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Biomedical subjects

D Holtzman

Publications and source records attributed to D Holtzman.

At least 91 records · Page 5Linked to original sources

Maturation of potassium-stimulated respiration in rat cerebral cortical slices.

Maximal dinitrophenol-stimulated respiration and K+-stimulated respiration were measured polarographically in cerebral cortical slices taken from rats aged 2-60 days. Increasing K+ concentrations produced an increase in respiration in slices from animals aged 15 days and older, but not in slices from animals aged 10 days and younger. Dinitrophenol-stimulated respiration, or the maximal respiratory capacity of the tissue, showed a similar increase between 10 and 15 days of age. At each age the maximal respiratory capacity was 6-8 ng at 0/mg protein min greater than the maximal K+-stimulated respiration.

2,4-Dinitrophenol↗

Scanning electron microscopic study of lead effects on cerebral astrocytes in primary culture.

The effects of lead acetate on the cell surface of primary cultured astrocytes from dissociated neonatal rat cerebrums were studied using scanning electron microscopy. Astrocytes, grown for two weeks in a modified Eagle's minimal essential medium containing 20% calf serum, were exposed to lead (1, 10, 30, 50, or 100 micrograms Pb/ml) for four days. Astrocytes grown in lead-free medium showed membrane folds (ruffles) and microvilli on the surfaces of perikarya. Vesicular structures or blebs (gliosomes) were scattered on the surfaces of perikarya and branched cell processes. Cultures exposed to 1 microgram Pb/ml were indistinguishable from controls. After exposure to 10 and 30 micrograms Pb/ml, microvilli disappeared, membrane folds were less extensive, and the number of surface blebs increased. Astrocytes exposed to 50 micrograms Pb/ml showed no surface membrane folds or microvilli while the blebs increased sufficiently to cover the surface of the perikarya. Cells treated with the highest lead concentration (100 micrograms/ml) were shrunken and perikarya again were covered with blebs. Transmission electron microscopy of the cells exposed to 10-100 micrograms Pb/ml showed membrane bound vacuoles and areas of cytoplasmic clearing, some of which may correspond to the surface blebs seen by SEM. These studies suggest that the changes in the cell surface resulting from lead exposure represent a toxic effect of lead on primary cultured astrocytes.

Animals↗

Hyperthermia-induced seizures in the rat pup: a model for febrile convulsions in children.

Seizures were produced in rat pups by ambient hyperthermia. Seizure threshold temperatures, measured rectally and intracerebrally, increased between 2 and 10 days of age. Electrocortical paroxysmal discharges were confirmed in hyperthermic 6- and 10-day-old pups. The increasing resistance to hyperthermic seizures with maturation and the electroencephalographic changes induced by hyperthermia are similar to those in young children.

Age Factors↗

Factors influencing the growth and respiration of rat cerebral astrocytes in primary culture.

Cell densities and respiratory rates of astrocytes from neonatal rat brain grown in primary culture were determined after 20-30 days in vitro. Cells grown in flasks reached lower densities (microgram DNA/cm2) and higher protein:DNA ratios than cells grown in petri dishes. Respiratory rates were lower for cells grown in flasks compared to cells grown in dishes. The pH of the medium in flasks fell below 6.9 between feedings while the pH of the medium in dishes remained at about 7.2. Cells grown in dishes with the medium pH adjusted to 6.8 also showed lower final cell densities, higher protein:DNA ratios, and lower respiratory rates, compared to cells grown under similar conditions at pH 7.5. Intermediate values of each parameter were found in cells grown at pH 7.5 for one week and then at 6.8 for 20 days. We conclude that the effects of ambient pH account for the differences in growth characteristics and respiratory rates of astrocytes grown in dishes versus those grown in flasks.

Animals↗

Haloperidol-induced tardive dyskinesia in a child with Gilles de la Tourette's disease.

A 7-year-old boy with multiple tic or Gilles de la Tourette's disease was treated with haloperidol. Within five months, lingual-buccal-facial movements developed that were characteristic of tardive dyskinesia. This new movement disorder disappeared after treatment with haloperidol was stopped. To our knowledge, this is the first report of tardive dyskinesia complicating the use of haloperidol in the treatment of multiple tic syndrome in a child.

Child↗

Respiration in rat cerebral astrocytes from primary culture.

Respiration was measured polarographically in astrocytes from dissociated neonatal rat cerebra grown in primary culture. Cells grown in a modified Eagle's minimal essential medium containing 20% fetal calf serum for 14 to 21 days respired at a rate of 34.23 n at. equiv 0 mg protein-1 min-1. Cells which were grown in this medium for 14 days and the grown in serum-free medium containing 0.25 mM dibutyrylcyclic-AMP (dbcAMP) for three to six days, had respiratory rates 20% higher than in cells from untreated control cultures (P = 0.005). Maximal inhibition by oligomycin required 200 pmole per mg protein for dbcAMP-treated cells and 80 pmole per mg protein for untreated cells. Oligomycin inhibited the respiration of both dbcAMP-treated and untreated cells by about 70%. At a concentration of 175 nmole per mg protein, 2,4-dinitrophenol (DNP) produced a maximal stimulation of respiration, which was 191% of the resting rate in dbcAMP-treated cells and 218% of the resting rate in untreated cells. The maximal DNP-stimulated respiratory rates were the same in dbcAMP-treated and untreated cells.

Animals↗

Shark heart mitochondria: effects of external osmolality on respiration.

Shark mitochondrial respiration was studied in media with osmolalities between 160 and 1500 milliosmoles. The respiratory control ratio, a marker for functional integrity of the isolated mitochondria, was maximal at 1000 millismoles and decreased during hypotonic or hypertonic exposure. Shark mitochondria function best at their native tonicity, a value that produces abnormal function in mammalian mitochondria.

Adenosine Diphosphate↗

Effect of cephaloridine on respiration by renal cortical mitochondria.

The effects of the nephrotoxic antibiotic, cephaloridine, were studied in rabbit renal cortical mitochondria. Mitochondria from animals which received a toxic dose of 200 mg/kg of the drug 2 hr before sacrifice (in vivo exposure) had significantly decreased rates of respiration compared with those of mitochondria from untreated control animals. In vitro exposure of normal mitochondria to cephaloridine resulted in a qualitatively similar decrease of respiration. With both in vivo and in vitro exposure, inhibition was greatest with ADP-dependent respiration using succinate as substrate. The severity of in vitro inhibition of respiration showed some correlation to the degree of in situ cytotoxicity at different cephaloridine concentrations. The results are in agreement with the finding of a reduction of rates of respiration in renal tubule suspensions after similar in vivo and in vitro exposure to cephaloridine. These studies provide preliminary evidence that cephaloridine nephrotoxicity may be mediated through an inhibitory effect on mitochondrial respiration.

Adenosine Diphosphate↗

In vitro effects of inorganic lead on isolated rat brain mitochondrial respiration.

The effects of lead acetate on respiration in cerebral and cerebellar mitochondria from immature and adult rats were studied polarographically. With all substrates low lead concentrations produced an increase in respiration. Higher concentrations produced an inhibition of both this lead-induced respiration and ADP-dependent (State 3) respiration. Lead-induced respiration required inorganic phosphate and was inhibited by oligomycin, suggesting a coupling to oxidative phosphorylation. Inhibition of respiration was produced by much lower lead concentrations with NAD-linked citric acid cycle substrates than with succinate or alpha-glycerophosphate. In partially disrupted mitochondria, NAD-linked substrate oxidation was inhibited at lead concentrations which did not affect NADH oxidation. Thus, in brain mitochondria the NAD-linked dehydrogenases, located in the matrix space, were more sensitive to inhibition by lead than were inner membrane enzymes. All in vitro lead effects on mitochondrial respiration were comparable in cerebral and cerebellar mitochondria isolated from both immature and adult rats.

Animals↗

Effects of triiodothyronine on oxidative phosphorylation in immature rat brain mitochondria.

Oxidative phosphorylation was measured polarographically in brain mitochondria isolated from 1 to 3-week-old normal and triiodothyronine-treated rat pups. Adenosine diphosphate (ADP)/oxygen ratios with nicotinamide-adenine dinucleotide (NAD)-linked substrates, but not with succinate, were increased in brain mitochondria from experimental animals at each age. Control ratios and respiratory rates were not affected. Thus, the normal maturational increase in ADP/oxygen ratios with NAD-linked substrates is accelerated in brain mitochondria from rats treated with triiodothyronnie from birth. This effect on efficiency of oxidative phosphorylation is similar to that of throid hormones on other properties of the maturing brain.

Age Factors↗