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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 109 records · Page 6Linked to original sources

Identification of a new variant, HLA-Cw*1507, differing from Cw*1502 only at the KIR-related dimorphism of codons 77 and 80.

We describe here a novel allele, HLA-Cw*1507, identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT). Cw*1507 is similar to Cw*1502 with differences at nucleotide positions 302 (A to G) and 312 (A to C) in exon 2. The substitutions observed in Cw*1507, change codon 77 from AAC (asparagine) to AGC (serine) and codon 80 from AAA (lysine) to AAC (asparagine), compared to Cw*1502. Residues 77 and 80 of HLA-C alleles are located in the alpha 1 domain, where they can influence interaction between antigenic peptides and the T-cell receptor. Also, the dimorphism at these residues from asparagine and lysine to serine and asparagine, respectively, are known to modulate interaction with the natural killer (NK) cell killer inhibitory receptor (KIR). The new HLA-Cw*1507, together with Cw*1502, represents the fourth pair of HLA-C alleles differing only at the KIR-related dimorphic codons 77 and 80.

Base Sequence↗

Identification of an HLA-A11 serological variant and its characterization by sequencing based typing.

We have identified an HLA-A11 variant allele, A*1105, segregating in a Caucasoid family. The variant antigen expressed by this allele failed to cross-react with most Caucasoid anti-HLA-A11 antisera tested. Sequencing based typing has been used to characterize this new allele and this showed that it has a novel mutation at a polymorphic position (502) in exon 3. In comparison with A*1101, the mutation (A-->G) results in an amino acid change from positively-charged lysine to negative glutamate and this may explain the altered HLA-A11 serological profile exhibited by this antigen. The new allele was found in a patient with acute lymphoid leukaemia (ALL), her father and two siblings.

Alleles↗

Characterization of a novel HLA-A*24 allele containing an HLA-A*03 sequence motif.

HLA-A*2418 is described for the first time. It segregates in a Mendelian fashion. Serological analyses indicate that the new allele encodes epitopes from both HLA-A9 and -A3 specificities. Results from nucleotide sequencing analyses of polymerase chain reaction (PCR) amplification products derived from genomic and cDNA are compatible with those findings.

Alleles↗

The community gerontological nurse: themes from a needs analysis.

With the move of care into the community, the role of nurses caring for older people is changing. However, nurses may not be adequately prepared to cope with this changing role, especially if their training and experience have been primarily hospital based. This study involves an educational needs analysis of registered nurses working in the care of older people in nursing homes and clients' own homes. It is based on focus groups with registered nurses and individual interviews with other professionals, as well as group discussions with older people. The aim of this project is to provide research-based input into the design of a new community care of older people module, to be offered at Napier University, Edinburgh from February 1998. The results presented here consist of three themes or patterns that have emerged from the interview data. The specialist/generalist theme concerns issues of role definition and gerontological specialism. The social/medical theme addresses the shift towards a social model of care when nurses move into the community settings. Finally, the physical health/mental health theme represents the need for greater integration of skills and knowledge from both mental health and general health nursing in the field of community care for older people. The results indicate the need for significant attitude changes and provide a major challenge to educationalists.

Aged↗

The development of the advanced role of rural nurses in New Zealand.

This paper offers an informative insight into the development of the advanced role of rural nursing practice in New Zealand. Provided is a futuristic vision of nurses' contribution for the provision of primary rural health care. The concept of advanced nursing practice will be discussed within the context of the interdisciplinary healthcare team. It is argued that as nurses take on advanced practice, it is essential they receive appropriate clinical and theoretical skills to ensure they are in a position to provide competent and clinically safe, effective health care in an ethical, efficient manner. A description of a survey, undertaken by the author, studying rural nurses' skills provides the recommendation for the development of an appropriate postgraduate course at Masters level, designed specifically for primary rural nurses for the advanced role. The provision of this advanced education together with preparation and support, can pave the way for the highly skilled and knowledgeable nurses of the future working in collaboration with the interdisciplinary rural healthcare team and rural community.

Attitude of Health Personnel↗

Nonlinear kinetics and new approaches to complex reaction mechanisms.

This paper reviews recent developments in the field of nonlinear chemical kinetics. Five topics are dealt with: (a) new approaches to complex reaction mechanisms, stoichiometric network analysis, classification of chemical oscillators and formulation of their mechanisms by deduction from experiments, and correlation metric construction of reaction pathways from measurements; (b) thermodynamic and stochastic theory of nonequilibrium processes, the eikonal approximation, the evaluation of stochastic potentials, experimental tests of the thermodynamic and stochastic theory of relative stability, and fluctuation-dissipation relations in nonequilibrium chemical systems; (c) chemical kinetics and cellular automata and lattice gas automata; (d) theoretical approaches and experimental studies of stochastic resonance in chemical kinetics; and (e) rate processes in disordered systems, stochastic Liouville equations, stretched exponential relaxation in disordered systems, and universality classes for rate processes in systems with static or dynamic disorder.

Journal Article↗

Cardiac-specific overexpression of RhoA results in sinus and atrioventricular nodal dysfunction and contractile failure.

RhoA is a low-molecular-weight GTPase that has been implicated in the regulation of hypertrophic cardiac muscle cell growth. To study the role of RhoA in control of cardiac function in vivo, transgenic mice expressing wild-type and constitutively activated forms of RhoA under the control of the cardiac-specific alpha-myosin heavy chain promoter were generated. Transgene-positive mice expressing high levels of either wild-type or activated RhoA showed pronounced atrial enlargement and manifested a lethal phenotype, often preceded by generalized edema, with most animals dying over the course of a few weeks. Echocardiographic analysis of visibly healthy wild-type RhoA transgenic mice revealed no significant change in left ventricular function. As their condition deteriorated, significant dilation of the left ventricular chamber and associated decreases in left ventricular contractility were detected. Heart rate was grossly depressed in both wild-type and activated RhoA-expressing mice, even prior to the onset of ventricular failure. Electrocardiography showed evidence of atrial fibrillation and atrioventricular block. Interestingly, muscarinic receptor blockade with atropine did not elicit a positive chronotropic response in the transgenic mice. We suggest that RhoA regulates cardiac sinus and atrioventricular nodal function and that its overexpression results in bradycardia and development of ventricular failure.

Animals↗

Effects of side lying on lung function in older individuals.

BACKGROUND AND PURPOSE: Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. SUBJECTS AND METHODS: Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. RESULTS: Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. CONCLUSION AND DISCUSSION: Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Aged↗

Cardiopulmonary responses of middle-aged men without cardiopulmonary disease to steady-rate positive and negative work performed on a cycle ergometer.

BACKGROUND AND PURPOSE: Understanding physiological responses to negative work allows therapists to be more knowledgeable when they prescribe this form of exercise. The physiological responses of 12 men without cardiopulmonary disease, aged 39 to 65 years (X=49.7, SD=9.3), to negative work (eccentric muscle contractions) and to positive work (concentric muscle contractions) were compared. SUBJECTS AND METHODS: Subjects performed the 2 types of work on a motorized cycle ergometer at pedaling frequencies of 35, 55, and 75 rpm with a constant power output of 60 W. Steady-rate values of oxygen consumption (VO2), heart rate (HR), minute ventilation (VE), tidal volume (VT), and breathing frequency (fb) were obtained during 6 test conditions (positive and negative work at each of the 3 pedaling frequencies). RESULTS: Values for all measures were greater during positive work than during negative work, except for fb. During positive work, values for all variables were greatest at 75 rpm, except for fb. During negative work, VO2 and HR were greater at 75 and 35 rpm than at 55 rpm, and VE and VT were greater at 75 rpm than at 55 rpm. Breathing frequency was not different among pedaling frequencies. CONCLUSION AND DISCUSSION: The results confirmed that negative work performed on a cycle ergometer is associated with low metabolic cost in older men without cardiopulmonary disease. Although VE was determined primarily by changes in VT during negative work, a comparable disproportionate increase in fb was observed at the start of negative work. Such changes in breathing patterns have implications for the prescription of negative work for patients with lung disease.

Adult↗

Association of low-voltage alpha EEG with a subtype of alcohol use disorders.

BACKGROUND: Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. METHODS: We evaluated these findings using an independent, similarly established, dataset of 120 subjects. We also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. RESULTS: In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 times) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low-amplitude alpha activity that was associated with alcohol use disorders. CONCLUSIONS: The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders.

Adolescent↗

Transitions between the injection of heroin and amphetamines.

AIMS: To assess in current injecting heroin and amphetamine users to what extent their history of injecting represents a transition from amphetamine to heroin. DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: One hundred and fifty-one primary heroin injectors and 145 primary amphetamine injectors recruited through advertisements, needle exchanges, methadone maintenance clinics and by word of mouth. FINDINGS: Six major transition patterns were detected: heroin-heroin (n = 61), amphetamines-heroin (n = 60), heroin-amphetamines-heroin (n = 30), amphetamines-amphetamines (n = 80), amphetamines-heroin-amphetamines (n = 41) and heroin-amphetamines (n = 24). A logistic regression analysis predicting presence or absence of a transition from the original primary drug indicated that length of injecting career, years of education and original drug injected were independent predictors. Thus, the longer the injecting career, the greater the likelihood of a transition. If the original drug injected was amphetamine, the greater the likelihood of transition; and the more prior years of education, the lower the chances of a transition. CONCLUSIONS: While there was a small preponderance of movement from primary amphetamine injecting to primary heroin injecting, there was also movement in the other direction. Heroin use is not necessarily a stable endpoint for injecting careers.

Adolescent↗

The c-myc coding region determinant-binding protein: a member of a family of KH domain RNA-binding proteins.

The half-life of c- myc mRNA is regulated when cells change their growth rates or differentiate. Two regions within c- myc mRNA determine its short half-life. One is in the 3'-untranslated region, the other is in the coding region. A cytoplasmic protein, the coding region determinant-binding protein (CRD-BP), binds in vitro to the c- myc coding region instability determinant. We have proposed that the CRD-BP, when bound to the mRNA, shields the mRNA from endonucleolytic attack and thereby prolongs the mRNA half-life. Here we report the cloning and further characterization of the mouse CRD-BP, a 577 amino acid protein containing four hnRNP K-homology domains, two RNP domains, an RGG RNA-binding domain and nuclear import and export signals. The CRD-BP is closely related to the chicken beta-actin zipcode-binding protein and is similar to three other proteins, one of which is overexpressed in some human cancers. Recombinant mouse CRD-BP binds specifically to c- myc CRD RNA in vitro and reacts with antibody against human CRD-BP. Most of the CRD-BP in the cell is cytoplasmic and co-sediments with ribosomal subunits.

Amino Acid Sequence↗

Noncytopathogenic bovine viral diarrhea virus (BVDV) reduces cleavage but increases blastocyst yield of in vitro produced embryos.

The growing application of in vitro embryo production systems that utilize slaughterhouse tissues of animals of unknown health status conveys the risk of disease transmission. One pathogen of concern in this regard is bovine viral diarrhea virus (BVDV), and the objective of this study was to investigate the effect of BVDV on in vitro embryonic development. A bovine in vitro embryo production system was experimentally infected with BVDV at 2 stages: prior to in vitro maturation by incubating cumulus-oocyte complexes (COC) with virus (strain Pe515; titer 10(6.2) tissue culture infective dose (TCID)50/mL) or vehicle for 2 h, and then during in vitro culture by the use of BVDV infected granulosa cells. Exposure to BVDV throughout in vitro production reduced cleavage rates (P = 0.01) but increased (P = 0.05) the number of embryos that reached the 8-cell stage when expressed as a percentage of cleaved oocytes. Blastocyst yield was increased by the presence of virus when expressed as a proportion of oocytes (P = 0.0034) or of those cleaved (P < 0.0001). The percentage of total blastocyst yield on Days 7, 8 and 9 for the control and virus treatments was 20, 51, 29 and 29, 41, and 29%, respectively, indicating that the rate of blastocyst development was nonsignificantly faster in the virus-treated group (P = 0.06). These results indicate that the presence of non-cytopathogenic BVDV in an in vitro production system may reduce cleavage rates but allow those cleaved to develop to blastocysts at a higher rate.

Animals↗

Purification and characterization of a polysome-associated endoribonuclease that degrades c-myc mRNA in vitro.

The regulation of mRNA half-lives is determined by multiple factors, including the activity of the messenger RNases (mRNases) responsible for destroying mRNA molecules. Previously, we used cell-free mRNA decay assays to identify a polysome-associated endonuclease that cleaves c-myc mRNA within the coding region. A similar activity has been solubilized and partially purified from a high salt extract of adult rat liver polysomes. Based on a correlation between protein and enzyme activity, the endonuclease is tentatively identified as a approximately 39-kDa protein. It cleaves the coding region stability determinant of c-myc mRNA with considerable specificity. Cleavages occur predominantly in an A-rich segment of the RNA. The endonuclease is resistant to RNase A inhibitors, sensitive to vanadyl ribonucleoside complex, and dependent on magnesium. In these and other respects, the soluble enzyme we have purified resembles the polysome-associated c-myc mRNase.

Animals↗

Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.

Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP-/- and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the betaARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy.

Animals↗