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Biomedical subjects

R Rasooly

Publications and source records attributed to R Rasooly.

12 recordsLinked to original sources

Ceramide-mediated apoptosis in lung epithelial cells is regulated by glutathione.

Reactive oxygen species (ROS) are mediators of lung injury, and glutathione (GSH) is the major nonprotein antioxidant that protects the cell from oxidative stress. We have recently shown that H(2)O(2) induces ceramide-mediated apoptosis in human lung epithelial cells. We hypothesized that ROS-mediated depletion of GSH plays a regulatory role in ceramide generation, and thus in the induction of apoptosis. Our present studies demonstrate that GSH at physiologic concentrations (1 to 10 mM) inhibits ceramide production in a time- and dose-dependent manner in A549 human alveolar epithelial cells. On the other hand, buthionine-sulfoximine-mediated depletion of intracellular GSH induces elevation of ceramide levels and apoptosis. In addition, GSH blocks H(2)O(2)-mediated induction of intracellular ceramide generation and apoptosis. These effects were not mimicked by oxidized GSH (GSSG) or other thiol antioxidants, such as dithiothreitol and 2-mercaptoethanol. Moreover, increase of intracellular H(2)O(2), mediated by inhibition of catalase by aminotriazole, also induces ceramide generation and apoptosis. These effects were blocked by N-acetylcysteine. Our results suggest that GSH depletion may be the link between oxidative stress and ceramide-mediated apoptosis in the lung.

Acetylcysteine↗

Isolation and analysis of fluP, a gene associated with hyphal growth and sporulation in Aspergillus parasiticus.

Aflatoxins (AF) are polyketide-derived mycotoxins that frequently contaminate food and feed crops, causing health risks to animals and humans. The fluP gene was cloned by screening an Aspergillus parasiticus genomic DNA library with a cDNA probe encoding part of a polyketide synthase (PKS), the 6-methylsalicylic acid synthase (MSAS) from Penicillium patulum. FluP was hypothesized to function as a PKS in AF biosynthesis. The predicted amino acid sequence of FluP demonstrated a high degree of identity to MSAS (55%), moderate identity to another fungal PKS protein encoded by wA from A. nidulans (22%) and low identity (<5%) to fungal fatty acid synthase (FAS) proteins. Disruption of fluP in A. parasiticus resulted in the loss of fluP transcript, a 3- to 4-fold reduction in hyphal growth rate, the appearance of a fluffy, cotton-like hyphal morphology, reduction or elimination of asexual spores and spore-bearing structures, and a twofold reduction in aflatoxin accumulation. Removal of selective pressure on fluP knockout transformants resulted in frequent reversion (10%) to the wild-type genotype and phenotype, establishing a direct link between gene disruption and the associated phenotype. The data suggest that fluP encodes a novel PKS associated with hyphal growth and cell development (sporulation), whose activity indirectly influences aflatoxin accumulation in A. parasiticus.

Aflatoxin B1↗

Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus.

Staphylococcus aureus causes pathologies ranging from minor skin infections to life-threatening diseases. Pathogenic effects are largely due to production of bacterial toxin, which is regulated by an RNA molecule, RNAIII. The S. aureus protein called RAP (RNAIII activating protein) activates RNAIII, and a peptide called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria, inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic RIP were protected from S. aureus pathology. Thus, these two molecules may provide useful approaches for the prevention and treatment of diseases caused by S. aureus.

Amino Acid Sequence↗

Separation anxiety: the etiology of nondisjunction in flies and people.

Two new studies examine the recombinational history of human chromosomes that nondisjoin at the first meiotic division in females. Our analysis of these studies suggests two possible etiologies of nondisjunction in terms of well-understood properties of chromosome mechanics. For both the X chromosome and for chromosome 21, 60-70% of nondisjoined chromosomes are derived from chiasmate bivalents, many of which display unusual patterns of exchange. The patterns of exchange and nondisjunction observed for human chromosome 21 parallel those exhibited by a mutation in Drosophila that impairs spindle assembly and function. Based on these similarities, we propose that nondisjunction of chromosome 21 in human females results from an age-dependent loss of spindle-forming ability. The recombinational histories of nondisjoining human X chromosomes are quite different from those of chromosome 21, but rather parallel those obtained for spontaneous nondisjunction in Drosophila females. The data for X chromosome disjunction in both species can be explained by a model in which nondisjunction is the consequence of the age-dependent movement of transposable elements. According to this model, nondisjunction is explained as the consequence of the repair of transposon-induced breaks in the DNA. Both models provide reasonable alternatives to biologically implausible explanations such as the 'production line hypothesis'.

Animals↗

Assessment of intraocular lens power on the basis of precataract refractive measurements.

Assessment of intraocular lens (IOL) power may rely, when biometric measurements of the eye are not available, on refraction previous to cataract development. Such an assessment, however, is generally considered unreliable. To improve the predictability of this method, we correlated refraction measurements with predictions of IOL power. In contrast to previous studies which used retrospective assessment of precataract refraction, this study included only noncataractous eyes and correlated the direct refractive measurements obtained with hypothetical IOL power values. These values were calculated by placing axial length and corneal power measurements of the same eyes in the SRK formula. We conclude that the regression formula obtained may improve the clinical judgment required for predicting lens implant power in cataractous eyes, on the basis of precataract refractive measurements.

Adolescent↗

Congenital and traumatic cataract. The effect on ocular axial length.

Elongation of the eye is one of the drawbacks of implanting intraocular lenses in children. To evaluate possible effects of cataract and aphakia on eye elongation, we measured the axial length in children with unilateral aphakia (15 children with congenital cataract and 27 with traumatic cataract) and in children with bilateral congenital cataract (operated on in 14 cases and not operated on in eight cases). In all cases of unilateral aphakia, the aphakic eye was consistently longer than the normal fellow eye. Excessive eye elongation was related to corresponding reduction in visual acuity. The presumed rate of elongation was quantitatively expressed using the time elapsed since surgery and the age of the child. In bilateral congenital cataract, the axial length measured in aphakic eyes that were operated on was similar to that in eyes that were not operated on. We suggest that unilateral cataract or aphakia is associated with excessive eye elongation of affected eyes. Eye elongation seems to be related to amblyopia and poor vision rather than to aphakia.

Adolescent↗

Arterial tortuosity and dilatation in Larsen syndrome.

Tortuosity and dilatation of the cranial and abdominal arteries are described in a case of Larsen syndrome. These uncommonly recognized anomalies lend support for a generalized mesenchymal disorder in Larsen syndrome.

Abdomen↗

Correlations between ocular optical components, height and head circumference.

Correlations between the ocular optical components, height and head circumference were investigated in 144 subjects. Refraction had a higher correlation with axial length than with corneal curvature. On the other hand, height and head circumference had a higher correlation with corneal curvature than with axial length. These results express the dependence of refraction on the axial length and suggest a similarity between corneal and skeletal growth, compared with the relatively independent elongation of the eye. Refraction correlated significantly with head circumference but not with height, relations which may be explained by considering some of the optical components that determine refraction, rather than treating refraction as a single factor.

Adolescent↗