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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 235 records · Page 13Linked to original sources
PubMed1995

Inhibition of cellular and SV40 DNA replication by the adeno-associated virus Rep proteins.

In order to define the mechanism used by the adeno-associated virus replication (rep) gene to mediate inhibition of cell proliferation, we have studied its effects on SV40 and cellular DNA replication. SV40 DNA replication was inhibited by the presence of the rep gene in human 293 cells, and the inhibition was not linked to suppression of SV40 early gene expression. Using double-immunofluorescence assays that measured both rep gene expression and bromodeoxyuridine incorporation, we found that the presence of the Rep78 and Rep68 proteins correlated with inhibition of cellular DNA synthesis in NIH3T3 cells. This links the rep gene's anti-proliferative effects to either: (i) a direct inhibition of DNA synthesis or (ii) a possible cell cycle block.

3T3 Cells↗
PubMed1995

Effect of coronary artery reperfusion on transmural myocardial remodeling in dogs.

BACKGROUND: The effects of reperfusion after coronary occlusion on transmural remodeling of the ischemic region early and late after nontransmural infarction must importantly affect the recovery of regional function. Accordingly, analysis of local volume and three-dimensional strain was performed using a finite element method to determine regional remodeling. Systolic and remodeling strains were measured using radiographic imaging of three columns (approximately 1 cm apart) of four to six gold beads implanted across the left ventricular posterior wall in 6 dogs. METHODS AND RESULTS: After a control study, infarction was produced by 2 to 4 hours of proximal left circumflex coronary artery occlusion followed by reperfusion. Follow-up studies were performed at 2 days, 3 weeks, and 12 weeks with the dogs under anesthesia and in closed-chest conditions. Biplane cineradiography was performed to obtain the three-dimensional coordinates of the beads. At 2 days, end-systolic strains were akinetic with loss of normal transmural gradients of shortening and thickening. Remodeling strains (RS) were determined by use of a nonhomogeneous finite element method by referring the end-diastolic configuration during follow-up studies to its control state at matched end-diastolic pressures and heart rates. Tissue volume at 2 days increased substantially, more at the endocardium (30 +/- 7%) than at the epicardium (5 +/- 12%, P < .01); the increase was associated with an average RS in the wall-thickening direction of 0.18 +/- 0.15 (P < .01) with all other RS near zero. At 12 weeks systolic function partially recovered, with normal wall thickening in the epicardium (radial strain, 0.081 +/- 0.056 [control] versus 0.113 +/- 0.088 [12 weeks]) but with dysfunction in the endocardium (0.245 +/- 0.108 [control] versus 0.111 +/- 0.074 [P < .01] [12 weeks]). This inability of the inner wall to recover function may be related to increased transmural torsional shear and negative longitudinal-radial transverse shear in the inner wall. Volume loss occurred at 12 weeks in the endocardium (-36 +/- 16%) corresponding to transmural gradients in longitudinal RS and both transverse shear RS. Negative longitudinal RS was greater at the endocardium (-0.20 +/- 0.10) than at the epicardium (-0.06 +/- 0.05, P < .01). CONCLUSIONS: These results indicate the presence of marked subendocardial edema 2 days after reperfusion following 2 to 4 hours of coronary occlusion. At 3 months after reperfusion, however, there was volume loss in the inner wall due to shrinkage along the myofiber direction with reduced transmural function and loss of longitudinal shortening, while both tissue volume and function recovered completely in the outer wall.

Animals↗
PubMed1995

Hereditary dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common and important cause of morbidity and mortality. Many factors can contribute to the development of this disorder, although most commonly the etiology is unexplained. However, recent studies in individuals with idiopathic DCM now reveal a heritable cause in 20-30% of individuals. Diverse modes of inheritance have been demonstrated, encompassing an autosomal dominant type (by far the most common), together with recessive and X-linked forms, and maternal inheritance through mitochondrial DNA. The hereditary forms of DCM (HDCM) predominantly affect the left ventricle, although inherited abnormalities affecting primarily the right ventricle also are described. HDCM may occur as a primary cardiomyopathy, or secondary to inherited systemic metabolic or neuromuscular disorders. The causative genes for primary HDCM of the autosomal dominant and recessive types have not yet been discovered, but the combination of family pedigree analysis and phenotyping by echocardiography, together with new genetic techniques, should now allow their identification. Knowledge of the gene or genes responsible for HDCM would improve diagnostic accuracy, facilitate genetic counseling, advance understanding of pathogenesis, and provide the starting point for new methods of treatment. Because of the frequently heritable nature of DCM, it is of great importance that a diligent search for all potentially affected family members be undertaken.

Cardiomyopathy, Dilated↗
PubMed1995

Dynamical analysis of neuromuscular transmission jitter.

Utilizing prolonged axonal stimulation single fiber EMG, neuromuscular transmission becomes a time-series of interpotential intervals (IPIs). In this form, the underlying processes of neuromuscular transmission can be studied using standard numerical techniques to determine whether these processes can be described by a simple mathematical model. In particular, neuromuscular transmission jitter can be examined in this way. In this article, we attempt to determine whether healthy jitter is noise or deterministic chaos. The presence of deterministic chaos was assessed by analysis of the IPI time-series using visual inspection of both phase-space plots and their principal component dimensions, and using the Grassberger-Procaccia algorithm to determine the correlation dimension of the time-series dynamics. These graphical and mathematical techniques provided little evidence for the existence of deterministic chaos. Linear autoregression time-series prediction also failed to account for the variability of the data and IPI histograms exhibited simple gaussian distributions. These results suggest normal neuromuscular transmission jitter is the result of intrinsic noise.

Action Potentials↗
PubMed1995

The use of economic evaluation in health care: Australian decision makers' perceptions.

Decision making about the alternative uses of health care resources is an issue of critical concern for governments and administrators in all health care systems. While many factors need to be taken into consideration when making these decisions, economic evaluation can help to determine the relative efficiency of different choices. Research in various countries suggests that economic evaluation is not being used by health care decision makers to the extent that health economists think that it should be. Interest in the use of economic evaluation is increasing in Australia but, to date, there has been no Australian research which looks at its use from the point of view of its potential users--the decision makers. This study fills that gap. It was found that there was a high level of awareness of economic evaluation among the group of decision makers interviewed and that some had used it in their decision making. However decisions often have to be made quickly and take into account factors other than efficiency, hence limiting the use of economics. Other problems limiting its use were availability of data and lack of expertise. Those interviewed suggested a number of ways in which the problems they identified could be overcome. In particular, they recommended that researchers doing economic evaluations should be more responsive to the needs of the decision makers using them.

Attitude of Health Personnel↗
PubMed1995

Heterogeneity of vasomotor response to acetylcholine along the human coronary artery.

OBJECTIVES: In view of the segmental occurrence of coronary atherosclerosis, we postulated that acetylcholine may cause heterogeneous vasomotion, depending on the extent of vessel analyzed, criteria for change in vessel caliber and dose of drug administered. BACKGROUND: Previous studies have reported that acetylcholine causes constriction of atherosclerotic arteries. This dysfunction of endothelium-dependent dilation may be seen without angiographically detectable disease. METHODS: We developed algorithms to quantitate the dimensions of a single coronary artery over virtually its entire length during a control state and during graded doses of intracoronary acetylcholine. On the basis of triplicate control angiograms, the limit of detection of a change from control diameter was 0.31 mm (> or = 2 SD). RESULTS: Analysis of multiple segments (each 5.6 +/- 1.1 [mean +/- SD] mm) along a single coronary artery revealed a heterogeneous response to acetylcholine in 27 of 31 patients at the 10(-4) mol/liter dose and in 29 of 31 patients when responses at 10(-6), 10(-5) and 10(-4) mol/liter doses were combined; in this latter analysis, constriction and dilation in the same vessel occurred in 45% of the patients. With acetylcholine, most of 349 segments demonstrated no change, but the greatest frequency of vasoconstriction (24.6%) and vasodilation (6.9%) was seen at the 10(-4) mol/liter dose. Inducible vasomotion was observed as far distally as 7.3 cm from the site of acetylcholine infusion. CONCLUSIONS: Response to intracoronary acetylcholine with mild coronary disease is heterogeneous; disparate dimensional responses may occur in different segments of the same vessel. Inclusion of all analyzable regions of a coronary artery and the use of a reproducibility limit for quantitative angiography are optimal for assessment of segmental coronary vasomotion.

Acetylcholine↗
PubMed1995

Genetic-algorithm selection of a regulatory structure that directs flux in a simple metabolic model.

A genetic algorithm (GA) is used to optimize parameters for allosteric regulation of enzymes in a model of a metabolic futile cycle, in which two metabolites are interconverted by a pair of irreversible enzymatic reactions. The cycle is regulated by end products of the surrounding pathway. The optimization criterion for the GA is the proper direction of chemical flux in the regulated cycle toward one or the other end product in response to a simple, time-dependent model of biochemical "need" based on externally imposed variation of the end product concentrations. An energetic cost, to be held to a minimum, is also imposed on the operation of the cycle. The best-performing individuals selected by the GA are found to switch rapidly the direction of net flux according to need. In different "environments" (specific time courses of end product concentrations), the GA produces better- or poorer-performing individuals. In some cases "generalists" and "specialists" are produced. The present approach provides, purely as a consequence of formally specifying the task of flux direction, the new result of numerical confirmation, in a simple model, of the intuition that negative feedback and reciprocal regulation are important for good flux direction in arbitrary environments, and gives rise to a diversity of structures, suggestive of the results of biological evolution.

Algorithms↗
PubMed1995

A model of excitation and adaptation in bacterial chemotaxis.

We present a model of the chemotactic mechanism of Escherichia coli that exhibits both initial excitation and eventual complete adaptation to any and all levels of stimulus ("exact" adaptation). In setting up the reaction network, we use only known interactions and experimentally determined cytosolic concentrations. Whenever possible, rate coefficients are first assigned experimentally measured values; second, we permit some variation in these rate coefficients by using a multiple-well optimization technique and incremental adjustment to obtain values that are sufficient to engender initial response to stimuli (excitation) and an eventual return of behavior to baseline (adaptation). The predictions of the model are similar to the observed behavior of wild-type bacteria in regard to the time scale of excitation in the presence of both attractant and repellent. The model predicts a weaker response to attractant than that observed experimentally, and the time scale of adaptation does not depend as strongly upon stimulant concentration as does that for wild-type bacteria. The mechanism responsible for long-term adaptation is local rather than global: on addition of a repellent or attractant, the receptor types not sensitive to that attractant or repellent do not change their average methylation level in the long term, although transient changes do occur. By carrying out a phenomenological simulation of bacterial chemotaxis, we find that the model is insufficiently sensitive to effect taxis in a gradient of attractant. However, by arbitrarily increasing the sensitivity of the motor to the tumble effector (phosphorylated CheY), we can obtain chemotactic behavior.

Adaptation, Biological↗
PubMed1995

Perception.

Explore the source record for details and available documents.

Humans↗
PubMed1995

Injecting and sexual risk-taking behaviour among regular amphetamine users.

A sample of 301 regular amphetamine users were interviewed regarding injecting and sexual risk-taking behaviours. Two-thirds of subjects were injecting the drug, with males being 1.8 times more likely to do so. Nearly half (41%) of injectors had shared injecting equipment in the preceding month. Females were twice as likely as males to report recent needle sharing. Having a regular sexual partner who injects amphetamines, using benzodiazepines and experiencing higher levels of psychopathology were independently associated with needle sharing. The number of sexual partners in the preceding six months was independently associated with having had paid sex in that period, and higher levels of polydrug use.

Adolescent↗
PubMed1995

Eradication of endemic methicillin-resistant Staphylococcus aureus infections from a neonatal intensive care unit.

To control infections with endemic methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal intensive care unit (NICU), triple dye was applied to the umbilical cords of infants in the intermediate-care but not the intensive-care area. The rate of MRSA infection, adjusted for time and intensity of care, decreased in the intermediate-care area (rate ratio, 0.35; 95% confidence interval [CI], 0.14-0.87; P < .01) but not in the intensive-care area (rate ratio, 0.92; 95% CI, 0.41-2.24; P = .48). After 22 months, the rate increased in both areas (Mantel-Haenszel rate ratio, 1.7; 95% CI, 1.0-2.8; P < .05) after overcrowding and understaffing increased. After temporary reduction of overcrowding and understaffing, extension of triple dye use to the intensive-care area and dedication of an infection control nurse to the NICU, MRSA colonization and infection rates decreased to near zero in both areas (infection rate ratios, 0.09 and 0.11, respectively; P < .005). The endemic MRSA strain, identified by pulsed-field gel electrophoresis, was eradicated.

Birth Weight↗
PubMed1995

Cutaneous melanoma: pathology, relevant prognostic indicators and progression.

Malignant melanoma, one of the most rapidly increasing malignancies in man, has recently received substantial attention in the world literature concerning application of traditional morphologic and newer immunologic and molecular biologic methods of predicting progression and ultimate clinical outcome. Although clinical features of patient sex, age and anatomic site of the lesion are important, classic morphologic variables defining prognosis remain the cornerstone of predicting disease outcome. Extent of radial growth phase and the two microstaging methods of measuring tumor thickness and determining level of invasion remain the critical disease progression predictors. Assessment of mitotic rate, number of tumor infiltrating lymphocytes, and determining the presence of regression, ulceration, and epithelioid cell component, microscopic satellites and vascular invasion are also important. More recently a variety of molecular and biochemical prognostic markers have been cited for prediction of disease recurrence and metastasis. Both overexpression and down regulation of a variety of cell adhesion molecules have been implicated in disease progression as has alterations in the plasminogen activation system. A series of growth factors, growth factor receptors, oncogenes and tumor suppressor genes have also been considered. Structural and numerical genomic DNA abnormalities, cell proliferation markers and DNA ploidy status have also been considered. Recently a variety of serum and blood markers indicating disease persistence or progression have been studied including melanin synthesis precursors and intermediate compounds of melanogenesis. Molecular detection by PCR of melanogenesis specific mRNA may become the most sensitive prognostic marker of the future. At present histopathologic and clinical criteria remain the cornerstones of predicting prognosis in malignant melanoma.

Disease Progression↗
PubMed1995

Station gender bias in a multiple-station test of clinical skills.

PURPOSE: To apply differential item functioning (DIF) procedures to investigate station gender bias in multiple-station tests of clinical skills, and to compare these results with those obtained by comparing the station-score distributions of men and women examinees. METHOD: The data were from 23 stations used in the selection of seven successive cohorts (1987-1993) of candidates to the Ontario Pre-Internship Program for graduates of foreign medical schools. The stations had been used on at least three occasions, with a minimum sample of about 210 candidates per station. Each station's score was expressed as both a binary score and a continuous score, and DIF was assessed using the Mantel-Haenszel procedure with the binary scores and analysis of covariance with the continuous scores. For each station, DIF effect sizes were calculated and compared with the gender-group mean differences. RESULTS: Using the binary scores, significant DIF was observed for three stations; using the continuous scores, significant DIF was observed for five stations. Significant gender differences were observed in the scores of nine stations. In eight, these differences favored women. Overall, in more stations the direction of DIF favored the men, while the women demonstrated higher levels of ability. CONCLUSION: The results suggest the importance of using a DIF approach for controlling the "ability factor" in studies of this kind: although significant gender differences were observed in the continuous score distributions of nine stations, generally these differences were not indicative of station gender bias.

Analysis of Variance↗
PubMed1995

Lifting and handling of patients by anaesthetists.

The process of transferring patients from the operating table was assessed in a district general hospital. The survey was conducted in two parts; a confidential questionnaire was sent to all members of the department and a month long assessment of three anaesthetists' caseload was undertaken. All the anaesthetists questioned had scanty knowledge of the relevant manual handling regulations. Although 70% of anaesthetists questioned lift and transfer patients on a regular basis, none had received any relevant training. Ninety-six percent of patient transfers were performed by two staff alone, even though there were five or more staff available to assist at 95% of transfers. Difficulty in transferring patients occurred in 32% of cases. Improvement of training anaesthetists in safe manual handling procedures is recommended.

Anesthesiology↗
PubMed1995

mRNA stability in mammalian cells.

This review concerns how cytoplasmic mRNA half-lives are regulated and how mRNA decay rates influence gene expression. mRNA stability influences gene expression in virtually all organisms, from bacteria to mammals, and the abundance of a particular mRNA can fluctuate manyfold following a change in the mRNA half-life, without any change in transcription. The processes that regulate mRNA half-lives can, in turn, affect how cells grow, differentiate, and respond to their environment. Three major questions are addressed. Which sequences in mRNAs determine their half-lives? Which enzymes degrade mRNAs? Which (trans-acting) factors regulate mRNA stability, and how do they function? The following specific topics are discussed: techniques for measuring eukaryotic mRNA stability and for calculating decay constants, mRNA decay pathways, mRNases, proteins that bind to sequences shared among many mRNAs [like poly(A)- and AU-rich-binding proteins] and proteins that bind to specific mRNAs (like the c-myc coding-region determinant-binding protein), how environmental factors like hormones and growth factors affect mRNA stability, and how translation and mRNA stability are linked. Some perspectives and predictions for future research directions are summarized at the end.

Animals↗
PubMed1995

Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure.

To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted.

Animals↗