Search PubMed⌕ Search

Biomedical subjects

R E White

Publications and source records attributed to R E White.

At least 73 records · Page 4Linked to original sources
PubMed1991

Somatostatin stimulates Ca(2+)-activated K+ channels through protein dephosphorylation.

The neuropeptide somatostatin inhibits secretion from electrically excitable cells in the pituitary, pancreas, gut and brain. In mammalian pituitary tumour cells somatostatin inhibits secretion through two distinct pertussis toxin-sensitive mechanisms. One involves inhibition of adenylyl cyclase, the other an unidentified cyclic AMP-independent mechanism that reduces Ca2+ influx by increasing membrane conductance to potassium. Here we demonstrate that the predominant electrophysiological effect of somatostatin on metabolically intact pituitary tumour cells is a large, sustained increase in the activity of the large-conductance Ca(2+)- and voltage-activated K+ channels (BK). This action of somatostatin does not involve direct effects of Ca2+, cAMP or G proteins on the channels. Our results indicate instead that somatostatin stimulates BK channel activity through protein dephosphorylation.

Animals↗
PubMed1991

The involvement of free radicals in the mechanisms of monooxygenases.

The occurrence of free radicals in the mechanisms of monooxygenases reflects the chemistry of dioxygen and the inertness of typical substrates. Thus, oxidation of such substrates requires attack by reduced dioxygen-derived free radicals. Consequently, a molecule of NAD(P)H must be invested for each substrate molecule oxidized. Furthermore, since free radicals are difficult to control, deviations from the intended reaction course are frequent. These considerations are illustrated by examination of the generation and fate of enzyme- and substrate-derived free radicals at various stages in the catalytic cycles of two monooxygenases important in xenobiotic biotransformation, dopamine beta-hydroxylase and cytochrome P-450.

Animals↗
PubMed1991

Enzymatic gating of voltage-activated calcium channels.

The model of calcium-channel gating described above, although almost certainly too simple, suggests a direct role for protein kinases and phosphatases in determining the kinetics of calcium channel gating on a subsecond time scale. In addition, it provides a unique perspective for understanding studies of calcium channel gating under widely different metabolic and pharmacological conditions. Although many of these effects may be specific to the dihydropyridine-sensitive or L-type calcium channel, they give an indication of the range of possibilities for integrating calcium-channel activity with cellular biochemistry.

Animals↗
PubMed1991

Regulation of Ca2+ current in frog ventricular cardiomyocytes by 5'-guanylylimidodiphosphate and acetylcholine.

1. Calcium currents (ICa) were measured in frog ventricular myocytes using the whole-cell patch clamp technique and a perfused pipette. The effect of internal perfusion with the hydrolysis-resistant GTP analogue, GppNHp (5'guanylylimidodiphosphate), on basal ICa and ICa stimulated with forskolin or isoprenaline was examined to gain insight into the role of G proteins in ICa regulation. 2. Without added guanine nucleotides, isoprenaline stimulated ICa approximately 14-fold with an EC50 of 0.09 microM. Forskolin stimulated ICa approximately 10-fold with an EC50 of 0.30 microM. 3. Internal 30 microM-GppNHp produced an approximately 80% decrease in ICa elevated by 0.3 microM-isoprenaline or 3 microM-forskolin. The inhibition of isoprenaline stimulation was due to a decrease in the maximal stimulation from approximately 14-fold to approximately 14-fold without a significant change in the EC50. In contrast, the reduction in forskolin stimulation was due to a 22-fold increase in the EC50 to 11.4 microM, with little change in maximal stimulation. 4. The inhibition of stimulated ICa by GppNHp is likely to be mediated by a G protein, because the effects of GppNHp are irreversible, and are blocked by excess GTP. ICa is affected similarly by GppNHp and by ACh. This suggests that GppNHp activates the same G protein that is normally activated by ACh, but activation by GppNHp occurs in the absence of agonist occupation of the muscarinic receptor. 5. The increase in the EC50 for forskolin produced by internal GppNHp was reversed by exposure to isoprenaline, which itself did not affect ICa amplitude. On average, exposure to isoprenaline in the presence of GppNHp caused an irreversible 81-fold decrease in the EC50 for forskolin to 0.14 microM. Stimulation of ICa by forskolin after internal GppNHp and exposure to isoprenaline was completely blocked by the protein kinase A inhibitor PKI(5-22). 6. These effects do not involve the phospholipase C system, because they are not mimicked by phorbol esters or internal inositol 1,4,5-trisphosphate (IP3) and are not blocked by bromophenacyl bromide or neomycin. 7. Direct effects of G proteins on ICa were not evident, because internal perfusion with PKI(5-22) completely inhibited isoprenaline- or forskolin-stimulated increases in ICa, and neither ACh nor internal GppNHp (30-500 microM) affected basal ICa or ICa elevated by internally perfused cyclic AMP. 8. These results suggest that the predominant site of action of the inhibitory G protein activated by either GppNHp or ACh is adenylyl cyclase. Furthermore, the internally perfused frog cardiomyocytes may provide a useful approach for probing the detailed interactions of G proteins, forskolin, and adenylyl cyclase in an intact cell.

Acetylcholine↗
PubMed1991

Synthesis and antibacterial activity of new C-10 quinolonyl-cephem esters.

A series of cephalosporins derived from cephalothin containing an ester-linked quinolonyl substituent at the C-10 position (C-10 quinolonyl-cephem esters) has been prepared and evaluated for in vitro antibacterial activity. The C-10 quinolonyl-cephem esters exhibited a broadened spectrum of activity when compared with cephalothin and the corresponding quinolones, including activity against beta-lactamase-producing bacteria.

Bacteria↗
PubMed1990

Vascular contraction induced by activation of membrane calcium ion channels is enhanced in streptozotocin-diabetes.

Previous results from our laboratory (White and Carrier, Enhanced Vascular Alpha-Adrenergic Neuroeffector System in Diabetes: Importance of Calcium. Am. J. Physiol. 255: H1036-1042, 1988) demonstrated that mesenteric arteries from streptozotocin (STZ)-diabetic rats exhibit an enhanced responsiveness to alpha adrenergic agonists. The present study demonstrates that this enhanced responsiveness is dependent upon the presence of extracellular calcium. Arteries from STZ-diabetic (10-12 weeks) rats developed greater contractile force in response to norepinephrine or KCl. Development of these effects was prevented by daily insulin treatment, indicating these alterations are related to the diabetic state. Similarly, the contractile response to extracellular calcium in the presence of norepinephrine (3 x 10(-6) M) or KCl (60 mM) was greater in arteries from STZ-diabetic animals. BAY K 8644, a calcium channel agonist, induced greater contraction in arteries from STZ-diabetic animals, as did activation of protein kinase C by phorbol dibutyrate. In contrast, contraction induced by release of calcium from intracellular sources (alpha-1 adrenoceptor-mediated or caffeine-induced) was unaltered by diabetes. These findings indicate that enhanced vascular contraction in STZ-diabetes is of a nonspecific nature, i.e., the contractile response to any agent which induces extracellular calcium-dependent contraction should be enhanced in diabetes. We propose that STZ-diabetes enhances the activity and/or number of calcium ion channels in vascular smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effects of magnesium on inactivation of the voltage-gated calcium current in cardiac myocytes.

The effects of changes in intracellular and extracellular free ionized [Mg2+] on inactivation of ICa and IBa in isolated ventricular myocytes of the frog were investigated using the whole-cell configuration of the patch-clamp technique. Intracellular [Mg2+] was varied by internal perfusion with solutions having different calculated free [Mg2+]. Increasing [Mg2+]i from 0.3 mM to 3.0 mM caused a 16% reduction in peak ICa amplitude and a 36% reduction in peak IBa amplitude, shifted the current-voltage relationship and the inactivation curve approximately 10 mV to the left, decreased relief from inactivation, and caused a dramatic increase in the rate of inactivation of IBa. The shifts in the current-voltage and inactivation curves were attributed to screening of internal surface charge by Mg2+. The increased rate of inactivation of IBa was due to an increase in both the steady-state level of inactivation as well as an increase in the rate of inactivation, as measured by two-pulse inactivation protocols. Increasing external [Mg2+] decreased IBa amplitude and shifted the current-voltage and inactivation curves to the right, but, in contrast to the effect of internal Mg2+, had little effect on the inactivation kinetics or the steady-state inactivation of IBa at potentials positive to 0 mV. These observations suggest that the Ca channel can be blocked quite rapidly by external Mg2+, whereas the block by [Mg2+]i is time and voltage dependent. We propose that inactivation of Ca channels can occur by both calcium-dependent and purely voltage-dependent mechanisms, and that a component of voltage-dependent inactivation can be modulated by changes in cytoplasmic Mg2+.

Animals↗
PubMed1988

Physicians and the organizational evolution of medicine.

Within medicine there is growing uneasiness and debate about changes in medical care delivery. Much of this concern centers on the evolution of organizations and the role of physicians. The emergence of multi-institutional organizations, the rise of investor-owned health care corporations, and the expansion of group medical practice illustrate the increasing organizational influence in medicine. Added to these trends are new financial incentives confronting both physicians and organizations so that the environment increasingly favors conflict. This article reviews the primary strategies for resolving physician-organization conflicts, including cooperation between physicians and organizations, having physician representatives in governance and management, restructuring incentives, and restructuring organizations. Although these strategies have various merits, we suggest that every physician has a personal responsibility to become more involved in organization and management issues. Physicians can play an important role in guiding the evolution of medicine.

Conflict, Psychological↗
PubMed1988

Effects of intracellular free magnesium on calcium current in isolated cardiac myocytes.

Magnesium ions play a fundamental role in cellular function, but the effects of changes in the concentration of intracellular ionized magnesium ([Mg2+]i) on cell physiology have only recently received experimental attention. Increasing [Mg2+]i from 0.3 to 3.0 mM in cardiac cells by internal perfusion has only small effects on the basal voltage-gated calcium current (ICa) or on ICa elevated by dihydropyridine calcium channel agonists. In contrast, ICa elevated by cyclic adenosine monophosphate (cAMP)-dependent phosphorylation decreases by more than 50 percent. The effect of [Mg2+]i is not due to changes in the concentration of cAMP or in the velocity of phosphorylation but rather appears to be a direct effect on the phosphorylated channel or on channel dephosphorylation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Enhanced vascular alpha-adrenergic neuroeffector system in diabetes: importance of calcium.

Mesenteric arteries from streptozotocin (STZ)-diabetic rats developed greater contractile force in response to norepinephrine and related alpha-agonists than arteries from age-matched controls. Subsequent experiments attempted to define the mechanisms underlying these findings. Transmural nerve stimulation of mesenteric arteries from both groups of animals revealed a similar optimal frequency and voltage of stimulation; however, arteries from STZ-diabetic rats developed greater contractile force than controls. Second, determination of selective alpha-adrenergic antagonist affinities (pA2 values) revealed qualitatively similar postjunctional alpha 1-adrenoceptors in both groups of arteries. Third, disruption of the endothelium did not abolish the enhanced responsiveness of arteries from STZ-diabetic rats. In contrast, the increased vascular responsiveness in STZ-diabetes was associated with a greater dependency on extracellular calcium, with no change in the response to alpha-agonist-induced release of calcium from cellular stores. Thus the enhanced responsiveness of mesenteric arteries from STZ-diabetic rats to alpha-adrenergic agonists cannot be attributed to neuronal deterioration, altered postjunctional alpha-adrenoceptor subtypes, endothelium degeneration, or enhanced release of intracellular calcium but is associated with a greater dependency on extracellular calcium.

Adrenergic alpha-Agonists↗
PubMed1988

Service- and facility-sharing.

The Veterans Administration and the United States Air Force hospitals in Albuquerque recently established a service- and facility-sharing arrangement. In this article, the authors share lessons learned from planning and executing the arrangement-lessons that any organization considering a large-scale joint venture will want to keep in mind.

Hospital Bed Capacity, 300 to 499↗
PubMed1988

Managing organizational mergers.

Reimbursement, competition, and other significant trends in the health field have stimulated an increase in mergers among health care organizations. Mergers inevitably produce significant ramifications for clinicians. Nurses have discovered that mergers produce a greater need for efficient patient care, but not necessarily the mechanism or guidance for achieving this goal. Nursing administrators are responsible for minimizing the negative impact of a merger on nurses while simultaneously promoting merger goals. Despite this increase in mergers and the subsequent challenge to clinicians, little information is available about how to manage mergers. This article reviews the impact of the merger between the Veterans Administration Medical Center and the Kirtland Air Force Base Hospital in Albuquerque, New Mexico. A nursing perspective is used to understand what problems arise and how nursing administrators can effectively manage these problems.

Attitude of Health Personnel↗
PubMed1987

Synovial fluid lipid abnormalities in various disease states: review and classification.

Although lipids are not usually present in large quantities in normal synovial fluids or in the usual synovial fluid seen in most rheumatologic conditions, their presence in synovial fluid may have diagnostic importance. As summarized in Table 2, analysis of synovial fluids for lipid constituents is relatively simple. On standing or after centrifugation, significant amounts of lipids may layer out and be visible as a supernatant. On microscopic examination, lipid droplets are usually easily seen and should be stainable with appropriate dyes (oil red O or Sudan III or IV), or may occasionally be visualized as intracellular or extracellular inclusions by polarized microscopy. Small (0.5 to 2.0 microns) intracellular inclusions containing triglycerides may be seen in neutrophils from most synovial fluids, and are of no diagnostic importance. Cholesterol crystals may be readily recognized microscopically by their characteristic flat, plate-like appearance and notched corners Synovial fluid may also be analyzed for cholesterol and triglycerides in routine clinical laboratories, and free fatty acids and lipolytic enzymes in special lipid laboratories. The presence of massive increases in cholesterol associated with microscopically visible cholesterol crystals is usually associated with chronic RA, occasionally in the setting of super-imposed bacterial infection. The presence of gross or microscopic lipid droplets is usually associated with trauma and hemorrhagic effusions. When present in this setting, the clinician should entertain a high suspicion for a significant intraarticular injury, such as fracture, meniscal tear, or severe ligamentous injury. In addition, however, several instances of non-traumatic inflammatory effusions associated with intracellular and extracellular lipid droplets have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗