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Biomedical subjects

D Sanders

Publications and source records attributed to D Sanders.

At least 127 records · Page 7Linked to original sources
PubMed1993

Surveillance for equity in maternal care in Zimbabwe.

The great hope and promise of post-independence efforts to promote equitable health care in Zimbabwe started with three years of dramatic improvement. Commitment to correcting inequities which were as discriminatory as any country in the world produced rapid extension of health centre infrastructure and the improvement of district hospitals. The major constraint was the entrenched pattern of sophisticated, high-technology health care left by colonial administrators which continued to monopolize resources. In spite of the excellent beginning, development of services for the poor was thwarted by recession, prolonged drought and external military destabilization. The cutbacks in funding for health care have been particularly severe as a result of economic adjustment policies imposed by IMF. Political pressure moved the health system toward private entrepreneurship returning to earlier patterns of discrimination in favour of whites and urban residents. Efforts to promote high-risk monitoring have had little impact among the poor and those living in remote areas. Equity has become symbolic rather than real. The government of Zimbabwe maintains a continuing commitment to the original goals of equity through primary health care. International agencies also would like to find a way to help reallocate services. There seems to be recognition that little will be accomplished in improving health conditions unless services are provided to those in greatest need. Disparities in maternal care are especially severe and can be improved only by building infrastructure to provide antenatal and perinatal services.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗
PubMed1993

Talking about sex.

Explore the source record for details and available documents.

Attitude to Health↗
PubMed1992

Potassium transport into plant vacuoles energized directly by a proton-pumping inorganic pyrophosphatase.

Potassium is accumulated in plant vacuoles against an inside-positive membrane potential. The mechanism facilitating energized K+ transport has remained obscure. However, electrogenic activity of the inorganic pyrophosphatase (H(+)-PPase) at the vacuolar membrane is dependent on cytoplasmic K+, raising the possibility that the enzyme translocates K+ into the vacuole. Membrane currents generated by the H(+)-PPase were measured (using a patch clamp technique) in intact vacuoles isolated from Beta vulgaris storage tissue. A significant orthophosphate-dependent outward current mediated by the enzyme in reverse mode is evoked only when potassium is present at the vacuolar face of the tonoplast, suggesting that potassium is a translocated ion. Furthermore, current-voltage analysis of the effects of extravacuolar potassium and pH on the reversal potential of the H(+)-PPase-generated current points to direct translocation of K+ and H+ by the enzyme. Thus the H(+)-PPase represents a distinct class of eukaryote translocase and could facilitate vacuolar K+ accumulation in vivo.

Biological Transport, Active↗
PubMed1992

Evidence for a link between specific proteolysis and inhibition of [3H]-noradrenaline release by the light chain of tetanus toxin.

The light chain of tetanus toxin is known to inhibit the Ca(2+)-evoked release of [3H]-noradrenaline from digitonin-permeabilized bovine adrenomedullary cells in culture but does not change the basal outflow or the total cellular radioactivity. Evidence for the involvement of proteolysis in this effect was obtained by three approaches. First, the permeabilized cells were exposed to a series of enzymes. The endoproteinase Glu-C mimicked the inhibition produced by the light chain. Second, protease inhibitors of different specificities were assessed for blockade of the action of light chain on [3H]-noradrenaline release from permeabilized cells. Blockade was complete with EDTA (2.5 mmol/l) or 1,10-o-phenanthroline (1 mmol/l), and absent with the highest concentrations tested of diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, pepstatin, leupeptin, bestatin, phosphoramidon, thiorphan or trans-epoxysuccinic acid (E64) which is regarded as an inhibitor of thiol proteases. This inhibitor spectrum suggested that light chain might be a metalloprotease. Finally a sequence-His-Glu-Leu-X-His-occurring in the light chains of tetanus toxin and of the botulinum neurotoxins A, C, D, E was also found in many endoproteinases and an aminopeptidase. The motif is known to constitute their active site and to bind Zn2+. In fact Zn2+ (0.6-0.9 mol/mol) was found in thoroughly dialysed two-chain tetanus toxin. The three approaches jointly support the hypothesis that the light chain of tetanus toxin, and probably of all clostridial neurotoxins, inhibits [3H]-noradrenaline release from adrenomedullary cells by degradation of (a) specific, still unknown protein(s) involved in exocytosis.

Adrenal Medulla↗
PubMed1992

Plant membrane transport.

Recent developments in plant membrane transport, particularly concerning the vacuolar and plasma membranes, have increased our understanding of molecular aspects of primary pumps, carrier systems and ion channels.

Biological Transport↗
PubMed1992

Vacuolar H(+)-translocating pyrophosphatases: a new category of ion translocase.

The membrane surrounding the central vacuole of plant cells contains an H(+)-translocating ATPase (H(+)-ATPase) and an H(+)-translocating inorganic pyrophosphatase (H(+)-PPase). Both enzymes are abundant and ubiquitous in plants but the H(+)-PPase is unusual in its exclusive use of inorganic pyrophosphate (PPi) as an energy source. The lack of sequence identity between the vacuolar H(+)-PPase and any other characterized ion pump implies a different evolutionary origin for this translocase. The existence of the vacuolar H(+)-PPase, in conjunction with increasing recognition of PPi as a key metabolite in plant systems, necessitates reconsideration of ATP as the primary energy source for membrane transport in plant cells.

Amino Acid Sequence↗
PubMed1992

Taxonomic status of Kitasatosporia, and proposed unification with Streptomyces on the basis of phenotypic and 16S rRNA analysis and emendation of Streptomyces Waksman and Henrici 1943, 339AL.

Species classified within the genus Kitasatosporia share many of the phenotypic characteristics typical of streptomycetes. By using a probabilistic identification scheme, they were identified with Streptomyces exfoliatus cluster 5, a species group within Streptomyces. The four species studied hybridized with a 16S rRNA genus probe for Streptomyces spp., indicating a close relationship between the two genera. The kitasatosporias were resistant to selected polyvalent streptomycete phages tested. Quantitative analysis showed that meso-diaminopimelic acid varied from 49 to 89% in Kitasatosporia species and from 1 to 16% in Streptomyces species depending on growth conditions. On the basis of 16S rRNA analysis, it is proposed to reduce Kitasatosporia to synonymy with Streptomyces. As a result, the new names proposed are Streptomyces mediocidicus comb. nov., Streptomyces phosalacineus comb. nov., Streptomyces setae comb. nov., and Streptomyces griseolosporeus comb. nov., nom. nov.

Base Sequence↗
PubMed1992

Kinetics of the Vacuolar H-Pyrophosphatase : The Roles of Magnesium, Pyrophosphate, and their Complexes as Substrates, Activators, and Inhibitors.

The responses of the vacuolar membrane (tonoplast) proton-pumping inorganic pyrophosphatase (H(+)-PPase) from oat (Avena sativa L.) roots to changes in Mg(2+) and pyrophosphate (PPi) concentrations have been characterized. The kinetics were complex, and reaction kinetic models were used to determine which of the various PPi complexes were responsible for the observed responses. The results indicate that the substrate for the oat root vacuolar H(+)-PPase is Mg(2)PPi and that this complex is also a non-competitive inhibitor. In addition, the enzyme is activated by free Mg(2+) and competitively inhibited by free PPi. This conclusion differs from that reached in previous studies, in which it was proposed that MgPPi is the substrate for plant vacuolar H(+)-PPases. However, models incorporating MgPPi as a substrate were unable to describe the kinetics of the oat H(+)-PPase. It is demonstrated that models incorporating Mg(2)PPi as the substrate can describe some of the published kinetics of the Kalanchoë daigremontiana vacuolar H(+)-PPase. Calculations of the likely concentrations of Mg(2)PPi in plant cytoplasm suggest that the substrate binding site of the oat vacuolar H(+)-PPase would be about 70% saturated in vivo.

Journal Article↗
PubMed1992

Regulation of vacuolar h-pyrophosphatase by free calcium : a reaction kinetic analysis.

The H(+)-translocating inorganic pyrophosphatase (H(+)-PPase) associated with vesicles of the vacuolar membrane (tonoplast) isolated from beet (Beta vulgaris L.) is subject to direct inhibition by Ca(2+) and a number of other divalent cations (Co(2+), Mn(2+), Zn(2+)). By contrast, the H(+)-translocating ATPase (H(+)-ATPase) located on the same membrane is insensitive to Ca(2+). Here we examine the mechanism and feasibility of regulation of the vacuolar H(+)-PPase by cytosolic free Ca(2+) under the conditions thought to prevail in vivo with respect to Mg(2+), inorganic pyrophosphate (PPi), and pH. The minimal reaction scheme that satisfactorily describes the effects of elevated Ca(2+) or CaPPi on the enzyme is one that invokes equilibrium binding of substrate (Mg(2)PPi) at one site, inhibitory binding of Mg(2)PPi to a lower-affinity second site, binding of activator (Mg(2+)) at a third site, and direct binding of Ca(2+) or CaPPi to a fourth site. Changes in enzyme activity in response to selective manipulation of either Ca(2+) or CaPPi are explicable only if Ca(2+), rather than CaPPi, is the inhibitory ligand. This conclusion is supported by the finding that CaPPi fails to mimic substrate in protection of the enzyme from inhibition by N-ethylmaleimide. Furthermore, the reaction scheme quantitatively and independently predicts the observed noncompetitive effects of free Ca(2+) on the substrate concentration dependence of H(+)-PPase activity. The results are discussed in relation to the previous proposal that CaPPi is the principal inhibitory ligand of the vacuolar H(+)-PPase (M. Maeshima [1991] Eur J Biochem 196: 11-17) and the possibility that in vivo modulation of cytosolic free Ca(2+) might constitute a specific mechanism for selective regulation of this enzyme, and consequently for stabilization of PPi levels in the cytoplasm of plant cells.

Journal Article↗
PubMed1991

Expression of functional bovine cholesterol side chain cleavage cytochrome P450 (P450scc) in Escherichia coli.

Escherichia coli expression vectors containing the trc promoter and the complete DNA sequence of either the precursor or the mature form of bovine adrenocortical cholesterol side chain cleavage cytochrome P450 (P450scc) were transformed into E. coli strain JM109 and transcription induced with isopropyl-beta-D-thiogalactopyranoside (IPTG). Immunoreactive cytochrome P450scc was produced using the plasmid containing the mature P450scc sequence but not with the plasmid containing the sequence of the precursor form of P450scc, even though P450scc RNA was detectable in both cases. The mature form of P450scc was detected spectrophotometrically in a reduced CO-difference spectrum in E. coli (40-60 nmol/liter culture). Cholesterol and hydroxylated derivatives (22-hydroxycholesterol and 25-hydroxycholesterol) produce a type 1 substrate-binding spectrum in IPTG-induced, transformed E. coli. The P450scc was found to be associated with the E. coli membrane fraction and the enzymatic activity of side chain cleavage of 25-hydroxycholesterol was reconstituted using solubilized membranes, in the presence of purified bovine adrenocortical adrenodoxin and NADPH-adrenodoxin reductase (turnover number; 15.4 nmol/min/nmol P450). This bacterial expression system provides functional P450scc, in the absence of other forms of P450, which can be used for evaluation of enzymatic and spectral properties of this mitochondrial P450 by site-directed mutagenesis.

Animals↗
PubMed1991

Vacuolar proton-pumping pyrophosphatase in Beta vulgaris shows vectorial activation by potassium.

Previous work with membrane vesicles has demonstrated an absolute dependence on K+ for proton translocation by the inorganic pyrophosphatase (H(+)-PPase: EC 3.6.1.1) from the vacuolar membrane (tonoplast) of higher plants. Using intact vacuoles from sugar beet (Beta vulgaris) storage tissue, we have monitored PP1-dependent currents by patch clamp in 'whole vacuole' mode. Serial K+ substitutions were made at both tonoplast faces. The results show that K+ activation occurs only at the cytosolic face.

Biological Transport↗
PubMed1991

Challenges to equity in health and health care: a Zimbabwean case study.

The current economic crisis in Africa has posed a serious challenge to policies of comprehensive and equitable health care. This paper examines the extent to which the Zimbabwe government has achieved the policy of "Equity in Health" it adopted at independence in 1980, that is provision of health care according to need. The paper identifies groups with the highest level of health needs in terms of both health status and economic factors which increase the risk of ill health. It describes a series of changes within the health sector in support of resource redistribution towards health needs, including a shift in the budget allocation towards preventive care, expansion of rural infrastructures, increased coverage of primary health care, introduction of free health services for those earning below Z$150 a month in 1980, increased manpower deployment in the public sector and the reorientation of medical training towards the health needs of the majority. The implementation of equity policies in health have however been challenged by several trends and features of the health care system, these becoming more pronounced in the economic stagnation period after 1983. These include the reduction in allocations to local authorities, increasing the pressure for fees, the static nominal level of the free health care limit despite inflation, the continued concentration of financial, higher cost manpower and other resources within urban, central and private sector health care and the lack of effective functioning of the referral system, with high cost central quaternary facilities being used as primary or secondary level care by nearby urban residents. While primary health care expansion has clearly been one of the success stories of Zimbabwe's health care post 1980, the paper notes plateauing coverage, with evidence of lack of coverage in more high risk, socio-economically marginal communities. Measures to address these continuing inequalities are discussed. Their implementation is seen to be dependent on increasing the capacity and organisation of the poor to more strongly influence policy and resource distribution in the health sector.

Financial Management↗
PubMed1991

Hyperopic thermokeratoplasty: clinical evaluation.

A new procedure, hyperopic thermokeratoplasty (HTK), developed in the Soviet Union for the correction of hyperopia, uses controlled thermal burns of the corneal stroma with a retractable probe tip preset to penetrate the cornea at 95% depth. The coagulations are applied in a radial pattern for spherical hyperopia. Only the peripheral cornea is treated and the effect is titrated by varying the optical zone and number of rays. The thermal effect flattens the peripheral cornea and steepens the central cornea. In this report, we prospectively evaluated the refractive results of a group of 61 HTK patients. Mean preoperative spherical equivalent was 3.9 diopters (D). Mean follow-up to date is 5.2 months, with 44% of cases evaluated at six months and 31% at one year. The initial effect of surgery (at one day) was a mean decrease in hyperopia of 6.0 D (standard error of the mean [S.E.] = 0.3 D), resulting in a mean spherical equivalent of -2.1 D (S.E. = 0.2 D). There was a steep regression of effect between one day and two months at which point average refraction was close to emmetropia. After two months, there was a gradual but continuing regression of effect, leveling off after six months. At five to six months, 63% of cases were undercorrected by at least a diopter; at 9 to 12 months, 83% of cases were undercorrected. The overall change in spherical equivalent at each time increased as optical zone size decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A high prevalence of hypothyroidism in association with endemic goitre in Zimbabwean schoolchildren.

One-hundred-and-eighty-eight ostensibly normal, pubertal schoolchildren, aged 9-16 years, residing in Chinamora Communal Land, Zimbabwe, had blood taken to assess thyroid function. Total goitre rate in the area was 44 per cent in primary schoolchildren: 91 of the subjects tested were goitrous. Thyroid stimulating hormone levels (TSH) were above normal (5.0 mu/l) in 66 subjects overall, of whom 39 were goitrous. The 36 subjects with TSH levels above 7.0 mu/l also had total thyroxine (T4) estimations performed: of these, 19 were below 60 nmol/l. The results indicate a high prevalence of hypothyroidism in this at risk group. The implications of these results are discussed, notably the impairment of mental function that is likely to result.

Adolescent↗
PubMed1990

Amino acid substitutions Phe66----Leu and Ser126----Pro abolish cortisol and aldosterone synthesis by bovine cytochrome P450(11)beta.

A cDNA clone encoding the complete protein sequence of the precursor form of bovine cytochrome P450(11)beta has been constructed using a combined technique of first strand cDNA synthesis by reverse transcription followed by polymerase chain reaction. Upon expression of this cDNA in COS 1 cells the P450(11)beta is found to be proteolytically processed and localized in the mitochondrion. This cDNA encodes the major form of P450(11)beta found in bovine adrenal cortex (designated 11 beta-3; Kirita, S., Morohashi, K., Hashimoto, T., Yoshioka, H., Fujii-Kuriyama, Y., and Omura, T. (1988) J. Biochem. 104, 683-686) and is capable of catalyzing 11 beta-hydroxylation of deoxycorticosterone, 11-deoxycortisol, and androstenedione in COS 1 cells as well as aldosterone synthesis from deoxycorticosterone. In addition, a second form of P450(11)beta (herein designated 11 beta-4), having no detectable 11 beta-hydroxylase activity or aldosterone synthase activity, was found in the local bovine population by this cloning procedure. These two forms of P450(11)beta (11 beta-3 and 11 beta-4) contain five amino acid differences between them, all located within the amino-terminal half of the molecules. By changing 2 of the amino acids in the inactive form to the corresponding amino acids in the active form (Leu66----Phe and Pro126----Ser) both 11 beta-hydroxylase and aldosterone synthetase activities were completely restored. Neither of these changes alone led to detectable activity. Thus, upon expression in mitochondria of heterologous cells, bovine P450(11)beta catalyzes both 11 beta-hydroxylation and aldosterone synthesis as reported previously for the purified enzyme in an in vitro reconstituted system, and Phe66 and Ser126 seem to be important residues in maintaining both activities.

Adrenal Cortex↗