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Biomedical subjects

G Cohen

Publications and source records attributed to G Cohen.

At least 289 records · Page 16Linked to original sources

Apnoea in the newborn infant.

Clinical apnoea in infants is defined as a pause in breathing of more than 20 s duration or a briefer pause associated with bradycardia. Such events are uncommon in term infants and usually are due to some precipitating factor. They occur more commonly in preterm infants and there is an exponential increase in incidence with decreasing gestational age at birth. Although insults such as infection or hypoxia can accentuate the problem, the major factor appears to be immaturity. Studies of brain-stem maturity using auditory evoked responses indicate that infants with immature responses have a higher incidence of apnoea. Brain-stem immaturity has also been implicated in histopathological studies of infants dying from Sudden Infant Death Syndrome (SIDS). In preterm infants, upper airway obstruction occurs commonly at the end of longer events and some infants have a predominantly obstructive pattern. These latter infants are often neurologically abnormal and have had prolonged endotracheal intubation. Both of there factors could be associated with disordered control of upper airway patency. This notion is supported by the finding of upper airway instability during nasal occlusion in these infants. A link with SIDS is uncertain, although preterm infants with chronic pulmonary insufficiency, usually following a prolonged intubation, are said to be at particularly high risk of dying suddenly and unexpectedly during infancy.

Apnea↗

[Standard thoracic radiography in recent pneumonectomized patients. Its contribution to the diagnosis of empyema and bronchopleural fistula].

Case reports of 110 patients undergoing pneumonectomy were reviewed to assess value of standard postoperative chest radiography for detection of early complications, consisting mainly of empyema and/or bronchopleural fistula. Most radiologic modifications observed do not represent abnormal findings, although two signs can contribute to the radiologic diagnosis of empyema: the central superimposed air/fluid levels and the secondary mediastinal displacement, but even these signs are inconstant and of late onset. Five signs may be of significance for the diagnosis of bronchopleural fistula: in addition to the two described above there are the rapid fall in principal air/water level, the increase in subcutaneous emphysema and the late onset contralateral alveolar syndrome. The diagnosis of a bronchopleural fistula prior to the development of clinical symptoms was possible in one of two cases.

Bronchial Fistula↗

Excision of hemivertebrae in children with congenital scoliosis.

This study reports the authors' experience with excision of hemivertebrae in the treatment of congenital scoliosis. Although it is limited to 10 cases, it is significant because of the 9 years follow-up. The first patients treated have already passed the age of puberty and this is the most interesting aspect of the study.

Age Factors↗

Hydroxyl radical attack on dopamine.

Hydroxyl radicals were generated in the presence of 1 mM dopamine (3,4-dihydroxyphenylethylamine) at pH 7.2 (50 mM phosphate buffer) by the following two mechanisms: 1) a classic Fenton-type reaction between hydrogen peroxide and a ferrous chelate (ferrous diethylenetriaminepentaacetate) and 2) the cyclical redox reactions of iron-EDTA/ascorbate. Three ring-monohydroxylated products of dopamine were detected by high performance liquid chromatography with electrochemical detection: 2-hydroxydopamine, 5-hydroxydopamine, and 6-hydroxydopamine in an approximate ratio of 3:2:1. Scavengers of hydroxyl radicals (dimethyl sulfoxide, mannitol, ethanol) suppressed the yields of products in a concentration-dependent manner. The formation of nonphysiologic hydroxylated forms of dopamine can provide a probe for the formation of hydroxyl radicals in dopamine neurons.

Ascorbic Acid↗

[Fatal hematemesis due to erosion of a retro-esophageal right subclavian artery by an esophagogastric tube].

A case of fatal haematemesis due to erosion of a retro-oesophageal right subclavian artery by a nasogastric tube is reported. In view of this exceptional but extremely serious complication, no oesophageal tube should be used in patients known to have this abnormal anatomical arrangement. Systematic treatment of aberrant subclavian arteries should perhaps be considered when it can be performed during thoracic surgery.

Aged↗

In vivo production of ethylene from 2-keto-4-methylthiobutyrate in mice.

The use of 2-keto-4-methylthiobutyric acid (KMB), the alpha-keto analog of methionine, was studied as a potential means of detecting free radical generation in vivo. KMB-dependent ethylene production (presumably from free radical interception), and ethane production from in vivo lipid peroxidation, were monitored simultaneously by measuring the rate of exhalation of these hydrocarbons by mice. Injection of KMB (1 g/kg) into mice resulted in an 8-fold increase in ethylene production above endogenous levels seen in saline-injected controls (1.47 +/- 0.35 vs 0.17 +/- 0.02 nmoles/100 g/hr respectively). Administration of CCl4 (3.0 g/kg) to initiate hepatic lipid peroxidation, 20 min prior to KMB injection, augmented the production of ethylene (2.37 +/- 0.10 nmoles/100 g/hr). Lipid peroxidation following injection of CCl4 was monitored via the increased exhalation of ethane. Pretreating the mice with vitamin E (100 mg/kg daily for 3 days), an inhibitor of lipid peroxidation, did not result in a significant change in ethylene production from KMB by itself or after prior injection of CCl4. However, vitamin E did suppress ethane production initiated by CCl4. Similar results were obtained with mouse liver slices studied in vitro. Metyrapone (150 mg/kg), an inhibitor of hepatic mixed function oxidase activity, also suppressed significantly the CCl4-stimulated production of ethane, but not the CCl4-stimulated production of ethylene from KMB. It appears that ethylene production from KMB does not derive from free radicals generated during in vivo lipid peroxidation since suppression of lipid peroxidation by vitamin E or metyrapone did not suppress ethylene production.

Animals↗

1-Methyl-4-phenylpyridine (MPP+) is toxic to mesencephalic dopamine neurons in culture.

1-Methyl-4-phenylpyridine (MPP+) is the product of oxidative metabolism by monoamine oxidase of the Parkinson-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPP+ was tested for neurotoxicity on the dopaminergic neurons of embryonic rat midbrain in culture. Compared with MPTP, MPP+ was a more potent neurotoxin for the cultured dopamine (DA) neurons as determined by decrease in [3H]DA uptake by the cultures and decrease in endogenous levels of DA and homovanillic acid. Catecholamine histofluorescence demonstrated the loss of fluorescing fibers after exposure to MPP+. The reduced analogue of MPTP, namely 1-methyl-4-phenylpiperidine, had no significant neurotoxic action on the dopaminergic neurons in culture.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Studies on the mechanism of action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Explants of embryonic rat substantia nigra in organotypic culture are sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at concentrations approximating the doses given in vivo to monkeys. Fluorescence microscopy and 3H-dopamine uptake measurements reveal that the toxicity is selective for dopamine neurons, whereas other neurons and cells in the culture appear normal by phase contrast microscopy. Reduced MPTP (piperidine analog) is inactive in the tissue culture model, while fully oxidized MPTP (pyridinium analog) destroys dopamine neurons. Pargyline and deprenyl, two monoamine oxidase inhibitors, inhibit the neurotoxic action of MPTP. Pargyline and deprenyl also protect monkeys in vivo. The results implicate monoamine oxidase in the mechanism of action of MPTP. Two possible mechanisms for protection by monoamine oxidase are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Distribution of 3H-soman in mice.

3H-soman (specific activity 10 Ci/mMol), a potent irreversible cholinesterase inhibitor, was administered IV to mice in a dose of one LD-50, which corresponds to 0.25 mCi/mouse. Animals were sacrificed at 5 min, 2 h and 24 h, and whole body autoradiography was performed. High levels of radioactivity in lung and skin were observed at all time intervals after injection. The central nervous system showed very low concentrations of radioactivity, which remained so for 24 h post-injection. Considerable accumulation of 3H-soman in the urine and gall-bladder, and in the intestinal lumen, may indicate these as pathways of soman excretion. Quantitative determinations of radioactivity in various tissue samples were consistent with the above-mentioned findings. It is concluded that the nature of the persistent binding of soman to lung and skin is striking, and may indicate the existence of specific sites for soman depots.

Animals↗

Isolation of the catalase A gene of Saccharomyces cerevisiae by complementation of the cta1 mutation.

As a first step in an analysis of the DNA regions involved in the control of the catalase A gene of Saccharomyces cerevisiae by glucose, heme, and oxygen this gene has been cloned. Catalase A-deficient mutants were obtained by UV mutagenesis of a ctt1 mutant strain specifically lacking catalase T. All the catalase A-deficient mutants obtained fall into one complementation group. The single recessive mutation causing specific lack of catalase A was designated cta1. Several overlapping DNA fragments complementing the cta1 mutation were obtained by transforming ctt1 cta1 double mutants with a yeast gene library in vector YEp13. Hybrid selection of RNA with the help of one of the cloned DNAs followed by in vitro translation of this RNA and identification of the protein synthesized with catalase A-specific antibodies showed that the catalase A structural gene has been cloned. A single copy of this gene is present in the yeast genome. Transcription of the catalase A gene cloned into vector YEp13 is repressed by glucose. The DNA isolated hybridizes to a 1.6 kb polyA+-RNA virtually absent from heme-deficient cells, presumably catalase A mRNA.

Alleles↗

Pituitary 5-hydroxytryptamine nerves--a possible link with pituitary hormone secretion.

A short review of the present knowledge on the innervation of the pituitary gland by 5-hydroxytryptamine (5-HT) containing nerves is given. This is followed by results of recent experiments in which the concentrations of 5-HT in different lobes of the rat hypophysis were measured under conditions in which pituitary hormone secretion was increased. A prolonged increase in hormone secretion induced by dehydration and increased sodium chloride intake resulted in a decrease in the 5-HT concentrations in the anterior lobe (AL). The 5-HT content of the neural (NL) and the intermediate lobe (IL) of these rats was hardly changed whereas that of DA was about doubled. Acute stimulation of pituitary hormone secretion by exsanguination under ether anaesthesia also caused a fall in the 5-HT content of the AL. In contrast, in the NL and in the IL of these rats, the 5-HT concentrations were significantly increased. This indicates that the 5-HT system in the AL reacts differently from those in the NL and IL. Pituitary dopamine (DA) contents were not affected by ether and exsanguination. Thus, the pituitary DA and the pituitary 5-HT neuronal systems are activated independently in different endocrine states. The concentrations of 5-HT were also measured in 10 groups of normal male or female rats in the course of 2 years and compared with those of DA. The concentrations of 5-HT were lowest in the AL with little variation between the different groups. In the rest of the tubero-hypophyseal system the concentrations of 5-HT were at least 3, and up to 10 times, higher than in the AL, with larger inter group variations. The DA concentrations in the AL were only 10-20% of those of 5-HT; in the other regions they were equal to or higher than those of 5-HT.

Acute Disease↗

In vitro studies of 2,4-dihydroxyphenylalanine, a prodrug targeted against malignant melanoma cells.

We have evaluated the chemotherapeutic potential of 2,4-dihydroxyphenylalanine, a targeted prodrug that can be hydroxylated by tyrosinase (monophenol monooxygenase, EC 1.14.18.1) within melanoma cells to form the cellular toxin 2,4,5-trihydroxyphenylalanine (6-hydroxydopa). 2,4-Dihydroxyphenylalanine proved to be cytotoxic to both B-16 and Cloudman melanoma cells in vitro. The immediate effects of 2,4-dihydroxyphenylalanine included inhibition of DNA, RNA, and protein syntheses. In contrast, no decrease in macromolecular synthesis or viability was seen against cultures of MJY-alpha mammary tumor or L-1210 leukemia, two cell types that do not contain tyrosinase. Within the melanoma cultures, greater cytotoxicity was seen against melanotic (tyrosinase-containing) cells than against amelanotic (tyrosinase-lacking) cells. The cytotoxicity of 2,4-dihydroxyphenylalanine was blocked by 1-phenylthiourea, an inhibitor of tyrosinase. These results show that 2,4-dihydroxyphenylalanine is toxic to melanoma cells and that activation of 2,4-dihydroxyphenylalanine requires the presence of tyrosinase.

Animals↗

Deprenyl protects dopamine neurons from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion.

1-Methyl-4-phenylpyridinium ion (MPP+) is the product of the metabolic oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidase (MAO). MPP+ is toxic to 3,4-dihydroxyphenylethylamine (dopamine, DA) neurons in explant cultures of rat embryonic midbrain. Addition of 2.5 microM MPP+ to the feeding medium for 6 days results in significant reduction of the DA levels in the cultures (to 19% of control) as well as in the uptake of [3H]DA (to 32% of control). When the cultures are treated with the MAO inhibitor deprenyl (10 microM) 24 h prior to and during exposure to MPP+, the DA neurons are protected from the toxicity of the drug. In the combined deprenyl plus MPP+ treatment, the levels of DA in the cultures remain at the control range and the [3H]DA uptake is reduced to only 73% of control. These results indicate that MAO is involved in the toxicity of MPP+ on DA neurons.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

[Tissue identification of carotid lesions using ultrasound].

Technical progress in echotomography has made it possible to identify a number of structures within the atheromatous lesion itself. Such echotomographic data were compared with peroperative findings and histology of the endarterectomy specimen in the context of carotid pathology. Appearances were differentiated in terms of the density and homogeneity of the echos obtained. Heterogeneous and relatively undense lesion corresponded in the majority of cases with moveable intraluminal matter or intraplaque hematomas. False negatives were due in one case to technical impossibility (calcifications) and in one case to multiple ulcerations. Regular and homogeneous appearances corresponded to fibrous plaques, rich in collagen and free of potential emboligenic material. Preoperatively, echotomography may be used to assess the histological characteristics of a plaque with a high degree of sensitivity and good specificity. This new approach may help in the choice of treatment and will improve knowledge of the natural history of carotid lesions necessary for the study of preventive treatment, in particular in asymptomatic patients.

Arteriosclerosis↗

[Late renal revascularization].

Late renal revascularization could be indicated in totally occluded renal artery with hypertension and or renal insufficiency. Six cases of secondary revascularization after occlusion of renal artery are reported here. In three cases severe renovascular hypertension was the indication for renal revascularization. In three other cases, indication was proposed for renal insufficiency. In four cases, renal revascularization for totally occluded renal artery have been beneficial for the patients. In two cases of terminal renal insufficiency, chronical hemodialysis could be suppressed. In the others two cases, hypertension was clearly improved. The criteria for renal revascularization before and during surgery are discussed here. The kidney length, the cortico-medullary ratio at kidney echography, and the visualization of a nephrography during angiography are the principal criteria before surgery for renal revascularization. The macroscopic aspect of the kidney, the immediate results of renal biopsy and the importance of a blood reflow in the renal artery are the principal criteria during surgery, but must be discussed because there are no definitive criteria. Renal revascularization shall be proposed when totally occluded renal artery is associated with renal insufficiency and/or hypertension, especially when the other side can be affected by the same disease.

Adult↗

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine destroys dopamine neurons in explants of rat embryo mesencephalon.

Explants of embryonic rat mesencephalon were grown in organotypic culture. Addition of 10 microM 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the culture medium for 4 to 7 days resulted in loss of dopamine cell bodies and fiber outgrowths, as observed by fluorescence histochemistry. At the same time, the cultures showed decreased uptake of tritium-labeled dopamine. However, no signs of generalized toxicity were evident when the explant cultures were viewed by light and phase-contrast microscopy. These results show that MPTP exerts a relatively selective destructive action in dopamine neurons in vitro, similar to the action observed in humans and monkeys in vivo. Pargyline (10 microM), a monoamine oxidase inhibitor, protected the dopamine neurons in the explants. Organotypic cultures provide an experimental model for the study of the properties of MPTP in vitro.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗