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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 253 records · Page 14Linked to original sources
PubMed1989

Studies on the formation of 6-hydroxydopamine in mouse brain after administration of 2,4,5-trihydroxyphenylalanine (6-hydroxyDOPA).

2,4,5-Trihydroxyphenylalanine (6-OH-DOPA) destroys central and peripheral noradrenergic neurons, while sparing dopaminergic neurons. Previous studies indicate that 6-OH-DOPA toxicity is mediated by the formation of 6-hydroxydopamine. However, levels of 6-hydroxydopamine in brain following peripheral administration of 6-OH-DOPA have not been documented. In the current study, 6-OH-DOPA and 6-hydroxydopamine were measured in brain by HPLC with electrochemical detection after intraperitoneal injection of 6-OH-DOPA. When mice were injected with 100 mg 6-OH-DOPA/kg, 6-hydroxydopamine levels in the striatum were highest (1.9 microgram/g) at 15 min and fell slowly to 24% of the peak value at 4 h. Experiments with reserpine indicated that the relatively stability of 6-hydroxydopamine was largely dependent upon storage in synaptic vesicles. Reserpine (10 mg/kg) lowered striatal 6-hydroxydopamine levels to 21.6% of control (non-reserpine-treated) values at 1 h, and to 8.9% of control values at 4 h. Levels of 6-hydroxydopamine in the striatum at 1 h were increased 113% by pargyline (100 mg/kg), 145% by alpha-methyldopahydrazine (carbidopa; 25 mg/kg), and 261% by pargyline and carbidopa together. Levels of dopamine in the striatum were unchanged at 2.5 h after 200 mg 6-OH-DOPA/kg (with pargyline and 50 mg carbidopa/kg), whereas levels of norepinephrine in the frontal cortex fell by 77%. At the same time, 6-hydroxydopamine levels were 8.8-fold higher in the striatum (5.54 micrograms/g) than in the cortex (0.63 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Upper airway muscle activity during nasal occlusion in newborn babies.

Submental electromyorgams (SM EMG) were recorded from 20 preterm babies (gestational age 30 +/- 2 wk, postmenstrual age at study 35 +/- 2 wk) (mean +/- SD) and 3 full-term infants (7-14 days old). SM EMG was evaluated during eupnea and brief experimental airway occlusion. Phasic inspiratory SM EMG was rarely seen during eupnea. SM EMG tended to increase on the first occluded effort, although this increase was not statistically significant in most babies. All infants showed progressive breath-by-breath augmentation of phasic SM EMG during occlusions in rapid-eye-movement (REM) as well as quiet (QS) sleep; phasic increases in SM EMG were similar during REM and QS occlusions in the majority (16/22) of babies. Periods of airway closure were detected during 24 occlusions in 5 infants; phasic SM EMG was reduced on these occasions. The results are consistent with the idea that recruitment of upper airway muscles contributes to the stability of the airway of the preterm human.

Electromyography↗
PubMed1989

The general practitioner as an effective sex counsellor.

Sexual concerns are common and opportunities for general practitioners to deal with them are numerous. This paper discusses the range of opportunities for providing sex education, anticipatory counselling and appropriate therapy in the context of the usual activities of general practitioners. Some of the requirements to fulfil this role effectively are identified.

Australia↗
PubMed1988

Sequence of the Saccharomyces cerevisiae CTA1 gene and amino acid sequence of catalase A derived from it.

The nucleotide sequence of a 2785-base-pair stretch of DNA containing the Saccharomyces cerevisiae catalase A (CTA1) gene has been determined. This gene contains an uninterrupted open reading frame encoding a protein of 515 amino acids (relative molecular mass 58,490). Catalase A, the peroxisomal catalase of S. cerevisiae was compared to the peroxisomal catalases from bovine liver and from Candida tropicalis and to the non-peroxisomal, presumably cytoplasmic, catalase T of S. cerevisiae. Whereas the peroxisomal catalases are almost colinear, three major insertions have to be introduced in the catalase T sequence to obtain an optimal fit with the other proteins. Catalase A is most closely related to the C. tropicalis enzyme. It is also more similar to the bovine liver catalase than to the second S. cerevisiae catalase. The differences between the two S. cerevisiae enzymes are most striking within four blocks of amino acids consisting of a total of 37 residues with high homology between the three peroxisomal, but low conservation between the S. cerevisiae catalases. The results obtained indicate that the peroxisomal catalases compared have very similar three-dimensional structures and might have similar targeting signals.

Amino Acid Sequence↗
PubMed1988

Production of ethane by rats treated with the colon carcinogen, 1,2-dimethylhydrazine.

Ethane was exhaled by rats treated with the colon carcinogen, 1,2-dimethylhydrazine (DMH). At 1 hr, ethane production (mean +/- SD) was 0.2 +/- 0.2 nmol/kg (controls) and 5.2 +/- 1.3, 13.7 +/- 3.4, and 27.7 +/- 9.6, respectively, for DMH injections of 0.15 mmol/kg (20 mg/kg of the dihydrochloride salt), 0.45 mmol/kg, and 1.35 mmol/kg. Rates of ethane evolution tapered off after 2 hr, but persisted for up to 3 hr at the lower dose, and up to 5-6 hr at the higher dose. Although ethane is produced in vivo during lipid peroxidation, experiments with vitamin E, a potent lipid antioxidant, indicated that lipid peroxidation was unlikely to be the source of ethane in DMH-treated rats: pretreatment with vitamin E had no effect on ethane formation from DMH but did suppress ethane production from rats treated with carbon tetrachloride, an inducer of hepatic lipid peroxidation. When rats were injected with 1,2-diethylhydrazine in place of DMH, large amounts of ethane and ethylene were produced (9800 and 5600 nmol/kg/hr). The hydrocarbon gases exhaled by rats may arise from dimerization of methyl radicals (.CH3) generated during the metabolism of DMH, and from ethyl radicals (.CH2CH3) generated during the metabolism of 1,2-diethylhydrazine. Previously, it was shown that methane and ethane are formed from methyl radicals in vitro. Other investigators have observed formation of hydrocarbon gases during the in vitro metabolism of monoalkylhydrazines by microsomes, and ethyl radicals, derived from monoethylhydrazine, have been detected by electron spin-resonance spectroscopy. The results presented here suggest that in vivo metabolism of DMH may produce methyl radicals. Methyl radicals are capable of interacting with biomolecules. Their indiscriminate reaction with tissue constituents may be a contributory factor in DMH-induced carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1988

De novo and maintenance DNA methylation by a mouse plasmacytoma cell DNA methyltransferase.

A DNA methyltransferase of Mr = 140,000 that is active on both unmethylated and hemimethylated DNA substrates has been purified from the murine plasma-cytoma cell line MPC 11. The maximal rate of methylation was obtained with maintenance methylation of hemimethylated Micrococcus luteus or M13 DNAs. At low enzyme concentrations, the highest rate of de novo methylation occurred with single-stranded DNA or relatively short duplex DNA containing single-stranded regions. Strong substrate inhibition was observed with hemimethylated but not unmethylated DNA substrates. Fully methylated single-stranded M13 phage DNA inhibited neither the de novo nor the maintenance reactions, but unmethylated single-stranded M13 DNA strongly inhibited the maintenance reaction. The kinetics observed with hemimethylated and single-stranded substrates could be explained if the enzyme were to bind irreversibly to a DNA molecule and to aggregate if present in molar excess. Such aggregates would be required for activity upon hemimethylated but not single-stranded DNA. For de novo methylation of duplex DNA, single-stranded regions or large amounts of methyltransferase appear to be required. The relative substrate preference for the enzyme is hemimethylated DNA greater than fully or partially single-stranded DNA greater than fully duplex DNA.

Animals↗
PubMed1988

Isolation and characterization of a linear DNA plasmid from Streptomyces clavuligerus.

A linear DNA plasmid (pSCL) has been isolated from Streptomyces clavuligerus by a method employing high concentrations of protease. Rate-zonal sedimentation on sucrose gradients was used to purify the plasmid. The plasmid is 12 kb in length and appears to be linked to protein at its 5' termini. A restriction endonuclease map of the plasmid for ten enzymes has been determined. Evidence for terminally repeated sequences is provided by cross-hybridization analysis.

DNA Restriction Enzymes↗
PubMed1988

Cloning and comparative sequence analysis of the gene coding for isopenicillin N synthase in Streptomyces.

The genes coding for isopenicillin N synthase (IPNS) in Streptomyces jumonjinensis and S. lipmanii were isolated from recombinant phage lambda libraries using the S. clavuligerus IPNS gene as a heterologous probe. The S. jumonjinensis IPNS gene has an open reading frame coding for 329 amino acids, identical in size to that of the previously cloned S. clavuligerus IPNS gene. A partial nucleotide sequence was also determined for the S. lipmanii IPNS gene. Comparison of the predicted amino acid sequences of all three streptomycete IPNS proteins shows that they exhibit more than 70% similarity, close to that found in comparisons among fungal IPNS proteins and significantly greater than that found, approximately 60%, between Streptomyces and fungal IPNS proteins. We conclude that procaryotic and eucaryotic IPNS genes are subgroups of a single family of microbial IPNS genes. Hybridization probes prepared from IPNS genes of the above streptomycete species were used to detect analogous genes in eight other strains that included both penicillin and cephalosporin producers and non-producers. Each producer strain responded with all three probes implying the presence of an IPNS gene. Surprisingly, several non-producer strains also responded with one or two of the probes. Our results suggest that IPNS-related genes may be more prevalent in Streptomyces than previously believed.

Amino Acid Sequence↗
PubMed1988

Studies on the autoxidation of dopamine: interaction with ascorbate.

An oxygen electrode was used to monitor the reaction between dopamine (DA, 1-20 mM) and oxygen at pH 7.4 and 37 degrees C, in both the presence and absence of ascorbate (10 mM). The selected concentrations approximate levels within DA neurons. Diethylenetriaminepentaacetic acid (DTPA, 0.1 mM) was used to suppress catalysis by trace metals in the reagents. Separate experiments with catalase showed that oxygen consumption could be equated with the formation of hydrogen peroxide. Depending upon the experimental conditions, ascorbate acted either as an antioxidant, suppressing oxygen consumption (H2O2 production) to 6-8% of the expected rate, or as a prooxidant, amplifying oxygen consumption by 640%. The antioxidant action is consistent with the scavenging of superoxide radicals by ascorbate. The prooxidant action is probably the result of redox cycling of a pre-melanin oxidation product derived from DA. Analyses conducted by high-performance liquid chromatography with electrochemical detection revealed formation of a product with a very low oxidation potential; the product was not 6-hydroxydopamine. These observations may be relevant to concepts of toxicity mediated by DA within neuronal systems.

Ascorbic Acid↗
PubMed1988

Vasodilator activity of human alpha-calcitonin gene-related peptide in the feline mesenteric vascular bed.

Human alpha-calcitonin gene-related peptide (CGRP) is a substance immunohistochemically present in a number of organ systems; however, the biologic significance of this peptide is uncertain. The present study was undertaken to investigate the effects of CGRP in the feline mesenteric vascular bed under conditions of controlled blood flow. Bolus injections of CGRP decreased mesenteric perfusion pressure in a dose-related fashion. When compared with nitroglycerin, CGRP possesses markedly greater vasodilator activity in the intestinal vascular bed of the cat. Because circulating levels of CGRP have been identified, the present data suggest CGRP may play a role in the regulation of systemic vasomotor tone and regional hemodynamics, as well as involve altered calcium metabolism seen with other calcium-regulating hormones in hypertensive states.

Animals↗
PubMed1988

Increase in extracellular dopamine in the striatum during cerebral ischemia: a study utilizing cerebral microdialysis.

Unilateral ligation of the left common carotid artery in anesthetized Mongolian gerbils resulted in a steep rise in extracellular dopamine in the ipsilateral striatum in 9 out of 19 animals. Extracellular dopamine was measured by cerebral dialysis in vivo and reached a peak of 0.19 mM at 40 min. At the same time, the level of homovanillic acid fell, whereas the levels of ascorbate and 3,4-dihydroxyphenylacetic acid remained relatively constant. In a separate group of animals studied with a combined dialysis/electrochemistry probe, a rise in the in vivo chronoamperometric signal in three out of six animals correlated with a rise in extracellular dopamine. The number of animals responding in these experiments (roughly 50%) corresponds to the frequency of incompetent Circle of Willis, as well as literature reports of the frequency of signs of stroke in unanesthetized gerbils. These results show a remarkable accumulation of dopamine in extracellular fluid in response to cerebral ischemia. Released dopamine appears to be responsible for the elevated in vivo electrochemical signal previously reported.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Depletion of brain glutathione in preweanling mice by L-buthionine sulfoximine.

Previous studies indicated that DL-buthionine sulfoximine (DL-BSO), an agent that inhibits the biosynthesis of GSH in liver and other peripheral organs, fails to suppress levels of GSH in the CNS. In the current study, preweanling mice responded to repeated injections of L-BSO with marked declines (79.6-86.5%) of GSH content in brain and spinal cord. In adult mice, the same treatment schedule produced only modest declines (17.8-29.2%) of GSH content in brain and a 55.9% decline in spinal cord. Pretreatment of preweanling mice with L-BSO represents a tool for studying the role of GSH in the CNS.

Aging↗
PubMed1988

WR-2721 entry into the brain across a modified blood-brain barrier.

Radioprotection of the CNS by WR-2721 has not been possible because of its inability to cross the blood-brain barrier (BBB) and so gain access to the neural tissue. Modification of the BBB using hypertonic arabinose (1.8 m), injected via the internal carotid artery (ica), permitted entry of ip-injected [14C]WR-2721 into the ipsilateral cerebral hemisphere. The BBB-modified hemisphere had a 5.34-fold increased uptake compared to nonmodified controls. Delivery as a bolus via the ica further enhanced uptake after BBB opening; WR-2721 was 3.73 times greater than by ip injection. A 20-fold increase of WR-2721 brain uptake has been calculated for ica administration with the BBB opened as compared to the ip route without BBB modification. Toxicity of ip-administered WR-2721 with the BBB open was only 1.4 times greater than non-modified controls and 1.96 times more toxic when delivered via the ica. These data demonstrate significant uptake of WR-2721 into the CNS, a previously unprotected organ, and provide a model for future radioprotective studies.

Amifostine↗
PubMed1988

[Chronic endophthalmitis caused by Propionibacterium acnes in a pseudophakic patient].

This paper reports the case of a chronic endophthalmitis with hypopion produced by propionibacterium acnes (p. a.) in a patient operated on for cataract and implanted with a posterior chamber intraocular lens. This granulomatous uveitis appeared 8 days after surgery and did not heal with a systemic corticoid-antibiotics treatment. The diagnosis was obtained by vitreous analysis. The responsibility of p. a. must be always searched in case of chronic endophthalmitis in pseudophakic patients: a specific treatment has to be used.

Aged↗