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Biomedical subjects

J Simons

Publications and source records attributed to J Simons.

At least 91 records · Page 5Linked to original sources

Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control.

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.

Adolescent↗

Poliovirus-specific major histocompatibility complex class I-restricted cytolytic T-cell epitopes in mice localize to neutralizing antigenic regions.

A major histocompatibility complex (MHC) class I-restricted cytotoxic T-lymphocyte (CTL) response is induced in BALB/c mice upon immunization with poliovirus serotype 1 (Mahoney strain). A similar class I-restricted response is also induced upon immunization with purified VP1 capsid proteins. Thus, poliovirus-specific MHC class I CTL responses can be induced independently of viral infection in murine hosts. In experiments using recombinant vaccinia virus vectors expressing different segments of the poliovirus capsid proteins and synthetic peptides, two regions of the VP1 capsid protein appear to contain epitopes recognized by this bulk CTL population. These epitope regions contain a Kd-restricted peptide-binding motif. Interestingly, each of these CTL epitopes is located near previously defined neutralizing antigenic sites.

Amino Acid Sequence↗

Identification of T-helper epitopes in the VP1 capsid protein of poliovirus.

Poliovirus-specific T lymphocytes were isolated from virus-immunized mice of different H-2 haplotypes. Immunological characterization of this population indicates that the effector population involved in the observed poliovirus-specific proliferative response was that of CD4-positive T-helper cells. Proliferative responses also were induced within these T-lymphocyte populations upon stimulation with either purified VP1 capsid protein or VP1 synthetic peptides. By using these synthetic peptides, several T-helper epitopes were identified. Generally, proliferative responses were observed in three regions of VP1. Two regions spanning VP1 residues 86 to 120 and 201 to 241 were recognized by T lymphocytes from BALB/c (H-2d), C57BL/6 (H-2b), and C3H/HeJ (H-2k) backgrounds. Analyses using synthetic peptides of nonoverlapping sequences indicated that the region spanning residues 201 to 241 may contain several T epitopes and may account for the strong proliferative response observed. In addition, for two of the three haplotypes examined, T epitopes were observed within residues 7 to 24 of VP1. Additional epitopes which appeared to be restricted to specific H-2 backgrounds were identified. T epitopes within VP1 that are common between different strains of mice appeared to lie within previously identified neutralizing antigenic sites in poliovirus.

Amino Acid Sequence↗

Physical activity and growth, maturation and performance: a longitudinal study.

The effects of increased physical activity upon physical growth, maturation and performance were investigated in samples of 32 active and 32 nonactive Belgian boys followed longitudinally from 13 to 18 yr of age. Active boys participated in sports activities for more than 5 h.wk-1.yr-1 during each of the first 3 yr of the study, in addition to compulsory physical education. Nonactive boys participated in less than 1.5 h.wk-1.yr-1 during the first 3 yr of the study, but did participate in required school physical education. Anthropometric dimensions included lengths, breadths, circumferences, and skinfolds. A physical fitness test battery was administered at each observation including nine health- and performance-related tests. Skeletal maturation was assessed; sociocultural determinants and sports participation were obtained through written questionnaires verified by a control interview. No significant effects of increased physical activity were observed on growth in somatic dimensions, including skinfolds, age at peak height velocity, skeletal maturation, and most of the physical fitness components. More active boys obtained better results from 14 yr onward only for pulse recuperation and for bent arm hang. These results can be generalized to the average population but do not necessarily apply for highly trained and selected elite athletes.

Adolescent↗

Coronary risk factors six to twelve months after coronary artery bypass surgery. 1986 compared with 1990.

A 1986 study found that coronary risk factors were receiving insufficient attention in patients who had recently undergone coronary artery bypass grafting. This issue was readdressed in a like group of 100 patients from the same surgical unit three and a half years later, in 1990, to ascertain whether risk factor management had improved over the period. An increased proportion of patients in 1990 were undergoing active management of hypertension and hyperlipidaemia. Only 25% of patients in 1990 manifested hypercholesterolaemia (cholesterol levels greater than or equal to 6.5 mmol/L) compared with 60% in 1986. Five per cent of patients in 1990 manifested diastolic hypertension (diastolic pressure greater than or equal to 95 mmHg) compared with 23% in 1986. Such patients appear better managed in 1990 than they were in 1986.

Adult↗

High level expression of functional full length human thyroid hormone receptor beta 1 in insect cells using a recombinant baculovirus.

We have cloned the human thyroid hormone receptor beta 1 (hThR beta) from the human breast cancer cell line T47D using the PCR technique. A recombinant baculovirus transfer vector pVL1392/hThR beta was constructed and the full length receptor was expressed in the insect cell line Spodoptera frugiperda (Sf9). Approx. 10-15 x 10(6) receptors are expressed/cell which implies a production level of 2.5-4.0 mg hThR beta/l of cell culture. The expressed hThR beta displayed a single class of binding sites for T3 with high affinity. Western blot analysis using a polyclonal antibody indicated that the molecular weight of the baculovirus expressed receptor is approx. 50 kDa. Crude nuclear extract of hThR beta labeled with [125I]T3 sedimented as a 4 S peak on a glycerol gradient. No receptor could be detected in the cytoplasm indicating its proper translocation to the nuclear compartment. An oligonucleotide containing a palindromic thyroid hormone response element is specifically recognized and retarded in a gel-mobility-shift assay in the presence of nuclear extract of Sf9 cells expressing hThR beta. These data suggest that hThR beta expressed in Sf9 cells is functional and displays characteristics virtually indistinguishable from those of the thyroid hormone receptor (ThR) extracted from mammalian cells. Furthermore, the data indicate that the baculovirus expression system is adequate for large-scale production of receptor for detailed structural and functional studies.

Animals↗

Leakage after lateral condensation with finger spreaders and D-11-T spreaders.

The purpose of the study was to determine the leakage after lateral condensation with the use of finger spreaders and D-11-T spreaders. Fifty root canals were instrumented, and laterally condensed with gutta-percha and Grossman's cement. In 20 canals finger spreaders were used for the condensation and in a further 20 canals D-11-T spreaders were used. After 24 h in 100% humidity, the roots were painted with nail polish except for their apical 2 mm, which remained exposed. Five canals were not obturated (negative control) and five canals were obturated and the apices sealed with sticky wax (positive control). The expressed root tips were suspended in 2% methylene blue dye for 48 h. The teeth were then split longitudinally and the apical leakage measured and compared for each group. The results obtained by the positive and negative control teeth confirmed the effectiveness of the methodology used. Average dye penetration for the finger spreaders was statistically significantly less than for the D-11-T spreaders. Dye penetration of more than 0.5 mm occurred in 6 roots for the finger spreaders and in 12 roots for the D-11-T spreaders.

Dental Leakage↗

Dubbo study of the elderly: sociological and cardiovascular risk factors at entry.

A prospective study of elderly Australians commenced in 1988 in Dubbo, NSW. Its goals are to identify predictors of mortality, hospitalisation and placement in long-term care, with special focus on risk factors for cardiovascular disease. The study population were non-institutionalised subjects, comprising 1237 males and 1568 females 60 years and over. This report describes the baseline findings: demographic, educational and economic data; tobacco and alcohol usage, self-medication and other habits; medical contacts and past diagnosis; prescribed medication and in study diagnosis; psychosocial variables, functional health and social support; blood lipid and lipoprotein data; blood pressure, spirometry and glucose data; heights and weights. Where comparison has been feasible, the findings in Dubbo closely resemble those obtained from the rest of Australia. The findings presented provide the basis for aetiological studies of future outcomes.

Aged↗

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease.

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P2) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P2 allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P2 allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P2 allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65-5.19).

Alleles↗

The Dubbo study of the health of elderly: correlates of coronary heart disease at study entry.

A prospective study of the health of elderly Australians recently commenced in Dubbo, NSW, the study population comprising 1,237 males and 1,568 females 60 years and older. The prevalence rates of coronary heart disease (CHD) and its associated risk factors have been examined in the baseline data. The age-standardized rate of CHD was 23.8/100 in males and 18.1/100 in females. The prevalence rate increased with age until 79 years in males, thereafter declining. The rate increased steadily with age in females. In a multiple logistic model, the following possible predictors of CHD were included: age, cigarette smoking, use of alcohol, exercise, religiosity, years of education, hypertension, diabetes, family history of CHD, body mass index, lipid and lipoprotein variables. The presence of CHD in males was significantly predicted by age, hypertension (odds ratio, OR = 1.40), family history (OR = 2.05), and high density lipoprotein (HDL) cholesterol (OR = 0.78). The significant predictors in females were age, years of education (OR = 0.82), hypertension (OR = 1.45), family history (OR = 1.77), serum triglycerides (OR = 1.30), and HDL cholesterol (OR = 0.73). Hypertension was found to be a stronger predictor of CHD in the younger age group (60-69 years), while diabetes was a predictor of CHD in older males (70-79 years). Our findings require confirmation in the prospective study now in progress.

Age Factors↗

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↗

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↗

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↗

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↗

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↗

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↗