Showing papers by "Newcastle University published in 1989"

Serial study of factors influencing changes in cardiac output during human pregnancy

Abstract: Serial hemodynamic measurements were performed in 13 women on two occasions before conception and then at monthly intervals throughout pregnancy. Cardiac output (CO) was measured by Doppler and cross-sectional echocardiography at the aortic, pulmonary, and mitral valves. Cardiac chamber size and ventricular function were investigated by M-mode echocardiography. CO increased from a mean of 4.88 l/min before the conception to a maximum of 7.21 l/min at 32 wk, the increase being significant by 5 wk after the last menstrual period. Heart rate and left ventricular performance increased during the first trimester. Heart rate increased further during the second trimester, during which left atrial and left ventricular end-diastolic dimensions increased, suggesting an increase in venous return. Derived values of total peripheral vascular resistance fell during the first 20 wk. These changes were associated with a progressive increase in valve orifice area and left ventricular wall thickness during pregnancy.

Expression of c-erbB-2 Oncoprotein: A Prognostic Indicator in Human Breast Cancer

Abstract: Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c- erbB -2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c- erbB -2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.

Control and function of sebaceous glands

Abstract: This review describes the various types of sebaceous glands, their locations, and where possible their different functions. All sebaceous glands are similar in structure and secrete sebum by a holocrine process. However, the nature of this secretion and the regulation of the secretory process seem to differ among the various types of glands. Methods for measuring sebum secretion and assessing sebaceous gland activity are also described. The area of major interest during the last 20 years has undoubtedly been the mechanisms that control sebaceous gland function. Most studies have focused on the endocrine control and in particular on the role of androgens and pituitary hormones, although evidence suggests that nonendocrine factors may also be important. However, many questions remain and during the next few years attention will certainly be given to the role of retinoids and their mode of action in the treatment of acne.

The 2-oxo acid dehydrogenase complexes: recent advances.

Abstract: The 2-oxo acid dehydrogenase complexes represent the classic examples of multienzyme complexes, a knowledge of whose structure and function has wide implications for our understanding of macromolecular assembly and organization and of protein structure and function Each complex consists of multiple copies of three enzymes, termed El, E2 and E3 El is a 2-oxo acid dehydrogenase which has thiamin pyrophosphate as an essential co-factor E2 is a dihydrolipoamide acyltransferase, with a covalently attached lipoic acid cofactor, and E3 is an FAD-containing dihydrolipoamide dehydrogenase The components catalyse consecutive steps in the overall reaction, as outlined in Fig 1 These complexes have molecular masses of several million [mammalian pyruvate dehydrogenase complex (PDC) is slightly larger than a ribosome] and are truly self-assembling [1,2] These macromolecules are not however merely of interest from a structural viewpoint Each of the 2-oxo acid dehydrogenase complexes occupies key positions in intermediary metabolism and the activity of each mammalian complex, located within mitochondria, is under stringent control by hormones and dietary factors PDC oxidatively decarboxylates pyruvate to acetyl-CoA, an irreversible step in the utilization of carbohydrate, whilst 2-oxoglutarate dehydrogenase complex (OGDC) is a potentially regulatory enzyme of the tricarboxylic acid cycle Branched-chain 2-oxo acid dehydrogenase complex (BCOADC) catalyses an irreversible step in the catabolism of several essential amino acids, including the branched-chain amino acids [2] PDC and OGDC have narrow substrate specificities, with OGDC being essentially specific for 2-oxoglutarate, whereas PDC will oxidize 2-oxobutyrate, in addition to pyruvate, at a significant rate [3] In contrast, BCOADC has a relatively broad specificity, oxidizing 4-methylthio-2-oxobutyrate and 2-oxobutyrate at comparable rates and with similar Km values as for the three branched-chain 2-oxo acid substrates, namely 3-methyl-2-oxobutyrate, 4-methyl-2oxopentanoate and 3-methyl-2-oxopentanoate [3-5] BCOADC will also oxidize pyruvate, but the Km value is

Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism.

Abstract: Hormone-sensitive lipase is phosphorylated at a single site (site 2) in vitro by the AMP-activated protein kinase, without any direct effect on the activity of the enzyme. The amino acid sequence around this site has been determined. Ca2+/calmodulin-dependent protein kinase II also phosphorylates hormone-sensitive lipase predominantly at this site, whilst cyclic-GMP-dependent protein kinase phosphorylates exclusively the regulatory site (site 1) which is also phosphorylated by cyclic-AMP-dependent protein kinase. Phosphorylation of site 2 has been found to inhibit subsequent phosphorylation and activation of hormone-sensitive lipase by the cyclic-AMP-dependent and cyclic-GMP-dependent protein kinases, indicating that site-2 phosphorylation may have an antilipolytic role in vivo.

The cost of diabetes.

Abstract: This paper estimates the cost of diabetes in England and Wales in 1984 to be in excess of 259.5 million pounds. The costing methodology used follows the 'cost of illness' framework. This framework defines three elements for costing: direct, indirect and psychological, although the latter element is left out of the calculation because monetary valuations for this element have never been adequately estimated. Direct costs include resources used to prevent, detect, and treat diabetes. Indirect costs relate to the loss of productive output caused by absenteeism, early retirement, and premature mortality. The estimate which has been obtained is likely to be an underestimate because of the weaknesses and gaps in the data sets. The estimate of the total lost earnings from diabetes varied greatly according to the choice of absentee rate. If there was no significant difference between absenteeism in the diabetic community and the non-diabetic community then the cost of diabetes would be 259.5 million pounds. If on the other hand the diabetic community was prone to three times as much absenteeism as the non-diabetic community then the cost of diabetes would rise to 602.5 million pounds. The costs of diabetes as a subsidiary diagnosis are extremely difficult to identify. They have been estimated in this study to be 86 million pounds but this is thought to be an overestimate. Nevertheless the cost of diabetes is significant and thus the search for more efficient treatment regimens may reduce such costs as well as enhance the quality of life of the patients concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Pancreas Transplantation on the Glomerular Structure of Renal Allografts in Patients with Insulin-Dependent Diabetes

Abstract: The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up,...

‘Burnout’, absence and turnover amongst British nursing staff

Abstract: In a predictive study of qualified nursing staff in long-stay settings, ‘burnout’ variables, role ambiguity and perceived support from their superior were assessed. Absence through sickness and job turnover were then measured over the subsequent two years. Ambiguity about authority predicted frequency of short absences in the subsequent 12 months. Perceived lack of support and emotional exhaustion predicted the frequency of absences of more than four days, and more than seven days, respectively, in the subsequent 12 months. Feelings of depersonalization were correlated with departure from the job during the subsequent two years. Hypotheses are offered to draw together these particular findings, emphasizing the mediating role which feelings of ‘professional depression’ may play.

A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis.

Abstract: A trial of n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis has been conducted over a 5 year period. Ambulant patients (312) with acute remitting disease were randomly allocated to treatment or placebo. Both groups were given dietary advice to increase the intake of n-6 polyunsaturated fatty acids and the treatment group in addition received capsules containing n-3 polyunsaturated fatty acids. Analysis of clinical outcome at the end of 2 years of treatment was made in terms of the duration, frequency and severity of relapses and the number of patients who had improved or remained unchanged. The results showed no significant difference at the usual 95% confidence limits but there was a trend in favour of the group treated with n-3 polyunsaturated fatty acids in all parameters examined.

Visuospatial working memory in Parkinson's disease.

Abstract: Visuospatial impairment is frequently reported in Parkinson's disease but the psychological mechanisms which subserve the impaired abilities and the way in which breakdown of the mechanisms leads to performance deficits have not been precisely delineated. This paper reports experimental investigations designed to test the hypothesis that the locus of the impairment is the visuospatial subsystem of working memory. Subjects were a group of sixteen patients with Parkinson's disease of mild to moderate severity and a matched control group. They performed complex visuospatial and verbal memory tasks. The Parkinsonian group were significantly slower than the control group when performing the visuospatial task. They were not significantly slower and made no more errors than the control group on the verbal task. The findings are compatible with the hypothesis that the visuospatial subsystem of working memory is impaired in Parkinson's disease. It is demonstrated that the impairment is not the result of a reduction in the capacity of this subsystem but is due to difficulty in utilising information stored in the subsystem to perform complex visuospatial tasks.

Analgesic effects of different frequencies of transcutaneous electrical nerve stimulation on cold-induced pain in normal subjects.

Abstract: The efficacy of transcutaneous electrical nerve stimulation (TENS) in producing analgesia in cold-induced pain was assessed using a range of 5 stimulating frequencies (10 Hz, 20 Hz, 40 Hz, 80 Hz and 160 Hz) in 83 normal healthy subjects. TENS significantly elevated ice pain threshold when compared with sham and control groups. TENS frequencies between 20 and 80 Hz produced greatest analgesia, while frequencies below and above this level (10 Hz and 160 Hz), although significantly elevating ice pain threshold, produced effects of a lesser magnitude. The frequency of pulse delivery was the governing factor as no significant differences in stimulus intensity were observed across the treatment groups. Measurement of ice pain tolerance was found to be unreliable under the present conditions. No significant relationships were observed between personality variables as measured by Eysenck Personality Questionnaires and the degree of TENS response.

Indicators of Quality of Life: Some Methodological Issues

Abstract: The importance of combining ‘subjective’ and ‘objective’ indicators in assessing the quality of life has been increasingly stated as a research goal. A new methodology for measuring quality of life which is an attempt to satisfy this objective is discussed. It includes a perceptually derived set of weightings and ‘objectively’ measured indicators of social, economic, and environmental characteristics of the largest thirty-eight cities in Britain. The weighting system, the selected indicators, and the resulting rankings of British cities are assessed in comparison with the local prosperity index. The strength of the approach is shown to lie in the fact that this more closely reflects the evaluation process used by the public in assessing the quality of life.

Thermodynamic phase transitions of Kerr-Newman black holes in de Sitter space

Abstract: A curious feature of black holes which rotate and/or carry electric charge is that as the rotation and/or charge is increased the black hole undergoes a second-order phase transition in which its specific heat changes from negative to positive. Here this phase transition is investigated for black holes in de Sitter-like universes.

Recovery of Visual Fields in Acute Stroke: Homonymous Hemianopia Associated with Adverse Prognosis

Abstract: In a prospective study of 157 patients (median age 73 years) admitted to hospital within 72 hours of acute cerebral hemisphere stroke, there was clinical evidence of homonymous hemianopia (HH) as assessed by confrontation in 99 (63%). Patients were followed with serial neurological examinations for 28 days. Complete recovery of visual fields occurred in 14 (17%) of the 81 patients with a complete HH on admission and in 13 (72%) of the 18 patients with a partial HH on admission. Cumulative fatality at 28 days was greater in patients with a complete HH (49%), compared with patients with a partial HH (11%). These two patterns of recovery and outcome probably reflect the differing extent of cerebral damage in the two groups.

Characterization and Quantitation of the Epidermal Growth Factor Receptor in Invasive and Superficial Bladder Tumors

Abstract: Epidermal growth factor receptors (EGFr) have been measured on primary human bladder tumor membranes by 125I-EGF ligand binding. High affinity receptors were detected on both superficial (Kd 0.2-1.45 nM; mean, 0.86 nM; median, 0.88 nM) and invasive tumors (Kd 0.19-2.38 nM; mean, 0.9 nM, median, 0.79 nM). There was one class of binding sites and EGFr concentration was quantified by competitive binding and Scatchard analysis. The EGFr was further characterized and shown to be cleaved at the major autophosphorylation site by a calcium-activated mechanism. Thus the EGFr from primary bladder tumors exhibits similar biochemical characteristics to those in established cell lines. Tumors classified as invasive on the basis of muscle invasion had higher EGFr levels [EGF binding, 99 +/- 252 (SD) fmol/mg protein; median, 21; n = 24] than superficial tumors (12 +/- 12 fmol/mg protein; median, 11; n = 23) or normal bladder mucosa (9 +/- 12 fmol/mg protein; median, 6; n = 6) (P = 0.05). When the two largest subgroups of superficial and invasive tumors were compared (15 pTa, 16 T3), the invasive tumors had significantly higher EGFr levels (P less than 0.05). EGFr may therefore be involved in mechanisms of tumor progression. EGFr may be a target for selective therapy with EGF-linked drugs in a subset of invasive bladder cancers.

Output from Visible-light Activation Units and Depth of Cure of Light-activated Composites

Abstract: A simple and reproducible method for monitoring the intensity of radiation from composite light-activation units has been developed. The method depends upon the use of a cadmium sulfide photo-conductive cell, the electrical resistance of which varies with the amount of light falling upon its surface. Filters were used for selection of the wavelength of light that is thought to be most effective in activating polymerization. The use of broad-band wavelength filters failed to give results for light intensity that correlated with depth of cure. Narrow-band interference filters, having a band width of only 10 nm and being selective within the wavelength range of from 460 to 480 nm, produced results for light intensity that correlated with depth of cure.The depths of cure for various types of composite material were measured with use of a penetrometer that enabled the thickness of unpolymerized material at the base of the test mould to be determined. The depth of cure was inversely proportional to the attenuat...

Carbon Dioxide Concentrating Mechanisms and the Evolution of CAM in Vascular Epiphytes

Abstract: Historically, research into the mechanism of photosynthesis has proceeded discontinuously: following the elucidation of the Calvin cycle, the C3 basis of photosynthesis seemed to have been resolved. However, several independent lines of research then led to the description of photosynthetic adaptations involving initial carboxylation products as C4 acids in C4 plants (Kortschak et al. 1965; Hatch and Slack 1966) and in the crassulacean acid metabolism of succulents (CAM: Ranson and Thomas 1960; Wolf 1960). Thus it was shown that a C4-acid pathway could spatially (C4 plants) and temporally (CAM) improve the efficiency of C3 carboxylation by reducing photorespiration, acting in effect as a C02 concentrating mechanism (Osmond et al. 1982; Osmond 1984, 1987).

Geographical Inequalities: The Spatial Bias of the New Communications Technologies

Abstract: L'article propose une reflexion sur les differents problemes poses par les nouvelles technologiques de communication, problemes de distribution sociale, la repartition des moyens de communication variant en fonction des sites geographiques (ville/campagne, pays pauvres/pays riches, etc.)

Conserved serine-rich sequences in xylanase and cellulase from Pseudomonas fluorescens subspecies cellulosa: internal signal sequence and unusual protein processing.

Abstract: Summary The complete nucleotide sequence of the xynA gene coding for a xylanase (XYLA) expressed by Pseudomonas fluorescens subspecies cellulosa, has been determined. The structural gene consists of an open reading frame of 1833 bp followed by a TAA stop codon. Confirmation of the nucleotide sequence was obtained by comparing the predicted amino acid sequence with that derived by N-terminal analysis of purified forms of the xylanase. The signal peptide present at the N terminus of mature XYLA closely resembles signal peptides of other secreted proteins. Truncated forms of the xylanase gene, in which the sequence encoding the N-terminal signal peptide had been deleted, still expressed an enzyme which was secreted in Escherichia coli. XYLA contains domains which are homologous to an endoglucanase expressed by the same organism. These structures include serine-rich sequences. Bal31 deletions of xynA revealed the extent to which these conserved sequences, in XYLA, were essential for xylanase activity. Downstream of the TAA stop codon is a G + C-rich region of dyad symmetry (δG = 24kcal) characteristic of E. coli Rho-independent transcription terminators.

Comparison of the prevalence and associated features of abnormal albumin excretion in insulin-dependent and non-insulin-dependent diabetes.

Abstract: Overnight albumin excretion rates were measured in 940 diabetic patients, 416 with insulin dependent and 524 with non-insulin dependent diabetes, and in 106 healthy volunteers. A significantly higher number of non-insulin dependent diabetic patients had abnormal albumin excretion compared with the insulin-dependent group (X2 = 15.2, p less than 0.002). Ten per cent of non-insulin-dependent and 7 per cent of insulin-dependent diabetic patients had albumin excretion rates in the range 30-150 micrograms/min and thus were at risk of the cardiovascular and renal complications of diabetes. Six per cent of non-insulin-dependent and 5 per cent of insulin-dependent diabetic patients had albumin excretion rates above 150 micrograms/min and thus were entering the phase of clinical diabetic nephropathy. Multivariate analysis revealed that male sex and retinopathy in insulin-dependent diabetes, and systolic blood pressure and retinopathy and peripheral vascular disease in non-insulin-dependent diabetes, were significantly related to albumin excretion. Only one patient with insulin-dependent diabetes of less than 5 years known duration had an albumin excretion rate in the range 30-150 micrograms/min, whereas such an excretion rate indicating patients at risk was observed at all durations of non-insulin-dependent diabetes. It is possible that during the long silent phase of non-insulin-dependent diabetes, before diagnosis, significant renal damage occurred.

Fatal Lactic Acidosis in Infancy with a Defect of Complex III of the Respiratory Chain

Abstract: We report our studies on the metabolic defects which caused a newborn infant to present with a severe lactic acidemia (25 mM) and to die on the 3rd d after birth despite intensive supportive measures. The mitochondrial fractions prepared from skeletal muscle and liver oxidised NAD+-linked substrates and succinate slowly. Spectrophotometric assays for complexes I, II, and HI of the respiratory chain demonstrate a specific defect of complex III in the skeletal muscle and liver mitochondrial fractions. The concentrations of cytochrome b were 75% lower in the skeletal muscle and heart mitochondria than in control preparations. The amount of non-heme iron sulphur protein of complex III was low in skeletal muscle, liver, and heart. This case differs from previous reports of complex III deficiency in three respects: the patient presented in the neonatal period, the defect was expressed in several tissues, and it was fatal.

The thiol-activated toxin streptolysin O does not require a thiol group for cytolytic activity.

Abstract: Site-directed mutagenesis of the TGC codon in a cloned streptolysin O (SLO) gene exchanged the single Cys residue in SLO for either Ala or Ser. The parent wild-type SLO (SLO.Cys-530) and the SLO.Ala-530 and SLO.Ser-530 mutant toxins, expressed in Escherichia coli, were purified and analyzed. Wild-type SLO.Cys-530 and the SLO.Ala-530 mutant showed no significant differences in their specific hemolytic activities, while the SLO.Ser-530 mutant had a reduced (ca. 25%), but still considerable, specific hemolytic activity as compared with that of wild-type SLO. The parent and mutant toxins extracted from lysed erythrocyte membranes had similar sedimentation profiles on sucrose density gradients, suggesting that the mutations did not affect the ability of SLO to form oligomers in membranes. These results show that the widely held assumption that the in vitro cytolytic activity of SLO requires an essential Cys residue is not true.