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Biomedical subjects

D Sanders

Publications and source records attributed to D Sanders.

At least 145 records · Page 8Linked to original sources

Voltage sensitivity of H+/Ca2+ antiport in higher plant tonoplast suggests a role in vacuolar calcium accumulation.

The electrogenicity of H+/Ca2+ exchange in vacuolar membrane (tonoplast) vesicles from Beta was studied to elucidate the role of this transport system in vacuolar Ca2+ accumulation. To overcome the inherently high proton permeability of tonoplast vesicles, the pH difference established by the primary H(+)-ATPase was titrated to a uniform value by variation of the concentration either of ATP or of a permanent anion (Cl-). This enabled manipulation of membrane potential independently of the transmembrane pH difference, with a higher inside-positive membrane potential produced at lower Cl- concentrations. The rate and the extent of uncoupler-sensitive Ca2+ uptake are both stimulated about 2-fold in conditions of more positive membrane potential, suggesting that the transport system translocates positive charge outward during Ca2+ uptake. A minimum integral H+:Ca2+ stoichiometry of 3 results in a driving force for Ca2+ accumulation in the vacuole amounting to -140 mV in typical physiological conditions. It is concluded that the antiporter is thermodynamically competent to account for Ca2+ accumulation in plant vacuoles and that its reversal in vivo is unlikely.

Acridine Orange↗

Experimental approach to the study of immune function in children with possible human immunodeficiency virus infection.

The clinical immunology laboratory is often called on to assess risk in pediatric patients with clinical evidence of immunodeficiency and possible human immunodeficiency virus (HIV) exposure while antibody tests are being considered or are underway. Since non-HIV-related conditions including neoplasia, certain viruses, and primary immunodeficiency can potentially produce lymphocyte subset imbalance and functional impairment, there is need for a laboratory approach to differential analysis of pediatric immunodeficiency. In addition, laboratory methods may also influence the results obtained. In order to investigate these issues, we screened pediatric patients with and without HIV exposure. Altered lymphocyte subset expression and function were found among non-HIV-infected pediatric patients. The use of percentage and absolute lymphocyte numbers was found to affect the results obtained in a significant manner. Some patients who were chronic blood transfusion recipients were found to have blocking factors, presumably alloantibodies, in serum, which affected detection of lymphocyte surface antigens. In this population, age at seroconversion was a factor influencing subsequent levels of CD4+ T lymphocytes. Significant differences in CD4+ T lymphocyte percentages were also observed in children congenitally exposed to HIV compared with controls, even among those children with CD4/CD8 ratios greater than 1.0, who therefore had possibly escaped infection. Immune changes in children should be interpreted with caution.

Adolescent↗

Characterization of Cl- transport in vacuolar membrane vesicles using a Cl(-)-sensitive fluorescent probe: reaction kinetic models for voltage- and concentration-dependence of Cl- flux.

The effects of Cl- concentration and membrane potential (delta psi) on Cl- influx in isolated vesicles of vacuolar membrane (tonoplast) from red beet (Beta vulgaris L.) storage tissue have been characterized using the Cl(-)-sensitive fluorescent probe, 6-methoxy-1-(3-sulfonatopropyl)quinolinium (SPQ). The initial rate of Cl- transport into the vesicles was enhanced both by the imposition of a positive delta psi and by increases in extravesicular Cl- concentration. The kinetic mechanism underlying these responses was investigated by examining the accuracy with which the data could be described by several transport models. A model based on constant field theory yielded a poor description of the data, but satisfactory fits were generated by pseudo-two-state reaction kinetic models based on classical carrier schemes. Fits were equally good when it was assumed that charge translocation accompanied Cl- entry, or when charge was carried by the unloaded transport system, as long as only a single charge is translocated in each carrier cycle. Expansion of the models to three states enabled description of the Cl- concentration dependence of transport by changes in a single, voltage insensitive rate constant which is tentatively identified with Cl- binding at the external surface of the membrane. The derived value of the dissociation constant between Cl- and the transport system is estimated at between 30 and 52 mM.

Biological Transport↗

Development and evaluation of a training course for practice nurses: helping people to stop smoking.

This paper describes a 2-day training course for practice nurses in advice-giving to smokers. The course incorporated information on the epidemiology, physiology and psychology of smoking and a strategy for giving advice based upon the health-beliefs model. The course was systematically evaluated on measures of knowledge about health and smoking and on confidence in various advice-giving activities. The results showed that the nurses gained significantly in both knowledge and confidence following the course. The prospect of further training courses for practice nurses in other areas of health promotion is discussed.

Attitude of Health Personnel↗

Cytosolic calcium homeostasis in fungi: roles of plasma membrane transport and intracellular sequestration of calcium.

Cytosolic free calcium ([Ca2+]c) has been measured in the mycelial fungus Neurospora crassa with Ca2(+)-selective microelectrodes. The mean value of [Ca2+]c is 92 +/- 15 nM and it is insensitive to external pH values between 5.8 and 8.4. Simultaneous measurement of membrane potential enables the electrochemical potential difference for Ca2+ across the plasma membrane to be estimated as about -60 kJ.mol-1-a value that cannot be sustained either by a simple Ca2(+)-ATPase, or, in alkaline conditions, by straightforward H+/Ca2+ exchange with a stoichiometric ratio of less than 5 H+/Ca2+. We propose that the most likely alternative mechanism of Ca2+ efflux is ATP-driven H+/Ca2+. In accord with this proposal, depletion of the ATP level from 2.5 to 0.5 mM by CN- elicits an increase in [Ca2+]c, but only in alkaline conditions in which the putative H+/Ca2(+)-ATPase would be selectively stalled. The insensitivity of Ca2+ homeostasis to CN- in more acid conditions implies that the Km (ATP) of the transport system is 100 microM or less. The increase in [Ca2+]c in the presence of CN- at pH 8.4 (50 nM.min-1) is compared with 45Ca2+ influx (0.62 mM.min-1) under the same conditions. The proportion of entering Ca2+ remaining free in the cytosol is only 8 x 10(-5), and since the concentration of available chelation sites on Ca2(+)-binding proteins is unlikely to exceed 100 microM, a major role for the fungal vacuole in short-term Ca2+ homeostasis is indicated. This notion is supported by the observation that cytosolic Ca2+ homeostasis is disrupted by a protonophore, which rapidly abolishes the driving force (a transmembrane pH difference) for Ca2+ uptake into fungal vacuoles.

Adenosine Triphosphate↗

Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P45017 alpha (CYP17) gene.

17 alpha-Hydroxylase deficiency is characterized by defects in either or both of the 17 alpha-hydroxylase/17,20-lyase activities. We have elucidated the molecular basis of the combined deficiency of these activities in a Japanese female who is genotypically male and the child of a consanguineous marriage. The complete exonic sequence of the patient's CYP17 (P45017 alpha) gene revealed a seven-basepair duplication (GCGCACA) in exon 2 which leads to a frame shift and, subsequently, a premature stop codon. Because this stop codon occurs N-terminal to the heme-binding sequence, the presence of this mutation leads to the absence of a functional P45017 alpha-protein in adrenal cortex and testis. This, in turn, leads to an absence of sex steroids and excessive secretion of steroids with mineralocorticoid activity and, consequently, female external genitalia and hypertension in this 46XY patient.

Adolescent↗

Electrophysiologic actions and antifibrillatory efficacy of subacute left stellectomy in a conscious, post-infarction canine model of ischemic ventricular fibrillation.

The autonomic nervous system appears to modulate ventricular arrhythmias associated with acute myocardial ischemia. This study investigated the electrophysiologic effects and antifibrillatory actions of subacute left stellectomy in a conscious, post-infarction canine model of sudden cardiac death. Twenty-two dogs with a previous anterior wall myocardial infarction and inducible ventricular arrhythmias were randomized to undergo either left stellectomy (n = 12) or remain as sham-denervated controls (n = 10). Five to 7 days post left stellectomy, there were no significant changes in heart rate, electrocardiographic intervals or ventricular refractoriness compared to sham-denervated controls. Acute posterolateral ischemia was produced in left stellectomy and sham-denervated dogs by anodal current-induced thrombosis via a previously positioned electrode in the left circumflex coronary artery. Ventricular fibrillation developed within 1 hour of the onset of ischemia (early ventricular fibrillation) in 3/12 (25%) left stellectomy dogs versus 8/10 (80%) sham-denervated controls (P less than 0.05). However, 24-hour mortality rate was 5/12 (42%) after left stellectomy versus 8/10 (80%) after sham denervation (P = 0.072). Small differences in regional myocardial norepinephrine content, which is a marker for neuronal integrity, occurred in the mid-posterolateral and mid-anteroseptal regions of the left ventricle after left stellectomy. Overall norepinephrine concentration after left stellectomy was 409.70 +/- 9.90 ng/g vs 428.07 +/- 10.84 ng/g in sham controls (P = NS). In summary, subacute left stellectomy significantly reduces the incidence of ventricular fibrillation occurring within 1 hour of the onset of acute posterolateral ischemia at a distance to a previous myocardial infarction in conscious dogs, and tends to reduce the ischemic post-infarction mortality at 24 hours after the onset of ischemia. This protective effect of left stellectomy is not due to any alteration in cardiac electrophysiologic parameters measured prior to the development of acute posterolateral ischemia, nor is it related to regional denervation as determined by myocardial tissue concentration of residual norepinephrine.

Animals↗

Astigmatism control for the cataract surgeon: a comprehensive review of surgically tailored astigmatism reduction (STAR).

It is increasingly possible for the cataract surgeon to control astigmatism. Based on a review of 4,000 consecutive patients, three categories of astigmatism and cataract patients are identified. A specific approach to astigmatism control for each category is discussed. Preliminary results on the use of astigmatic keratotomy in conjunction with cataract surgery are presented.

Aged↗

Randomized controlled trial of anti-smoking advice by nurses in general practice.

Practice nurses are playing an increasingly prominent role in preventive care, including the provision of anti-smoking advice during routine health checks. A randomized controlled trial was designed to assess the effectiveness of anti-smoking advice provided by nurses in helping smokers to stop smoking. A total of 14,830 patients aged 16-65 years from 11 general practices completed a brief questionnaire on general health, including smoking status, at surgery attendance. The doctor identified 4330 smokers and randomly allocated 4210 to control or intervention groups. The doctor asked those in the intervention group to make an appointment with the practice nurse for a health check. The attendance rate at the health check was 26%. Smokers were sent follow-up questionnaires at one month and one year, and those who did not respond to two reminders were assumed to have continued to smoke. There was no significant difference in reported cessation between the intervention and control groups at one month or one year. However, there was a significant difference in the proportion of patients who reported giving up within one month and who had not lapsed by one year--0.9% in controls and 3.6% in the intervention group (P less than 0.01). Nevertheless, the effect of the nurse intervention itself may be small as the sustained cessation rate in attenders was only 42.4% higher than in non-attenders. The deception rate in reporting cessation, as measured by urinary cotinine, was of the order of 25%.

Adolescent↗

Smoke screens.

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Community Health Nursing↗

The economy, the health sector and child health in Zimbabwe since independence.

This paper examines the changes in the economic environment which have taken place in Zimbabwe since independence in April 1980, concentrating on those which are relevant to health. It also describes the post-independence restructuring of the health sector itself. Finally, it considers some changes which have taken place in the health status of children. Despite a prolonged drought, economic recession and the imposition of economic stabilisation measures, there is evidence of a sharp improvement in infant and young child mortality. This has resulted almost certainly from an energetic expansion and reorientation of health care provision, and particularly from greatly improved access to immunisation and oral rehydration therapy. The adverse effects of drought and stabilisation measures have been partially offset by aid-supported relief feeding and particular health programmes. However, the economic crisis has resulted in a decline in real incomes for a large number of households since the immediate post-independence boom. This is reflected in high levels of childhood undernutrition which seem to have remained static despite the health care drive. This emerging divergence between death rates and quality of life as reflected by nutrition levels is reflective on the one hand of rapid expansion in effective health care provision, and on the other of little change in socio-economic conditions for the majority of the population.

Child↗

Quantitative and rapid estimation of h fluxes in membrane vesicles : software for analysis of fluorescence quenching and relaxation.

Proton transport is often visualized in membrane vesicles by use of fluorescent monoamines which accumulate in acidic intravesicular compartments and undergo concentration-dependent fluorescence quenching. Software for an IBM microcomputer is described which permits logging and editing of changes in fluorescence monitored by a Perkin-Elmer LS-5 luminescence spectrometer. An accurate estimate of the instantaneous rate of fluorescence quenching or recovery is then facilitated by least squares fitting of fluorescence data to a nonlinear function. The software is tested with tonoplast vesicles from Beta vulgaris. Quenching of acridine orange fluorescence by ATP-driven (primary) transport and relaxation of quenching by Na(+)/H(+) antiport can both be fitted with single exponential functions. Initial rates of ATP- and Na(+) -dependent fluorescence changes are derived and can be used for K(m) determinations. The method constitutes a simple and efficient alternative to manual analysis of analog fluorescence traces and results in a reliable quantitative measurement of the relative rate of proton transport in membrane vesicle preparations.

Journal Article↗

Involuntary movements of the lower extremity following dorsal root entry zone lesions in a man treated for phantom limb pain.

A patient developed continuous patterned involuntary movements of abduction-adduction, flexion-extension of his right lower extremity following surgical placement of spinal dorsal root entry zone lesions for the treatment of phantom limb pain. The stereotype movements were monitored by video and electromyographic recording of quadriceps femoris and hamstring muscles. Administration of para-chlorophenylbutyric acid (baclofen) dramatically stopped the involuntary movements and electromyographic silence ensued. Voluntary muscle movements were preserved. The theoretical implications of this unique movement disorder and central patterning of motor activity within the spinal cord are discussed.

Baclofen↗