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Biomedical subjects

D Sanders

Publications and source records attributed to D Sanders.

At least 109 records · Page 6Linked to original sources
PubMed1994

Mechanism of high-affinity potassium uptake in roots of Arabidopsis thaliana.

Potassium is a major nutrient in higher plants, where it plays a role in turgor regulation, charge balance, leaf movement, and protein synthesis. Terrestrial plants are able to sustain growth at micromolar external K+ concentrations, at which K+ uptake across the plasma membrane of root cells must be energized despite the presence of a highly negative membrane potential. However, the mechanism of energization has long remained obscure. Therefore, whole-cell mode patch clamping has been applied to root protoplasts from Arabidopsis thaliana to characterize membrane currents resulting from the application of micromolar K+. Analysis of whole cell current/voltage relationships in the presence and absence of micromolar K+ enabled direct testing of K+ transport for possible energization by cytoplasmic ATP and the respective trans-membrane gradients of Na+, Ca2+, and H+. Subtracted current/voltage relations for K(+)-dependent membrane currents are independent of ATP and reverse at potentials that imply H(+)-coupled K+ transport with a ratio of 1 H+:K+. Furthermore, the reversal potential of the K+ current shifts negative as external H+ activity is decreased. K(+)-dependent currents saturate in the micromolar concentration range with an apparent Km of 30 microM, a value in close agreement with previously reported Km values for high-affinity K+ uptake. We conclude that our results are consistent with the view that high-affinity K+ uptake in higher plants is mediated by a H+:K+ symport mechanism, competent in driving K+ accumulation to equilibrium ratios in excess of 10(6)-fold.

Arabidopsis↗
PubMed1994

Vacuolar H(+)-pumping ATPase variable transport coupling ratio controlled by pH.

The eukaryote endomembrane system contains a class of H(+)-pumping ATPase (H(+)-ATPases) of the vacuolar type (V-ATPases) that are responsible for the acidification of organelles. Their action is critical to numerous physiological processes, but the regulatory mechanisms that may control activity are not yet fully understood. The ratio of H+ transported per ATP hydrolyzed (n) has been determined thermodynamically for the red beet V-ATPase by using patch clamp. The value of n was found to range from 1.75 to 3.28 and was strictly dependent on cytoplasmic and lumenal pH. This suggests a mechanism by which V-ATPases are regulated by and might therefore control cytoplasmic and lumenal pH. Furthermore, the substantial capacity of plant vacuoles for H+ accumulation to pH 3 or lower can only be explained by the finding that n can adopt a value of < 2.

Anti-Bacterial Agents↗
PubMed1994

Smoking and cancer: smoking cessation.

Smoking is the single most important cause of cancer. The risk of developing cancer is reduced by stopping smoking and decreases substantially after five years. Reduction in smoking must be central to any programme aimed seriously at the prevention of cancer. An individual approach, based in primary care, has the potential to bring about modest but important reductions in risk. Many randomised trials have shown the effectiveness of various smoking cessation interventions in primary care. Given resource limitations in primary care, individual effort should be focused on those at highest risk who are motivated to stop smoking. A population strategy has considerable advantages over the high risk approach as the potential for reducing morbidity and mortality in the whole population is much greater. The government must acknowledge its major responsibility; the outstanding example of its failure to do this is its persistent refusal to ban outright all forms of advertising and promotion of tobacco. There is clear evidence that a ban would contribute to a reduction in smoking prevalence and especially in the uptake of smoking by children.

Adolescent↗
PubMed1994

Human hair growth in vitro: a model for the study of hair follicle biology.

The factors that regulate hair follicle growth are still poorly understood. In vitro models may be useful in elucidating some aspects of hair follicle biology. We have developed an in vitro human hair growth model that enables us to maintain isolated human hair follicles for up to 10 days, during which time they continue to grow at an in vivo rate producing a keratinised hair fibre. We have shown that epidermal growth factor (EGF) in our system mimics the in vivo depilatory action of EGF in sheep, and suggest that this occurs as a result of EGF stimulating outer root sheath (ORS) cell proliferation which results in the disruption of normal mechanisms of cell-cell interaction in the hair follicle. We identify transforming growth factor-beta (TGF-beta) as a possible negative regulator of hair follicle growth and show that physiological levels of insulin-like growth factor-I (IGF-I) can support the same rates of hair follicle growth as supraphysiological levels of insulin. Furthermore, in the absence of insulin hair follicles show premature entry into a catagen-like state. This is prevented by physiological levels of IGF-I. Finally we demonstrate that the hair follicle is an aerobic glycolytic, glutaminolytic tissue and discuss the possible implications of this metabolism.

Aerobiosis↗
PubMed1994

Paediatric pneumonia in Zimbabwe: management and pharmaceutical costs of inpatient care.

Acute respiratory infection exacts a heavy toll on the children of Zimbabwe. During 1986-7 significant resources were committed to manage this condition that accounted for 35 per cent of outpatient visits. Moreover, pneumonia or acute lower respiratory infection (ALRI) represented the greatest proportion of paediatric hospital inpatient discharge diagnoses (32 per cent) and was responsible for 33 per cent of under 5 deaths in Harare. Case management and pharmaceutical cost patterns for paediatric ALRI inpatients are compared for representative rural district and provincial hospitals and an urban central hospital in Harare. The case-mix of patients was similar at all three hospital levels. Significantly, mildly ill patients between the ages of 7 months and 5 years were uniformly over-treated based on management protocols recommended both in the Essential Drug List for Zimbabwe and by the World Health Organization (WHO). The resulting excessive expenditure was Z$26000 (1Z$ = 0.59U$$ in 1986) for this category of patient in 1986. Reasons for the lack of compliance with WHO management protocols are explored.

Adolescent↗
PubMed1994

Disruptive effects of protein on performance of liquid membrane-based ion-selective microelectrodes.

The effects of addition of protein [bovine serum albumin (BSA)] to the calibration solutions of various liquid membrane-based ion-selective microelectrodes have been assessed. Protein at typically cytosolic levels of 100 mg/ml had no effect on the response of Na(+)-, K(+)-, Mg(2+)-, Ca(2+)-, H(+)-, NO3(-)-, and Cl(-)- selective microelectrodes at ion concentrations well above the respective detection limits. By contrast, this level of protein resulted in a pronounced increase in the detection limits of Na(+)-, K(+)-, Mg(2+)-, Ca2+, and Cl(-)-selective microelectrodes; H+ and NO3- microelectrodes were largely unaffected by the protein. The effect of BSA on detection limit is independent of pH and ionic strength, nor is it due to hysteresis, to binding of ions to the protein, or to the generation of junction potentials. More extensive studies on Na(+)-selective microelectrodes revealed that other proteins and large molecules (e.g., polyethylene glycol) also increase detection limits, with the extent of this effect apparently correlated positively with the molecular weight. Because biological macromolecules at physiological concentrations can influence the properties of alkali- and alkali earth cation-selective microelectrodes, care must be taken if the use of these electrodes entails cytosolic measurements close to their detection limits.

Equipment Failure↗
PubMed1994

Voltage-gated Ca2+ release channels in vacuolar membranes from beet storage roots and guard cells.

The ubiquity and wide-ranging roles of Ca(2+)-mediated stimulus-response coupling in plant cells is likely to demand flexibility in the duration and amplitude of the cytosolic Ca2+ signal. The presence of both ligand- and voltage-gated Ca2+ release channels at the vacuolar membrane suggests that this flexibility might be achieved through differential regulation of these discrete channel classes. The properties and distribution of voltage-gated vacuolar Ca2+ channels is described in this chapter. In beet storage roots, the channels display a single channel conductance of 12 pS (5-20 mM Ca2+ on the lumenal side), Ca2+:K+ selectivity = 15:1 and a unitary current which saturates as a function of (physiological) negative voltages at about 0.5 pA. Channel opening is enhanced by negative voltages and by intravacuolar (lumenal) Ca2+. Variation of lumenal Ca2+ concentration has enabled the binding sites both for ionic selectivity and for Ca2+ gating to be mapped with respect to their fractional electrical distance across the membrane. Voltage-gated Ca2+ channels with similar permeation properties also reside in the vacuolar membranes of Vicia faba and Commelina communis guard cells. Although these channels exhibit somewhat higher unitary conductances and voltage-saturating currents than the beet channel, they are similar in many other respects, including sensitivity to Gd3+. We conclude that the widespread distribution of an emerging class of voltage-gated Ca2+ channel in the vacuolar membrane of plants points towards a fundamental role of these channels in plant cell biology.

Calcium↗
PubMed1994

The introverted medical school--time to rethink medical education.

Curricular reform in the education of medical students is highlighted within the context of changing patterns of provision of health care. A number of industrialised countries' medical schools have accepted that they have a 'social contract' to respond to the health needs of the populations they serve. Such a contract, and the commitment to populations which it would necessitate, is also relevant in the South African context.

Curriculum↗
PubMed1994

Evaluation of autologous shed blood for autotransfusion after orthopaedic surgery.

Autologous shed blood for autotransfusion was evaluated at four medical centers in a prospective randomized study. One hundred twenty-eight patients were studied after hip replacement, knee replacement, or spine fusion. The efficacy of autologous shed blood in reducing homologous transfusion was evaluated. The relative risk of transfusion with homologous blood was 0.4 in patients who received shed blood compared with patients who did not receive shed blood. The reinfusion of shed blood reduced the requirement for homologous blood by 60%. Two filter systems were evaluated in reinfusing autologous shed blood. The Pall RC100 filter appeared to be more effective than the Pall 40-mu screen filter in removing fat particles and white blood cells. No significant clinical abnormalities were discovered after autotransfusion with autologous shed blood. Evaluation of clotting studies showed no significant differences between patients who received shed blood and patients who received liquid-preserved red blood cells. These data indicate that unwashed autologous shed blood from orthopaedic wound drainage is a safe and effective substitute for transfusion of autologous predonated blood or homologous liquid-preserved red blood cells.

Adult↗
PubMed1993

Production of biologically active light chain of tetanus toxin in Escherichia coli. Evidence for the importance of the C-terminal 16 amino acids for full biological activity.

The activity of the light (L) chain of tetanus toxin, and of mutants constructed by site-directed mutagenesis, was studied by expression and purification of the proteins from E. coli. Wild-type recombinant L chain (pTet87) was active in the inhibition of exocytosis from cultured bovine adrenal chromaffin cells, although at a level 5-15% of that of L chain purified from tetanus toxin. L chain mutants which terminated at Leu-438 (pTet89), or which contained a Cys-to-Ser mutation at residue 439 (pTet88) were equally as active as the full-length recombinant protein. The reduced activity of pTet87 L chain correlated with C-terminal proteolysis of the protein upon purification. A tryptic fragment derived from native light chain and which terminated at Leu-434 also showed reduced activity in the exocytosis assay, consistent with a requirement of the C-terminal region of the L chain for maximal activity. pTet87 L chain, but neither of the mutants, could be associated with purified H (heavy) chain to form a covalent dimer which induced the symptoms of tetanus in mice. The ability to form biologically active toxin using recombinant L chain will be of great value in structure-function studies of tetanus toxin.

Adrenal Medulla↗
PubMed1993

Disulfide formation in reduced tetanus toxin by thioredoxin: the pharmacological role of interchain covalent and noncovalent bonds.

The interchain disulfide bond of tetanus toxin is known to be cleaved by reduced thioredoxin and by rat brain homogenate. We now show that this bond, but not the disulfide loop in the heavy chain of the toxin, can be restored quickly and completely by oxidized thioredoxin. Oxidized glutathione was at least 100 times less potent and less specific. Reduced tetanus toxin did not measurably (KD below 50 nM) dissociate into its chains, as revealed by HPLC gel chromatography under nondenaturing conditions. Accordingly, when the reduced toxin or its recombined chains were injected into mice, general toxicity was diminished but not abolished, as compared with the native form. Inhibition of Ca(2+)-evoked [3H]noradrenaline release was assayed in cultured adrenomedullary cells after permeabilization with digitonin. Reduced two-chain tetanus toxin was as active as the isolated light chain in this system, and the action of the light chain was only slightly diminished by the addition of excess heavy chain. The results show that thioredoxin can both open and close the covalent bond between the chains of tetanus toxin, and that the reduced chains remain linked by noncovalent forces. The role of the thioredoxin system for reversible activation of tetanus toxin in vivo remains to be established.

Adrenal Medulla↗
PubMed1993

Predictors of successful smoking cessation following advice from nurses in general practice.

At follow-up of 751 subjects receiving a brief nurse-administered anti-smoking intervention in general practice, 135 subjects (18%) reported stopping smoking, of whom 44 (6%) reported sustained cessation for one year. The demographic, social and attitudinal characteristics of these subjects were compared with 616 subjects who continued to smoke. The most important predictors of cessation were intention to stop (OR 5.1, 95% CI 2.1-12.0), personal rating of likelihood of cessation (OR 4.9, 95% CI 2.8-8.5), nurse rating of likelihood of cessation (OR 4.0, 95% CI 2.2-7.4), and smoking habit of partner (1.9, 95% CI 1.3-2.9). As practice nurses are able to distinguish likely quitters from those who are not motivated and less likely to succeed, it is important to decide whether it is more cost effective to target support at the motivated or to spend more time encouraging less motivated. The most challenging, but possibly the most rewarding, task is to try to reduce the high proportion of new ex-smokers who relapse. Although 41.1% (95% CI 28.1, 58.0) of those expressing a definite intention to stop smoking gave up, only 17.9% (95% CI 8.9, 30.4) achieved sustained cessation. However, as sustained cessation is strongly predicted by social variables, such as marital status and time spent in the company of smokers, preventing relapse may not be easy to achieve through medical intervention alone.

Adolescent↗