Biomedical subjects

J Cary

Publications and source records attributed to J Cary.

8 recordsLinked to original sources

PubMed2005

Guiding of relativistic laser pulses by preformed plasma channels.

Guiding of relativistically intense (>10(18) W/cm2) laser pulses over more than 10 diffraction lengths has been demonstrated using plasma channels formed by hydrodynamic shock. Pulses up to twice the self-guiding threshold power were guided without aberration by tuning the guide profile. Transmitted spectra and mode images showed the pulse remained in the channel over the entire length. Experiments varying guided mode power and simulations show a large plasma wave was driven. Operating just below the trapping threshold produces a dark current free structure suitable for controlled injection.

Journal Article↗

PubMed2004

High-quality electron beams from a laser wakefield accelerator using plasma-channel guiding.

Laser-driven accelerators, in which particles are accelerated by the electric field of a plasma wave (the wakefield) driven by an intense laser, have demonstrated accelerating electric fields of hundreds of GV m(-1) (refs 1-3). These fields are thousands of times greater than those achievable in conventional radio-frequency accelerators, spurring interest in laser accelerators as compact next-generation sources of energetic electrons and radiation. To date, however, acceleration distances have been severely limited by the lack of a controllable method for extending the propagation distance of the focused laser pulse. The ensuing short acceleration distance results in low-energy beams with 100 per cent electron energy spread, which limits potential applications. Here we demonstrate a laser accelerator that produces electron beams with an energy spread of a few per cent, low emittance and increased energy (more than 10(9) electrons above 80 MeV). Our technique involves the use of a preformed plasma density channel to guide a relativistically intense laser, resulting in a longer propagation distance. The results open the way for compact and tunable high-brightness sources of electrons and radiation.

Journal Article↗

PubMed1994

Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasiticus.

The nor-1 gene was cloned previously by complementation of a mutation (nor-1) in Aspergillus parasiticus SU-1 which blocked aflatoxin B1 biosynthesis, resulting in the accumulation of norsolorinic acid (NA). In this study, the nucleotide sequences of the cDNA and genomic DNA clones encompassing the coding region of the nor-1 gene were determined. The transcription initiation and polyadenylation sites of nor-1 were located by primer extension and RNase protection analyses and by comparison of the nucleotide sequences of the nor-1 genomic and cDNA clones. A plasmid, pNA51-82, was created for one-step disruption of the nor-1 gene by inserting a functional copy of the nitrate reductase (niaD) gene from A. parasiticus into the coding region of the nor-1 gene. Transformation of A. parasiticus NR-3 (niaD Afl+) with pNA51-82 resulted in niaD+ transformants that accumulated NA and produced reduced levels of aflatoxin as determined by thin-layer chromatography and enzyme-linked immunosorbent assay analyses of extracts from mycelia and the growth medium. Southern analysis of genomic DNA isolated from the NA-accumulating transformants indicated that the wild-type nor-1 gene in the chromosome had been replaced by the nonfunctional allele carried on pNA51-82. This recombinational inactivation event provides direct evidence that the nor-1 gene is functionally involved in aflatoxin biosynthesis. Comparison of the predicted nor-1 amino acid sequence with sequences in the GenBank and EMBL databases suggested that the protein is a member of the family of short-chain alcohol dehydrogenases, consistent with its proposed function as a keto reductase.

Aflatoxins↗

PubMed1992

Isolation and characterization of a gene from Aspergillus parasiticus associated with the conversion of versicolorin A to sterigmatocystin in aflatoxin biosynthesis.

DNA isolated from the wild-type aflatoxin-producing (Afl+) fungus Aspergillus parasiticus NRRL 5862 was used to construct a cosmid genomic DNA library employing the homologous gene (pyrG) encoding orotidine monophosphate decarboxylase for selection of fungal transformants. The cosmid library was transformed into an Afl- mutant, A. parasiticus CS10 (ver-1 wh-1 pyrG), deficient in the conversion of the aflatoxin biosynthetic intermediate versicolorin A to sterigmatocystin. One pyrG+ Afl+ transformant was identified. DNA fragments from this transformant, recovered by marker rescue, contained part of the cosmid vector including the pyrG gene, the ampr gene, and a piece of the original genomic insert DNA. Transformation of these rescued DNA fragments into A. parasiticus CS10 resulted in production of wild-type levels of aflatoxin and abundant formation of sclerotia. The gene responsible for this complementation (ver-1) was identified by Northern RNA analysis and transformation with subcloned DNA fragments. The approximate locations of transcription initiation and polyadenylation sites of ver-1 were determined by an RNase protection assay and cDNA sequence analysis. The predicted amino acid sequence, deduced from the ver-1 genomic and cDNA nucleotide sequences, was compared with the EMBL and GenBank data bases. The search revealed striking similarity with Streptomyces ketoreductases involved in polyketide biosynthesis.

Aflatoxins↗

PubMed1992

CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension.

Chronic hypoxic pulmonary hypertension (PH), associated with increased pulmonary arterial pressure (PPA) and right ventricular hypertrophy (RVH), correlates significantly with calcitonin gene-related peptide (CGRP) and somatostatin (SOM) levels in lung and blood. CGRP's role in regulation of PPA in chronic hypoxia and its potential interactions with SOM were investigated. CGRP, its antibody (ab) and blocker, CGRP-(8-37), SOM-14, SOM-28, and SOM-ab, respectively, were infused into the pulmonary circulation of hypobaric hypoxia rats for 4, 8, and 16 days. Thereafter, under pentobarbital sodium anesthesia, PPA was measured in the right ventricle and main pulmonary artery. Chronic CGRP infusion prevented PH at all times, whereas immunoneutralization and receptor blocking exacerbated PH. SOM-28 also exacerbated while SOM-14 and SOM-ab decreased PH. RVH generally reflected the PPA. Radioimmunoassay confirmed successful infusion of the peptides with negligible peptide degradation in the pumps throughout 16 days and showed complete immunoneutralization of CGRP with its ab. Peptide levels in lung tissue suggest inhibition of CGRP release by SOM-28 and increased plasma SOM with CGRP infusion. In vitro pharmacological studies suggest that CGRP exerts a receptor-mediated nonadrenergic, nonmuscarinic vasodilatory effect in the lung which is independent of endothelium-derived relaxing factor and does not involve ATP-dependent potassium channels. We conclude that endogenous CGRP plays an important role in pulmonary pressure homeostasis during hypoxia, by directly dilating pulmonary vasculature, thus ameliorating the development of chronic hypoxic pulmonary hypertension in rats.

Animals↗

PubMed1991

Theophylline disposition in adolescents with asthma.

Adolescents frequently require medication for acute and chronic illnesses. A proper dosage schedule is needed to achieve efficacy without toxicity during adolescence when there are marked changes in body size and organ function. Theophylline disposition was studied in 70 asthmatic adolescents, ages 8-18 years, to determine if pubertal changes in body size, composition, and organ function are associated with changes in drug disposition. Forty-eight youngsters were studied as outpatients and 22 while hospitalized. Half-life (t1/2) was computed for all patients. Volume of distribution and clearance were determined for inpatients only. Chronological age and anthropometric growth parameters were measured. Lean body mass (LBM) was derived from anthropometric measurements. Half-life was significantly correlated with developmental stage (Tanner r = 0.42, age r = 0.33, p less than 0.01), and body size (height r = 0.39, LBM r = 0.33, weight r = 0.33, p less than 0.01). LBM (kg/kg) was significantly correlated with volume of distribution (L/kg) (r = 0.59, p less than 0.01). Best-fits for t1/2 contained two variables: t1/2 = -4.57 + 1.31 (sex) + 0.0687 (height) (r = 0.48) and t1/2 = -3.54 + 1.32 (sex) + 0.0725 (LBM) (r = 0.43). Chronological age alone is not a useful basis for determining medication dosages due to the heterogeneity in rates of development and body size among adolescents. Half-life increases with increasing height or LBM. Although compliance is clearly an important factor in achieving optimal control of symptoms, this study demonstrates that dose adjustment during times of rapid growth during puberty is equally important.

Adolescent↗

PubMed1979

Variability in interpretation of pulmonary function tests.

We asked 26 pulmonary physicians to interpret results of ten consecutive pulmonary function tests from one laboratory. There was frequent disagreement in their assessment of respiratory impairment. This is likely due to the variety of criteria for grading the severity of obstructive and restrictive defects. Since the narrative interpretation of pulmonary function data may influence patient care, physicians should consider the numerical magnitude of the derangements, as well as the descriptive terms applied.

Humans↗

PubMed1975

Thermal evaluation of breast disease using local cooling.

A simple, inexpensive local cooling system for thermal evaluation of breast disease is described. Skin temperature measured during a 10-minute cooling process averaged 1.2degrees C higher over 31 proved cancers and 0.6degrees C lower over 18 benign masses. Forty-nine masses averaged 1.7 cm in diameter and were 1.5 cm deep; 23 of 31 malignancies (74%), 16 of 18 benign growths (88%), and 46 of 52 "normals" (88%) would have been correctly diagnosed, while results for 10 of 22 women (45%) with asymmetrical diffuse non-malignant disease would have been falsely classified positive.

Breast Diseases↗