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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 73 records · Page 4Linked to original sources
PubMed2000

Amplification in human breast cancer of a gene encoding a c-myc mRNA-binding protein.

The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance. The CRD-BP gene has 15 exons and 14 introns, is single-copy, and is located on chromosome 11 in mice and 17 in humans, close to HER-2/neu. The CRD-BP gene is moderately amplified in 12 of 40 human breast cancers; it is highly amplified in 2 others (14.4 and 20 copies). Despite their proximity, CRD-BP and HER-2/neu genes can be amplified independently. Amplification of a gene that might up-regulate c-Myc abundance could accelerate breast cancer.

Animals↗
PubMed2000

Extraretinal control of saccadic suppression.

We measured the time course of saccadic suppression and tested whether suppression results entirely from retinal image motion or has an extraretinal source. We measured contrast thresholds for low-frequency gratings modulated either in luminance, at 17 cd/m(2) and 0.17 cd/m(2), or color at 17 cd/m(2). Gratings were flashed on a uniform background before, during, or after voluntary 12 degrees saccades and, additionally in the case of luminance modulated gratings, saccades simulated by mirror motion. A 10-fold decrease in contrast sensitivity was found for luminance-modulated gratings with saccades, but little suppression was found with simulated saccades. Adding high-contrast noise to the display increased the magnitude and the duration of the suppression during simulated saccades but had little effect on suppression produced by real saccades. Suppression anticipates saccades by 50 msec, is maximal at the moment of saccadic onset, and outlasts saccades by approximately 50 msec. At lower luminance, suppression is reduced, and its course is shallower than at higher luminance. Simulated saccades produce shallower suppression over a longer time course at both luminances. No suppression was found for chromatically modulated gratings. Differences between real and simulated saccades in the magnitude and time course of sensitivity loss suggest that saccadic suppression has an extraretinal component. We model the effects of saccades by adding a signal to the visual input, so as to saturate the nonlinear stage of visual processing and make detection of a test stimulus more difficult.

Adult↗
PubMed2000

Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization.

Dendritic spines receive most excitatory inputs in the CNS and compartmentalize calcium. Although the mechanisms of calcium influx into spines have been explored, it is unknown what determines the calcium decay kinetics in spines. With two-photon microscopy we investigate action potential-induced calcium dynamics in spines from rat CA1 pyramidal neurons in slices. The [Ca(2+)](i) in most spines shows two decay kinetics: an initial fast component, during which [Ca(2+)](i) in spines decays to dendritic levels, followed by a slower decay phase in which the spine follows dendritic kinetics. The correlation between [Ca(2+)](i) in spine and dendrite at the breakpoint of the decay kinetics demonstrates diffusional equilibration between spine and dendrite during the slower component. To explain the faster initial decay, we rule out saturation or kinetic effects of endogenous or exogenous buffers and focus instead on (1) active calcium extrusion and (2) buffered diffusion of calcium from spine to dendrite. The presence of an undershoot in most spines indicates that extrusion mechanisms can be intrinsic to the spine. Supporting the two mechanisms, pharmacological blockade of smooth endoplasmic reticulum calcium (SERCA) pumps and the length of the spine neck affect spine decay kinetics. Using a mathematical model, we find that the contribution of calcium pumps and diffusion varies from spine to spine. We conclude that dendritic spines have calcium pumps and that their density and kinetics, together with the morphology of the spine neck, determine the time during which the spine compartmentalizes calcium.

Action Potentials↗
PubMed2000

Neurodevelopmental and psychosocial aspects of Turner syndrome.

Turner syndrome (TS) is the complex phenotype of human females with complete or partial absence of the second sex chromosome, or monosomy X. A characteristic neurocognitive and psychosocial profile has also been described in TS females. Typically, specific deficits in visual-spatial/perceptual abilities, nonverbal memory function, motor function, executive function, and attentional abilities occur in TS children and adults of varying races and socioeconomic status. TS-associated psychosocial difficulties occur in the areas of maturity and social skills. We hypothesize that a subset of the neurocognitive deficits (visual-spatial/perceptual abilities) are genetically determined and result from abnormal expression of one or more X chromosome genes. In addition, a different subset of these neurocognitive deficits (memory, reaction time, and speeded motor function) result from estrogen deficiency and are at least somewhat reversible with estrogen treatment. The TS-associated psychosocial problems are most likely linked to these core neurocognitive deficits and do not reflect a separate and independent component of the syndrome. Turner syndrome research has progressed significantly over the last decade. The field has moved from descriptive reports based on single individuals or small clinical samples to the use of experimental designs with larger, more diverse and representative samples. This degree of variability among individuals with Turner syndrome in all domains (karyotype or genetic constitution, physical attributes, neurocognitive and social functioning) suggests the need to identify risk and protective factors contributing to the heterogeneity in the phenotype. Active education about TS and participation in patient advocacy groups such as the Turner Syndrome Society of the United States (http://www. turner-syndrome-us.org/) has provided new information for TS adults and families as well as a supportive peer group. MRDD Research Reviews 2000;6:135-141.

Adaptation, Psychological↗
PubMed2000

Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy.

Beneficial cardiac effects of growth hormone (GH) have been shown in heart failure in several settings, but studies are lacking on this and other forms of treatment in the cardiomyopathic (CM) mouse heart. In mice with dilated cardiomyopathy due to disruption of the muscle LIM protein (MLP) gene [MLP null mice (MLP-/-)], natural history was first assessed by an initial echocardiogram at 8 weeks and a later follow-up study (n = 31). In most mice, left ventricular (LV) dilation increased and/or function decreased by 5 months, and 3 of 12 mice followed for 9 months died. At the end of follow-up, 22 MLP-/- mice (average age 10.2 months) had both LV dilation and reduced LV function and were selected for studies of GH effects on cardiac function and gene expression; mice were randomized to vehicle (controls) or recombinant human (rh) GH and restudied after 2 weeks. In the GH-treated group compared to the control group, LV % fractional shortening and LV wall thickness (echocardiography) were increased, the LV dP/dtmax (catheter-tip micromanometry) was enhanced, and LV relaxation (tau) improved; however, the LV weight was not significantly increased. The LV expression of many genes was altered in MLP-/- mice, and several were influenced by GH. Thus, short-term RhGH treatment improved LV function in a setting of chronic cardiac deterioration and significantly reduced elevated LV mRNA expression of some (ANP, BNP) but not other members of the embryonic gene program. The MLP null cardiomyopathic mouse can be useful for exploring altered signaling and therapeutic interventions in heart failure.

Animals↗
PubMed2000

Identification of the null HLA-A2 allele, A*0232N.

We have identified a null HLA-A*02 allele, HLA-A*0232N, by using a combination of serology, flow cytometry, polymerase chain reaction using sequence-specific primers (PCR-SSP) and full-length sequencing. The null HLA-A2 allele was identified in an Asian individual originally typed by serology as an apparently homozygous HLA-A3, B51. Subsequent genotyping by PCR-SSP identified the genotype as HLA-A*0201, *0301, B*51, Cw*1402. The serological type and lack of detectable HLA-A2 was confirmed using monoclonal antibody typing reagents. Flow cytometry studies failed to identify any cell surface HLA-A2 expression on the patient's peripheral blood lymphocytes. Genotyping using a PCR-SSP set designed to detect null alleles revealed the mutation had not been previously described. Full-length sequencing of the allele identified an allele which was subsequently named HLA-A*0232N. This allele is identical to HLA-A*0201 except for a novel point mutation (T for C) at position 493 which creates a premature stop codon. The sequencing enabled the development of a monospecific A*0232N PCR-SSP reaction which was used to screen 973 DNA samples: no further examples of A*0232N were identified.

Alleles↗
PubMed2000

An HLB-B null allele (B*0808N) caused by a nucleotide deletion in exon 3, found in the family of a bone marrow transplant recipient.

We have identified a variant HLA-B allele, B*0808N, segregating through two generations of healthy individuals, whilst HLA typing the family of a bone marrow patient. Serological typing identified a disparity between the father (A1, A3 B7 DR7) and the brother (A1, A2 B56 DR1, DR7) of the patient. Low/medium resolution polymerase chain reaction using sequence-specific primers (PCR-SSP) revealed a B*08 allele undetectable by serological methods. High resolution DNA typing by polymerase chain reaction-sequencing based typing (PCR-SBT), revealed a nucleotide deletion at position 131 (C) in exon 3, the only difference between the new allele and B*0801. The deletion results in a frame shift in the protein coding sequence, introducing a premature termination codon (TGA) in exon 4. Although a B*08 allele is present in these individuals, the deletion prevents correct expression of the antigen on the cell surface.

Alleles↗
PubMed2000

Identification of an HLA-B7 serological variant and its characterization by sequencing based typing.

We have identified an HLA-B*07 variant allele, B*0716, in a Caucasoid cadaver kidney donor. The HLA class I type by polymerase chain reaction using sequence-specific primers (PCR-SSP) was A*01, 32; B*07, 08; Cw*07. Serological typing, using monoclonal and polyclonal anti-HLA antisera, gave disparate results for the B antigens. Monoclonal antibodies identified B7 and B8 antigens but polyclonal antisera recognised only the B8 antigen. PCR using sequencing based typing (PCR-SBT) confirmed the presence of both B*0703 and B*0801 alleles but with a mutation in one of the alleles. The HLA-B*07 allele was isolated by allele-specific PCR and was shown to have a mutation, G-->T, at 292 in exon 2. This mutation changes codon 74, which encodes aspartic acid (GAC) present in all previously identified B*07 alleles, to tyrosine (TAC) in the variant. The serological results suggest that codon 74 is a crucial part of a B7 antigen-specific epitope recognised by tissue typing polyclonal antisera.

Alleles↗
PubMed2000

Identification of a novel allele, B*15012, by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing.

We report here a new allele, B*15012, identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT). B*15012 differs to B*15011 (previously named B*1501) by a single nucleotide, at position 435 of codon 120. B*15011 encodes AAG and B*15012 encodes AAA at codon 120, this difference does not result in an amino acid change.

Alleles↗
PubMed2000

The nature of benzodiazepine dependence among heroin users in Sydney, Australia.

AIMS: To determine the extent to which heroin users meet criteria for benzodiazepine dependence, to examine the appropriateness of these criteria for assessing benzodiazepine dependence among this population, and to assess what other substance use, depressive and anxiety disorders are associated with benzodiazepine dependence. DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: Two hundred and twenty-two heroin injectors recruited through advertisements, needle exchanges, methadone maintenance clinics and by word of mouth. FINDINGS: Twenty-six per cent (52/202) of those who had used benzodiazepines received a life-time diagnosis of benzodiazepine dependence, with 22% of current benzodiazepine users being dependent. A principal components analysis revealed that a unidimensional construct underlies the benzodiazepine dependence syndrome. Those respondents with life-time benzodiazepine dependence were more likely than others to meet criteria for anxiety or depressive disorders. CONCLUSIONS: The inclusion of the benzodiazepine dependence syndrome in DSM-III-R (and DSM-IV) is justified. A disturbingly high proportion of heroin users meet the criteria for benzodiazepine dependence, a condition that should be regarded as a significant marker for co-morbidity among this group.

Adolescent↗
PubMed2000

The use of antidepressants among injecting drug users in Sydney, Australia.

AIMS: To ascertain the prevalence and patterns of antidepressant use among IDU in Sydney and to determine any harm associated with antidepressant use. DESIGN: Cross-sectional survey. SETTING: Sydney, Australia. PARTICIPANTS: Two hundred and one Sydney injecting drug users (IDU) recruited through advertisements, needle exchanges, methadone maintenance clinics and by word of mouth. FINDINGS: Forty per cent of subjects had used antidepressants, 21% in the preceding 6 months. Similar proportions of subjects had used tricyclics (26%) and selective serotonin reuptake inhibitors (SSRIs) (24%), with 8% reporting use of a monoamine oxidase inhibitor. Recent use favoured the SSRIs; however, there was still widespread use of tricyclics. The injection of antidepressants was rare, with only three subjects reporting ever having injected the drugs. Antidepressant use was associated with higher levels of polydrug use, poorer health, higher levels of psychiatric distress and a greater risk of heroin overdose. The excess risk of overdose was specifically associated with tricyclics, rather than SSRIs. CONCLUSIONS: The study confirmed that, like other pharmaceutical products, the use of antidepressants was common among IDU in Sydney. The prescription of tricyclics to heroin users would appear to increase their risk of overdose. If it is considered appropriate to prescribe antidepressants to IDU, it would appear safer to prescribe SSRIs.

Adolescent↗
PubMed2000

Fatal heroin overdoses resulting from non-injecting routes of administration, NSW, Australia, 1992-1996.

AIMS: To document cases of fatal heroin overdose in New South Wales by non-injecting routes of administration, and to compare the characteristics and toxicology of these cases with injecting fatalities. DESIGN: Examination of coronial files. SETTING: New South Wales, Australia. PARTICIPANTS: All fatal heroin overdose cases in NSW between 1992 and 1996. FINDINGS: There were 10 cases of death resulting from non-injecting routes of heroin administration between 1992 and 1996, representing 1% of cases. In three cases the route of administration was by inhalation, in five cases by nasal administration and in two cases by swallowing. The mean age of cases was 29.6 years, and nine of the cases were male. The median blood morphine concentration of non-injectors was 0.31 mg/l (range 0.06-0.99 mg/l). Drugs other than morphine were also detected in seven cases. CONCLUSIONS: Heroin overdose deaths are not restricted to the injection of heroin. While injection may constitute a greater overdose risk-factor, there is no safe, overdose-free way to use heroin.

Administration, Inhalation↗
PubMed2000

Models of dilated cardiomyopathy in the mouse and the hamster.

Dilated cardiomyopathy (DCM) is a heart muscle disorder characterized by atrial and ventricular dilation often with relative wall thinning, severe systolic and diastolic ventricular dysfunction, and frequent findings of heart failure. Using genetically engineered mice, a number of studies have attempted to determine the role of specific genes, as well as to mimic the phenotype of human DCM. Naturally occurring and acquired animal models of DCM also have been investigated. In this brief review, we will focus on small animal models of DCM, particularly those in the mouse, together with some comments on the autosomal-recessive cardiomyopathy of the hamster. These animal models can be categorized into several general groups in accordance with the presumed role of the gene mutation involved, including intrasarcomeric and extrasarcomeric cytoskeletal abnormalities, which resemble some forms of hereditary human DCM, and overexpression or disruption of genes that control molecules participating in intracellular signaling pathways, including the beta-adrenergic system and calcium regulation. Modifications in the latter two pathways can cause or alleviate DCM in animal models, suggesting their importance in myocyte adaptive and survival mechanisms.

Animals↗
PubMed2000

Levy diffusion in a force field, huber relaxation kinetics, and nonequilibrium thermodynamics: H theorem for enhanced diffusion with Levy white noise

A characteristic functional approach is suggested for Levy diffusion in disordered systems with external force fields. We study the overdamped motion of an ensemble of independent particles and assume that the force acting upon one particle is made up of two additive components: a linear term generated by a harmonic potential and a second term generated by the interaction with the disordered system. The stochastic properties of the second term are evaluated by using Huber's approach to complex relaxation [Phys. Rev. B 31, 6070 (1985)]. We assume that the interaction between a moving particle and the environment can be expressed by the contribution of a large number of relaxation channels, each channel having a very small probability of being open and obeying Poisson statistics. Two types of processes are investigated: (a) Levy diffusion with static disorder for which the fluctuations of the random force are frozen and last forever and (b) diffusion with strong dynamic disorder and independent Levy fluctuations (Levy white noise). In both cases we show that the probability distribution of the position of a diffusing particle tends towards a stationary nonequilibrium form. The characteristic functional of concentration fluctuations is evaluated in both cases by using the theory of random point processes. For large times the fluctuations of the concentration field are stationary and the corresponding probability density functional can be evaluated analytically. In this limit the fluctuations depend on the distribution of the total number of particles but are independent of the initial positions of the particles. We show that the logarithm of the stationary probability functional plays the role of a nonequilibrium thermodynamic potential, which has a structure similar to the Helmholtz free energy in equilibrium thermodynamics: it is made up of the sum of an energetic component, depending on the external mechanical potential, and of an entropic component, depending on the concentration field. We show that the conditions for the existence and stability of the nonequilibrium steady state, which emerges for large times, can be expressed in terms of the stochastic potential. For Levy white noise the average concentration field can be expressed as the solution of a fractional Fokker-Planck equation. We show that the stochastic potential is a Lyapunov function of the fractional Fokker-Planck equation, which ensures that all transient solutions for the average concentration field tend towards a unique stationary form.

Journal Article↗
PubMed2000

Master equation approach to synchronization in diffusion-coupled nonlinear oscillators

We study the influence of internal fluctuations on phase synchronization in oscillatory reaction-diffusion systems through a master equation approach. In the limit of large system size, the probability density is analyzed by means of the eikonal approximation. This approximation yields a Hamilton-Jacobi equation for the stochastic potential, which may be reduced to coupled nonlinear diffusion equations for the phase of oscillation and (conjugate) "momentum." We give explicit expressions for the coefficients of these equations in terms of averages over the deterministic periodic orbit. For one-dimensional systems, we obtain an explicit solution for the stationary stochastic potential: the width in phase, which is defined as the root mean square fluctuation in phase, characterizes the roughness of phase locking, and diverges with the system size L according to a power law w approximately Lalpha, with alpha=1/2. To study higher-dimensional systems, we show that the eikonal approximations of the diffusion-coupled oscillator problem and the Kardar-Parisi-Zhang (KPZ) equation (in the limit of small noise intensity) are equivalent. The KPZ equation governs some forms of surface growth, and the height of a growing front corresponds to the phase (the 2pi periodicity in phase is ignored) in the diffusion-coupled oscillator problem. From the equivalence, we obtain the result that spatially synchronized states may exist only in systems with a spatial dimension greater than or equal to 3; for dimensions 1 and 2, a "rough" state exists in which the width (in phase) diverges algebraically with the system size, alpha>0.

Journal Article↗
PubMed2000

Statistical fractal adsorption isotherms, linear energy relations, and power-law trapping-time distributions in porous media

Drazer and Zanette [Phys. Rev. E 60, 5858 (1999)] have reported on interesting experiments which show that trapping-time distributions in porous media obey a scaling law of the negative power-law type. Unfortunately, their theoretical interpretation of the experimental data has physical and mathematical inconsistencies and errors. Drazer and Zanette assume the existence of a distribution of local adsorption isotherms for which the random parameter is not a thermodynamic function, but a kinetic parameter, the trapping time. Moreover, they mistakenly identify the reciprocal value of a rate coefficient with the instantaneous (fluctuating) value of the trapping time. Their approach leads to mathematically inconsistent probability densities for the trapping times, which they find to be non-normalizable. We suggest a different theory, which is physically and mathematically consistent. We start with the classical patch approximation, which assumes the existence of a distribution of adsorption heats, and introduce two linear energy relationships between the activation energies of the adsorption and desorption processes and the adsorption heat. If the distribution of the adsorption heat obeys the exponential law of Zeldovich and Roghinsky, then both the adsorption isotherm and the probability density of trapping times can be evaluated analytically in terms of the incomplete beta and gamma functions, respectively. Our probability density of the trapping times is mathematically consistent; that is, it is non-negative and normalized to unity. For large times it has a long tail which obeys a scaling law of the negative power-law type, which is consistent with the experimental data of Drazer and Zanette. By using their data we can evaluate the numerical values of the proportionality coefficients in the linear energy relations. The theory suggests that experimental study of the temperature dependence of the fractal exponents helps to elucidate the mechanism of the adsorption-desorption process.

Journal Article↗