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Biomedical subjects

E Cunningham

Publications and source records attributed to E Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1994

Phospholipase D: a downstream effector of ARF in granulocytes.

Activation of the phospholipase D (PLD) pathway is a widespread response when cells are activated by agonists that bind receptors on the cell surface. A 16-kD cytosolic component can reconstitute guanosine triphosphate (GTP)-mediated activation of phospholipase D in HL60 cells depleted of their cytosol by permeabilization. This factor was purified and identified as two small GTP-binding proteins, ARF1 and ARF3. Recombinant ARF1 substituted for purified ARF proteins in the reconstitution assay. These results indicate that phospholipase D is a downstream effector of ARF1 and ARF3. The well-established role of ARF in vesicular traffic would suggest that alterations in lipid content by PLD are an important determinant in vesicular dynamics.

ADP-Ribosylation Factor 1↗
PubMed1993

An essential role for phosphatidylinositol transfer protein in phospholipase C-mediated inositol lipid signaling.

Transmembrane signaling by the phospholipase C-beta (PLC-beta) pathway is known to require at least three components: the receptor, the G protein, and the PLC. Recent studies have indicated that if the cytosol is allowed to leak out of HL60 cells, then G protein-stimulated PLC activity is greatly diminished, indicating an essential role for a cytosolic component(s). We now report the complete purification of one component based on its ability to reconstitute GTP gamma S-mediated PLC activity and identify it as the phosphatidylinositol transfer protein (PI-TP). Based on the in vitro effects of PI-TP, we surmise that it is involved in transporting PI from intracellular compartments for conversion to PI bisphosphate (PIP2) prior to hydrolysis by PLC-beta 2/PLC-beta 3, the endogenous PLC isoforms present in these cells.

Amino Acid Sequence↗
PubMed1991

P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study.

BACKGROUND: The administration p.r.n. (as needed) of sedative medications is a widespread practice in the management of acute dyscontrol of child psychiatric inpatients. Its efficacy, however, has never been tested in a controlled clinical trial. METHOD: Twenty-one male inpatients, aged 5-13 years, participated in a double-blind, placebo-controlled study of the p.r.n. use of diphenhydramine, a sedative antihistaminic often used in child psychiatry wards. The patients' DSM-III-R diagnoses were conduct disorder, attention-deficit hyperactivity, and major depression. Each patient in acute dyscontrol blindly received either oral or intramuscular doses of diphenhydramine 25-50 mg (N = 9) or placebo (N = 12). The Conners Abbreviated 10-Item Teacher Rating Scale and the Clinical Global Impressions scale were completed before and 0.5, 1, and 2 hours after the dose. RESULTS: Repeated measures ANOVA showed significant time effects, but no difference due to drug. The intramuscular route tended to be more effective than the oral, regardless of whether active drug or placebo was given. CONCLUSION: The data indicate that if p.r.n. administrations are effective, this is a placebo effect. Likewise, intramuscular administrations are more effective because of a route effect ("the needle") and not because of a specific pharmacologic activity.

Administration, Oral↗
PubMed1990

Extracorporeal regional complexing haemodialysis treatment of acute inorganic mercury intoxication.

A 70-year-old white female presented approximately 24 h after ingesting three 475 mg tablets (1.425 g) of mercuric chloride in a suicide attempt. Acute renal failure necessitated the initiation of haemodialysis approximately 4 d after the ingestion. Treatment with BAL (2,3-dimercaptopropanol) resulted in only small increases in mercury output into dialysate. A new procedure involving the extracorporeal infusion of the chelating agent dimercaptosuccinic acid (DMSA) into the arterial blood line during haemodialysis was initiated. This procedure of Extracorporeal Regional Complexing Haemodialysis (ERCH) had been effective in increasing methylmercury removal in patients poisoned by contaminated grain. The first DMSA-ERCH procedure was performed 6 d after poisoning. There was a dramatic increase in mercury output into the dialysate. During three treatment sessions of 80 min each, 1189 micrograms of mercury were removed from the patient. The dialysed mercury represented the only mercury output since the patient was anuric and not producing faeces. DMSA-ERCH appears to be much more effective than BAL and haemodialysis in the treatment of acute inorganic mercury poisoning. The long interval between poisoning and initiation of treatment probably contributed to the patients ultimate demise, 28 d after poisoning. Efficacy of the DMSA-ERCH procedure for inorganic mercury poisoning is likely to be improved as the interval between exposure and treatment is reduced.

Aged↗
PubMed1990

The influence of alpha-adrenergic agents on tonic accommodation.

This study has examined the effect of an alpha-1 adrenergic agonist (phenylephrine HCl, 2.5%) and a non-selective alpha antagonist (thymoxamine HCl, 0.5%) on tonic accommodation (TA). TA was measured at 1 min intervals throughout a 45 min period using an objective infra-red optometer (Canon Autoref R-1). Additionally pupil diameter and the near-point of accommodation (NPA) were monitored in order to assess the efficacy of the instilled drug. A double-blind protocol was adopted between thymoxamine, phenylephrine and a saline control for 7 emmetropic subjects. There was no significant difference between the values of TA obtained under the three pharmacological conditions. However, both adrenergic agents induced changes in pupil diameter and NPA. Furthermore in all conditions TA increased by approximately 0.25D while the subject sat passively in darkness. The data indicates that alpha-adrenergic innervation alters the closed-loop accommodative response independently of TA.

Accommodation, Ocular↗
PubMed1989

The Pocket Speech Aid.

A rapid-access but limited vocabulary communication aid for the non-vocal and speech impaired is useful in some well defined situations. The design and construction of such a device is described. Three distinct situations have been identified where an aid is essential and an initial evaluation has shown the Pocket Speech Aid to be very successful.

Biomedical Engineering↗
PubMed1988

Differential effects of DNA gyrase inhibitors on the genetic transformation of Neisseria gonorrhoeae.

Inhibitors of DNA gyrase in Escherichia coli exerted differential effects on the genetic transformation of Neisseria gonorrhoeae. When competent cells of the gonococcus were exposed to novobiocin before the uptake of transforming antibiotic resistance DNA, there was a 50 to 60% reduction in the number of transformants compared with the number of control untreated cells. Norfloxacin, a more potent inhibitor of DNA gyrase and an analog of nalidixic acid, nearly abolished the production of transformants by recipient cells. On the contrary, exposure of competent cells to nalidixic acid had no effect on transformant yield. The target of these inhibitors appears to be at the level of recombination. Possible mechanisms are discussed.

Nalidixic Acid↗
PubMed1985

Familial pulmonary valve stenosis, atrial septal defect, and unique electrocardiogram abnormalities.

The familial association of pulmonary stenosis, atrial septal defect, and unique electrocardiographic abnormalities involving a mother and two children is reported. Familial pulmonary stenosis not occurring as part of a named syndrome or without associated multiple congenital abnormalities is rare. The constellation of pulmonary stenosis, atrial septal defect, and the particular electrocardiogram abnormalities present here is to our knowledge previously unreported. The pattern of inheritance is consistent with an autosomal dominant mode of transmission.

Cardiomyopathy, Hypertrophic↗
PubMed1984

Renal handling of sodium and calcium in hypercalciuria.

The renal handling of Ca in response to Na intake was evaluated in 12 patients with hypercalciuria and active kidney stone disease. There was no depression of urinary Ca excretion in response to the hypocalciuric effect of metolazone. Patients were hospitalized and their Ca and Na excretions measured while on a 190-mEq Na, 800-mg Ca, 1200-mg PO4- diet. These measurements were then repeated after Na intake decreased to 35 mEq/day while other variables, including diuretic dose and Ca intake, were unchanged. Two distinct responses were elicited by patients after Na restriction. In group I or the "responders" (n = 4), Ca excretion was reduced from 255 +/- 31 to 62 +/- 6 mg/24 hr. In the control group (n = 4), Ca excretion decreased from 95 +/- 8 to 57 +/- 11 mg/24 hr at similar levels of Na excretion. In group II or the "nonresponders" (n = 8), Ca excretion fell from 317 +/- 31 to 154 +/- 17 mg/24 hr when Na excretion was less than 50 mEq/24 hr. Metolazone with Na restriction normalized urine Ca excretion to the same order as in control subjects in group I. This is indicative of a mild Ca leak or a salt-sensitive leak. Despite diuretic and Na restriction most of the patients with hypercalciuria (group II) did not reabsorb Ca in a normal manner. This is indicative of a severe reabsorptive defect for Ca despite normal Na handling.

Body Weight↗
PubMed1984

Blood pressure control in pregnant rabbits: norepinephrine and prostaglandin interactions.

The relationship between norepinephrine (NE) and prostaglandins in the regulation of systemic blood pressure during pregnancy was examined in conscious rabbits. The arterial prostaglandin E2 (PGE2) concentration was higher in pregnant than in nonpregnant rabbits. Resting blood pressure was slightly lower in the gravid animals. The pressor response to incremental doses of intravenous NE was blunted in the pregnant rabbits. Meclofenamate, a cyclooxygenase inhibitor, failed to alter the resting blood pressure in either group of animals, although it reduced PGE2 levels more than 60% in the pregnant rabbits. The pressor response to NE was significantly increased only in the pregnant rabbits when the NE infusion was repeated following meclofenamate. Pregnant rabbits could also be differentiated from nonpregnant by their higher peripheral blood levels of NE and their uniform hypotensive response to alpha-adrenergic blockade. These observations define an altered responsiveness to both endogenous and exogenous NE in pregnant rabbits that appears to be related to an increase in vasodilator prostaglandins.

Animals↗
PubMed1982

Metolazone therapy of active calcium nephrolithiasis.

Metolazone, a nonthiazide diuretic with the hypocalciuric effect of the thiazides, was evaluated in patients with idiopathic calcium nephrolithiasis. During the mean 3-yr treatment period, there was a 77% decrease in stone incidence in 38 male patients (from 2.10 to 0.49 stones/patient/year). Urine calcium decreased 51% (from 231 +/- 19 to 114 +/- 7 mg/24 hr after 13 mo therapy). The treatment response was the same when these patients were divided into normocalciuric (n = 23), borderline hypercalciuric (n = 10), and hypercalciuric groups (n = 5). In six other patients with high sodium intake there was no decrease in urine calcium on stone formers regardless of the initial level of urine calcium excretion. High sodium intake may blunt and low intake potentiate the hypocalciuric effect of metolazone.

Calcium↗
PubMed1979

Influenza-associated myoglobinuric renal failure.

Acute myoglobinuric renal failure developed in three patients during the course of influenza virus infection. Muscle enzyme levels were elevated in all patients. Myoglobin was detected in the urine or serum by immunodiffusion. Recent influenza infection was documented by elevated hemagglutination inhibition titers. One patient died, whereas the remaining two patients completely recovered renal function. These patients with influenza infection represented more than half of the cases of myoglobinuric renal failure seen on the medical services of the study institutions during ths same period. These observations suggest that the association between influenza infection and myoglobinuric renal failure may be more common than previously suspected.

Acute Kidney Injury↗