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Biomedical subjects

D Sanders

Publications and source records attributed to D Sanders.

At least 19 recordsLinked to original sources
PubMed2001

Effect of thymectomy on human peripheral blood T cell pools in myasthenia gravis.

The human thymus is required for establishment of the T cell pool in fetal life, but postnatal thymectomy does not lead to immunodeficiency in humans. Because thymectomy in humans is performed for treatment of myasthenia gravis (MG), we have studied patients with MG for effects of thymectomy on peripheral blood (PB) naive (CD45RA(+), CD62L(+)) and memory (CD45RO(+)) T cells. We have also determined the effect of thymectomy on levels of PB cells containing signal joint TCR delta excision circles (TRECs), a molecular marker of thymus emigrants that have divided few times after leaving the thymus. In 17 nonthymectomized and 26 thymectomized MG patients studied at varying times after thymectomy (1 day to 41 years), we found no significant mean difference in PB T cell TREC levels between ages 40 and 80 years. However, both thymectomized and nonthymectomized MG patients had lower PB T cell TREC levels than did age-matched normal subjects (p < 0.0001 for both). These data demonstrated that MG itself or treatment for MG decreased thymopoiesis independent of thymectomy. Next, to control for disease activity and treatment, we prospectively studied 10 MG patients before and from 27 to 517 days after thymectomy. We found that thymectomy decreased CD4 or CD8 T cell TREC concentrations most when thymopoiesis was active before thymectomy (six of six patients), but had little effect in patients when thymopoiesis was minimal (four of four patients). In contrast, there was no significant effect of thymectomy on absolute numbers of naive PB T cells. Thus, in MG, removal of a thymus with active thymopoiesis resulted in a significant fall in PB TREC(+) T cells postthymectomy.

Adolescent↗
PubMed2001

Mobilization of Ca2+ by cyclic ADP-ribose from the endoplasmic reticulum of cauliflower florets.

The NAD+ metabolite cADP-Rib (cADPR) elevates cytosolic free Ca2+ in plants and thereby plays a central role in signal transduction pathways evoked by the drought and stress hormone abscisic acid. cADPR is known to mobilize Ca2+ from the large vacuole of mature cells. To determine whether additional sites for cADPR-gated Ca2+ release reside in plant cells, microsomes from cauliflower (Brassica oleracea) inflorescences were subfractionated on sucrose density gradients, and the distribution of cADPR-elicited Ca2+ release was monitored. cADPR-gated Ca2+ release was detected in the heavy-density fractions associated with rough endoplasmic reticulum (ER). cADPR-dependent Ca2+ release co-migrated with two ER markers, calnexin and antimycin A-insensitive NADH-cytochrome c reductase activity. To investigate the possibility that contaminating plasma membrane in the ER-rich fractions was responsible for the observed release, plasma membrane vesicles were purified by aqueous two-phase partitioning, everted with Brij-58, and loaded with Ca2+: These vesicles failed to respond to cADPR. Ca2+ release evoked by cADPR at the ER was fully inhibited by ruthenium red and 8-NH2-cADPR, a specific antagonist of cADPR-gated Ca2+ release in animal cells. The presence of a Ca2+ release pathway activated by cADPR at higher plant ER reinforces the notion that, alongside the vacuole, the ER participates in Ca2+ signaling.

Adenosine Diphosphate Ribose↗
PubMed2001

Pyridostigmine bromide and the long-term subjective health status of a sample of female reserve component Gulf War veterans: a brief report.

The role of pyridostigmine bromide (PB) pills in explaining the long-term subjective health status of a sample of over 100 female Reserve Component Gulf War veterans was examined through regression analysis. Results fell just short of significance (p < .06) for the prediction of subjective health approximately six years after the war and were clearly not significant for the prediction of subjective health at previous times. Results parallel Golomb's 1999 RAND report, which found suggestive but not conclusive evidence for the possible adverse effects of Gulf War veterans' consumption of pyridostigmine bromide pills. Our data suggest that use of more than 10 pills may have been especially risky with respect to long-term subjective health.

Adult↗
PubMed2001

Petrolatum versus Resurfix ointment in the treatment of pressure ulcers.

This study compares the therapeutic effects of a new topically applied, nonprescription medication that has been introduced for re-epithelialization of ulcers and erosions of the skin, with petrolatum in treating pressure ulcers of shallow depth (Stage I and Stage II). A 6-week, randomized, double-blind study was performed on 19 patients with Stage I or Stage II pressure ulcers. The patients received either the new nonprescription medication or petrolatum, which served as a control. After the course of the study, the study ointment effected resolution in a majority of pressure ulcers (9 out of 10), while only one out of three ulcers treated with petrolatum resolved in the same time period. These preliminary results show that the study ointment is a safe and effective treatment for Stage I and II pressure ulcers.

Aged↗
PubMed2001

Evaluating the clinical management of severely malnourished children--a study of two rural district hospitals.

BACKGROUND: Severe malnutrition is an important cause of preventable mortality in most South African hospitals. Work recently done in two rural Eastern Cape hospitals supports the literature which shows that many deaths occur as a result of outdated clinical practices and that improving these practices reduces case fatality rates. Rapid assessment of clinical management in paediatric wards is necessary to highlight areas for improvement. OBJECTIVE: To assess the management of severely malnourished children in two rural district hospitals and to recommend improvements for their care. METHODS: Based on draft World Health Organisation (WHO) guidelines for inpatient care of children with severe malnutrition, data collection instruments were developed in conjunction with the district nutrition team to assess the quality of care given to malnourished children in two Mount Frere hospitals, Eastern Cape. Data were collected through retrospective review of case records, with detailed studies of selected cases, structured observations of the paediatric wards, and interviews with ward sisters and doctors. RESULTS: The combined case fatality rate for severe malnutrition was 32%. Inadequate feeding, poor management of rehydration and infection, lack of resources, and a lack of knowledge and motivation among staff were identified as areas that need attention. CONCLUSION: The clinical management of severely malnourished children can be rapidly assessed to highlight areas for improvement. Involving staff in the assessment process has led to their active involvement in improving the management of malnourished children in their hospitals.

Child↗
PubMed2000

Recombinant cytochrome rC557 obtained from Escherichia coli cells expressing a truncated Thermus thermophilus cycA gene. Heme inversion in an improperly matured protein.

Cytochrome rC(557) is an improperly matured, dimeric cytochrome c obtained from expression of the "signal peptide-lacking" Thermus thermophilus cycA gene in the cytoplasm of Escherichia coli. It is characterized by its Q(00) (or alpha-) optical absorption band at 557 nm in the reduced form (Keightley, J. A., Sanders, D., Todaro, T. R., Pastuszyn, A., and Fee, J. A. (1998) J. Biol. Chem. 273, 12006-12016). We report results of a broad ranging, biochemical and spectral characterization of this protein that reveals the presence of a free vinyl group on the porphyrin and a disulfide bond between the protomers and supports His-Met ligation in both valence states of the iron. A 3-A resolution x-ray structure shows that, in comparison with the native protein, the heme moiety is rotated 180 degrees about its alpha,gamma-axis; cysteine 14 has formed a thioether bond with the 2-vinyl of pyrrole ring I instead of the 4-vinyl of pyrrole ring II, as occurs in the native protein; and a cysteine 11 from each protomer has formed an intermolecular disulfide bond. Numerous, minor perturbations exist within the structure of rC(557) in comparison with that of native protein, which result from heme inversion and protein-protein interactions across the dimer interface. The unusual spectral properties of rC(557) are rationalized in terms of this structure.

Crystallography↗
PubMed2000

Calcium release from the endoplasmic reticulum of higher plants elicited by the NADP metabolite nicotinic acid adenine dinucleotide phosphate.

Higher plants share with animals a responsiveness to the Ca(2+) mobilizing agents inositol 1,4,5-trisphosphate (InsP(3)) and cyclic ADP-ribose (cADPR). In this study, by using a vesicular (45)Ca(2+) flux assay, we demonstrate that microsomal vesicles from red beet and cauliflower also respond to nicotinic acid adenine dinucleotide phosphate (NAADP), a Ca(2+)-releasing molecule recently described in marine invertebrates. NAADP potently mobilizes Ca(2+) with a K(1/2) = 96 nM from microsomes of nonvacuolar origin in red beet. Analysis of sucrose gradient-separated cauliflower microsomes revealed that the NAADP-sensitive Ca(2+) pool was derived from the endoplasmic reticulum. This exclusively nonvacuolar location of the NAADP-sensitive Ca(2+) pathway distinguishes it from the InsP(3)- and cADPR-gated pathways. Desensitization experiments revealed that homogenates derived from cauliflower tissue contained low levels of NAADP (125 pmol/mg) and were competent in NAADP synthesis when provided with the substrates NADP and nicotinic acid. NAADP-induced Ca(2+) release is insensitive to heparin and 8-NH(2)-cADPR, specific inhibitors of the InsP(3)- and cADPR-controlled mechanisms, respectively. However, NAADP-induced Ca(2+) release could be blocked by pretreatment with a subthreshold dose of NAADP, as previously observed in sea urchin eggs. Furthermore, the NAADP-gated Ca(2+) release pathway is independent of cytosolic free Ca(2+) and therefore incapable of operating Ca(2+)-induced Ca(2+) release. In contrast to the sea urchin system, the NAADP-gated Ca(2+) release pathway in plants is not blocked by L-type channel antagonists. The existence of multiple Ca(2+) mobilization pathways and Ca(2+) release sites might contribute to the generation of stimulus-specific Ca(2+) signals in plant cells.

Brassica↗
PubMed2000

The salty tale of Arabidopsis.

High concentrations of sodium chloride are toxic to most plant species. New insights into the mechanisms by which plants tolerate salt have emerged from the identification of genes in Arabidopsis thaliana that play a critical part in physiological resistance to salt.

Adaptation, Physiological↗
PubMed2000

Where do all the ions go? The cellular basis of differential ion accumulation in leaf cells.

Leaf cells accumulate solutes differently depending on their cell type. The accumulation profiles of inorganic ions have been well documented for the mesophyll and epidermis, particularly in cereals. These cell types accumulate ions such as phosphate and calcium to strikingly different extents. Understanding the processes that control ion accumulation could reveal how plants respond to either a limiting supply of important micro- and macronutrient ions or to potentially toxic loads of salts or heavy metal ions. Research has recently begun to reveal the processes that underlie this remarkable sorting of nutrient ions within the leaf.

Edible Grain↗
PubMed2000

Expression of a truncated tobacco NtCBP4 channel in transgenic plants and disruption of the homologous Arabidopsis CNGC1 gene confer Pb2+ tolerance.

Recently we reported on a plasma membrane tobacco protein (designated NtCBP4) that binds calmodulin. When overexpressed in transgenic plants, NtCBP4 confers Pb2+ hypersensitivity associated with enhanced accumulation of this toxic metal. To further investigate possible modulation of Pb2+ tolerance in plants, we prepared transgenic plants that express a truncated version of this protein (designated NtCBP4DeltaC) from which its C-terminal, with the calmodulin-binding domain and part of the putative cyclic nucleotide-binding domain, was removed. In contrast to the phenotype of transgenic plants expressing the full-length gene, transgenic plants expressing the truncated gene showed improved tolerance to Pb2+, in addition to attenuated accumulation of this metal. Furthermore, disruption by T-DNA insertion mutagenesis of the Arabidopsis CNGC1 gene, which encodes a homologous protein, also conferred Pb2+ tolerance. We suggest that NtCBP4 and AtCNGC1 are components of a transport pathway responsible for Pb2+ entry into plant cells.

Adaptation, Physiological↗
PubMed2000

Differential ion accumulation and ion fluxes in the mesophyll and epidermis of barley.

In barley (Hordeum vulgare L.) leaves, differential ion accumulation commonly results in inorganic phosphate (Pi) being confined to the mesophyll and Ca(2+) to the epidermis, with preferential epidermal accumulation of Cl(-), Na(+), and some other ions. The pattern was confirmed in this study for major inorganic anions and cations by analysis of barley leaf protoplasts. The work focused on the extent to which differences in plasma membrane ion transport processes underlie these observations. Ion transport across the plasma membrane of barley epidermal and mesophyll protoplasts was investigated electrophysiologically (by microelectrode impalement and patch clamping) and radiometrically. Data from both approaches suggested that similar types of ion-selective channels and membrane transporters, which catalyze the transport of Ca(2+), K(+), Na(+), and Pi, exist in the plasma membrane of the two cell types. In general, the simple presence or absence of ion transporters could not explain cell-type-specific differences in ion accumulation. However, patch-clamp data suggested that differential regulation of instantaneously activating ion channels in the plasma membrane could explain the preferential accumulation of Na(+) in the epidermis.

Calcium↗
PubMed2000

Sodium-dependent nitrate transport at the plasma membrane of leaf cells of the marine higher plant Zostera marina L.

NO(3)(-) is present at micromolar concentrations in seawater and must be absorbed by marine plants against a steep electrochemical potential difference across the plasma membrane. We studied NO(3)(-) transport in the marine angiosperm Zostera marina L. to address the question of how NO(3)(-) uptake is energized. Electrophysiological studies demonstrated that micromolar concentrations of NO(3)(-) induced depolarizations of the plasma membrane of leaf cells. Depolarizations showed saturation kinetics (K(m) = 2.31 +/- 0.78 microM NO(3)(-)) and were enhanced in alkaline conditions. The addition of NO(3)(-) did not affect the membrane potential in the absence of Na(+), but depolarizations were restored when Na(+) was resupplied. NO(3)(-)-induced depolarizations at increasing Na(+) concentrations showed saturation kinetics (K(m) = 0.72 +/- 0.18 mM Na(+)). Monensin, an ionophore that dissipates the Na(+) electrochemical potential, inhibited NO(3)(-)-evoked depolarizations by 85%, and NO(3)(-) uptake (measured by depletion from the external medium) was stimulated by Na(+) ions and by light. Our results strongly suggest that NO(3)(-) uptake in Z. marina is mediated by a high-affinity Na(+)-symport system, which is described here (for the first time to our knowledge) in an angiosperm. Coupling the uptake of NO(3)(-) to that of Na(+) enables the steep inwardly-directed electrochemical potential for Na(+) to drive net accumulation of NO(3)(-) within leaf cells.

Cell Membrane↗
PubMed2000

Understanding mail survey response rates among male reserve component Gulf War era veterans.

In this study of current and former male Reserve and National Guard members from the State of Ohio, it was expected that veterans who were older, had more years of military service, who had participated in the Persian Gulf War, who were Euro-Americans, who were higher in rank, who had higher residential stability in Ohio, who belonged to the Air Force, who had higher formal education, and who belonged to the National Guard would have a greater investment in U.S. society as defined by 11 demographic variables. It was assumed that those with greater investment in society would more often have valid addresses and would be more likely to respond to a survey on military issues, thereby biasing sample outcomes in those directions. Results for male veterans were consistent with the hypothesis that investment in the society system would predict validity of addresses and response rates. In other words, results supported the idea that those veterans who might be expected to have a greater investment in U.S. society were more likely to be located and to respond (once located) to a survey concerning Desert Storm-era military service and its aftermath. Implications for future Desert Storm research are discussed.

Adult↗