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D Oliver

Publications and source records attributed to D Oliver.

At least 37 records · Page 2Linked to original sources
PubMed2000

Gating of Ca2+-activated K+ channels controls fast inhibitory synaptic transmission at auditory outer hair cells.

Fast inhibitory synaptic transmission in the central nervous system is mediated by ionotropic GABA or glycine receptors. Auditory outer hair cells present a unique inhibitory synapse that uses a Ca2+-permeable excitatory acetylcholine receptor to activate a hyperpolarizing potassium current mediated by small conductance calcium-activated potassium (SK) channels. It is shown here that unitary inhibitory postsynaptic currents at this synapse are mediated by SK2 channels and occur rapidly, with rise and decay time constants of approximately 6 ms and approximately 30 ms, respectively. This time course is determined by the Ca2+ gating of SK channels rather than by the changes in intracellular Ca2+. The results demonstrate fast coupling between an excitatory ionotropic neurotransmitter receptor and an inhibitory ion channel and imply rapid, localized changes in subsynaptic calcium levels.

Animals↗
PubMed2000

Tyr-326 plays a critical role in controlling SecA-preprotein interaction.

SecA is an essential ATP-dependent motor protein that interacts with the preprotein and translocon to drive protein translocation across the eubacterial plasma membrane. A region containing residues 267-340 has been proposed to comprise the preprotein binding site of Escherichia coli SecA. To elucidate the function of this region further, we isolated mutants using a combination of region-specific polymerase chain reaction (PCR) mutagenesis and a genetic and biochemical screening procedure. Although this region displayed considerable plasticity based on phylogenetic and genetic analysis, Tyr-326 was found to be critical for SecA function. secA mutants with non-conservative substitutions at Tyr-326 showed strong protein secretion defects in vivo and were completely defective for SecA-dependent translocation ATPase activity in vitro. The SecA-Y326 mutant proteins were normal in their membrane, SecYE and nucleotide-binding properties. However, they exhibited a reduced affinity for preprotein and were defective in preprotein release, as assessed by several biochemical assays. Our results indicate that the region containing Tyr-326 functions as a conformational response element to regulate the preprotein binding and release cycle of SecA.

Adenosine Diphosphate↗
PubMed2000

Polyamines as gating molecules of inward-rectifier K+ channels.

Inward-rectifier potassium (Kir) channels comprise a superfamily of potassium (K+) channels with unique structural and functional properties. Expressed in virtually all types of cells they are responsible for setting the resting membrane potential, controlling the excitation threshold and secreting K+ ions. All Kir channels present an inwardly rectifying current-voltage relation, meaning that at any given driving force the inward flow of K+ ions exceeds the outward flow for the opposite driving force. This inward-rectification is due to a voltage-dependent block of the channel pore by intracellular polyamines and magnesium. The present molecular-biophysical understanding of inward-rectification and its physiological consequences is the topic of this review. In addition to polyamines, Kir channels are gated by intracellular protons, G-proteins, ATP and phospholipids depending on the respective Kir subfamily as detailed in the following review articles.

Animals↗
PubMed2000

Serum itraconazole concentrations and clinical responses in Candida-associated denture stomatitis patients treated with itraconazole solution and itraconazole capsules.

The aim of this study was to compare the concentrations of itraconazole in serum and saliva after treatment with itraconazole cyclodextrin solution or itraconazole capsules in Candida-associated denture stomatitis patients without evidence of immunodeficiency. Forty patients were randomly assigned to receive either itraconazole cyclodextrin solution or itraconazole capsules, both at a dosage of 100 mg bd for 15 days. On completion of treatment palatal erythema was assessed and an oral rinse and imprint cultures were collected. Serum and saliva samples were collected at the same time and itraconazole concentrations measured using reverse-phase high-performance liquid chromatography. Itraconazole susceptibilities of Candida albicans and Candida glabrata strains isolated at baseline were measured by a broth microdilution method. Serum itraconazole concentrations achieved did not differ significantly between the two preparations (P = 0.39) although a significantly higher number of patients in the itraconazole cyclodextrin group (P < 0.001) had detectable levels of itraconazole in their saliva compared with the capsule group. Mycologically cured patients had slightly, though not significantly (P = 0.28), higher serum itraconazole concentrations than those from whom yeasts were not eradicated. It was concluded that both formulations of itraconazole were equally effective in treatment of denture stomatitis. Among immunocompetent patients, the absorption of the liquid preparation is no greater than that of the capsules. Therapeutic success in this group was achieved with lower serum itraconazole concentrations than have been reported for immunocompromised groups.

Adult↗
PubMed2000

Do hospital fall prevention programs work? A systematic review.

OBJECTIVES: To analyze published hospital fall prevention programs to determine whether there is any effect on fall rates. To review the methodological quality of those programs and the range of interventions used. To provide directions for further research. DESIGN: Systematic review of published hospital fall prevention programs. Meta-analysis. METHODS: Keyword searches of Medline, CINAHL, monographs, and secondary references. All papers were included that described fall rates before and during intervention. Risk ratios and 95% Confidence Intervals (95% CI) were estimated and random effects meta-analysis employed. Begg's test was applied to detect possible publication bias. Separate meta-analysis regressions were performed to determine whether individual components of multifaceted interventions were effective. RESULTS: A total of 21 papers met the criteria (18 from North America), although only 10 contained sufficient data to allow calculation of confidence intervals. A rate ratio of <1 indicates a reduction in the fall rate, resulting from an intervention. Three were randomized controlled trials (pooled rate ratio 1.0 (CI 0.60, 1.68)), seven prospective studies with historical control (0.76 (CI 0.65, 0.88)). Pooled effect rate ratio from these 10 studies was 0.79 (CI 0.69, 0.89). The remaining 11 studies were prospective studies with historical control describing fall rates only. Individual components of interventions showed no significant benefit. DISCUSSION: The pooled effect of about 25% reduction in the fall rate may be a result of intervention but may also be biased by studies that used historical controls not allowing for historical trends in the fall rate before and during the intervention. The randomized controlled trials apparent lack of effect might be due to a change in practice when patients and controls were in the same unit at the same time during a study. Studies did not analyze compliance with the intervention or opportunity costs resulting from the intervention. Research and clinical programs in hospital fall prevention should pay more attention to study design and the nature of interventions.

Accidental Falls↗
PubMed2000

Revised translation start site for secM defines an atypical signal peptide that regulates Escherichia coli secA expression.

The secretion-responsive regulation of Escherichia coli secA occurs by coupling its translation to the translation and secretion of an upstream regulator, secM (formerly geneX). We revise the translational start site for secM, defining a new signal peptide sequence with an extended amino-terminal region. Mutational studies indicate that certain atypical amino acyl residues within this extended region are critical for proper secA regulation.

Adenosine Triphosphatases↗
PubMed1999

Expression density and functional characteristics of the outer hair cell motor protein are regulated during postnatal development in rat.

1. The non-linear capacitance (Cnon-lin) of postnatal outer hair cells (OHCs) of the rat was measured by a patch-clamp lock-in technique. Cnon-lin is thought to result from a membrane protein that provides the molecular basis for the unique electromotility of OHCs by undergoing conformational changes in response to changes in membrane potential (Vm). Protein conformation is coupled to Vm by a charged voltage sensor, which imposes Cnon-lin on the OHC. Cnon-lin was investigated in order to characterize the surface expression and voltage dependence of this motor protein during postnatal development. 2. On the day of birth (P0), Cnon-lin was not detected in OHCs of the basal turn of the cochlea, whilst it was 89 fF in apical OHCs. Cnon-lin increased gradually during postnatal development and reached 2.3 pF (basal turn, P9) and 7.5 pF (apical turn, P14) at the oldest developmental stages covered by our measurements. The density of the protein in the plasma membrane, deduced from non-linear charge movement per membrane area, increased steeply between P6 and P11 and reached steady state (4200 e- microm-2) at about P12. 3. Voltage at peak capacitance (V) shifted with development from hyperpolarized potentials shortly after birth (-88.3 mV, P2) to the depolarized potential characteristic of mature OHCs (-40.8 mV, P14). This developmental difference in V was also observed in outside-out patches immediately after patch excision. During subsequent wash-out V shifted towards the depolarized value found in the adult state, suggesting a direct modulation of the molecular motor. 4. Thus, the density of the motor protein in the plasma membrane and also its voltage dependence change concomitantly in the postnatal period and reach adult characteristics right at the onset of hearing.

Animals↗
PubMed1998

Thyroid hormone receptor beta-dependent expression of a potassium conductance in inner hair cells at the onset of hearing.

To elucidate the role of thyroid hormone receptors (TRs) alpha1 and beta in the development of hearing, cochlear functions have been investigated in mice lacking TRalpha1 or TRbeta. TRs are ligand-dependent transcription factors expressed in the developing organ of Corti, and loss of TRbeta is known to impair hearing in mice and in humans. Here, TRalpha1-deficient (TRalpha1(-/-)) mice are shown to display a normal auditory-evoked brainstem response, indicating that only TRbeta, and not TRalpha1, is essential for hearing. Because cochlear morphology was normal in TRbeta-/- mice, we postulated that TRbeta regulates functional rather than morphological development of the cochlea. At the onset of hearing, inner hair cells (IHCs) in wild-type mice express a fast-activating potassium conductance, IK,f, that transforms the immature IHC from a regenerative, spiking pacemaker to a high-frequency signal transmitter. Expression of IK,f was significantly retarded in TRbeta-/- mice, whereas the development of the endocochlear potential and other cochlear functions, including mechanoelectrical transduction in hair cells, progressed normally. TRalpha1(-/-) mice expressed IK,f normally, in accord with their normal auditory-evoked brainstem response. These results establish that the physiological differentiation of IHCs depends on a TRbeta-mediated pathway. When defective, this may contribute to deafness in congenital thyroid diseases.

Aging↗
PubMed1998

PIP2 and PIP as determinants for ATP inhibition of KATP channels.

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of KATP channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4, 5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned KATP channels (Kir6.2 and SUR1). These phospholipids acted on the Kir6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of KATP-mediated currents. These results represent a mechanism for control of excitability through phospholipids.

ATP-Binding Cassette Transporters↗
PubMed1998

Sequence and phylogenetic analysis of the Borrelia burgdorferi secA gene.

A Borrelia burgdorferi secA homologue was cloned and the complete DNA sequence was determined. The deduced protein sequence consists of 899 amino acids and shows a high degree of homology to SecA homologues from other Bacteria and photosynthetic plastids. The presence of the secA gene in Spirochetes suggests that this gene is present in most if not all major lineages within Bacteria. The ease of isolation of secA by conservation of its ATP-binding motifs combined with its extreme conservation in protein secretion pathways and the presence of a phylogenetic sequence marker in one of its ATP-binding domains makes this gene useful for phylogenetic analysis of Bacteria and photosynthetic plastids.

Adenosine Triphosphatases↗
PubMed1998

A model for making outcomes research standard practice in clinical dietetics.

In today's rapidly changing health care environment, it is imperative that dietitians demonstrate the importance of their role as health care providers by initiating and participating in outcomes research. Patient care should be based on empirical studies, and clinical dietitians should participate in or be at the helm of such investigations. Nutrition research is usually accomplished and reported by persons with MD or PhD degrees who do not have clinical training in nutrition and does not often address situations encountered by dietitians in clinical settings. This article examines the extent to which clinical dietitians are conducting and reporting outcomes research, their attitudes about such research, and how they think they could best acquire the skills needed to incorporate outcomes research into their practice. Results indicate that clinical dietitians are not writing a substantial percentage of articles and that reports of outcomes research are not commonly included in clinical nutrition journals. Clinical dietitians appear to value the inclusion of research in clinical practice, but they are not spending a great amount of time doing research. Dietitians report being comfortable about participating in research but not about designing, conducting, and reporting research. Results from several surveys were used to develop a model for integrating research in clinical practice. This model includes the research process as a basis for clinical practice. A model for collaborative efforts between clinical and academic dietitians is also proposed and emphasizes the responsibility of academic dietetics training programs in the integration of research and clinical practice.

Attitude of Health Personnel↗
PubMed1998

Interaction of permeant and blocking ions in cloned inward-rectifier K+ channels.

Blocking cloned inward-rectifier potassium (Kir) channels from the cytoplasmic side was analyzed with a rapid application system exchanging the intracellular solution on giant inside-out patches from Xenopus oocytes in <2 ms. Dependence of the pore-block on interaction of the blocking molecule with permeant and impermeant ions on either side of the membrane was investigated in Kir1.1 (ROMK1) channels blocked by ammonium derivatives and in Kir4.1 (BIR10) channels blocked by spermine. The blocking reaction in both systems showed first-order kinetics and allowed separate determination of on- and off-rates. The off-rates of block were strongly dependent on the concentration of internal and external bulk ions, but almost independent of the ion species at the cytoplasmic side of the membrane. With K+ as the only cation on both sides of the membrane, off-rates exhibited strong coupling to the K+ reversal potential (E(K)) and increased and decreased with reduction in intra and extracellular K+ concentration, respectively. The on-rates showed significant dependence on concentration and species of internal bulk ions. This control of rate-constants by interaction of permeant and impermeant internal and external ions governs the steady-state current-voltage relation (I-V) of Kir channels and determines their physiological function under various conditions.

Animals↗
PubMed1998

Brown-midrib maize (bm1)--a mutation affecting the cinnamyl alcohol dehydrogenase gene.

Brown-midrib (bm) mutants of maize have modified lignin of reddish-brown colour. Although four independent bm loci are known, only one of the mutant genes has been previously identified. We report here that maize bm1, one of the less characterised mutants, shows severely reduced CAD activity in lignified tissues, resulting in the production of a modified lignin. Both the total lignin content and the structure of the polymer are altered by the mutation. We further describe the isolation and characterisation of the maize CAD cDNA and mapping of the CAD gene. CAD maps very closely to the known location of bm1 and co-segregates with the bm1 locus in two independent recombinant inbred populations. These data strongly support the premise that maize bm1 directly affects expression of the CAD gene.

Alcohol Oxidoreductases↗
PubMed1998

Regulation of Escherichia coli secA by cellular protein secretion proficiency requires an intact gene X signal sequence and an active translocon.

secA is translationally regulated by the protein secretion proficiency state of the Escherichia coli cell. This regulation was explored by making signal sequence mutations in the gene upstream of secA, gene X, which promotes secA translational coupling. Gene X signal sequence mutants were constitutive for secA expression, while prlA alleles partially restored secA regulation. These results show that interaction of the pre-gene X protein with the translocon is required for proper secA regulation. Furthermore, gene X signal sequence mutations disrupted secA regulation only in the cis configuration. We propose that nascent pre-gene X protein interacts with the translocon during its secretion to constitute the secretion sensor.

Adenosine Triphosphatases↗