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S Grady

Publications and source records attributed to S Grady.

At least 19 recordsLinked to original sources
PubMed2001

Design, synthesis, and biological evaluation of a series of simple and novel potential antimalarial compounds.

A series of compounds bearing an endocyclic -N-O- moiety with potential antimalarial activity based on simple derivatives of the tropolone purpurogallin was prepared by means of a hetero Diels-Alder reaction using nitrosobenzene as a dienophile. The rationale behind the design of these compounds is presented, together with the synthetic route to derivatives bearing aromatic and aliphatic esters of the C4'-position hydroxyl group of the purpurogallin framework, as well as biological data obtained from in vitro assays against Plasmodium falciparum and Trypanosoma cruzi. Several of the new compounds have activities in the 3-9 microM range, and provide leads for the development of a novel class of antiparasitic drugs with improved biological and pharmacological properties.

Animals↗
PubMed1998

Pharmacological characterization of nicotinic receptor-stimulated GABA release from mouse brain synaptosomes.

Several recent electrophysiological studies have demonstrated that nicotinic agonists stimulate the release of gamma-aminobutyric acid (GABA) from rodent brain tissue. Our studies used a neurochemical approach to characterize nicotinic receptor-stimulated [3H]-GABA release from mouse brain synaptosomes. Nicotine increased [3H]-GABA release from synaptosomes preloaded with [3H]-GABA in a concentration-dependent manner. This release appeared rapidly, was Ca++ dependent, and was partially (about 50%) blocked by 100 nM tetrodotoxin and totally blocked by mecamylamine and dihydro-beta-erythroidine. alpha-Bungarotoxin had no effect. Twelve nicotinic agonists were compared for their effects on [3H]-GABA release. The agonists differed in potency (EC50) and efficacy (Emax). The EC50 and Emax values were significantly correlated (r = 0.95, P <.001 for EC50; r = 0.93, P <.01 for Emax) to values obtained for these same agonists when 86Rb+ efflux was determined. A significant correlation (r = 0.84, P <.01) was found when the EC50 values for agonist-stimulated [3H]-GABA release and IC50 values for agonist inhibition of [3H]-L-nicotine binding were compared. Differences in [3H]-GABA release were detected in 12 brain regions and maximal release was significantly correlated with [3H]-nicotine binding. The pharmacological and regional comparisons suggest that the nAChR that stimulates [3H]-GABA release is the one that binds [3H]-nicotine with high affinity (alpha4beta2). Unequivocal evidence that the receptor that modulates nicotine-stimulated [3H]-GABA release contains a beta2 subunit was obtained in a study using wild-type, heterozygous and homozygous beta2 null mutant mice. [3H]-GABA release and [3H]-nicotine binding decreased along with the number of copies of the null mutant gene.

Animals↗
PubMed1997

The variability of exposure over time: a prospective longitudinal study.

Four hundred and forty personal air measurements were carried out on 54 workers, employed in the main processes in six different factories (6-13 in each). Potential exposure was to lead, benzene and dust. Ten randomly repeated hygiene surveys were carried out over 1 year. In order to estimate the magnitude of the variability in workers' exposure over time, its sources, the variance between workers and the variance within a worker, a nested unbalanced analysis-of-variance model was fitted to the log-transformed data. Of the total exposure variance, the within variance of a worker's exposure over time was 51% (geometrical standard deviation, GSD = 3.1) and the between workers, factories and air contaminants variance was 49%. The exposure variance between all the workers was due mainly to variance between workers within the same factory (67%). Outdoor locations, mobility of the worker and mobility of the sources of exposure result in a positive influence on both the variance between (26%, ANOVA) and the variance of a worker over time (39%, regression). These variables are therefore important in the sampling strategy of workers' exposure. For valid compliance testing and assessment of workers' exposure the mean and the within- and between-variance of the workers' exposure over time should be considered. The exposure should be measured several times a year randomly in order to prevent workers misclassification. To assess yearly exposure, a GSD = 3.1 can be used to calculate confidence limits for the arithmetic mean of worker's exposure measurements, in circumstances similar to those in this study.

Air Pollution↗
PubMed1992

Characterization of nicotinic receptor-mediated [3H]dopamine release from synaptosomes prepared from mouse striatum.

This study establishes that presynaptic nicotinic receptors modulate dopamine release in the mouse striatum. Nicotinic agonists elicit a dose-dependent increase in the release of [3H]dopamine from synaptosomes prepared from mouse striatum. At low concentrations, this release is Ca2+ dependent, whereas at higher concentrations Ca(2+)-independent, mecamylamine-insensitive release was also observed. The Ca(2+)-dependent nicotine-evoked release was not blocked by alpha-bungarotoxin but was effectively blocked by neuronal bungarotoxin as well as several other nicotinic receptor antagonists. The relationship between potency for stimulation of release for agonists and potency for inhibition of release for antagonists was compared to the affinity of these compounds for the [3H]nicotine binding site. The overall correlation between release and binding potency was not high, but the drugs may be classified into separate groups, each of which has a high correlation with binding. This finding suggests either that more than one nicotinic receptor regulates dopamine release or that not all agonists interact with the same receptor in an identical fashion.

Animals↗
PubMed1991

Incertohypothalamic A13 dopamine neurons: effect of gonadal steroids on tyrosine hydroxylase.

In this study the effect of gonadectomy and steroid treatment on the dorsal component of the incertohypothalamic dopamine system or nucleus A13 was assessed by immunocytochemistry using an antibody raised to tyrosine hydroxylase (TH). A computer graphic system interfaced to a microscope was used to count and measure the diameters of TH-positive neurons and display the data in the three-dimensional space of the nucleus. In males, castration resulted in a dramatic decrease in the reaction product representative of TH. The number of TH-positive cells in the A13 DA nucleus decreased to 25% of intact levels. In females, ovariectomy also caused an impressive loss in the TH-immunostainable material, but this was not indicated by a change in the total number of TH-positive neurons. In both sexes the loss in TH immunostain was confined mainly to the mid-portion of the nucleus. Hormone treatment restored the TH immunostain (cell number and size) to and/or above intact levels in both sexes. These data suggest that A13 TH immunostain is stimulated by gonadal steroids in male and female rats.

Animals↗
PubMed1990

Effect of backrest position on intracranial and cerebral perfusion pressures.

Prevention of secondary injury resulting from increased intracranial pressure (ICP) and the promotion of adequate cerebral blood flow are major concerns of health care professionals caring for the neurologic patient. For the past two decades studies have indicated raising the head of the bed lowers ICP. However, when perfusion pressure has been measured along with ICP, results have been conflicting. Some investigators found cerebral perfusion pressure (CPP) decreased with head elevation; others found no change. This study examined the effect of four backrest positions (flat, head elevated 30 degrees, head elevated 30 degrees with knee gatch elevated and reverse Trendelenberg) on ICP, CPP and transcranial doppler flow velocities in four subjects. Each was placed in the flat position for 15 minutes followed by 15 minutes in one of the three randomly assigned elevated backrest positions. Findings suggest backrest position should be individually assigned after analysis of the response of the ICP, CPP and blood flow velocities to that position.

Adult↗
PubMed1986

Serum formate concentrations in methanol intoxication as a criterion for hemodialysis.

To evaluate the utility of serum formate concentrations, four patients were studied after ingestion of a methanolic copying fluid. All patients were initially intoxicated. Twelve to twenty-four hours later, signs and symptoms included nausea, abdominal pain, hypokalemia, acidosis (three patients), and pathologic ocular findings (two patients). All patients were treated with ethanol and folate. The two patients with ocular signs and acidosis had high serum formate concentrations (75 and 55 mg/dL, respectively). One of the two patients had a high methanol concentration (222 mg/dL) and required hemodialysis; the other patient did not (methanol concentration, 24 mg/dL). In the other two patients without ocular signs, initial formate concentrations were undetectable (limit of detection, 0.5 mg/dL); however, one patient required hemodialysis because the methanol concentration was 72 mg/dL. Formate is the mediator of ocular injury and acidosis. In these patients formate concentrations correlated with the clinical condition but methanol concentrations did not.

Acidosis↗
PubMed1983

Epidemic and endemic HLA-B and DR associations in mucocutaneous lymph node syndrome.

HLA-A,B and DR antigens were evaluated in 51 patients with mucocutaneous lymph node syndrome (Kawasaki disease) during both endemic and epidemic periods in the Boston area. Although 80% of patients were HLA-B5 (70% HLA-Bw51) during endemic periods, there were no HLA-B5 individuals during the epidemic period. There was, however, an increased incidence of HLA-Bw44 during the Boston epidemic. Such different associations in endemic versus epidemic periods suggest possible different, as yet unknown, inciting agents.

Boston↗
PubMed1983

Assessment of left ventricular contractility in patients receiving doxorubicin.

The usual indices of left ventricular systolic performance have been incapable of accurately recognizing early myocardial impairment in many patients treated with doxorubicin. Recently, several new load-independent, highly sensitive indices of left ventricular contractility have been developed including the slope value of the endsystolic pressure (Pes)-dimension (Des) relation and the position of the left ventricular end-systolic wall stress (sigma es)-percent fractional shortening (% delta D) relation. We used these indices to study 46 patients receiving either low dose or high dose doxorubicin. Results were compared with data from 30 healthy subjects. Resting % delta D failed to accurately recognize left ventricular dysfunction in 9 of 17 patients with low normal values. These patients had reduced afterload, as measured by sigma es, permitting normal extent of left ventricular fiber shortening despite impaired contractility as quantified by diminished Pes-Des slope values. There was 98% concordance between the relative position of the sigma es-% delta D relation and the slope value of the Pes-Des, relation. These indices offer an improved means of recognizing and quantitating impaired contractility in patients treated with doxorubicin.

Adolescent↗
PubMed1983

Immunoregulatory T cell abnormalities in mucocutaneous lymph node syndrome.

We recently demonstrated that during the acute phase of mucocutaneous lymph node syndrome (MCLS)3 there was a significant reduction in circulating T8+ suppressor/cytotoxic T cells and an increased number of Ia/Dr-bearing T4+ T cells, which suggests the presence of circulating activated helper T cells (1). Furthermore, the vast majority of patients with acute MCLS had a significantly elevated number of circulating B cells spontaneously secreting IgG and IgM. In the present study, the possible role of the immunoregulatory T cell abnormalities in the polyclonal B cell activation was investigated by assaying the ability of T cells and T cell factors from patients with acute MCLS to induce immunoglobulin production by normal B lymphocytes. We also examined the capacity of normal T cells to suppress immunoglobulin production by activated B cells from patients with acute MCLS.

Antibody-Producing Cells↗
PubMed1982

Compression of intrapulmonary bronchi by abnormally branching pulmonary arteries associated with absent pulmonary valves.

In 3 patients with absent pulmonary valve syndrome and absent ductus arteriosus, the lungs were injected and analyzed postmortem using morphometric techniques. Two patients had tetralogy of Fallot and 1 had D-transposition of the great arteries, the latter being the first autopsy-proved case of absent pulmonary valve with transposition. In addition to the expected dilatation of the central pulmonary arteries and compression of the mainstem bronchi, postmortem pulmonary arteriography revealed a bizarre pattern of hilar branching. Instead of single segmental arteries, tufts of arteries arose which entwined and compressed the intrapulmonary bronchi. In all 3 patients the histologic structure of the pulmonary arteries was abnormal. The elastic lamina of the media of the right and left pulmonary arteries were increased in number outside the lung, but were decreased within the lung. At both sites, the elastic laminae were thickened and fragmented. In the 2 ventilator-dependent patients, there was slight medial hypertrophy and extension of muscle into normally nonmuscular arteries. In 1 of the 2 cases in which the number of bronchial generations was counted, they were decreased, and in the 1 case in which bronchial count was unknown, alveolar multiplication was severely impaired. Therefore, our data may explain why, in some patients with absent pulmonary valve syndrome, relief of compression of the mainstem bronchi alone does not appreciably alleviate or reverse severe respiratory disease.

Bronchi↗
PubMed1979

The significance of concordance in mammographic interpretations.

Twenty-eight women participating in a screening program had a breast cancer diagnosed subsequent to the report of a negative mammogram which was read by only one of a group of radiologists. Fourteen occurred prior to a scheduled routine screening visit (interval cancers) and 14 were detected during such an examination. The negative mammograms from the 28 cancer patients, together with those from 120 women without cancer (controls) were independently reviewed by each member of a panel of three radiologists. Forty-six percent of the cancer cases and 5.8% of the controls were interpreted as positive by two or more of the radiologists. These findings suggest that agreement among several independent reviewers enchances the value and accuracy of mamography by reducing the number of false negative interpretations.

Breast Neoplasms↗