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Biomedical subjects

J A Scott

Publications and source records attributed to J A Scott.

At least 91 records · Page 5Linked to original sources

Inducible nitric oxide synthase and vascular reactivity in rat thoracic aorta: effect of aminoguanidine.

We tested the hypothesis that selective inhibition of the inducible form of nitric oxide (NO) synthase with aminoguanidine would prevent the loss of vascular contractility after exposure to endotoxin [lipopolysaccharide (LPS)]. Aortic rings were dissected from Sprague-Dawley rats, suspended in organ baths containing Krebs solution, and tested for vascular reactivity. Vessels incubated with LPS (1 microgram/ml) for 5 h exhibited a significant decrease in the maximal contractile response to phenylephrine. Aminoguanidine (100 microM) restored the maximal contractile response of LPS-treated vessels to the level of the control vessels. Aminoguanidine was approximately 250-fold less potent than NG-nitro-L-arginine methyl ester in inhibiting the constitutive NO synthase in vascular tissue as determined by its ability to further increase tone of submaximally contracted aortic rings. NO synthase activity was determined in vascular tissue incubated with and without LPS. Vessels incubated with LPS exhibited a marked increase in the levels of inducible NO synthase activity compared with control vessels. This increase was restored to control levels when tissue homogenates were incubated with aminoguanidine. We conclude that aminoguanidine is a selective concentration-dependent inhibitor of the inducible form of NO synthase and may be a useful probe to evaluate the role of inducible NO synthase in the abnormal vascular contractility characteristic of endotoxemia and sepsis.

Animals↗

Nonadrenergic noncholinergic relaxation of human pulmonary arteries is partially mediated by nitric oxide.

Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contribute to the maintenance of low vascular resistance characteristic of the pulmonary circulation. Previous studies have demonstrated that nitric oxide (NO) is the principal NANC neurotransmitter in guinea pig pulmonary arteries. We examined whether NANC relaxation could be demonstrated in human pulmonary arteries, and the role of NO in this phenomenon. Fresh human pulmonary artery rings, with and without an intact endothelium, were mounted in organ baths containing Krebs' solution and precontracted with U44069 (0.3 microM). Adrenergic and cholinergic neurotransmitter pathways were blocked with guanethidine and atropine, respectively (10 microM each). In both endothelium-intact and -denuded vessels, electrical field stimulation (EFS, 1 to 10 Hz, 100 V) resulted in a frequency-dependent relaxation (maximal relaxation of 25 +/- 4% and 15 +/- 2% in endothelium-intact and -denuded vessels, respectively). Tetrodotoxin (0.3 microM) abolished the EFS-induced relaxation. L-NG-nitro-arginine methyl ester (L-NAME, 10 microM), was used to block enzymatic synthesis of NO. In both endothelium-intact and -denuded vessels, L-NAME reduced NANC relaxation to approximately 50% of control values. This reduction was reversible with the application of L-arginine (100 microM). We conclude that NANC relaxation exists in human pulmonary arteries and that it is partly mediated through NO.

Arginine↗

Descriptors of breathlessness in cardiorespiratory diseases.

The purposes of this study were: to examine the decriptors of breathlessness chosen by a large sample of patients with cardiorespiratory disease; to determine test-retest reliability of a patient's selection of the descriptors; and to assess whether a patient's recall of the experience of breathlessness is the same as that provoked by physical activity. Questionnaire data were collected at an initial visit for patients who complained of breathlessness and at a second visit in a subgroup of patients. A total of 218 patients who sought medical care for difficulty breathing due to one of seven different conditions were recruited from an outpatient pulmonary disease clinic at a university medical center. Patients selected statements that described qualities of breathlessness from a 15-item questionnaire and completed pulmonary function tests. At a subsequent visit (4 to 15 d later) a subgroup of 16 patients with chronic obstructive pulmonary disease (COPD) repeated the questionnaire at rest (to assess reliability) and after walking in a hallway to provoke a moderate intensity of breathlessness (to compare recall with direct experiences). The relationship among descriptors was evaluated by cluster analysis. The "work/effort" cluster was common for all diagnoses. Each condition was characterized by more than one cluster except COPD. Each diagnosis was associated with a unique set of dusters (e.g., asthma with "work/effort" and "tight," interstitial lung disease with "work/effort" and "rapid" breathing). Percent agreement for all descriptors selected at Visits 1 and 2 (recall) was 79% (r = 0.82; p = 0.001). Percent agreement at Visit 2 between descriptors for recall and for breathlessness provoked by walking was 68% (r = 0.69; p = 0.004). We conclude that patients with different cardiorespiratory conditions experience distinct qualities of breathlessness. Patients' recall of their sensations of breathlessness is reliable and comparable to dyspnea with walking. Employing a questionnaire containing descriptors of breathlessness may help to establish a specific diagnosis and to identify mechanisms whereby a specific intervention relieves dyspnea.

Adult↗

Pleural effusion and ventilation/perfusion scan interpretation for acute pulmonary embolus.

UNLABELLED: This study was conducted to determine if pleural effusion size affects ventilation/perfusion (V/Q) scan interpretation algorithms for acute pulmonary embolus (PE). METHODS: Retrospective analysis identified 163 consecutive patients undergoing angiography for PE with radiographic evidence for pleural effusion. V/Q scanning was performed in 94 (58%) of cases and reported using original Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria. Effusions were classified as small, large and/or bilateral. Radiographic and scintigraphic results were compared with regard to size and location of abnormalities. RESULTS: Of the 163 patients, 57 (35%) had angiographically-proven PE, 77 (47%) had at least one large pleural effusion and 86 (53%) had a small effusion; 33 (43%) with large effusions and 24 (28%) with small effusions had emboli at angiography. Thirty-six of 119 patients (30%) with clear chest radiographs (a control group) had PE. Thus, large effusions were associated with a higher incidence of PE than those with small effusions or clear lungs (p < 0.05). Of those with V/Q scanning, 26 of 94 (28%) had a solitary large effusion, with 12 (46%) positive for emboli. V/Q-matched abnormalities limited to effusion size were found in 16 with a solitary large effusion and 10 with a solitary small effusion. In both groups, 50% were angiographically positive for emboli. Twenty-three (66%) of 35 with bilateral effusions had corresponding V/Q-matched defects at one (n = 11) or both (n = 12) lung bases, and 9 (39%) were positive for emboli. In total, 45% with a V/Q-matched defect of equivalent size to the effusion were angiographically positive for PE. CONCLUSION: Pulmonary emboli are associated with pleural effusions of all sizes. Matched V/Q defects corresponding to radiographically-evident pleural effusions are of intermediate probability for PE. Thus, revision of the traditional lung scan interpretive criteria based upon pleural effusion size is not warranted.

Acute Disease↗

Down syndrome consequent to a cryptic maternal 12p;21q chromosome translocation.

A 9-year-old, mildly mentally retarded girl presented with phenotypic manifestations of Down syndrome. G-banded chromosomal analyses of peripheral blood lymphocytes from the patient and her parents, and skin fibroblasts from the patient, did not detect any abnormality. Molecular analysis of 15 highly polymorphic chromosome 21 dinucleotide repeat markers demonstrated a partial duplication of the Down syndrome critical region (D21S55, subband 21q22.2) of maternal origin in the patient. The segmental trisomy was confirmed by FISH analysis using the cosmid probe D21S55. Further analysis demonstrated that the trisomy was due to segregation of an apparently balanced cryptic translocation from the mother. The patient's karyotype is 46,XX,-12,tder(12)t(12;21)(p13.1;q22.2)mat.

Child↗

Polytolypin, a new antifungal triterpenoid from the coprophilous fungus Polytolypa hystricis.

Polytolypin [1], a new pentacyclic triterpenoid exhibiting antifungal and antibiotic activity, has been isolated from cultures of Polytolypa hystricis (JS189), a fungal colonist of porcupine dung. Two known compounds [2 and 3] were also isolated. Polytolypin was obtained by chromatographic fractionation of the EtOAc extract of P. hystricis liquid cultures, and the structure was assigned on the basis of 2D nmr and hrms data.

Animals↗

Diagnosis of chronic obstructive pulmonary disease and differentiation from asthma.

Asthma and chronic obstructive pulmonary disease are both common diseases, which together afflict approximately 25 million Americans. Although expiratory airflow obstruction is the common physiologic abnormality, asthma and chronic obstructive pulmonary disease are characterized by unique pathologic findings, clues from clinical histories, and laboratory test results. Despite some overlap in these characteristics, it is usually possible to differentiate these two conditions. This distinction is important for the healthcare provider to communicate a realistic prognosis to the patient and the patient's family, and to institute appropriate therapy.

Asthma↗

Diversity of cytochrome P450 genes in the mosquito, Anopheles albimanus.

Degenerate oligonucleotide primers were designed for conserved regions of cytochrome P450 proteins of the CYP4 family and were used to amplify cDNA or genomic DNA from different strains of the New World malaria vector, Anopheles albimanus (Weidemann). The PCR products were cloned, sequenced and compared to each other and to members of the P450 family CYP4. Seventeen new P450 genes were identified in five CYP4 subfamilies. Five of the ten PCR products of genomic DNA were shown to contain a short (60-79 bp) intron at the same position as introns in the Drosophila CYP4D2 and CYP4E1 genes.

Amino Acid Sequence↗

Molecular phylogeny of the Anopheles gambiae complex suggests genetic introgression between principal malaria vectors.

The six Afrotropical species of mosquitoes comprising the Anopheles gambiae complex include the most efficient vectors of malaria in the world as well as a nonvector species. The accepted interpretation of evolutionary relationships among these species is based on chromosomal inversions and suggests that the two principal vectors, A. gambiae and Anopheles arabiensis, are on distant branches of the phylogenetic tree. However, DNA sequence data indicate that these two species are sister taxa and suggest gene flow between them. These results have important implications for malaria control strategies involving the replacement of vector with nonvector populations.

Animals↗

Apiosporamide, a new antifungal agent from the coprophilous fungus Apiospora montagnei.

Bioassay-guided fractionation of an EtOAc extract from the mycelium of the coprophilous fungus Apiospora montagnei has furnished a new antifungal metabolite, named apiosporamide [1], and the known dihydroisocoumarin cis-(3R,4R)-4-hydroxymellein [4]. The structure of 1 was assigned on the basis of HMBC, HMQC, NOESY, and hrms data. Elucidation of the structure was complicated by the fact that several nmr signals appeared only under certain conditions.

Acetylation↗

Surgically induced diffuse scleritis following cataract surgery.

We report 21 cases, representing 3.1% of a total of 682 cataract patients, of surgically induced diffuse scleritis (SIDS) following planned extracapsular cataract extraction with intraocular lens insertion. The mean age was significantly lower in the patients with SIDS (mean 62.5 years; SD 13.68) when compared with the non-scleritic group (mean 73.6 years; SD 10.2; Mann-Whitney U-test, p = 0.0003). There was an association of SIDS with general anaesthetic (chi-squared test, p = 0.0008). Twenty of 21 patients responded to oral non-steroidal anti-inflammatory agents with good visual result.

Adult↗

High-level expression of the bacterial opd gene in Drosophila melanogaster: improved inducible insecticide resistance.

The bacterial parathion hydrolase gene (opd) was expressed in transformed D. melanogaster under the control of an hsp70 promoter. Transformed lines carrying chimaeric genes designed for either cytoplasmic or secretory expression exhibited high- or low-level heat-shock-inducible transient resistance to paraoxon respectively. Greatest levels of resistance occurred approximately 12-16 h after heat shock and well after periods of maximal transcription. Insecticide resistance conferred by the cytoplasmic form of opd is expressed as a semidominant trait.

Animals↗