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Biomedical subjects

R Feuerstein

Publications and source records attributed to R Feuerstein.

11 recordsLinked to original sources
PubMed1994

The LIM/double zinc-finger motif functions as a protein dimerization domain.

Protein-protein interactions resulting in dimerization and heterodimerization are of central importance in the control of gene expression and cell function. Proteins that share the 52-residue LIM/double zinc-finger domain are involved in a wide range of developmental and cellular controls. Some of these functions have been hypothesized to involve protein dimerization. In the present report we demonstrate, using both in vitro and cell-based studies, that a representative LIM protein, human cysteine-rich protein (hCRP), can efficiently homodimerize. The dimerization ability of hCRP is mapped to the LIM domains, can be transferred to an unrelated protein by fusion of a single minimal LIM/double zinc-finger segment, occurs in the absence as well as the presence of DNA, and appears to depend on coordination of two zinc atoms in the finger doublet. These observations support a specific role for protein dimerization in the function of proteins containing the LIM/double zinc-finger domain and expand the general spectrum of potential interactions mediated by zinc-finger motifs.

Amino Acid Sequence↗
PubMed1994

A potent antioxidant, SB209995, inhibits oxygen-radical-mediated lipid peroxidation and cytotoxicity.

The antioxidant activity of SB209995, a metabolite of carvedilol in human, was studied and compared with its parent compound, carvedilol. SB209995 or carvedilol inhibited iron-catalyzed lipid peroxidation assessed as thiobarbituric acid-reactive substance generated in brain homogenate with IC50s of 0.30 and 8.1 mumol/l, respectively. The oxidation of low-density lipoprotein (LDL) by macrophages or that initiated by Cu2+ ions was inhibited by SB209995 with IC50s of 59 nmol/l and 1.7 mumol/l, respectively. Under the same conditions, the IC50s of carvedilol were 3.8 and 17.1 mumol/l, respectively. Furthermore, SB209995 protected cultured endothelial cells against hydroxyl radical (OH.) or superoxide (O2-)-mediated lipid peroxidation and cytotoxicity, assessed as lactate dehydrogenase release and cell death. The results indicate that SB209995 is a more potent antioxidant than carvedilol and may contribute to the therapeutic effects of carvedilol.

Animals↗
PubMed1992

Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger.

The antioxidant effect of carvedilol, a new vasodilating, beta adrenoceptor blocker was studied and compared with five other beta blockers. Carvedilol rapidly inhibited Fe(++)-initiated lipid peroxidation, measured as thiobarbituric acid reactive substance (TBARS), in rat brain homogenate with an IC50 of 8.1 microM. Under the same conditions, the IC50 values of atenolol, pindolol propranolol, celiprolol and labetalol were over 1.0 mM. Carvedilol protected against Fe(++)-induced alpha-tocopherol depletion in rat brain homogenate with an IC50 of 17.6 microM; propranolol, celiprolol and labetalol, up to 200 microM, did not show any effect. Using dihydroxyfumarate/Fe(++)-ADP as a OH.radical generating system and 5,5-dimethyl pyrroline-N-oxide (DMPO) as a trapping agent, the characteristic DMPO-OH signals were monitored by electron paramagnetic resonance. Carvedilol dose-dependently decreased the intensity of the DMPO-OH signal, with an IC50 of 25 microM, whereas propranolol, at 500 microM, and U74500A, a 21-aminosteroid, at 100 microM, had no effect. The antioxidant effect of carvedilol mainly resides in the carbazole moiety, and the substitution of a hydroxyl group at certain positions on the phenyl ring of either carbazole or the ortho-substituted phenoxylethylamine part of carvedilol resulted in an increase in antioxidant activity. Furthermore, the protective effect of carvedilol analogs against OH.-mediated neuronal death positively correlated to their antioxidant effect. We conclude that carvedilol is a far more potent antioxidant than other commonly used beta blockers. The apparent mechanism of carvedilol's inhibition of lipid peroxidation is mainly via scavenging free radicals. This novel property of carvedilol may contribute to the known cardioprotective activity of this compound.

Adrenergic beta-Antagonists↗
PubMed1988

Social perceptions of the effects of Down syndrome facial surgery: a school-based study of ratings by normal adolescents.

This study examines how 277 normal adolescents from five Israeli schools perceive the Down syndrome face before and after plastic surgery. A seven-point Likert scale was used to rate slides of normal and Down syndrome faces on four dimensions. Down syndrome patients were seen as less attractive, intelligent, good-hearted, and socially appealing than normal individuals. The slides were in nonapparent order and contained preoperative and 1-year postoperative views of eight plastic surgical patients. Paired t tests were used to examine operative changes, and all four dimensions showed overall postoperative improvement (p less than 0.001), but case-to-case variation was considerable. A linear relationship was found between change in appearance ratings and change in intelligence ratings. Findings suggest that when improvements in facial appearance are realized, peer normal social perceptions of the Down syndrome child may be enhanced. The relationship between school placement, intellectual level, and surgical decision making is discussed.

Adolescent↗
PubMed1986

Rehabilitation of the face in patients with Down's syndrome.

Fifty patients with Down's syndrome underwent surgery for improvement of the facial stigmata. Partial glossectomy, lateral canthoplasty, and nose, cheek, and chin augmentation were the common procedures. With a follow-up of 18 to 24 months, the results were recorded by a multidisciplinary team with similar judgments on the glossectomy, the most satisfactory procedure, and some discrepancy on the other procedures, canthoplasty, and cheek augmentation. There were no infections or extrusion of prostheses, and a rather high incidence of extrusion of prostheses, and a rather high incidence of bone resorption was noted in the mandibular area. The facial changes were satisfactory in the majority of the cases in both medical and nonmedical evaluation and improved self-confidence, especially in the older patients. The satisfactory results here presented advocate certain procedures for attenuation of the Down's syndrome stigmata and improvement of some functions by diminishing the size of the tongue.

Adolescent↗
PubMed1979

Cognitive modifiability in retarded adolescents: effects of instrumental enrichment.

The Instrumental Enrichment program, designed to modify the cognitive structures of retarded, disadvantaged adolescents, was contrasted with a General Enrichment program both in a residential setting and a day center. This study is based on 57 matched pairs drawn from the total research sample of 218 adolescents. One group in a residential center (n = 24) and one group in a day center (n = 33) received Instrumental Enrichment; one group in a residential center (n = 24) and one group in a day center (n = 33) received General Enrichment. The Instrumental Enrichment program extended over 2 years, and the subjects were pre- and posttested on a battery of criterion measures: general and specific cognitive tests, scholastic achievement, classroom interaction, and self-concept. The results indicated significantly better performance by the groups receiving Instrumental Enrichment than by the groups receiving General Enrichment on the tests of specific cognitive functions and scholastic achievement and on some of the classroom interaction scales. Results for the residential groups compared with the day-center groups revealed significant differences on the tests of scholastic achievement, in favor of the residential groups and on the classroom interaction scales in favor of the day-center groups.

Achievement↗