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Biomedical subjects

J R Cook

Publications and source records attributed to J R Cook.

At least 127 records · Page 7Linked to original sources
PubMed1984

Dexamethasone inhibition of rat hepatoma growth and alpha-fetoprotein synthesis.

The effect of dexamethasone on hepatoma growth and differentiation, as well as the production of alpha-fetoprotein (AFP) and albumin, was investigated. Treatment of rats with dexamethasone strongly reduced (by 83 to 98%) the serum levels of AFP in rats bearing Morris hepatomas 7777, 8994, 7288c , and 9618A2 . Reduced AFP levels were due in part to a large reduction in tumor load in dexamethasone-treated rats. Hepatoma weights, on the average, were reduced by 64 to 90% relative to controls, while a large bowel transplantable tumor was affected only slightly. Lower serum AFP levels in rats with hepatomas 7777, 8994, and 9618A2 also resulted from reduced AFP synthesis, as indicated by lower cytoplasmic AFP levels. Cytoplasmic albumin levels were higher in dexamethasone-treated rats bearing hepatomas 7777, 8994, and 7288c than they were in rats which did not receive dexamethasone. RNA dot hybridization also indicated that dexamethasone reduced the amount of AFP mRNA in hepatoma 7777 while increasing albumin mRNA. Two-dimensional gel electrophoresis of tumor cytosol proteins showed that dexamethasone reduced synthesis of all AFP variants which could be detected by this technique. A number of abundant hepatoma-associated and liver-associated proteins were not significantly affected by dexamethasone.

Animals↗
PubMed1983

Effect of 5-azacytidine on rat liver alpha-fetoprotein gene expression.

Neonatal rats given 5-azacytidine intraperitoneally (30 micrograms/animal/day) on days 1-5 postpartum had 55% lower serum alpha-fetoprotein levels on day 6 compared to saline injected controls. On day 14, alpha-fetoprotein levels were 4-fold lower in 5-azacytidine treated animals. Cytosol alpha-fetoprotein was proportionately reduced. There were no significant changes in liver to body weight ratio, total serum protein, and both serum and cytosol albumin levels. The molecular basis for decreased serum alpha-fetoprotein levels was found to be a reduced concentration of alpha-fetoprotein mRNA in the livers of 5-azacytidine injected animals. These results are discussed with respect to the effects of 5-azacytidine on DNA methylation and cell differentiation.

Aging↗
PubMed1982

The complement of cytoplasmic tRNAs, including queuosine-containing tRNAs, in adult and senescent Wistar rat liver and their levels of aminoacylation.

Our previous studies showed that both total cytoplasmic tRNAs and aminoacyl-tRNA synthetases isolated from senescent (24-30 month) female Wistar rat liver were less capable of supporting cell-free protein synthesis than were the same fractions isolated from adult (10-13 month) rat liver. The present study investigates the molecular basis for this age-related result. No significant age-related differences were found in the extent of aminoacylation of the liver cytoplasmic tRNA population, the total tRNA synthetase activity, the rate of aminoacylation of individual tRNAs, or in the overall complement of tRNA species as detected by two-dimensional gel electrophoresis. In homologous senescent aminoacylation assays, consisting of tRNAs and tRNA synthetases from senescent animals, alanine, arginine and aspartic acid were charged to a greater extent and methionine to a lesser extent compared to homologous adult assays. In heterologous assays, adult synthetases were significantly more active than senescent synthetases when charging isoleucine, methionine, phenylalanine, proline and glutamic acid, and less active when charging alanine, aspartic acid and serine. Also, senescent synthetases charged both adult and senescent tRNAs with methionine to a lesser extent than did adult synthetases. In homologous senescent assays with queuosine-containing tRNAs, asparagine, aspartic acid and histidine were charged to a greater extent and tyrosine to a lesser extent compared to homologous adult assays. Results with queuosine-tRNAs are discussed in terms of their potential ability to lower the efficiency of translation in senescent liver.

Aging↗
PubMed1981

The role of mRNA levels and cellular localization in controlling sn-glycerol-3-phosphate dehydrogenase expression in tissues of the mouse.

sn-Glycerol-3-phosphate dehydrogenase (glycerol-P dehydrogenase, EC 1.1.1.8) activity levels in seven tissues of adult mice vary approximately 100-fold from a low of 0.1 unit/mg of protein in the cerebral cortex to a high of 8 units/mg of protein in the brown fat of cold-adapted mice; the brown fat accounts for approximately 1% of the total tissue protein. This high degree of variation in the quantitative expression of an enzyme in different tissues has provided us with a system for analyzing the mechanism by which tissue specific variation for a given gene product is controlled. To this end we have measured the amount of immunoreactive enzyme and the level of translatable glycerol-P dehydrogenase mRNA and have localized the glycerol-P dehydrogenase-positive cells by immunocytochemistry. We have found that the amount of enzyme protein in a tissue is strongly correlated with the level of its translatable mRNA (correlation coefficient = 0.996) and that in several cases the differences among tissues can be explained by differences in the numbers of glycerol-P dehydrogenase-positive cells.

Adipose Tissue, Brown↗
PubMed1981

Decreased protein synthesis by polysomes, tRNA and aminoacyl-tRNA synthetases isolated from senescent rat liver.

A cell-free in vitro protein-synthesizing system isolated from adult(10-13-month) and senescent(24-30-month) female Wistar rat liver is described. Optimal concentrations of polysomes, aminoacyl-tRNA synthetases, tRNA, Mg 2+, K+, and labeled amino acids are reported for this in vitro system. Both are rate and extent of protein synthesis are lower with the system from senescent liver compared to that from adult liver. Senescent polysomes, tRNA synthetases, and tRNA all contribute to this decrease. Free adult or senescent polysomes support protein synthesis to the same extent. However, compared to adult polysomes, senescent membrane-bound polysomes support less protein synthesis and account for an increased proportion of the total polysome fraction. Ribonuclease and protease activities are low in the adult and the senescent in vitro systems and do not account for the decreased protein synthesis with the latter.

Aging↗
PubMed1978

Culture pH, CO2 tension, and cell division in Euglena gracilis Z.

Growth characteristics of Euglena gracilis Z as functions of culture pH, CO2 tension, temperature, and lighting regime were investigated. The results are consistent with the possibility that cell division is preceded by a lowered intracellular pH. Also consistent with this possibility is the finding that division rhythmicity can be induced by periodic changes in CO2 tension. It is suggested that the rhythmicity is induced by changes in intracellular pH produced by carbonic acid.

Carbon Dioxide↗
PubMed1978

Simple procedure for determining octanol--aqueous partition, distribution, and ionization coefficients by reversed-phase high-pressure liquid chromatography.

The described simple, accurate, and precise reversed-phase high-pressure liquid chromatographic procedure is in excellent agreement with 1-octanol shake-flask partition or distribution coefficients over a 3.5 log range. A chemically bonded octadecylsilane support is persilated and coated with 1-octanol. With 1-octanol-saturated buffers as mobile phases, a stable baseline (compared to 1-octanol adsorbed on silica) is obtained rapidly, and the log relative retention times are highly correlated with unit slope to log distribution or partition coefficients obtained from the classical shake-flask procedures. Only relatively basic, unhindered pyridines deviate, probably because of binding with residual silinol sites. In addition, if the apparent pKa or pKab of an ionizable compound lies within the pH operating range of the column support, the apparent pKa or pKab usually can be determined simultaneously with log P by measuring the log distribution coefficient at several pH values. The procedure gives rapid results, requires little material, and can tolerate impurities.

Chemistry, Pharmaceutical↗
PubMed1976

Input from trigeminal cutaneous afferents to neurones of the inferior olive in rats.

Extracellular recordings were obtained from inferior olivary neurones of the rat. The responses of fifty neurones evoked by electrical stimulation of a branch of the trigeminal nerve were recorded. Maxillary nerve stimulation was most effective. The response was characterized by an early discharge (single spike and wave, typically with latencies between 16 and 30 msec) and a weak late discharge which followed a period of inhibition of about 100 msec. Half of the neurones responded to one branch of the trigeminal nerve only whereas the other neurons displayed a varying degree of convergence, including sometimes a convergence from limb nerves. Forty-nine olivary neurones were tested for cutaneous receptive fields. Ten out of these had small receptive fields (less than 20% of the contralateral face) and a low threshold to mechanical stimuli. Twenty neurones which had larger receptive fields responded also to low-threshold or to medium-threshold (i.e. non-nociceptive) mechanical stimuli. None of the neurones displayed receptive fields more extensive than half of the contralateral face and some of the larger fields had a small, low-threshold focus. Olivary neurones responding to electrical stimulation of trigeminal nerves or mechanical stimulation of the face were located in the medial segment of the olivary complex (dorsal accessory and principal olive). A few cells only were located in the lateral segment. It is concluded that neurones of the inferior olive receive a substantial input from trigeminal afferents and are capable of transmitting precise somatotopical information to the cerebellum.

Afferent Pathways↗
PubMed1976

Optic nerve colobomas of autosomal-dominant heredity.

Fifteen members of a family had congenital colobomas of the optic nerves, all of which were bilateral. The bolobomas appeared as enlargement of the physiologic cup with severely affected eyes having huge cavities in the site of the disc. A variable amount of glial tissue was present within the colobomas. Either macular or extramacular serous detachment or sequelae were present in 21 of the 30 affected eyes, and often led to total blindness. Radioisotope cisternography in one patient failed to implicate cerebrospinal fluid as the source of the subretinal fluid. The disorder is apparently inherited as an autosomal dominant.

Adolescent↗
PubMed1976

Cyclic changes in chloroplast structure in synchronized Euglena gracilis.

In populations of Euglena gracilis strain Z synchronized by cultivation on a repetitive light-dark cycle, chloroplasts undergo cyclic changes in strucutre. During most of the light period chloroplasts are relatively compact with closely appressed lamellae; during the dark (division) period the chloroplasts become quite distended. This change persists for at least one cycle even when the cells are left in continuous light, suggesting that the periodicity may be related more to the age of the cell than to a direct effect of light. In addition, the pyrenoid in synchronized cells has a transient existence, being present only in the first half of the light period.

Animals↗