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Biomedical subjects

A Clark

Publications and source records attributed to A Clark.

At least 163 records · Page 9Linked to original sources
PubMed1994

Mechanisms of exercise intolerance in cardiac failure: abnormalities of skeletal muscle and pulmonary function.

The syndrome of chronic heart failure is characterized by exercise intolerance. Exercise is limited by shortness of breath and fatigue, and either symptom occurs in the same patient depending on the type of exercise performed. Exercise capacity correlates poorly with indices of central hemodynamic function, but the increased ventilatory response in chronic heart failure correlates well with exercise capacity. Possible pulmonary causes have been explored, including increased dead space ventilation, abnormal airway function, and abnormal diffusion capacity. However, the finding of hypocapnia and hyperoxemia in arterial blood during exercise in patients with heart failure suggests that blood gas values reflect hyperventilation, and that any abnormality of pulmonary function is secondary to changes elsewhere. Skeletal muscle is abnormal in chronic heart failure, and shows changes in structure, bulk, exercise capacity, blood flow, and intrinsic metabolic activity. The relative importance of these abnormalities is not clearly determined, but the possible presence of an ergo- or metaboloreceptor connection between abnormal exercising muscle and the ventilatory response to exercise suggest a mechanism linking the two cardinal symptoms of chronic heart failure.

Airway Resistance↗
PubMed1994

Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation.

In an open, nonblind clinical trial, clomipramine reduced adventitious movements and compulsions in five previously medicated prepubertal boys with autistic disorder and severe mental retardation. Poorly adapted rating scales, interrater variability, subject heterogeneity, different treatment histories, and environmental stresses confounded the assessment of treatment effects.

Autistic Disorder↗
PubMed1994

Expression of IGFBP-1 in normal and cirrhotic human livers.

Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is also associated with elevated insulin levels and insulin resistance. In animal models hepatic regeneration is associated with increased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To further our understanding of the regulation of IGFBP-1 in cirrhosis we have studied steady state levels of IGFBP-1 mRNA in human liver from three groups of patients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic liver transplantation (n = 4); group 2, patients undergoing major liver resection with no histological evidence of chronic liver disease (n = 4); and group 3, patients undergoing orthotopic transplantation for chronic liver failure (n = 9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patients IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin. IGFBP-1 mRNA was detectable in all the human liver samples with the greatest levels seen from the normal livers of group 2 patients. Insulin levels were elevated in the cirrhotic group 3 patients compared to a normal range as were IGFBP-1 levels. There was no relationship between circulating levels of IGFBP-1 and IGFBP-1 gene expression. In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of insulin suggesting that there are factors other than insulin regulating IGFBP-1 gene expression.

Adult↗
PubMed1994

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans.

The cellular mechanisms responsible for conversion of islet amyloid polypeptide (IAPP) into insoluble amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM) are not clear. Overexpression of IAPP and the amino acid sequence of human IAPP (hIAPP) have both been implicated. To examine factors involved in amyloid formation, transgenic mice expressing the hIAPP or rat IAPP (rIAPP) gene were generated. These mice had elevated plasma IAPP concentrations, and they were normoglycemic and normoinsulinemic. No amyloid deposits were detected by light microscopy. To examine the ultrastructure of islets, pancreatic tissue was studied from hIAPP and rIAPP transgenic mice and from age-matched control mice by immunoelectron microscopy. IAPP was immunolocalized in beta-cell secretory granules of all mice, and the COOH- and NH2-terminal flanking peptides of hIAPP were localized in beta-cell granules of hIAPP mice. Accumulations of nonfibrillar perivascular IAPP-immunoreactive material were found between capillaries and beta-cells in hIAPP transgenic mice but not in rIAPP transgenic or control mice. Similar nonfibrillar masses were identified in islets of an NIDDM patient. Secondary lysosomes in beta-cells and macrophages of hIAPP transgenic mice showed dense labeling for IAPP. We suggest that hIAPP is degraded more slowly than rIAPP or mouse IAPP by beta-cell lysosomes. Accumulations of IAPP in islet perivascular spaces may represent the early stages of islet amyloid formation.

Aged↗
PubMed1994

Increased blood pressure variability during 24h blood pressure monitoring as an early sign of autonomic dysfunction in non-insulin-dependent diabetics.

To evaluate the presence of early autonomic dysfunction in non-insulin-dependent diabetics we examined 24h control of blood pressure (1/4 hourly readings day and 1/2 hourly at night, using TM 2420) in 20 non-insulin-dependent diabetics, controlled only on diet or oral hypoglycaemics and 20 age/sex/BP matched non-diabetics selected from a random population survey. The two groups were aged 52 +/- 9 years and 53 +/- 8 years, respectively. Both groups included normotensives and mild hypertensives in equal numbers but none was on antihypertensive treatment. The groups were well matched for daytime systolic blood pressure (SBP; 132.2 +/- 11.4 vs. 131.2 +/- 10.3) and diastolic blood pressure (DBP; 82.1 +/- 8.3 vs. 81.1 +/- 7.0). The diabetics had a significantly greater heart rate (HR) both during the day (79.6 +/- 9.5 vs. 72.3 +/- 8.8: P = 0.015) and during sleep (67.7 +/- 6.8 vs. 62.5 +/- 8.9). There was increased BP variability in the diabetics during the day (standard deviation of SBP; 16.9 +/- 6.2 vs. 13.3 +/- 4.7: P < 0.05) but the difference for DBP variability was not significant. The day-night difference for SBP, DBP, HR and HR variability was the same in both groups. We conclude that in these patients there was evidence for an alteration in BP variability (which may reflect baroreflex insensitivity) at a stage where there was no alteration in day-night rhythms of BP or HR. The increased HR both at day and night may also reflect baroreflex dysfunction and/or sympathovagal imbalance.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System↗
PubMed1993

Allergy to octyl gallate causing stomatitis.

Octyl gallate is an antioxidant (European Community number 311). It is used as a preservation agent in a wide variety of foods and other non-dietary substances. We report a case of a 49-year-old female with a 10-year history of 'burning mouth' and clinical erythema of the tongue, who, after investigation, proved to be allergic to octyl gallate. Management with an exclusion diet proved effective in both controlling the burning sensation and resolving the erythema of the tongue.

Antioxidants↗
PubMed1993

Relation between early introduction of solid food to infants and their weight and illnesses during the first two years of life.

OBJECTIVE: To assess the relations between early introduction of solid food and infant weight, gastrointestinal illness, and allergic illnesses during the first two years of life. DESIGN: Prospective observational study of infants followed up for 24 months after birth. SETTING: Community setting in Dundee. PATIENTS: 671 newborn infants, of whom 455 were still available for study at 2 years of age. MAIN OUTCOME MEASURES: Infants' diet, weight, and incidence of gastrointestinal illness, respiratory illness, napkin dermatitis, and eczema at 2 weeks and 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 months of age. RESULTS: The infants given solid food at an early age (at < 8 weeks or 8-12 weeks) were heavier than those introduced to solids later (after 12 weeks) at 4, 8, 13, and 26 weeks of age (p < 0.01) but not at 52 and 104 weeks. At their first solid feed those given solids early were heavier than infants of similar age who had not yet received solids. The incidence of gastrointestinal illness, wheeze, and nappy dermatitis was not related to early introduction of solids. There was a significant but less than twofold increase in respiratory illness at 14-26 weeks of age and persistent cough at 14-26 and 27-39 weeks of age among the infants given solids early. The incidence of eczema was increased in the infants who received solids at 8-12 weeks of age. CONCLUSION: Early introduction of solid food to infants is less harmful than was previously reported. Longer follow up is needed, but, meanwhile, a more relaxed approach to early feeding with solids should be considered.

Body Weight↗
PubMed1993

Diabetes mellitus in Macaca mulatta monkeys is characterised by islet amyloidosis and reduction in beta-cell population.

Diabetes mellitus in Macaca mulatta rhesus monkeys is preceded by phases of obesity and hyperinsulinaemia and is similar to Type 2 (non-insulin-dependent) diabetes mellitus in man. To relate the progression of the disease to quantitative changes in islet morphology, post-mortem pancreatic tissue from 26 monkeys was examined. Four groups of animals were studied: group I--young, lean and normal (n = 3); group II--older (> 10 years), lean and obese, normoglycaemic (n = 9); group III--normoglycaemic and hyperinsulinaemic (n = 6); group IV--diabetic (n = 8). Areas of islet amyloid, beta cells and islets were measured on stained histological sections. Islet size was larger in animals from groups III (p < 0.01) and IV (p < 0.0001) compared to groups I and II. The mean beta-cell area per islet in micron 2 was increased in group III (p < 0.05) and reduced in group IV (p < 0.001) compared to groups I and II. Mean beta-cell area per islet correlated with fasting plasma insulin (r = 0.76, p < 0.001) suggesting that hyper- and hypoinsulinaemia are related to the beta-cell population. Amyloid was absent in group I but small deposits were present in three of nine (group II) and in four of six (group III) animals, occupying between 0.03-45% of the islet space. Amyloid was present in eight of eight diabetic animals (group IV) occupying between 37-81% of the islet area. Every islet was affected in seven of eight diabetic monkeys. There was no correlation of degree of amyloidosis with age, body weight, body fat proportion or fasting insulin. Islet amyloid appears to precede the development of overt diabetes in Macaca mulatta and is likely to be a factor in the destruction of islet cells and onset of hyperglycaemia.

Aging↗
PubMed1993

Pulp capping with Bioglass and autologous demineralized dentin in miniature swine.

The purpose of this study was to compare the responses of mechanically exposed dental pulps which had been capped with three dissimilar materials: a bioactive ceramic (Bioglass), autologous demineralized dentin matrix (DDM), and a calcium hydroxide product (Life), with Teflon discs as controls. Mechanical dental pulp exposures were made after preparation of deep buccal Class V cavities in 48 teeth in four miniature swine. The exposures were capped and the cavity preparations restored with zinc oxide-eugenol (IRM) cement. The animals were killed after 90 days, the coronal 2/3 of the teeth removed, and sections prepared for either histological or microradiographic examination. The pulpal inflammatory reactions and the degree of reparative dentin formation were assessed from demineralized serial sections. A qualitative assessment of the degree of mineralization of the reparative dentin was made from microradiographs of undecalcified sections. The observations suggest that reparative dentin formation occurs under a variety of pulp-capping materials, but the structure of the reparative dentin varies with the material and the condition of the underlying pulp.

Analysis of Variance↗
PubMed1993

Complex genetics of type 2 diabetes: thrifty genes and previously neutral polymorphisms.

Type 2 diabetes is likely to be a polygenic disease, with a combination of major and minor genes affecting obesity, insulin secretion, and insulin action. Amongst these inputs, the 'thrifty genotype' hypothesis is most likely to apply to the predisposition to develop obesity, since the ability to store scarce fuels in periods of starvation could lead to obesity given a western lifestyle. Other genetic variations that were neutral with respect to food deprivation could be harmful with food excess. These could include 'defects' in islet cell function: examples could be mutations in the glucokinase gene and the genetic factors leading to amyloid deposition. The occurrence of associated lipid abnormalities or hypertension is probably due to additional specific genetic determinants that also become exaggerated by a modern lifestyle. The interactions between different genetic and environmental inputs are complex, and will probably be elucidated piecemeal as different genetic determinants are identified.

Amyloid↗
PubMed1993

Effect of urinary incontinence on sexual activity in women.

The effects of urinary incontinence on sexual activity were assessed with a questionnaire. Forty-four women were asked about the symptoms of urgency and frequency as well as incontinence. Fifty-six percent of the women experienced urinary incontinence during sexual activity. Sixty-six percent experienced incontinence, urgency or frequency during sexual activity. The women were asked to give recommendations to alleviate or adapt to urinary symptoms. A treatment model for intervention was developed based on the Permission, Limited Information, Specific Suggestion, Intensive Therapy model.

Adaptation, Psychological↗
PubMed1992

The post-translational processing and intracellular sorting of PC2 in the islets of Langerhans.

Proinsulin conversion in the insulin secretory granule is mediated by two sequence-specific endoproteases related to the Kex2 homologues, PC2 and PC3 (Bennett, D. L., Bailyes, E. M., Nielsen, E., Guest, P. C., Rutherford, N. G., Arden, S. D., and Hutton, J. C. (1992) J. Biol. Chem. 267, 15229-15236; Bailyes, E. M., Bennett, D. L., and Hutton, J. C. (1992) Enzyme, in press). Radiolabeling studies using isolated rat islets showed that PC2 was synthesized initially as a 76-kDa glycoprotein which was converted by limited proteolysis to the mature 64-66-kDa form. Conversion was initiated approximately 1 h after synthesis and proceeded via intermediates of 71, 68, and 66 kDa with a t1/2 of 140 min. Release of only the 66- and 64-66-kDa radiolabeled forms of PC2 was induced by glucose and then only at times more than 2 h following synthesis. Proinsulin conversion, by contrast, was more rapid (delay = 30 min, t1/2 = 60 min), and release commenced as soon as 1 h after synthesis with the secreted material being comprised of the precursor, intermediate, and mature forms of insulin. Ultrastructural analysis of islet beta cells showed that PC2 was concentrated in secretory granules. Subcellular fractionation combined with immunoblot analysis showed that insulinoma secretory granules contained only the mature 64-66-kDa form of PC2, whereas fractions enriched in Golgi and endoplasmic reticulum contained a mixture of the 76- and 66-kDa forms of the enzyme. These results indicate that post-translational proteolysis of PC2 is initiated before sorting into the regulated pathway of secretion and that the relative proportions of proinsulin and PC2 packaged into secretory granules will change with physiological conditions.

Amidohydrolases↗
PubMed1992

Failure to detect cytomegalovirus DNA in pancreas in type 2 diabetes.

We have attempted to confirm the finding of cytomegalovirus (CMV) nucleic acid sequences in pancreas sections from patients with type 2 diabetes in a large population since this finding has major implications for the pathogenesis of the disorder. A highly sensitive nested polymerase chain reaction method was developed to detect the immediate-early CMV gene in DNA extracted from wax-embedded tissue sections. We could not confirm the previous findings; CMV DNA was not detected in pancreas sections from 43 type 2 diabetic patients or from 38 non-diabetic age-matched subjects, although the method detected CMV DNA, even in very low concentrations, in positive controls.

Adult↗
PubMed1992

The sequence location of the actin metal.

We have incorporated Fe2+ into the high-affinity metal-ion-binding site of actin. By supplying the system with oxygen from air and a reductant (dithiothreitol or ascorbate), we have induced free-radical generation, with the intent of causing peptide cleavage at the metal-ion-binding site. By analysis of the resulting fragments from actin in the F-form, we have deduced that cuts occurred at positions 159-160 and 301-302 (at the latter location we could not be sure if more than one cut occurred). We considered that these two cuts occurred in the chain strand coursing from the outer to the inner domain and vice-versa. Our results harmonize very well with the recently reported atomic structure of actin [Kabsch, W., Mannherz, H.G., Suck, D., Pai, E.F. & Holmes, K.C. (1990) Nature 347, 37-44] and remove ambiguities that had remained in the structure. The results partly bear out the homology-based prediction of Strzelecka-Golaszewska et al. [Strzelecka-Golaszewska, H., Boguta, G., Zmorzynshi, S. & Moraczcwska, J. (1989) Eur. J. Biochem. 182, 299-305].

Actins↗