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Biomedical subjects

C Gorenstein

Publications and source records attributed to C Gorenstein.

At least 55 records · Page 3Linked to original sources
PubMed1987

A hypothesis concerning the role of endogenous colchicine-like factors in the etiology of Alzheimer's disease.

A hypothesis concerning the etiology of Alzheimer's disease is presented. It is argued that the formation of neurofibrillary tangles, paired helical filaments and senile plaques result from an increase in the activity of endogenous colchicine-like factors. The consequences of such an increase are 1) a blockade of axonal transport, 2) an accumulation of neurofilaments in the cytoplasm of neurons and 3) a redistribution of lysosomes from the cell bodies of neurons to the dendrites. In the absence of cytoplasmic lysosomal enzymes, the accumulated neurofilaments are cross-linked and metabolically stabilized by enzymes in the cell body. Neurons laden with neurofibrillary tangles and dendritic lysosomes would be prone to lysis and could participate in the formation of senile plaques.

Alzheimer Disease↗
PubMed1987

Examination of the transient distribution of lysosomes in neurons of developing rat brains.

We have previously observed that lysosomes redistribute from their normal location in neuronal cell bodies to the dendrites following an intracerebroventricular injection of an antimitotic such as colchicine, vinblastine or vincristine. In the present study, we have followed the developmental distribution of lysosomes in the brains of untreated rats, using a lysosomal marker enzyme, dipeptidylaminopeptidase II. A relatively high concentration of neuronal lysosomes was found in the dendrites of olfactory bulb mitral cell neurons and in hippocampal granule and pyramidal cell neurons from postnatal day 1 (P1) to P8. As the animals matured, the pattern of lysosomal enzyme distribution was reversed. Lysosomes became progressively less concentrated in the dendrites and more concentrated in neuronal cell bodies. In cerebellar Purkinje cells, lysosomes were only found in the cell bodies during the first week after birth. Between P9 and P19, lysosomes appeared in the dendrites of these neurons and, with maturity, progressively disappeared from the dendrites and were concentrated mainly in cell bodies. The presence of lysosomes in the dendrites of developing animals suggests that the transport of lysosomes to the dendrites, induced by microtubule poisons, mimics a physiological process which is normally present during development.

Animals↗
PubMed1986

Distribution of 'non-specific' cholinesterase-containing neurons in the dorsal thalamus of the rat.

This report describes the distribution of histochemically identified 'non-specific' cholinesterase (ChE)-containing neurons in the dorsal thalamus of the rat. Juvenile or young adult Long-Evans or Sprague-Dawley rats were sacrificed by formalin perfusion. Some animals received systemic injections of 1.5-2.0 mg/kg DFP 4-24 h prior to sacrifice. Separate series of 50 micron frozen sections were processed for cholinesterase histochemistry using acetylthiocholine, butyrylthiocholine, or propionylthiocholine as substrates. Adjacent sections processed with each of the 3 substrates allowed comparison of the distributions of neurons containing the histochemical reaction products. Neurons containing moderate to high concentrations of ChE reaction product were found in 3 distinct regions of the dorsal thalamus. First, neurons staining intensely for ChE were found in a cluster that corresponds to the thalamic reuniens nucleus. Second, a cluster of neurons staining intensely for ChE was found in a region that included the lateral part of the central lateral nucleus and extended laterally into the ventral-lateral part of the lateral dorsal nucleus. Third, moderate ChE staining was observed in the neurons of the anterior dorsal nucleus. Of these regions, only the anterior dorsal nucleus shows moderate to high levels of acetylcholinesterase. The function of ChE in normal brain function is unknown. It is particularly interesting, however, that the thalamic nuclei containing ChE-positive neurons send thalamocortical projections to the medial limbic cortex, including cingulate, retrosplenial and subicular cortices.

Acetylcholinesterase↗
PubMed1986

On the dose equivalence of flurazepam and triazolam.

Flurazepam (30 mg), triazolam (0.5 mg) and placebo were given in the morning to 6 normal volunteers in a double-blind crossover study. Subjects were evaluated by a large battery of psychophysiological tests before and 1 and 5 hours after drug administration. Triazolam was significantly more sedative than flurazepam and both were significantly different from placebo. Slope-ratio assay analysis of the results from the present study pooled with those from a similar previous study (C. Gorenstein and V. Gentil, Psychopharmacology, 80: 376-379, 1983) indicated that these doses are non-equivalent. We suggest that dose-equivalence studies based on the present method should be carried out early in the development of new hypnotic drugs.

Adolescent↗
PubMed1985

Distribution of dipeptidyl peptidase II (Dpp II) in rat spinal cord.

The histochemical localization of dipeptidyl peptidase II (Dpp II; E.C. 3.4.14.2) activity was demonstrated at the light microscope level in the rat spinal cord. Prominent staining was observed in motoneurons of the ventral horn and in medium to large neurons in the deep laminae of the dorsal horn, the intermediate gray, and in lamina X surrounding the spinal canal. Within neurons, Dpp II was localized largely in cell perikarya and large primary dendrites with no staining observed in cell nuclei. Neurons in the superficial dorsal horn lack Dpp II enzyme activity. Nonneuronal elements which also stained prominently were pericytes associated with blood vessels and ependymal cells lining the lumen of the spinal canal. A few oligodendrocytes and astrocytes were also stained, but they represented a minor component of the total amount of Dpp II activity. Following ventral root injury, Dpp-II-containing motoneurons degenerate; some glial cells in the region of degenerating neurons become Dpp II positive. The localized distribution of Dpp II in spinal cord neurons suggests that this proteolytic enzyme may play a role in the metabolism of an unidentified neuropeptide.

Animals↗
PubMed1985

Dendritic transport. I. Colchicine stimulates the transport of lysosomal enzymes from cell bodies to dendrites.

Injection of colchicine into the lateral cerebral ventricle of the rat was found to induce a paradoxical translocation of two lysosomal enzymes, dipeptidyl peptidase II (Dpp II) and acid phosphatase, from the soma of neurons to the dendrites. Following a single injection of colchicine, neuronal somata, which normally contain the bulk of these lysosomal enzymatic activities, become depleted of these enzymes, whereas dendrites become abnormally enriched. All neurons which contained these enzymes, except those of the mesencephalic nucleus of the trigeminal nerve, displayed this phenomenon. Lysosomal enzyme translocation into dendrites was observed in the mitral cell layer within 1 hr after a colchicine injection and could be induced in most neuronal populations by injections of colchicine as low as 25 micrograms. Five days after a 100-micrograms colchicine injection, a normal pattern of enzyme distribution was observed, indicating that the effect of colchicine was reversible. Enzyme translocation was not accompanied by gross changes in cell morphology, nor did it result in the specific loss of neuronal cell bodies which contained these enzymes. The results indicate that colchicine, under conditions known to inhibit axoplasmic transport, stimulates the transport of lysosomal enzymes from the cell body to the dendrites.

Acid Phosphatase↗
PubMed1985

Dendritic transport. II. Somatofugal movement of neuronal lysosomes induced by colchicine: evidence for a novel transport system in dendrites.

The effect of colchicine injections on the ultrastructural localization of dipeptidyl peptidase II (Dpp II) was studied in the mitral cells of the rat olfactory bulb. In control animals, electron-dense reaction product representing Dpp II activity was observed in lysosomes, lipofuscin granules, short cisternae located close to the granular endoplasmic reticulum, and dense granules. Lysosomes and lipofuscin granules were the most intensely stained organelles. Dpp II-containing organelles were localized mainly to the cell body and were randomly distributed in the perikaryal cytoplasm. Twenty-four hours after a 100-micrograms intracerebroventricular colchicine injection, the distribution of Dpp II-containing organelles was drastically altered. Short cisternae and dense granules containing Dpp II reaction product were noticeably absent in these preparations. Lysosomes and lipofuscin granules were depleted from the perikaryal cytoplasm and were concentrated in dendrites. Lysosomes were observed to extend for considerable distances in dendrites where they acquired elongated and dumbbell shapes. The shapes of some of these labeled lysosomes gave the impression that they were actively being "pulled" into the dendrites. These results indicate that microtubules sequester lysosomes to the perikaryal cytoplasm and suggest the presence of a novel transport system responsible for the movement of lysosomes from the cell body to the dendrites.

Animals↗
PubMed1983

Residual and acute effects of flurazepam and triazolam in normal subjects.

Residual and acute effects of flurazepam and triazolam were studied in two double-blind, crossover, placebo controlled, single-dose experiments. Psychological and physiological effects were determined 10 h after night administration (flurazepam 30 mg and triazolam 0.5 mg), and for 6 h after morning ingestion (flurazepam 15 mg and triazolam 0.25 mg). Both drugs produced similar "hangover" effects, impairing motor performance and increasing sleepiness on the following morning. After morning administration pronounced sedative effects were found with triazolam, while flurazepam effects were mild and hard to distinguish from placebo. The clinical relevance of these findings is discussed, suggesting that these drugs may be conceived as belonging to two different types of hypnotic agents.

Adult↗
PubMed1981

Tranylcypromine isomers: single-dose effects in normal human subjects.

Moderately high single doses of (+)- and (-)tranylcypromine were given to normal subjects, in the morning and evening, in two double-blind placebo-controlled experiments. Effects were determined up to 24h later by psychological and physiological measures. No significant differences were found on most measures, but the subjects consistently reported stronger effects after the (+)isomer. Both active drugs induced sedative effects when given in the morning. Following the evening administration, delayed sleep onset was reported after the (-)isomer, while the (+)isomer was associated with more awakenings during the night. The mechanisms responsible for these effects are discussed.

Adult↗
PubMed1981

Brain peptidase with a unique neuronal localization: the histochemical distribution of dipeptidyl-aminopeptidase II.

To assess whether specific peptidases regulate neuropeptide disposition, we have examined histochemically the localization of dipeptidyl-aminopeptidase II (DAP II). With beta-naphthylamide (beta-NA) substrates, this enzyme has a selectivity for lysyl-alanyl-beta-NA. DAP II staining is highly localized to specific neuronal populations with no staining over glia. Areas in the brain with high densities of DAP II staining include the mitral cells in the olfactory bulb, polymorphic cells in the hippocampus, the paraventricular nucleus of the hypothalamus, and the anterior dorsal thalamus, Purkinje cells, and deep nuclei in the cerebellum. Staining occurs in virtually all cell groups in the inferior colliculus, red nucleus, oculomotor nucleus, and mesencephalic nucleus of the trigeminal nerve, the stratum album of the superior colliculus, as well as most cells in the cochlear and superior olivary nuclei. DAP II localizations do not correlate fully with those on any known neuropeptide. Of the numerous peptides evaluated, only glucagon competes substantially for the DAP Ii substrate, reducing enzymatic activity by 50% at a 2 x 10(-5) M concentration.

Animals↗
PubMed1980

Enkephalinases.

Enkephalins can be degraded by a variety of peptidases. We have characterized several membrane-associated brain peptidases in an effort to determine which if any are concerned with the physiological inactivation of synaptically released enkephalin. We have distinguished two carboxyl-directed dipeptidylpeptidases, designated enkephalinase A1 and A2, that give rise to the Tyr-Gly-Gly fragment. Both enzymes are physically separable from angiotensin converting enzyme. Regional variations in enkephalinase A1 activity and opiate receptors are similar. A novel amino-terminal-directed dipeptidylpeptidase, enkephalinase B, which generates Tyr-Gly, has been identified. All of these enzymes as well as aminopeptidase have been solubilized from brain membranes by detergent treatment and have been mutually resolved by DEAE column chromatography. Enkephalinase A1 has been purified 1500-fold, to apparent homogeneity.

Aminopeptidases↗
PubMed1978

Isolation and characterization of an actinomycin D-sensitive mutant of Saccharomyces cerevisiae.

A single mutation in Saccharomyces cerevisiae conferred sensitivity to low concentrations of actinomycin D. Treatment with actinomycin D preferentially inhibited synthesis of rRNA's. Residual rRNA synthesized was processed normally. Total protein synthesis and inducibility of the enzyme maltase were relatively unaffected at concentrations of actinomycin D which severely inhibited rRNA synthesis.

Dactinomycin↗
PubMed1977

Synthesis and turnover of ribosomal proteins in the absence of 60S subunit assembly in Saccharomyces cerevisiae.

We have measured the synthesis and stability of ribosomal proteins in a temperature sensitive strain of yeast which at the restrictive temperature is specifically blocked in the processing of 27S ribosomal precursor RNA. We find that in the absence of 60S ribosomal subunit assembly, the synthesis of all the ribosomal proteins studied continued. However, the proteins of the 60S subunit fail to accumulate and are rapidly degraded.

Electrophoresis, Polyacrylamide Gel↗
PubMed1976

Coordinate regulation of the synthesis of eukaryotic ribosomal proteins.

We have developed a method of r the direct measurement, in eukaryotic cells, of the synthesis of ribosomal proteins, irrespective of the synthesis of ribosomes. In this way the synthesis of ribosomal proteins has been examined in mutant strains of Saccharomyces cerevisiae, which are unable to synthesize ribosomes under nonpermissive conditions. The results suggest that the synthesis of more than 40 ribosomal proteins is under coordinate control. Under nonpermissive conditions,the synthesis of each h protein declines exponentially to a basal level which is 10-20% fo normal. The kinetics of that decline suggest that an early, if not primary, result of the nonpermissive conditions is the cessation of production of new mRNA for eac of the ribosomal proteins. The coordinate regulation appears not to be influenced directly by the rate of transcription of ribosomal precursor RNA.

Adipose Tissue↗