Search PubMed⌕ Search

Biomedical subjects

A White

Publications and source records attributed to A White.

At least 217 records · Page 12Linked to original sources
PubMed1995

Cholesterol-related health behaviors in rural elderly persons.

1. Hypercholesterolemia in the elderly is a major risk factor for cardiovascular disease. 2. Elderly subjects were found to be concerned about their cholesterol, but awareness of beneficial cholesterol reduction strategies and desirable cholesterol levels were low. 3. Major concerns for the rural elder are accessibility to cholesterol screening, explanation of the results of screening, and education about dietary interventions. 4. Nurses developing health promotion programs for rural elders need to incorporate methods which promote accessibility to screening and follow-up, understandable written information, and family support.

Aged↗
PubMed1995

O6-methylguanine-DNA methyltransferase in human brain tumors detected by activity assay and monoclonal antibodies.

O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in 68 tissue samples taken from brain. A wide range in activity among samples was observed, with all nonmalignant samples showing transferase activity (Mer+) but approximately 15% of WHO grade II low-grade astrocytomas and WHO grade IV glioblastoma multiformes lacking activity (Mer-). On average, astrocytomas and glioblastomas showed less transferase activity than either nonmalignant tissue or meningiomas. Monoclonal antibodies specific for MGMT showed both cytoplasmic and nuclear staining of Mer+ brain tumor cells in culture but no staining of Mer- cells in culture. In pathology specimens from anaplastic astrocytomas, glioblastoma multiformes, and meningiomas, antibody staining revealed both cytoplasmic and nuclear MGMT, while one sample showed little or no MGMT-specific staining. These results help explain why nitrosoureas have been among the most successful agents in treatment of brain tumors and indicate the subcellular localization for the repair activity, which may be relevant to nitrosourea resistance.

Antibodies, Monoclonal↗
PubMed1995

Energy expenditure in children aged 1.5 to 4.5 years: a comparison with current recommendations for energy intake.

OBJECTIVE: To compare measurements of total energy expenditure in children aged 1.5-4.5 years with current recommendations for energy intake. DESIGN: Total energy expenditure was measured using the doubly labelled water technique and compared with 1991 UK recommendations for energy intake. SETTING: Community-based study in East Anglia and South East England. SUBJECTS: Ninety-three children aged 1.5-4.5 years recruited. Results available on 81 children. RESULTS: Mean values for total energy expenditure for the boys were 359, 341 and 327 kJ/kg in the age groups 1.5-2.5, 2.5-3.5 and 3.5-4.5 years respectively. In the girls, mean values for total energy expenditure were 347, 317 and 310 kJ/kg in the age groups 1.5-2.5, 2.5-3.5 and 3.5-4.5 respectively. These values were approximately 12% and 10% below current recommendations for energy intake in girls and boys respectively. CONCLUSION: These data add to the growing literature that indicate that energy expenditure in young children is significantly below previous estimates. Secular changes in habitual levels of physical activity might be responsible for reduced levels of physical activity.

Child Development↗
PubMed1995

Physical activity and body fatness in pre-school children.

The aim of this work was to investigate the relationship between levels of physical activity and body fatness in a group of pre-school children. A cross-sectional study was carried out, physical activity being assessed as the ratio of total energy expenditure/basal metabolic rate (TEE/BMR) and TEE minus BMR. TEE was measured by the doubly labelled water technique, BMR was predicted from body weight. Body fat content was assessed from measurements of total body water via stable isotope dilution. The subjects were 93 children, aged between 1.5 and 4.5 years, in South East England. Measurements of TEE were successful in 77 children. The correlation coefficient between the physical activity level (PAL) values and percentage body fat (sexes combined) was -0.52 (t = 5.3; P < 0.001). This figure indicates that a high level of body fat is associated with a low PAL value and that lower levels of body fat are associated with high PAL values. The correlation coefficient between TEE-BMR and percentage body fat was -0.51 (t = 5.1; P < 0.001). It was concluded that low levels of physical activity in pre-school children are associated with raised levels of body fat.

Adipose Tissue↗
PubMed1994

Crystal structure of the catalytic domain of the beta-1,4-glycanase cex from Cellulomonas fimi.

beta-1,4-Glycanases, principally cellulases and xylanases, are responsible for the hydrolysis of plant biomass. The bifunctional beta-1,4-xylanase/glucanase Cex from the bacterium Cellulomonas fimi, one of a large family of cellulases/xylanases, depolymerizes oligosaccharides and releases a disaccharide unit from the substrate nonreducing end. Hydrolysis occurs with net retention of the anomeric configuration of the sugar through a double-displacement mechanism involving a covalent glycosyl-enzyme intermediate. The active site nucleophile, Glu233, has been unambiguously identified by trapping of such an intermediate [Tull et al. (1991) J. Biol. Chem. 266, 15621-15625] and the acid/base catalyst, Glu127, by detailed kinetic analysis of mutants [MacLeod et al. (1994) Biochemistry 33, 6371-6376]. However, little is known about the enzyme's overall folding and its active site architecture. We report here the high-resolution crystal structure of the catalytic domain of Cex. The atomic structure refinement results in a model that includes 2400 protein atoms and 45 water molecules, with an R-factor of 0.217 for data extending to 1.8-A resolution. The protein forms an eight-parallel-stranded alpha/beta-barrel, which is a novel folding pattern for a microbial beta-glycanase. The active site, inferred from the location of Glu233, Glu127, and other conserved residues, is an open cleft on the carboxy-terminal end of the alpha/beta-barrel. An extensive hydrogen-bonding network stabilizes the ionization states of the key residues; in particular, the Asp235-His205-Glu233 hydrogen-bonding network may play a role in modulating the ionization state of Glu233 and in controlling local charge balance during the reaction.

Binding Sites↗
PubMed1994

Cholesteryl ester transfer protein inhibition by PD 140195.

The presence of plasma cholesteryl ester transfer protein (CETP) activity may be atherogenic, and, therefore, strategies to inhibit its activity or production may result in a beneficial effect on lipoprotein profiles and the disease process. The current report describes 4-phenyl-5-tridecyl-4H-1,2,4- triazole-3-thiol (PD 140195), a novel CETP inhibitor. The concentration-dependent inhibition of CETP by PD 140195 and the inhibitory monoclonal antibody (Mab) TP2 is demonstrated in a variety of in vitro assay systems. Molecular models of PD 140195 suggest a spatial mimicry of the cholesteryl ester structure. Despite the structural similarity, kinetic studies with a fluorescent cholesteryl ester analog suggest that the inhibition of transfer is not competitive. PD 140195 also selectively inhibited cholesteryl ester but not triglyceride transfer, while the Mab TP2 blocked CETP transfer of both. Studies were carried out to determine whether CETP inhibition observed in vitro could also be demonstrated in vivo. When PD 140195 was intravenously infused to anesthetized rabbits (up to 20 mg/kg), only transient CETP inhibition was observed. In vitro reconstitution studies in the presence of bovine serum albumin resulted in marked reduction of PD 140195 inhibitory activity. Thus, the low activity of PD 140195 in whole plasma probably results from binding to other plasma proteins.

Animals↗
PubMed1994

Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat.

To characterize the mechanisms of the pituitary-adrenal (P-A) response to tissue injury, rats were injected intramuscularly (IM) with turpentine. This resulted in marked elevations in the plasma concentrations of ACTH and corticosterone within the first hour after injection, which were attenuated by either total deafferentation of the medial basal hypothalamus (MBH) or neonatal capsaicin pretreatment. The plasma concentrations of corticosterone remained elevated for 18 h in the turpentine-injected rats, despite a return of ACTH toward control values (by 2-4 h). Bioactive concentrations of interleukin-6 (IL-6) in plasma rose markedly after turpentine, and its concentrations were significantly correlated with plasma corticosterone concentrations 4-8 h after turpentine. Pretreatment with IL-1 receptor antagonist (IL-1ra) attenuated the release of IL-6 and had a marginal effect on the corticosterone response 6 h after turpentine. These results suggest that the early and late phase of the P-A response to tissue injury are mediated by different mechanisms.

Acute-Phase Reaction↗
PubMed1994

Ca2+ release induced by cyclic ADP-ribose.

Cyclic ADP-ribose (cADPR) is the most potent Ca(2+)-mobilizing agent known. It has been found in many different cell types, where it is synthesized from its precursor NAD(+) by ADP-ribosyl cyclases. cADPR binds to Ca(2+) channels in the endoplasmic reticulum membrane to activate a Ca(2+)-release mechanism. This release is itself potentiated by elevated cytoplasmic Ca(2+) concentrations. Thus, cADPR may function as an endogenous regulator of Ca(2+)-induced Ca(2+) release, and there is excitement that it may also function as a Ca(2+)-mobilizing second messenger.

Journal Article↗
PubMed1994

Total energy expenditure and energy intake in the pre-school child: a comparison.

In a cohort (n 81) of healthy children aged 1.5-4.5 years, measurements of energy intake and energy expenditure were compared. Energy intake was calculated following a 4 d weighed record completed by the mother or guardian of the child. Total energy expenditure was measured using the doubly-labelled water technique. Mean energy intake and expenditure in the cohort were 4773 kJ/d and 4928 kJ/d respectively. The mean relative bias between the techniques was 154 kJ/d. In the older children (3.5-4.5 years) the mean relative bias was only 37 kJ/d. At the population level the measurements of energy intake and energy expenditure were extremely close, and the study has provided sufficient confidence in weighed intake methodology for it to be used in a major nationwide study of dietary intake and nutritional status of children aged 1.5-4.5 years.

Age Factors↗
PubMed1994

Azole-resistant Candida albicans: report of two cases of resistance to fluconazole and review.

We report the course of oropharyngeal infection by Candida albicans that was refractory to treatment with fluconazole in two patients infected by the human immunodeficiency virus (HIV). We also review the epidemiology of C. albicans with decreased in vitro and in vivo susceptibility to azole antifungal agents, the significance of such isolates, the known mechanisms by which C. albicans may become less susceptible to azole antifungal agents, and the efficacy of various treatments for mucosal candidiasis. The occurrence in HIV-infected patients of mucosal candidiasis that is refractory to therapy with fluconazole and is due to C. albicans that demonstrates decreased in vitro susceptibility to fluconazole has been reported since 1990. Following the release of miconazole and ketoconazole in the late 1970s, C. albicans with decreased in vitro susceptibility to these agents was isolated from patients with chronic mucocutaneous candidiasis who required repeated and prolonged courses of therapy. Subsequently, C. albicans with decreased in vitro-susceptibility to ketoconazole, clotrimazole, and itraconazole has been isolated from HIV-infected patients. Recent reports of the sexual and nosocomial transmission of wild-type C. albicans indicate the possibility of future person-to-person transmission of C. albicans with decreased in vitro susceptibility to azole antifungal agents.

AIDS-Related Opportunistic Infections↗
PubMed1994

ACTH precursors characterize the ectopic ACTH syndrome.

OBJECTIVE: ACTH is secreted by the pituitary following processing of larger molecular weight precursors, proopiomelanocortin and pro-ACTH. Ectopic ACTH syndrome refers to the secretion of ACTH by non-pituitary tumours, but the predominant circulating form of proopiomelanocortin-related peptides remains unclear. PATIENTS: Fifteen patients with ectopic ACTH syndrome were compared to 20 patients with pituitary-dependent Cushing's syndrome, 22 patients with small cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls. DESIGN AND MEASUREMENTS: Measurement of plasma ACTH and ACTH precursors using specific monoclonal-based immunoradiometric assays at 0900 h and, in five patients with ectopic ACTH syndrome, at 15-minute intervals for 6-24 hours. RESULTS: ACTH precursors were grossly elevated in patients with ectopic ACTH syndrome (median 2194, range 139-18000 pmol/l) compared to patients with Cushing's disease (median 33, 8-73 pmol/l, P < 0.001), patients with small cell lung carcinomas (38, 8-117 pmol/l, P < 0.001) and controls (26, 10-39 pmol/l, P < 0.001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median 34, 11-152 pmol/l) compared to patients with Cushing's disease (0900 h median 8, 3-19 pmol/l), but not to the same degree as ACTH precursors. In contrast with Cushing's disease, ACTH was secreted in a non-pulsatile fashion. ACTH precursors but not ACTH itself correlated with plasma cortisol in patients with ectopic ACTH syndrome (r = 0.65, P < 0.05). Chromatographic analysis of plasma from a patient with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the predominant circulating form. With the cross-reactivity of proopiomelanocortin and pro-ACTH in the ACTH IRMA of < 1 and < 10% respectively, ACTH precursors could represent all the ACTH immunoreactivity in patients with ectopic ACTH syndrome. CONCLUSIONS: Ectopic 'ACTH' is characterized by aberrant processing of proopiomelanocortin and should be more accurately referred to as 'ectopic ACTH precursor syndrome'.

ACTH Syndrome, Ectopic↗
PubMed1994

Effect of late hypothalamo-pituitary disconnection on the development of the HPA axis in the ovine fetus and the initiation of parturition.

The studies of Liggins et al. (1) in which fetuses stalk-sectioned from day 116 onwards delivered at or near term, suggested that a connection between the fetal hypothalamus and pituitary is not essential for parturition to occur. The objective of this study was to repeat these experiments on the effects of pituitary stalk sections at different gestational ages and include information on the plasma concentrations of key fetal hormones. We have used the more sophisticated technique of hypothalamo-pituitary disconnection (HPD) at either of two gestational age ranges (123-127 days or 133-135 days). Completeness of the procedure was assessed by demonstrating an attenuated prolactin response to chlorpromazine challenge. Following HPD, gestation was prolonged for at least eight days beyond term (146.2 +/- 1.5 days) in 9 of the 10 fetuses operated. Fetal plasma ACTH1-39 concentrations were not different between the HPD and control fetuses, increasing in all groups with increasing gestation. Fetal plasma cortisol concentrations increased (P < 0.01) in control fetuses over gestation. Cortisol concentrations did not change significantly in the day 125 HPD group following HPD but increased in the day 135 HPD group (P < 0.05) with advancing gestation. These latter concentrations, however were markedly less (P < 0.001) than those for control fetuses prior to parturition. Fetal and maternal plasma PGE2 concentrations increased (P < 0.01) in the control group over gestation but did not change following HPD. Maternal plasma progesterone concentrations decreased (P < 0.05) after day 143 in the control group but did not change in the HPD group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Human small cell lung cancer cell lines expressing the proopiomelanocortin gene have aberrant glucocorticoid receptor function.

Some human small cell lung carcinomas (SCLC) secrete proopiomelanocortin (POMC) derived peptides, but in contrast to the pituitary, glucocorticoids fail to inhibit this hormone production. We have previously described an in vitro model using human SCLC cell lines that express POMC and are resistant to glucocorticoids. We have now identified the glucocorticoid receptor (GR) in the SCLC cell line COR L24 using a whole cell ligand binding assay (Kd = 5.7 nM; Bmax = 11 fmol/million cells), while another cell line, DMS 79, lacked significant glucocorticoid binding. To analyze GR function both positive (GMCO) and negative (TRE)3-tkCAT), glucocorticoid-regulated reporter gene constructs were transfected into COR L24 cells. In the SCLC cell line, neither hydrocortisone nor dexamethasone (500-2,000 nM) significantly induced chloramphenicol acetyltransferase expression from GMCO; in addition, they did not suppress chloramphenicol acetyltransferase expression from (TRE)3-tkCAT. Similar results were obtained with two other POMC-expressing SCLC cell lines. Expression of wild type GR in COR L24 cells restored glucocorticoid signaling, with marked induction of GMCO reporter gene expression by dexamethasone (9,100 +/- 910%; n = 3), and an estimated EC50 of 10 nM. This failure of the GR explains the resistance of the POMC gene to glucocorticoid inhibition and may have implications for cell growth in SCLC.

Carcinoma, Small Cell↗
PubMed1994

A double-blind trial of captopril or bendrofluazide in newly diagnosed senile hypertension.

Hypertension is a major risk factor for stroke and heart disease in the elderly. Eighty-one hypertensive subjects with mild cognitive impairement, aged over 70 years, were drawn from a community screening programme and randomized to either 12.5 mg captopril twice daily or 2.5 mg bendrofluazide daily in a double-blind trial. Subjects were excluded if they had previously received antihypertensive treatment. The mean blood pressure was reduced from 193/101 mmHg to 154/87 mmHg by captopril and from 188/102 mmHg to 151/89 mmHg by bendrofluazide after 24 weeks; there was no significant difference between the two drugs. Seven subjects withdrew due to adverse events. Adverse events occurred more frequently during the 2-week placebo phase than during active treatment with either drug. The only significant detrimental changes in pre-existing conditions were in 3 subjects (2 captopril, 1 bendrofluazide) who were noted to have worsening of their cataracts. One subject on captopril and 4 subjects on bendrofluazide became hypokalaemic. The trial results support the use of captopril as an alternative to bendrofluazide as a first-line antihypertensive agent in the community for elderly people, but large studies are required to measure accurately effects on significant morbidity and mortality.

Aged↗