binding to mitochondrial uncoupling protein remained low throughout gestation, but increased dramatically after birth. Lambs born to shorn ewes possessed more mitochondrial protein and exhibited a significantly higher total thermogenic activity in BAT. Type I iodothyronine 5' deiodinase (EC 3.8.1.4) activity in BAT peaked at birth, as did hepatic iodothyronine 5' deiodinase activity and was significantly greater in lambs born to under-fed shorn ewes, which exhibited a higher plasma triiodothyronine concentration. Chronic maternal adaptations to prolonged cold exposure appear to enable pregnant ewes to compensate for the negative effects of under-feeding on fetal growth and development.

Adaptation, Physiological↗
PubMed1997

Quantitative MRI of the gray-white matter distribution in traumatic brain injury.

Quantitative analyses were performed on magnetic resonance images (MRIs) obtained from the brains of 31 traumatic brain-injured (TBI) patients and 25 normal control subjects. The quantitative analyses involved comparisons of the shapes of proton density gray scale pixel histograms obtained from both 3-mm and 5-mm slice thickness. Image segmentation was accomplished by a multispectral fuzzy C-means and/or k-nearest-neighbor (kNN) algorithms and manual classification was used to label segmented classes into CSF, white matter, and other. Shape descriptors were derived from the pixel intensity histograms of the combined gray matter and white matter classes for each MRI slice. Statistical analyses revealed significant differences in pixel intensity distributions between TBI and control subjects. Normal control subjects tended to exhibit bimodal gray matter-white matter histograms, whereas, TBI patients tended to exhibit unimodal gray matter-white matter histograms. In the control subjects the pixels intermediate in intensity between gray and white matter were located primarily at the border between the gray and white matter, whereas TBI patients exhibited a thickening of the number of intermediate pixels at the border as well as an increase in intermediate pixels in the middle of the gray and white matter. The greater the severity of TBI, then the larger the number of intermediate intensity pixels within and between gray and white matter. Further analyses demonstrated shifts in magnetic resonance relaxation times in gray and white matter in TBI patients, which suggested that the tendency toward unimodality in TBI patients represents a pathological reduction in brain differentiation due to measurable biophysical change.

Adult↗
PubMed1997

Influence of feeding and ambient temperature on thermoregulation in newborn lambs.

This study examined the effect of ambient temperature and feeding on brown adipose tissue (BAT) function and thermoregulation in lambs born either vaginally at term or by Caesarean section close to term. Immediately after birth lambs were placed in a warm (30 degrees C) or cool (15 degrees C) ambient temperature and measurements of colonic temperature and heat production recorded for 6 h. Lambs were fed 50 ml of colostrum when 5 h old. The amount of uncoupling protein and level of guanosine 5'diphosphate (GDP) binding in BAT was higher in vaginally delivered lambs than in lambs delivered by Caesarean section. For each delivery group, GDP binding was greater in lambs maintained at 30 degrees C than in lambs maintained at 15 degrees C. O2 consumption, CO2 production and colonic temperature only increased after feeding in lambs born by Caesarean section and maintained at 30 degrees C, a response that was accompanied by a decreased incidence of shivering. Irrespective of delivery temperature, plasma thyroid hormone concentrations and noradrenaline content of BAT were lower in lambs born by Caesarean section than in those born vaginally. Plasma cortisol concentrations were higher in lambs delivered by Caesarean section, as was adrenaline content of BAT in these lambs maintained at 30 degrees C. It is concluded that the thermoregulatory response to feeding in terms of changes in both recruitment of shivering and colonic temperature were observed only in lambs delivered by Caesarean section.

Adipose Tissue, Brown↗
PubMed1997

The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe.

The centromere enhancer is a functionally important DNA region within the Schizosaccharomyces pombe centromeric K-type repeat. We have previously shown that addition of the enhancer and cen2 centromeric central core to a circular minichromosome is sufficient to impart appreciable centromere function. A more detailed analysis of the enhancer shows that it is dispensable for centromere function in a cen1-derived minichromosome containing the central core and the remainder of the K-type repeat, indicating that the critical centromeric K-type repeat, like the central core, is characterized by functional redundancy. The centromeric enhancer is required, however, for a central core-carrying minichromosome to exhibit immediate centromere activity when the circular DNA is introduced via transformation into S. pombe. This immediate activation is probably a consequence of a centromere-targeted epigenetic system that governs the chromatin architecture of the region. Moreover, our studies show that two entirely different DNA sequences, consisting of elements derived from two native centromeres, can display centromere function. An S. pombe CENP-B-like protein, Abp1p/Cbp1p, which is required for proper chromosome segregation in vivo, binds in vitro to sites within and adjacent to the modular centromere enhancer, as well as within the centromeric central cores. These results provide direct evidence in fission yeast of a model, similar to one proposed for mammalian systems, whereby no specific sequence is necessary for centromere function but certain classes of sequences are competent to build the appropriate chromatin foundation upon which the centromere/kinetochore can be formed and activated.

Binding Sites↗
PubMed1997

Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs.

We examined the effect of route of delivery on brown adipose tissue (BAT) function and thermoregulation in lambs born either vaginally at term or by cesarean section close to term. Immediately after birth, lambs were placed in a warm (30 degrees C; WD) or cool (15 degrees C; CD) ambient temperature, and measurements of colonic temperature, plus heat production (i.e., oxygen consumption and carbon dioxide production), were recorded for 6 h. Over the first 30 min of life, colonic temperature remained constant in vaginally delivered lambs and was lower in the WD group. Following cesarean section delivery, colonic temperature declined rapidly, a response that was greater in the CD group. Cesarean section-delivered lambs had an increased reliance on shivering thermogenesis and restored colonic temperature after 2 h, and by 6 h these parameters were higher than in lambs born vaginally. Irrespective of delivery, temperature, plasma thyroid hormone concentrations and norepinephrine content of BAT were lower in lambs born by cesarean section compared with those born vaginally. Plasma cortisol concentrations and epinephrine content of BAT were greater in lambs born by cesarean section. The amount of uncoupling protein and level of guanosine 5'-diphosphate binding in BAT were higher in vaginally delivered than in cesarean section-delivered lambs, and for each group mean values were greater for CD than WD lambs. Cesarean section delivery results in altered thyroidal, adrenal, and sympathetic activity, which appears to have a marked influence on BAT function, thereby contributing to distinct differences in thermoregulation compared with lambs born vaginally.

Adipose Tissue↗
PubMed1997

Adipose tissue development during early postnatal life in ewe-reared lambs.

This study examines the precise time course that brown adipose tissue (BAT) takes to adopt the characteristics of white adipose tissue in postnatal lambs. Perirenal adipose tissue was sampled from ewe-reared lambs within 1 h of birth and at 1, 2, 4, 7, 14, 21 and 30 days of age and analysed for the amount of mRNA for uncoupling protein (UCP), the amount and activity of UCP, and protein, mitochondrial protein and lipid content. This was combined with measurements of colonic temperature and jugular venous plasma concentrations of thyroid hormones and insulin-like growth factor-1 (IGF-1). Over the first 4-7 days of age, large quantities of UCP mRNA were associated with a peak in plasma triiodothyronine concentration at 2 days of age followed by a maximal amount and activity of UCP at 4 days and a basal colonic temperature of 39.3 degrees C. Between 7 and 30 days there was a large increase in lipid deposition as the amount and activity of UCP and the amount of UCP mRNA declined to basal values and colonic temperature was maintained at 40 degrees C. A significant positive relationship between perirenal adipose tissue lipid content and plasma IGF-1 concentration was observed throughout the study period. It is concluded that ovine adipose tissue maturation occurs in two distinct phases over the first month of life. The precise time scale of this process could be regulated in part by the lamb's body temperature which determines whether adipose tissue is required for heat production (i.e. BAT) or as an endogenous energy source (i.e. white adipose tissue).

Adipose Tissue↗
PubMed1996

Pharmacokinetics and immunomodulatory properties of intravenously administered recombinant human interleukin-10 in healthy volunteers.

Normal volunteers received single doses of recombinant human interleukin-10 (rhIL-10; n = 6 per group) or placebo (n = 3 per group) by intravenous injection to characterize pharmacokinetics, tolerability, and immunomodulatory effects. Dosages were 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 25.0, 50.0, and 100.0 micrograms/kg. Dose-related adverse effects consisted of a mild-to-moderate flu-like syndrome characterized by fever with chills, headache, and myalgias at the highest dose. The mean terminal phase t1/2 ranged from 2.3 +/- 0.5 to 3.7 +/- 0.8 hours. Dose-related effects of rhIL-10 included transient increases of circulating neutrophils and monocytes and decreases of lymphocytes. rhIL-10 markedly suppressed, in a time- and dose-dependent manner, the synthesis of the inflammatory cytokines IL-1 beta and tumor necrosis factor alpha by whole blood stimulated ex vivo with bacterial lipopolysaccharide. Circulating numbers of CD14+/HLA-DR+ cells at 24 hours after the dose were increased in a dose-dependent manner. Effects on expression of HLA-DR by CD14+ cells were variable. There was no apparent effect on HLA-DR expression by CD20+ cells. The immunomodulatory effects of rhIL-10 merit further clinical investigation.

Adolescent↗
PubMed1996

Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist.

A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t1/2) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C(max)) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor.

Administration, Oral↗
PubMed1996

Women's health: dimensions and differentials.

This paper is concerned with the social patterning of ill-health amongst women in Britain. It uses the various health measures available in the Health and Lifestyle Survey (self-assessed health, disease/disability, illness, psycho-social well-being and fitness) to explore whether there are particular aspects of health systematically associated with social advantage and disadvantage, as measured by current or last occupation, employment status, household composition and household income. Among women aged 18-59, after controlling for age, number of psychological symptoms experienced in the past month showed the greatest social variation. Number of physical illness symptoms in the last month showed the least. Lone mothers with dependent children were found to have particularly poor psycho-social health, although this was confined to those in full-time employment. The presence of a long-standing disease/disability proved useful as a control for the influence of health selection in to and out of both employment and motherhood.

Adolescent↗
PubMed1996

Brown adipose tissue and liver development during early postnatal life in hand-reared and ewe-reared lambs.

This study examined the effects of modest changes in ambient temperature in hand-reared lambs (experiment one) and in ewe-reared lambs (experiment two). Lambs were killed at either 8 or 31 days of age and perirenal adipose tissue was identified as being brown adipose tissue (BAT) from measurements of thermogenic activity (i.e. GDP binding to uncoupling protein in isolated mitochondria) or thermogenic capacity (i.e. detection of uncoupling protein by immunoblotting). In addition, type I and II iodothyronine 5' monodeiodonase (5'MDI) activities were assayed in perirenal adipose tissue, plus type I 5'MDI activity in liver. Plasma samples were also taken for measurements of glucose, lactate, insulin, triiodothyronine (T3) and thyroxine (T4) concentrations. In experiment one, lambs were hand-reared at either warm (WR; 25 degrees C) or cool (CR; 10-15 degrees C) ambient temperatures. Mean growth rate over the first 8 days of life in CR lambs was 88 g/day and increased to 128 g/day over the first month of life. Growth rate in WR lambs was constant at 141 g/day. Thermogenic activity of BAT was significantly higher in CR than WR lambs, but total weight and tissue lipid content of perirenal adipose tissue were significantly lower in the CR group. In both WR and CR lambs, the thermogenic activity of BAT fell by an average of 71% between 8 and 31 days. At 31 days of age, uncoupling protein in mitochondria could be detected only by immunoblotting in adipose tissue sampled from CR lambs. There was no effect of ambient temperature on type I or type II 5'MDI activity in BAT or liver; it decreased in adipose but not liver tissue between 8 and 31 days of age. The plasma concentrations of glucose, insulin and T3 tended to decline with age in CR but not in WR lambs. In ewe-reared lambs perirenal adipose tissue weight and tissue lipid content more than doubled between 8 and 31 days of age, but the level of GDP binding decreased from 85 to 5 pmol/mg mitochondrial protein over this period. Liver weight increased by 55% between 8 and 31 days of age, but hepatic 5'MDI activity remained unchanged. The plasma concentrations of T3, T4 and lactate, but not glucose or insulin, increased between 8 and 31 days of age. It is concluded that hand-rearing lambs at a cool ambient temperature significantly delays postnatal development, to the extent that BAT characteristics are retained. Ewe-rearing lambs enhances the rate at which BAT adopts the characteristics of white adipose tissue, and it prevents the postnatal decline in plasma concentrations of thyroid hormones.

Adipose Tissue, Brown↗
PubMed1996

Effect of maternal glucose infusion on brown adipose tissue and liver development in the neonatal lamb.

The effect of maternal glucose infusion over the final 5-7 days of gestation in under-fed ewes on perirenal brown adipose tissue (BAT) and liver development in lambs over the first month of neonatal life was examined. During glucose infusion, higher maternal plasma concentrations of glucose and thyroid hormones, and lower plasma concentrations of non-esterified fatty acids and 3-hydroxybutyrate were observed, compared with saline-infused controls. These differences were not observed 1-1.5 h before parturition when plasma concentrations of glucose, lactate, cortisol and thyroid hormones all increased in control ewes. Lamb birthweight and liver and BAT weights were similar between groups, but lambs born to glucose-infused ewes had a higher hepatic glycogen content and greater iodothyronine 5'deiodinase activities in liver and BAT. The norepinephrine, epinephrine and dopamine contents were also greater in BAT sampled from lambs born to glucose infused ewes. Three lambs born to glucose-infused ewes failed to survive beyond the second week of life and exhibited abnormally low plasma triiodothyronine concentrations. It is concluded that maternal glucose infusion stimulates development of the fetal sympathetic nervous system during late gestation but this adaptation does not appear to improve postnatal survival.

3-Hydroxybutyric Acid↗