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Biomedical subjects

J Horowitz

Publications and source records attributed to J Horowitz.

At least 127 records · Page 7Linked to original sources
PubMed1983

Isolation and characterization of two 5-fluorouracil-substituted Escherichia coli initiator methionine transfer ribonucleic acids.

Escherichia coli initiator methionine tRNA labeled in vivo with 5-fluorouracil (FUra) has been isolated and characterized. The tRNA, with essentially all its uracil and uracil-derived minor bases replaced by FUra, was purified by sequential chromatography, first on diethylaminoethylcellulose (DEAE-cellulose), at pH 8.9, followed by chromatography on Sepharose 4B, using a reverse salt gradient, then on DEAE-Sephadex A-50, and finally on benzoylated DEAE-cellulose. The last step resolved two FUra-substituted tRNAfMet-iso-accepting species, each with a specific activity over 1500 pmol/A260. Kinetic analysis shows both are aminoacylated at the same rate; apparent KmS for the two are 0.92 and 0.94 microM, compared with 1.7 microM for normal tRNAfMet. Chromatographic differences between the two forms of fluorinated tRNAfMet persist after aminoacylation, and the two tRNAs are not interconverted by denaturation and renaturation. The isoacceptors have nearly identical nucleoside composition, and both contain 7-methylguanosine and 2'-O-methylcytidine as the only modified nucleosides. Analysis of complete RNase T1 digests of the two methionine tRNAs shows that they differ in only one oligonucleotide. The sequence 20FpApGp, derived from the dihydrouridine loop and stem region, which is found in one of the isoaccepting forms of the tRNA, is replaced by an oligonucleotide containing adenine and guanine, but no FUra in the other. A modified FUra, with the properties of a 5-fluoro-5,6-dihydrouracil derivative, is detected in this tRNA. 19F NMR spectra of the two species of FUra-substituted initiator tRNA show 9-10 resolved resonances for the 12 FUra residues incorporated. The spectra differ primarily in the shift of one peak in the form lacking the sequence 20FpApGp, from 4.8 ppm downfield from free FUra (= 0 ppm) to 14.9 ppm upfield from the standard.

Base Sequence↗
PubMed1983

Neurohypophyseal peptides and the eye: use of synthetic analogs in analyzing effects on the pupil.

Effects of neurohypophyseal (NHP) and synthetic analogs on the pupil of the rabbit were explored. This was prompted by the recent emergence of synthetic analogs with selective agonist and antagonist properties. The miotic effect of the NHP was examined in an isolated iris preparation. Minimum concentrations of arginine-vasopressin (AVP) needed to cause threshold pupillary constriction were approximately 10(-10) M. The miotic potency of several NHP analogs correlated best with their pressor activity. In addition, the synthetic NHP pressor antagonist d(CH2)5 Tyr(Me)AVP specifically antagonized the miotic effect, confirming that a pressorlike receptor mediates this pharmacologic action of the NHP. We also employed the technique of in vivo intravitreal administration of pharmacologic doses of the NHP in the rabbit. Once again, potent miotic activity was demonstrated. The relative miotic potency of the NHP in vivo provided further support to the relationship between the NHP "pressor" receptor and pupillary constriction. We believe that the use of a variety of NHP natural and synthetic analogs may also prove helpful in investigating potential physiological effects of the NHP on other intraocular smooth muscle.

Animals↗
PubMed1983

Should nutritional status be assessed routinely prior to cardiac operation?

One hundred consecutive adult patients undergoing cardiac operations at a single institution were evaluated preoperatively with regard to their nutritional status. Anthropometric, biochemical, and immunologic characteristics were evaluated in addition to cardiac biopsy specimens to determine right atrial glycogen concentration. Although some positive anthropometric, biochemical, and cell-mediated immunity characteristics were observed to have "statistically significant" correlations with morbidity and mortality for the group as a whole, nearly all of the values remained near or at normal limits. Lighter weight men with a smaller arm muscle circumference and lower concentration of total body fat had more complications than their heavier counterparts. Serum transferrin and cell-mediated immunity also formed weakly positive statistical correlations. Anthropometric correlations in women were of no value. Myocardial glycogen concentrations did not correlate with postoperative morbidity and mortality. Because nearly all of the patients had arteriosclerotic heart disease, the series as a whole may have been skewed toward a group with values too close to normal to differentiate them adequately. It is concluded that routine nutritional assessment is of no value in guiding nutritional management for individual patients, although when patients are analyzed as a group, interesting epidemiologic observations can be made.

Adult↗
PubMed1982

Enteral hyperalimentation in undernourished patients with cirrhosis and ascites.

Available enteral hyperalimentation solutions used to treat undernourished cirrhotic, ascitic patients with protein intolerance are excessive in water, sodium, and in some cases protein. This study investigated the use of enteral formulae tailored to the water, sodium, and protein tolerance of 10 undernourished subjects with ascites due to alcoholic liver disease (n = 8) and postnecrotic cirrhosis (n = 2). During a 10- to 60-day (mean +/- 80 = 37 +/- 19) hyperalimentation period, three subjects were treated with a low Na (1g Na/2000 kcal), high caloric density formula (2 kcal/ml); previous encephalopathy in seven remaining subjects required infusion of a low Na, low protein (40 g/day) modular high caloric density formula. The high caloric density formula protein content in 6/7 subjects was increased to 80 to 143 g without adverse effect. Nine subjects tolerated the program well and showed improvement in the following indices: serum albumin, creatinine/height, and midarm muscle and fat areas. In selected cases, enteral hyperalimentation solutions with appropriate composition can be safely and effectively administered to cachectic cirrhotic subjects with ascites.

Adult↗
PubMed1981

Measurement of liver and spleen volume by computed tomography. Assessment of reproducibility and changes found following a selective distal splenorenal shunt.

Liver and spleen size were measured in 11 normal subjects and 12 patients with cirrhosis. Volume was calculated by adding together the area measurements obtained from successive transverse abdominal scans. The normal mean volume of the liver (+/- S.D.) was 1,493 +/- 230 cm3 and that of the spleen was 219 +/- 76 cm3; interobserver variability was 4-8% and the day-to-day coefficient of variation was 6-10%. In cirrhotic patients studied prior to and 7-10 days after a distal splenorenal shunt, the mean liver volume fell from 1,642 to 1,529 cm3 (p less than 0.06) and the mean spleen volume from 660 to 507 cm3 (p less than 0.006), supporting the use of such a shunt in selective decompression of varices and maintenance of portal hypertension. This is a clinically useful method of measuring organ volume with the required sensitivity.

Adult↗
PubMed1981

Angiotensin converting enzyme concentrations in rabbits with talc-induced pulmonary granulomas.

Pulmonary foreign body granulomas were induced in rabbits by intravenous injection of a talc suspension, and serum angiotensin converting enzyme (ACE) concentrations were monitored for 50 days. One of 3 treated rabbits responded with a slight elevation of serum ACE in the third week after the first injection and for the remainder of the experimental period. Two treated rabbits and 2 control rabbits maintained serum ACE concentrations close to the starting values throughout the observation period of 50 days. We concluded that pulmonary talc granulomas and probably other foreign body granulomas do not elicit a major elevation of serum ACE in rabbits.

Animals↗
PubMed1980

Enzymatic esterification of vitamin A in the pigment epithelium of bovine retina.

The kinetic properties and subcellular distribution of an esterifying enzyme in the pigment epithelium of bovine retina have been studied using both [1-3H]retinol and [3H]retinol bound to cellular retinol-binding protein as substrates. The most active esterifying fraction in pigment epithelial cell preparations was the microsomes, but the lysosome plus mitochondria fraction also showed some activity, probably due to endoplasmic reticulum present as an impurity. The microsomal enzyme showed optimum activity at pH 7.5, and the reaction was linear up to 30 microgram protein and for the first 10-15 min. The apparent Km values were 16.6 . 10(-6) and 5.5 . 10(-6) M for [3H]retinol and bound [3H]retinol, respectively. This is the first time that retinol bound to cellular retinol-binding protein has been shown to undergo metabolic transformation. The microsomal esterifying activity was destroyed by boiling for 1 min, or after freezing for 2 months. No clear requirement for ATP, CoA or fatty acid could be demonstrated. Of all the other tissues examined under the same experimental conditions as those used for the pigment epithelium, only intestine showed measurable activity. With larger amounts of tissue protein and longer incubation periods, activity was also detectable in microsomes of liver, testis and retina.

Animals↗
PubMed1980

Effects of 5-fluorouracil on the formation of modified nucleosides in yeast transfer RNA.

Yeast cells grown in the presence of the drug FUra synthesize RNA in which Urd is partially replaced by FUrd. Transfer RNAs in which 1.5-50% of the Urd has been replaced by FUrd have been isolated and their base compositions measured to determine the effect of FUrd incorporation on posttranscriptional nucleoside modification. This replacement results in an extensive reduction in the amounts of Thd, H56Urd and psird found in mature tRNA. Quantitatively, the reduction of psird greater than or equal to Thd greater than H56Urd. The losses of psird, Thd and H56Urd are greater than can be accounted for by the stoichiometry of FUrd incorporation. The formation of 5-MeCyd is not affected by the drug, whereas the methylated purines show substoichiometric losses in FUrd-containing tRNAs. In Escherichia coli, we have not observed any effects of FUra on the methylated purine content, although the effects on psird, Thd and H56Urd are similar. These findings indicate that (a) in both pro- and eukaryotic systems the enzymes responsible for psird, Thd and H56Urd formation are affected by FUra treatment in a similar manner; (b) prokaryotic purine methylases may be more tolerant of structural aberrations resulting from FUrd incorporation than eukaryotic methylases and (c) different methylases within one system show different sensitivities as shown by those responsible for 1-MeAdo and 5-MeCyd formation.

Base Composition↗
PubMed1978

Replacement of pseudouridine in transfer RNA by 5-fluorouridine does not affect the ability to stimulate the synthesis of guanosine 5'-triphosphate 3'-diphosphate.

The requirement for ribothymidine and pseudouridine in the TpsiCG loop of tRNA for its activity in the ribosome and tRNA-stimulated synthesis of guanosine 5'-triphosphate 3'-diphosphate (pppGpp) by stringent factor has been tested by the use of a purified tRNAPhe (883 pmol of phenylalanine incorporated/A260 unit) in which 92% of the pseudouridine, 98% of the ribothymidine, 98% of the dihydrouridine, and 88% of the uridines were substituted by 5-fluorouridine. This tRNA was quantitatively as active as control tRNA in inducing pppGpp synthesis. With loose-couple ribosomes, the concentration of tRNA needed to give half-maximal reaction was 0.07 micrometer for both normal and fluorouridine-substituted tRNA, with vacant tight-couple ribosomes it was 0.05 micrometer, and with tight couples carrying poly(Phe)-tRNA at the P site the value was 0.02 micrometer. These results show that at the level of intact tRNA there is no special requirement for modified bases in the TpsiCG loop of tRNA in the synthesis of pppGpp.

Escherichia coli↗