PubMed Health⌕ Search

Biomedical subjects

J Simons

Publications and source records attributed to J Simons.

At least 37 records · Page 2Linked to original sources
PubMed1991

Myristoylation is important at multiple stages in poliovirus assembly.

The N-terminal glycine of the VP4 capsid subunit of poliovirus is covalently modified with myristic acid (C14 saturated fatty acid). To investigate the function of VP4 myristoylation in poliovirus replication, amino acid substitutions were placed within the myristoylation consensus sequence at the alanine residue (4003A) adjacent to the N-terminal glycine by using site-directed mutagenesis methods. Mutants which replace the alanine residue with a small hydrophobic residue such as leucine, valine, or glycine displayed normal levels of myristoylation and normal growth kinetics. Replacement with the polar amino acid histidine (4003A.H) also resulted in a level of myristoylation comparable to that of the wild type. However, replacement of the alanine residue with aspartic acid (4003A.D) caused a dramatic reduction (about 40 to 60%) in myristoylation levels of the VP4 precursors (P1 and VP0). In contrast, no differences in modification levels were found in either VP0 and VP4 proteins isolated from mature mutant virions, indicating that myristoylation is required for assembly of the infectious virion. The myristoylation levels of the VP0 proteins found in capsid assembly intermediates indicate that there is a strong but not absolute preference for myristoyl-modified subunits during pentamer formation. Complete myristoylation was observed in mature virions but not in assembly intermediates, indicating that there is a selection for myristoyl-modified subunits during stable RNA encapsidation to form the mature virus particle. In addition, even though mutant infectious virions are fully modified, the severe reduction in specific infectivity of both 4003A.D and 4003A.H purified viruses indicates that the amino acid residue adjacent to the N-terminal glycine apparently has an additional role early during viral infection and that mutations at this position induce pleiotropic effects.

Amino Acid Sequence↗
PubMed1990

Effects of an ethyl ester preparation of fish oils (Himega) on lipids and lipoproteins in hyperlipidaemia.

Clinical trials were conducted to assess the utility of HimegaR in the management of hyperlipidaemia. Himega is an ethyl ester concentrate from fish oil containing at least 50% n-3 fatty acid and minimal cholesterol. In Study 1, 13 subjects with primary hypertriglyceridaemia consumed Himega or a triglyceride-based fish oil in a randomised, double-blind crossover study for 12 weeks. Nine subjects took 2 g/day of n-3 fatty acid but four subjects with marked hypertriglyceridaemia took 4 g/day. Plasma triglycerides were reduced by approximately 50% with either product. There was a very similar effect on all lipid and lipoprotein parameters, including an 18% increase in LDL cholesterol and 23% increase in serum apolipoprotein B. In Study 2, nine subjects with primary hypercholesterolaemia took 2 g/day of n-3 fatty acid (Himega) or placebo (olive oil) in a randomised, double-blind crossover study for nine weeks. Plasma cholesterol was reduced by 6%, without significant change in LDL cholesterol. Fish oils in the form of ethyl esters or triglyceride are assimilated to a similar degree and lead to equivalent triglyceride-lowering in hypertriglyceridaemia, while simultaneously increasing LDL particle numbers. Himega does not reduce LDL levels in hypercholesteraemia, despite being a product with minimal cholesterol content.

Adult↗
PubMed1990

The Dubbo study: an Australian prospective community study of the health of elderly.

The proportion of Australian population over 60 years has risen progressively over the last 40 years and this growth is projected to continue. Major health problems of the elderly include coronary heart disease, cerebro-vascular disease, osteoporosis and fracture. The risk factors for coronary heart disease and stroke in middle-aged subjects have been extensively documented in prospective studies in Australia and elsewhere, and include lipid disorders, hypertension, cigarette smoking, diabetes and family history. Few prospective studies have been targeted exclusively on the elderly and information available with respect to vascular risk factors is fragmentary and contradictory. This is the background to a new prospective study of the health of elderly Australians now under way in Dubbo, NSW. The goals of the Dubbo Study are to identify predictors of mortality, hospitalisation and placement in long-term care, while specific aims are the study of risk factors for chronic diseases and disability. This report describes the study rationale, reasons for selecting Dubbo as the study site, methods and measures, participation rates and demography. The target population included all non-institutionalised subjects 60 years and over, domiciled in Dubbo, and is comprised of 1693 males and 2167 females. The attendance rate for an extensive medical and sociological baseline assessment over a 13 months' period was 73% for both sexes. The prospective study is now in place and within three to five years will be generating definitive information in the elderly.

Aged↗
PubMed1990

A descriptive study of adults with suspected learning disabilities.

This article documents a descriptive study of 80 adults considered to have learning disabilities. The study was initiated by the Language and Learning Disabled Adults Task Force in London, Ontario, for the purpose of developing a profile of the self-perceived characteristics and needs of the adult population with learning disabilities in Southwestern Ontario. The study also served as a vehicle for implementation of the Intake Questionnaire, an instrument with potential as a screening device for service agencies working with adults with learning disabilities. A self-referred and agency-referred sample of 80 adults completed the Intake Questionnaire. Data were collected in the areas of demography, education, employment, health, and psychosocial characteristics, aspirations, and cooperation with further testing. Results describe people with ongoing specific problems in education, employment, and psychosocial functioning who aspire to learn more about themselves and their learning disabilities.

Achievement↗
PubMed1990

Management of teeth with open apexes and necrotic pulps: representative cases.

This paper briefly reviews the pros and cons of five methods used to treat a tooth with a necrotic pulp and an open apex (incompletely developed root), and presents representative treatments of open apex cases. These treatments include customized cone, short-fill, periapical surgery, apexification, and one-visit apexification.

Adult↗
PubMed1989

Pulsatile release of gonadotropin-releasing hormone from hypothalamic explants is restrained by blockade of N-methyl-D,L-aspartate receptors.

We have shown previously that N-methyl-D,L-aspartate (NMDA) and kainate, two neuroexcitatory amino acids acting through distinct receptors, may induce the release of GnRH from hypothalamic explants. However, that effect could have no physiological significance, since very high concentrations (50 mM) of NMDA and kainate were required. Here, using agents blocking the activation of receptors to neuroexcitatory amino acids, we evaluated their possible physiological involvement in the pulsatile release of GnRH from the hypothalamus of 50-day-old male rats in vitro. In control conditions (10 nM glycine and 1 mM mg2+), the release of GnRH in 7.5-min fractions collected for 2-4 h showed an obvious pulsatile pattern. The mean (+/- 1 SD) interval between pulses, identified by PULSAR program, was 34.3 +/- 11.4 min. The stimulation of GnRH release by NMDA (50 mM) added to the medium for 7.5 min could be blocked reversibly in the presence of MK-801 (100 microM) using medium without glycine or enriched with Mg2+ (2 mM). The endogenous pulses of GnRH secretion were abolished in the presence of MK-801 or using increased Mg2+ concentrations as well as in the absence of glycine. In contrast, pulsatile release of GnRH was not affected in the presence of 6,7-dinitroquinoxaline-2,3-dione (0.1 mM), a selective inhibitor of kainate and quisqualate receptors which suppressed the increase in GnRH release induced by kainate (50 mM) without affecting the response to NMDA. These data indicate that the physiological mechanism of pulsatile GnRH secretion in the hypothalamus may involve endogenous neuroexcitatory factors acting through NMDA-sensitive receptors.

Animals↗
PubMed1989

[Goal related observation of motor behavior in psychiatry].

The goals to be attained by the patients frequently are determined by the various professions in psychiatry solely before the background of their various specialities. The new observation tool--LOVIPT--is aimed at enabling an integrative approach to be taken, leading from purposive observation of problem behaviour to the formulation of therapy goals. The potential range of objectives is worded in such a way that they can be taken over by other disciplines as well. Development and scientific validation are described in some detail.

Arousal↗
PubMed1988

Familial aggregation of coronary heart disease: partial mediation by high density lipoproteins?

The potential explanation of coronary heart disease inheritance by the major coronary risk factors was explored in a random sample of 1044 males, aged 40-70 years, who formed part of the Jerusalem Lipid Research Clinic Prevalence Study. Standardised data were available on personal and family history, coronary risk factors, resting and exercise electrocardiography. Twelve percent of subjects had coronary heart disease (previous myocardial infarction or electrocardiographic changes) and 20% had a family history of heart attack before 60 years in first degree relatives. In the presence of a family history of heart attack, the mean level of high density lipoprotein-cholesterol (HDL-C) was 5 mg/dl lower in cases of coronary heart disease than in controls. No such difference existed in the absence of a family history of heart attack. In multiple logistic regression, HDL-C was a significant negative predictor of coronary heart disease presence, but only in subjects having a positive family history. A 1 standard deviation (10 mg/dl) increment in HDL-C was associated with a two-thirds reduction in heart disease risk. Other risk factors did not predict the occurrence of coronary heart disease to any significant extent in subjects with a positive family history of heart attack. In an overall logistic model combining family history with other risk factors, the significant predictors of heart disease were: age, total plasma cholesterol, hypertension, family history and HDL-C. The interaction term, family history X HDL-C, was also a significant negative predictor of heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Coronary risk factors six to 12 months after coronary artery bypass graft surgery.

Hyperlipidaemia appears to be a major factor in the development of graft atherosclerosis in the five- to 10-year period after coronary artery bypass graft surgery. A preliminary survey of coronary risk factors was conducted in 103 consecutive patients, who lived in the Sydney metropolitan area and who had undergone coronary artery bypass graft surgery six to 12 months previously in a single hospital unit. The information was collected by reply-paid questionnaire (response rate, 93%) and by clinical assessment (measurement rate, 85%). The group was predominantly (86%) male and elderly (mean age, 62 years; 60% of men and 85% of women were aged over 59 years). Seven per cent of the group had undergone a second operation. Approximately two of every three subjects manifested hypercholesterolaemia, one in four subjects manifested hypertension and one in three subjects was overweight, but only one in 20 subjects currently smoked cigarettes. The findings were compared with those in a general population sample; the assumption was made that coronary risk factors would be overrepresented in a sample of patients in whom coronary artery bypass graft surgery had been required. The data suggested that cigarette smoking was receiving appropriate intervention (before or after surgery), that hypertension was receiving some intervention, and that hyperlipidaemia was receiving insufficient intervention. On a purely empirical basis, the appropriate use of a cardiac rehabilitation service is suggested as one possible way of preventing the return of a large number of patients with graft atherosclerosis in later years.

Adult↗
PubMed1987

Chylomicrons and chylomicron remnants in coronary artery disease: a case-control study.

Epidemiologic studies of coronary artery disease have largely overlooked the role of triglyceride-rich lipoproteins circulating in the post-prandial state. We have conducted a case-control study in males which examined fasting plasma lipoproteins and lipoproteins circulating 4 h after ingestion of a test meal containing fat and cholesterol. The cases were 82 subjects with coronary artery disease confirmed by angiography, while there were two control groups: one group of 38 'hospital controls' free of significant coronary disease by angiography, and a second group of 61 'workforce controls' free of coronary disease on historical grounds. Mean plasma and LDL cholesterol levels were significantly higher and HDL cholesterol levels were significantly lower in cases than in controls. The apo-B48/apo-B100 ratio in lipoproteins Sf greater than 60 obtained 4 h post-prandially, a relative measure of chylomicron and remnant presence, was significantly higher in cases than in controls. After pooling of all data, the prevalence of coronary artery disease was found to increase progressively with the concentration of plasma cholesterol and triglycerides, total cholesterol/HDL cholesterol ratio and the apo-B48/apo-B100 ratio in Sf greater than 60, the relative risk being highest for total cholesterol/HDL cholesterol ratio. After controlling for the confounding effects of age and other lipid factors via multiple logistic regression, apo-B48/apo-B100 ratio was still a significant predictor of coronary artery disease presence (z = 1.97, P less than 0.05) in a 'dose-response' fashion. The risk of coronary artery disease in the top quartile of apo-B48/apo-B100 distribution was 2.2-fold greater than that for the bottom quartile, after adjustment for the effects of other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Non-Purkinje cell GABAergic innervation of the deep cerebellar nuclei: a quantitative immunocytochemical study in C57BL and in Purkinje cell degeneration mutant mice.

Purkinje cell degeneration (pcd) mutant mice, 3-4 months old, were used to identify and quantify the non-Purkinje cell GABAergic innervation of deep cerebellar nuclei. Glutamic acid decarboxylase (GAD) immunoreactive structures appeared as dark dots throughout the 4 nuclei. Ultrastructural examination confirmed that each dot corresponded to an axon terminal. GAD-labeled boutons were large, contained tightly packed flattened vesicles and established Gray type II synapses with all nuclear neuronal populations. Thus, cytological criteria did not distinguish between Purkinje cell and non-Purkinje cell GAD-positive nerve terminals, since they shared many common features. The number of GAD-immunoreactive axon terminals in the deep nuclei of pcd cerebella was compared to that of normal C57BL mice. Despite an almost complete disappearance of Purkinje cells in the pcd mouse (less than 0.05% of these neurons remained in the mutants), the surface density of GAD-positive nerve terminals in the deep nuclear region was 37% of control value. Taking into account a volumetric decrease of 58% for the deep nuclei of the mutant cerebellum, we estimated the percentage of GAD-positive boutons innervating these nuclei to be 15% of normal values. This important residual innervation of the deep nuclei might arise from local GABAergic neurons, which were identified in the normal and mutant cerebella by immunostaining with an anti-GABA antibody.

Animals↗
PubMed1986

Education level and coronary risk factors in Australians.

There is an inverse association between social class ranking and mortality from coronary heart disease in Australia and in some other countries. To explain whether this association is related to differences in risk factors, the relationship between coronary risk factors and the highest level of education completed was explored for a reasonably representative cross-section of the adult Australian population. After adjustment for the effects of age, relative weight and alcohol intake, blood pressure was found to vary inversely with education level in both sexes. In men only plasma cholesterol, triglycerides and high density lipoprotein cholesterol levels showed no significant variation with education level. In women, plasma triglycerides and high density lipoprotein cholesterol levels varied inversely with education level after adjustment. There was less cigarette smoking among more highly educated men but no clear smoking trends among women. The findings broadly confirm the results of similar analyses which used occupation as the measure of social class and have implications for future community education programmes in that present strategies may be inappropriate for less highly-educated members of society.

Alcohol Drinking↗
PubMed1986

Antihypertensive and biochemical dose-response study of tripamide.

Tripamide is an experimental sulfonamide-derived diuretic antihypertensive agent. Twenty-four hospitalized patients with essential hypertension received placebo followed by 10, 25, 50, or 100 mg of tripamide daily in a randomized, double-blind design. All doses of tripamide significantly lowered standing arterial pressure. Changes in blood pressure, heart rate, and weight were not dose related, but the decrease in mean arterial pressure was significantly related to both age (P less than 0.02) and pretreatment blood pressure (P less than 0.05). Serum potassium levels were lowered significantly by the 25 and 100 mg daily doses of tripamide, whereas all doses of tripamide significantly reduced serum chloride levels and produced an increase in serum uric acid levels. Disparate time courses of antihypertensive and diuretic effects and the lack of a relationship between the increase in urine volume and the change in blood pressure suggest an additional antihypertensive action of tripamide or a delayed physiologic adaptation to volume depletion. Equal antihypertensive effects over the range of 10 to 100 mg/day, but greater hypokalemia at higher doses, suggest that future studies should employ the lower doses of tripamide.

Adult↗
PubMed1986

A multimodal system for reconstruction and quantification of neurologic structures.

The utility of computers and computer graphics as aids in the study of nervous system architecture is growing. However, modern histologic, immunocytologic and biochemical methods for revealing the underlying microarchitecture and macroarchitecture of the nervous system yield data formats requiring disparate computer acquisition, analysis and display approaches, capable of spanning many orders of magnitude of scale. This paper describes the Image Graphics Laboratory data acquisition, processing and display system, whose various components and programs may be used singly or in concert to enable definition of various tissue properties at different levels of resolution and integration. Examples are given of the system's use in light microscopic two-dimensional and three-dimensional reconstructions, autoradiographic reconstructions, reconstructions from projected images, reconstructions of impregnated cells (e.g., whole neurons) and peripheral nerve image analysis.

Animals↗