Search PubMed⌕ Search

Biomedical subjects

C Harvey

Publications and source records attributed to C Harvey.

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

Structure-function analysis of the rat prolactin promoter: phasing requirements of proximal cell-specific elements.

Expression of PRL, a member of the GH family of genes, is restricted to the lactotroph cells of the anterior pituitary. The proximal promoter of the rat PRL (rPRL) gene contains four factor-binding sites. Three nonadjacent elements, footprints (FP) I, III, and IV, are separated by an integral number of helical turns and bind a pituitary-specific factor, LSF-1. FP II binds another factor present in pituitary and nonpituitary cells. The mechanisms by which DNA-bound proteins influence RNA polymerase-II activity over large distances are not fully understood, but protein-protein interactions, with looping of intervening DNA, may bring distant sites into close proximity. Here, we demonstrate, using protein titration studies, that LSF-1 binds to the most proximal FP I element with the highest affinity, whereas it binds the more distal elements, FP III and FP IV, with progressively lower affinities. Time-course and salt-sensitivity studies reveal that binding of LSF-1 to all three pituitary-specific rPRL promoter sites occurs rapidly (less than or equal to 1 min) and requires fairly high salt concentrations (greater than or equal to 300 mM KCl) to destabilize protein-DNA interactions. Moreover, once bound, the pituitary nuclear factor(s) induces a conformational change in rPRL DNA structure with greatly delayed kinetics (greater than 15 min) and at a different salt concentration than are required for simply factor binding. Taken together, these data suggest a model in which LSF-1 initially binds fairly rapidly to multiple nonadjacent elements and then interacts with itself or other DNA-bound proteins much more slowly, possibly looping or bending the rPRL promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

New estimates of traumatic SCI prevalence: a survey-based approach.

New estimates of traumatic spinal cord injury (SCI) prevalence are developed from a survey specifically designed to identify the SCI population in both institutional and non-institutional settings. The survey utilised a mixed-mode sampling design based on probability sampling methods. Detailed interviews were conducted with SCI persons identified in this survey. We estimate that the traumatic SCI prevalence rate in the United States is 721 cases per million, and that there are about 177,000 SCI persons residing in the United States.

Epidemiologic Methods↗
PubMed1990

Ceranapril (SQ 29,852), an orally active inhibitor of angiotensin converting enzyme (ACE).

Ceranapril (SQ 29,852) is a new inhibitor of angiotensin I (AI) converting enzyme (ACE) belonging to the hydroxylphosphonate class. The purpose of the present report is to present the in vivo pharmacology of ceranapril in conscious animal models. In conscious, normotensive rats, ceranapril administered i.v. (ED50 = 63 nmol/kg) or p.o. (ED50 = 530 nmol/kg) inhibited an AI pressor response with potency equal to that of captopril. However, in conscious dogs, ceranapril was a relatively poor inhibitor of the AI pressor response after both i.v. (ED50 = 300 nmol/kg) and p.o. (ED50 = 18 mumol/kg) administration; in monkeys ceranapril was a good inhibitor of the AI pressor response after i.v. (ED50 = 60 nmol/kg) but not p.o. (ED50 = 18 mumol/kg) administration. In rats, the duration of ceranapril's inhibition of an AI pressor response was longer than an equimolar dose of captopril. Similarly, in SHR, ceranapril's blood pressure lowering effect had a longer duration than that of captopril. Ceranapril's ACE inhibitory effects were longer lasting in anephric rats than in sham rats, suggesting a renal route of excretion for ceranapril. Ceranapril administration to conscious female dogs resulted in significant increases in renal plasma flow and GFR. In SHR, doses of 23 and 68 mumol/kg resulted in significant blood pressure lowering that lasted 24 h. Oral doses of 2.3, 6.8, 23, and 68 mumol/kg in two-kidney, one-clip hypertensive rats resulted in significant and dose-related falls in arterial pressure, which again persisted for 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Blood pressure lowering and renal hemodynamic effects of fosinopril in conscious animal models.

The blood pressure lowering and renal hemodynamic effects of fosinopril, the chemically novel inhibitor of angiotensin I converting enzyme (ACE), was assessed in conscious animal models. In conscious dogs, intravenous infusion of SQ 27,519 [0.5 mg/kg (1.1 mumol/kg) bolus plus 0.1 mg/kg/min (0.22 mumol/kg/min)], the active moiety of the prodrug fosinopril, increased PAH clearance and GFR by 25 and 16%, respectively (p less than 0.05, each) without changing arterial pressure (AP). Urine volume, sodium excretion, and potassium excretion were elevated, although not significantly increased. In sodium-depleted cynomolgus monkeys, 1.5 and 5.0 mumol/kg (0.88 and 2.9 mg/kg) p.o. of fosinopril lowered arterial pressure from 115 +/- 5 to 99 +/- 5 mm Hg and from 116 +/- 3 to 87 +/- 4 mmHg, respectively (p less than 0.05, each). When given orally to SHR at 10 and 30 mg/kg (5.9 and 17.6 mumol/kg), fosinopril lowered AP by 23 (183 +/- 4 to 160 +/- 5 mm Hg) and 20 mm Hg (176 +/- 4 to 156 +/- 4 mm Hg), respectively. The combination of fosinopril [10 mg/kg (5.9 mumol/kg)] plus hydrochlorothiazide (10 mg/kg) reduced AP from 206 +/- 4 to 167 +/- 2 mm Hg when given orally to SHR. Fosinopril was more effective in two-kidney, one-clip hypertensive rats relative to SHR; AP fell from 201 +/- 9 to 160 +/- 7 mm Hg after 10 mg/kg (5.9 mumol/kg), and from 205 +/- 7 to 145 +/- 7 mm Hg after 30 mg/kg (17.6 mumol/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel-Dubousset instrumentation.

One hundred sixty patients with idiopathic scoliosis treated with Cotrel-Dubousset instrumentation (CDI) underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine. The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible. When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appear to provide the most physiologic sagittal contour. Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis.

Humans↗
PubMed1990

Sagittal plane analysis in idiopathic scoliosis patients treated with Cotrel-Dubousset instrumentation.

One hundred sixty patients with idiopathic scoliosis underwent preoperative and postoperative sagittal plane analysis of the thoracic spine, thoracolumbar junction, and lumbar spine. The data suggest that mild to moderate improvements in thoracic hypokyphosis are possible. When crossing the thoracolumbar junction, reversal of rod bend and reversal of hooks on the derotation rod appears to provide the most physiologic sagittal contour. Cotrel-Dubousset instrumentation to the mid and distal lumbar spine can preserve and, at times, enhance lumbar lordosis.

Adolescent↗
PubMed1990

Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2.25 mg, placebo 2.5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these) was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis.

Adult↗
PubMed1990

Patterns of cigarette smoking among Hispanics in the United States: results from HHANES 1982-84.

In the 1982-84 Hispanic Health and Nutrition Examination Survey, the prevalence of cigarette smoking was examined among Mexican Americans, Puerto Ricans, and Cuban Americans in the United States. Among 20-74 years olds, the age-adjusted smoking rates for Mexican American, Puerto Rican, and Cuban American men were high--42.5, 39.8, and 41.6 percent, respectively. Quite striking among Cuban American men was the high smoking rate among 20-34 year olds (50.1 percent), the highest smoking rate in the three Hispanic groups compared. The age-adjusted smoking rates for Mexican American, Puerto Rican, and Cuban American women were much lower than those for men-23.8, 30.3, and 24.4 percent, respectively. Both Puerto Rican and Cuban American men were more likely to be heavy smokers (52.3 and 64.1 percent, respectively, smoking a pack or more a day) as compared to the Mexican Americans (33.8 percent smoking a pack or more a day). The pattern was the same for women, with Mexican American women being lighter smokers (18.8 percent smoking a pack or more a day) as compared to heavy smoking among Puerto Rican and Cuban American women (35.1 and 48.6 percent, respectively, smoking a pack or more a day). Given the health hazards of smoking, future research and intervention are required for those groups with high exposure to cigarette smoking.

Adult↗
PubMed1989

Predicting relapse in schizophrenia: the development and implementation of an early signs monitoring system using patients and families as observers, a preliminary investigation.

Recognition of prodromal symptoms of schizophrenia offers the potential of early intervention to avert relapse and re-hospitalization (Carpenter & Heinrichs, 1983). The present study investigated how a strategy to detect prodromal signs might be effectively applied in the clinical setting. A standard monitoring system was developed involving completion of a new early signs scale (ESS) measuring changes in key symptoms phenomenologically (self-report) and behaviourally (observer report). The ESS was subject to rigorous psychometric evaluation and tested in a prospective pilot investigation. The ESS reliably identified early signs and predicted relapse with an overall accuracy of 79%. Several different patterns of relapse were identified. Observer reports compensated for loss of insight in some patients. In two cases where early signs indices were detected, prompt increases in medication appeared to arrest relapse and avert readmission. The ESS offers itself as a reliable, valid and administratively feasible measure and demonstrates considerable potential as a cost-effective procedure for secondary prevention.

Adult↗
PubMed1989

Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and preclinical in vivo pharmacology.

Fosinopril is the first member of a new chemical class of angiotensin I (AI) converting enzyme (ACE) inhibitors, the phosphinic acids. In vitro, SQ 27,519, the active moiety of the prodrug fosinopril, was a more potent inhibitor of purified rabbit lung ACE- (IC50 = 11 vs. 23 nM) and bradykinin-induced contractions of guinea pig ileum than captopril. In vivo, SQ 27,519 was equipotent to captopril as an inhibitor of an AI pressor response after intravenous (i.v.) administration to conscious rats and monkeys but appeared to be less potent in conscious dogs. After oral administration, fosinopril again was equipotent to captopril as an inhibitor of an AI pressor response in rats and monkeys and slightly less potent in dogs. However, both SQ 27,519 (i.v. studies) and fosinopril (oral studies) had a longer effect than captopril in all three species. When fosinopril was administered orally for 5 days, its effects on an AI pressor response were the same on days 1 and 5, suggesting lack of tolerance to the compound. The ACE inhibitory effect of captopril, but not fosinopril, was prolonged in conscious rats with glycerol-induced acute renal failure, suggesting that fosinopril is excreted by an extrarenal route. Finally, fosinopril had no effect on the pressor or chronotropic effects of norepinephrine (NE) or 1,1-dimethyl-4-phenylpiperinium (DMPP) or electrical stimulation of the sympathetic ganglia of pithed rats. Fosinopril attenuated the pressor, but not the chronotropic effects of tyramine. We conclude that fosinopril is a potent and long-lasting inhibitor of ACE in conscious animal models that does not impair adrenergic function or reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Characterization of immunologically important antigens and allergens of Aspergillus fumigatus.

Using a variety of immunochemical methods, including quantitative immuno-electrophoretic techniques, combined with gel filtration and iso-electric focusing, and production of monospecific antisera for identification and affinity purification, 4 major components of Aspergillus fumigatus have now been partially characterized. Numbering of these was derived from a reference allergic bronchopulmonary aspergillosis (ABPA) self-crossed radio-immuno-electrophoresis pattern of reactivity. Two major intracellular/cytoplasmic, concanavalin A (Con A)-binding antigens, Ag 7 and Ag 13, of molecular weights 150-200 and 70 kilodaltons (kD), respectively, were confirmed to be of importance for both ABPA and aspergilloma in specific sandwich enzyme-linked immunosorbent assays. A rapidly released component, Ag 5, of molecular weight 35 kD, proved both antigenic and allergenic, with aspergilloma patients having especially high-titre IgG antibodies. The major allergenic component Ag 3, of molecular weight 24 kD by gel filtration and 18 kD by SDS-PAGE was, like Ag 5, relatively heat-labile and non-Con-A-binding. Interestingly, T cell clones have been identified which respond primarily to an 18-kD fraction.

Allergens↗
PubMed1988

Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Possible relevance to drug-induced uroporphyria.

1. The hypothesis that uroporphyria-inducing drugs stimulate the oxidation of uroporphyrinogen by a microsomal NADPH-dependent mechanism was tested. 2. 3,4,3',4'-Tetrachlorobiphenyl, a very effective inducer of uroporphyria in chick-embryo hepatocyte cultures, stimulates the NADPH-dependent oxidation of uroporphyrinogen by chick-embryo microsomal fraction in vitro. 3. Two different actions of 3,4,3',4'-tetrachlorobiphenyl are apparently required for this effect: (a) induction of a microsomal system by treatment in vivo and (b) interaction with the induced microsomal fraction in vitro, producing an oxidizing species. 4. The analogue 2,4,2',4'-tetrachlorobiphenyl is relatively ineffective in both the production of porphyria in culture and the stimulation of porphyrinogen oxidation in vitro. 5. Rat hepatocytes do not develop uroporphyria when treated with polychlorinated biphenyls in culture, yet they respond to these drugs with typical induction of cytochrome P-448-dependent drug metabolism. 6. These data provide support for the hypothesis of an increased oxidation of uroporphyrinogen in drug-induced uroporphyria, but also suggest that induction of cytochrome P-448 is not the only factor involved. 7. Both I and III isomers of uroporphyrin and heptacarboxylate porphyrin accumulate when chicken hepatocytes are made uroporphyric by drugs; treatment with desferrioxamine causes a marked decrease in both isomers, suggesting that iron may be involved in the accumulation of both.

Aminolevulinic Acid↗
PubMed1988

The relationship between labor and route of delivery in the preterm infant.

The purpose of this prospective study was to evaluate the effects of the active phase of labor and route of delivery on the frequency of germinal layer/intraventricular hemorrhage in 89 infants with ultrasound-estimated fetal weights less than or equal to 1750 gm. Twenty-eight infants (31.5%) had germinal layer/intraventricular hemorrhage within 1 hour after birth and an additional 15 infants (17%) had germinal layer/intraventricular hemorrhage beyond 1 hour after birth. Infants with germinal layer/intraventricular hemorrhage had a significantly lower gestational age (p less than 0.003) and birth weight (p less than 0.007). Germinal layer/intraventricular hemorrhage within 1 hour after delivery was increased in the infants of women who experienced the active phase of labor regardless of the route of delivery. However, the incidence of germinal layer/intraventricular hemorrhage beyond 1 hour after delivery and the overall incidence were similar in the vaginal delivery and cesarean delivery groups. In addition, there was an increased incidence of progression to grades III and IV hemorrhage regardless of route of delivery in the infants whose mothers experienced the active phase of labor.

Apgar Score↗
PubMed1988

Leukotriene C4 generation from human eosinophils stimulated with IgG-Aspergillus fumigatus antigen immune complexes.

Sepharose beads coated with IgG stimulate eosinophils to produce leukotriene C4 (LTC4). This observation has been extended with specific immobilized IgG/antigen immune complexes to elicit mediator generation. An extract of Aspergillus fumigatus was covalently coupled to Sepharose beads and incubated with the IgG fraction of immune serum from patients with allergic bronchopulmonary aspergillosis. These beads elicited generation of 7.72 +/- 1.7 pmol of LTC4 immunoreactive material (n = 5) from 1 X 10(6) normal eosinophils of greater than 86% purity, and significantly less LTC4 (0.73 +/- 0.19 pmol per 10(6) cells; n = 3) was produced by eosinophils after incubation with beads treated with IgG from normal nonimmune serum. The maximum antibody-dependent release achieved represented approximately 20% of that induced by the calcium ionophore (A23187). LTC4 was measured by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography. The amount of LTC4 generated was dependent on the concentration of A. fumigatus-specific IgG, and mediator release was completely abolished by prior adsorption of the IgG fraction onto Sepharose-protein A (Staphylococcus aureus). Grass pollen-specific IgG antibody/antigen complexes, in combination with Sepharose beads, also triggered generation of LTC4 immunoreactive material. There was no evidence to suggest that IgE/A. fumigatus immune complexes triggered LTC4 generation, although IgE myeloma protein, in association with Sepharose beads, was a weak stimulus. The efficacy of the IgG immune complex-dependent stimulation of eosinophils suggests a possible physiologic mechanism whereby these cells could participate in the inflammatory changes associated with allergic bronchopulmonary aspergillosis and similar allergic disorders.

Antigen-Antibody Complex↗
PubMed1987

Diagnostic specificity of a sandwich ELISA for Aspergillus-related diseases.

A sandwich ELISA with specificity for a major antigen (Ag 7) of Aspergillus fumigatus has been compared with indirect ELISAs with use of crude antigenic (culture filtrate) extracts and found to have a sensitivity of 100% and specificity of 92.3% for antibody detection in sera of patients with allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma. In the Ag 7 ELISA, all sera from groups with ABPA (21) and aspergilloma (15) had positive titers, and mean values for both these groups were significantly higher (p less than 0.001) than control levels. By comparison, in the indirect ELISAs, most sera of patients with ABPA were positive; the sensitivity was 81% to 90%, and the specificity was 87%. Sera from other disease groups including sera from 13 patients with farmer's lung, 16 with tuberculosis, and 10 individuals with positive prick test to either A. fumigatus or Alternaria alternata were also tested by both types of assay. Up to five of these sera elicited significant positive results in the indirect ELISA, and although two sera were also positive in the Ag 7-specific ELISA, these latter titers were both below the range of values for the sera from patients with ABPA. With the use of an IgG calibration curve, the sensitivity of the assay was determined as within the range of 1 to 10 microgram of specific IgG antibody per milliliter. The Ag 7-specific ELISA is therefore a highly specific, sensitive assay for antibody detection in Aspergillus-related diseases.

Antibodies, Fungal↗