Biomedical subjects

Y Cohen

Publications and source records attributed to Y Cohen.

At least 253 records · Page 14Linked to original sources

PubMed1990

Autoantibodies in neoplasia. An unresolved enigma.

One hundred sixty-four sera samples of patients with malignant diseases were analyzed for the presence of autoantibodies to ssDNA, dsDNA, poly(I), Poly(G), cardiolipin, histones, RNP, Sm, Ro(SSA), and La (SSB). No distinction could be made between these patients and a comparative group composed of age-adjusted healthy subjects when measuring antibody levels to these autoantigens by the ELISA technique. This finding remained valid after further subgrouping of the patients according to age, sex, and histologic origin of the tumor. The authors conclude that in contrast to the known clinical coexistence of neoplasia in autoimmune states, there is no increased incidence of antinuclear autoantibodies in malignant conditions.

Adolescent↗

PubMed1990

Opposite dopaminergic activity in lateral and median hypothalamic nuclei in relation to the feeding effect of D-Ser2-Leu-Enk-Thr6 (DSLET).

The Leu-enkephalin analogue D-Ser2-Leu-Enk-Thr6 (DSLET) had been shown to enhance feeding in rats, increase dopaminergic activity in the striatum like other opiate agonists, and particularly to decrease dopaminergic activity in the hypothalamus. In this study, the latter effect was found to be localized in the hypothalamic nuclei involved in the regulation of feeding such as the paraventricular (PVN), ventromedian (VMH), dorsomedian (DMH) nuclei and the lateral hypothalamus (LH). DSLET produced the same decrease in dopaminergic activity in the LH as in the whole hypothalamus. In the median nuclei (PVN and VMH and to a lesser extent in the DMH), an opposite effect was observed, resembling that in the striatum. The relevance of these opposite variations with regard to the feeding effect of DSLET is discussed. The decreased dopaminergic activity in the LH would appear to be the most specifically related to the behavioural effect given the known role of dopamine in this region. These data reconcile apparently contradictory aspects of the role of dopamine and the functional opposition between the lateral and median hypothalamus in food intake control.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy.

Diffusion-weighted MR images were compared with T2-weighted MR images and correlated with 1H spin-echo and 31P MR spectroscopy for 6-8 h following a unilateral middle cerebral and bilateral carotid artery occlusion in eight cats. Diffusion-weighted images using strong gradient strengths (b values of 1413 s/mm2) displayed a significant relative hyperintensity in ischemic regions as early as 45 min after onset of ischemia whereas T2-weighted spin-echo images failed to clearly demonstrate brain injury up to 2-3 h postocclusion. Signal intensity ratios (SIR) of ischemic to normal tissues were greater in the diffusion-weighted images at all times than in either TE 80 or TE 160 ms T2-weighted MR images. Diffusion- and T2-weighted SIR did not correlate for the first 1-2 h postocclusion. Good correlation was found between diffusion-weighted SIR and ischemic disturbances of energy metabolism as detected by 31P and 1H MR spectroscopy. Diffusion-weighted hyperintensity in ischemic tissues may be temperature-related, due to rapid accumulation of diffusion-restricted water in the intracellular space (cytotoxic edema) resulting from the breakdown of the transmembrane pump and/or to microscopic brain pulsations.

Animals↗

PubMed1990

Early detection of ischemic injury: comparison of spectroscopy, diffusion-, T2-, and magnetic susceptibility-weighted MRI in cats.

Within one hour following MCA-occlusion in cats, heavily diffusion-weighted spin-echo MR images exhibited a well-defined hyperintensity in the gray matter and basal ganglia of the occluded side over normal side. This hyperintensity correlated with lactate and inorganic phosphate increases in peak areas from MR surface coil spectroscopy. T2-weighted MRI showed no significant abnormality in signal intensity from the occluded hemisphere within several hours post-occlusion. Using a paramagnetic MR contrast agent, dysprosium-DTPA-BMA together with heavily T2-weighted spin-echo or with T2*-weighted echo-planar (EPI) MR imaging, perfusion deficits resulting from MCA-occlusion were detected as a relative hyperintensity of ischaemic tissues compared to normally-perfused cerebral tissues in the contralateral hemisphere. Evidence of these deficits was observed within minutes of occlusion, and spatially correlated well with the hyperintensity seen on the diffusion-weighted images. Diffusion- and susceptibility-weighted MRI was superior to conventional T2-weighted MRI in the detection of early ischaemic events. In contrast to surface coil spectroscopy, both techniques mapped regions of jeopardy throughout the brain, which later showed T2-weighted hyperintensity and lack of vital (TTC) staining.

Animals↗

PubMed1990

Reversal of a feeding-reward system by dexfenfluramine: neurochemical involvement.

In addition to its anorectic properties, dexfenfluramine may inhibit some manifestations of feeding-related reward. We attempted to verify this effect by measuring paw-lick latency on the hot plate test in rats conditioned to expect a palatable food. The involvement of variations in beta-endorphinergic, dopaminergic and serotonergic systems was assessed. Despite an inherent effect of increasing paw-lick latency, dexfenfluramine (1.5 mg/kg IP) partly reversed the expectancy-induced increase in this latency. Saline-treated "expectant" rats displayed elevated plasma beta-endorphin levels and reduced hypothalamic 5-HIAA/5-HT and DOPAC/DA ratios. Only the decrease in the DOPAC/DA ratio was reversed by dexfenfluramine, suggesting an involvement of the dopaminergic system in this dexfenfluramine-sensitive reward system.

Animals↗

PubMed1990

A cholecystokinin agonist/antagonist according to dose and time of action: effect on food intake.

A new CCK pseudopeptide (Boc-Tyr (SO3)-Nle-psi-(COCH2) Gly-Trp-Nle-Asp-Phe-NH2) has been described in a previous study as a potent CCK agonist in the peripheral system and as an antagonist in the central nervous system. When administered alone by a peripheral route, this pseudopeptide was found to decrease food intake in free/feeding rats, and thus behaved as a CCK agonist. However, it reversed the decreased feeding effect induced by a full potent agonist (Boc(Nle 28-Nle 31)-CCK26-33). This antagonistic action occurred 3-4 h after treatment, at a time when the agonistic properties of the pseudopeptide alone had disappeared, but when the effect of the full potent agonist remained. The dose-response curve of the antagonistic action was bell-shaped. These results suggest that this new pseudopeptide is not only agonistic in the periphery and antagonistic in the central nervous system as shown in the previous study, but is also both agonistic and antagonistic on the same paradigm according to the dose and time of action.

Amino Acid Sequence↗

PubMed1990

Changes in brain neuropeptide Y induced by cholecystokinin peptides.

Cholecystokinin (CCK) and neuropeptide Y (NPY) are two peptides with opposite effects on the regulation of feeding behaviour. The possible interaction between these two systems has always been controversial. In this study, rat brain NPY levels were assayed after treatment with CCK 8 S and with a potent CCK agonist (Boc-(Nle 28-Nle 31)-CCK 26-33). CCK 8 S and its agonist analogue (50 micrograms/kg i.p.) both decreased hypothalamic and hippocampal NPY levels. This result suggests a negative relationship between NPY and CCK-peptides which is not surprising given their opposite role in the control of feeding. The hypothalamus and secondarily the hippocampus appear to be the site of this interaction; no change in NPY levels was observed in other brain areas (striatum and cortex). The same pattern of variation was found in the plasma, suggesting a direct release from the brain via a mechanism which remains to be investigated. The effect appeared later with the CCK analogue than with CCK 8 S itself; this is not surprising with regard to other behavioural and biochemical effects of the analogue and provides further characterization of its action.

Animals↗

PubMed1990

Effects of a new cholecystokinin analogue (JMV 236) on food intake and brain monoamines in the rat.

JMV 236, a new cholecystokinin-octapeptide-sulfate (CCK 8 S) derivative (Boc-Tyr (SO3)-Nle-Gly-Trp-Nle-Asp-Phe-NH2) has been synthesized in the Centre de Pharmacologie-Endocrinologie (Montpellier). This peptide has been shown to present the same activity as CCK 8 S on pancreatic amylase secretion and has the advantage of a better chemical stability. With a view to further characterization, the effect of JMV 236 on food intake and brain monoamine and metabolite variations was assayed in the rat after intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administrations. JMV 236 decreased food intake 2 and 3 hours after i.p. administration of 12.5 and 50 micrograms/kg but was inactive after i.c.v. injection. Its global action was similar to that of CCK 8 S, but was less marked with delayed onset of response. As in our previous work with CCK 8 S, JMV 236 was more potent in inducing monoaminergic variations after i.p. than after i.c.v. administration. The main effects were decreases in striatal dopamine metabolite levels and increases in hypothalamic and striatal serotonin metabolite (5-HIAA) levels. These effects are classically observed with CCK 8 S and are described in our previous reports. The interesting peptide will require further characterization and may serve as a possible reference compound for studies on CCK derivatives.

Animals↗

PubMed1990

Cholecystokinin-induced variations in hypothalamic serotonergic system of the "cafeteria" rat.

Cholecystokinin octapeptide sulfate (CCK 8 S) appears to act via a serotonergic mechanism on several behavioral paradigms, including satiety. In the present study, CCK 8 S was found to induce slight nonsignificant serotonergic changes in hypothalamic nuclei of the normal rat. In the "cafeteria" rat, however, it increased both 5-HT and 5-HIAA levels in the ventromedial hypothalamus (VMH), 5-HT levels in the paraventricular nucleus (PVN) and decreased 5-HIAA levels in the dorsomedial hypothalamus (DMH). These data suggest that the primary site of action of CCK 8 S is in the median hypothalamus, contrasting with an absence of effect in the lateral hypothalamus (LH). The involvement of 5-HT in the effect of CCK 8 S is further suggested. However, the relationship between these neurochemical changes and CCK 8 S-induced satiety is not clear. Nonetheless, a special sensitivity to CCK 8 S of the obese "cafeteria" rat is evidenced, which contrasts with a reduced response of genetic obesity models.

Animals↗

PubMed1990

Stability of brain intracellular lactate and 31P-metabolite levels at reduced intracellular pH during prolonged hypercapnia in rats.

The tolerance of low intracellular pH (pHi) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO2, for 75 min with 50% CO2, and for 10 min with 20% CO2. The maximum PaCO2 was 320 mm Hg. Cerebral intracellular lactate, pHi, and high-energy phosphate metabolites were monitored in vivo with 31P and 1H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO2, pHi fell by 0.57 +/- 0.03 unit, phosphocreatine decreased by approximately 20%, and Pi increased by approximately 100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with 1H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO2 was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pHi (approximately 6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗

PubMed1990

Absence of abundant binding sites for anesthetics in rabbit brain: an in vivo NMR study.

Using magnetic resonance spectroscopy, the authors tested whether cerebral concentrations of inhaled anesthetics do not increase proportionately at inspired concentrations exceeding 3% 1) because anesthetics bind to and saturate specific sites in the brain or 2) because anesthetic-induced depression of ventilation limits the increase in alveolar anesthetic partial pressure. New Zealand White rabbits were anesthetized with methohexital, 70% nitrous oxide, and local infiltration of 1% lidocaine. Cerebral concentrations of anesthetic were determined from 19F spectra acquired with nuclear magnetic resonance (NMR). Inspired, end-tidal, and arterial anesthetic concentrations, and end-tidal and arterial partial pressure of carbon dioxide were measured. Blood/gas partition coefficients were determined and used to convert arterial anesthetic concentration to partial pressures. In seven spontaneously breathing animals, halothane (1%; n = 5) or isoflurane (0.8%; n = 2) was administered at a constant inspired concentration for 20 min; NMR spectra were acquired between 10 and 20 min. Thereafter, the inspired concentration was increased and the process repeated until apnea occurred. Two additional rabbits were anesthetized with isoflurane and studied similarly but with higher inspired concentrations during mechanical ventilation. In spontaneously breathing animals, ventilatory depression occurred, documented by marked increases in PaCO2, and cerebral concentrations of anesthetic did not increase proportionately at inspired concentrations exceeding 3%. In contrast to an absence of a correlation of inspired and cerebral concentrations during spontaneous ventilation, arterial and cerebral concentrations correlated linearly during both spontaneous and mechanical ventilation (R2 greater than 0.969). These results are consistent with depression of ventilation, rather than binding to specific cerebral sites as an explanation for the nonlinear relationship between cerebral and inspired anesthetic concentrations.

Animals↗

PubMed1990

Photosynthesis in Ulva fasciata: V. Evidence for an Inorganic Carbon Concentrating System, and Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase CO(2) Kinetics.

Evidence of an inorganic carbon concentrating system in a marine macroalga is provided here. Based on an O(2) technique, supported by determinations of inorganic carbon concentrations, of experimental media (as well as compensation points) using infrared gas analysis, it was found that Ulva fasciata maintained intracellular inorganic carbon levels of 2.3 to 6.0 millimolar at bulk medium concentrations ranging from 0.02 to 1.5 millimolar. Bicarbonate seemed to be the preferred carbon form taken up at all inorganic carbon levels. It was found that ribulose-1,5-bisphosphate carboxylase/oxygenase from Ulva had a K(m)(CO(2)) of 70 micromolar and saturated at about 250 micromolar CO(2). Assuming a cytoplasmic pH of 7.2 (as measured for another Ulva species, P Lundberg et al. [1988] Plant Physiol 89: 1380-1387), and given the high activity of internal carbonic anhydrase (S Beer, A Israel [1990] Plant Cell Environ [in press]) and the here measured internal inorganic carbon level, it was concluded that internal CO(2) in Ulva could, at ambient external inorganic carbon concentrations, be maintained at a high enough level to saturate ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation. It is suggested that this suppresses photorespiration and optimizes net photosynthetic production in an alga representing a large group of marine plants faced with limiting external CO(2) concentrations in nature.

Journal Article↗

PubMed1990

Interaction of cholecystokinin and diazepam: effects on brain monoamines.

An antagonism between cholecystokinin (CCK) peptides and benzodiazepines (BZD) has been described in various paradigms. We sought to determine whether CCK and BZD are also antagonistic in their effects on brain neurotransmitter levels in the rat. No effect on the noradrenergic system was induced in any brain area by CCK 8 S and diazepam alone or in combination. Administered alone, sulfated CCK octapeptide (CCK 8 S) (5 micrograms/kg ip) and diazepam (5 mg/kg ip) were found to decrease DOPAC levels in the cortex and to induce 5-hydroxy-tryptamine accumulation in the hippocampus. When administered together, these variations were no longer observed. However, a slight tendency by each substance to decrease 3-methoxy-tyramine levels in the striatum, became significant when given in association. The differences in CCK-BZD interactions observed in the striatum, cortex and hippocampus suggest that different mechanisms of action are involved. The addition of the effects occurring in the striatum might involve a GABA-ergic mechanism.

5-Hydroxytryptophan↗

PubMed1990

Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system.

The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet. At very high diffusion-sensitizing gradient strengths, no clear evidence of anisotropic water diffusion was found in either cortical or subcortical (basal ganglia) gray matter. Signal intensities clearly dependent on orientation were observed in the cortical and deep white matter of the brain and in the white matter of the spinal cord. Greater signal attenuation (faster diffusion) was observed when the relative orientation of white matter tracts to the diffusion-sensitizing gradient was parallel as compared to that obtained with a perpendicular alignment. These effects were seen on both premortem and immediate postmortem images obtained in all axial, sagittal, and coronal views. Potential applications of this MR imaging technique included the stereospecific evaluation of white matter in the brain and spinal cord and in the characterization of demyelinating and dysmyelinating diseases.

Animals↗

PubMed1990

Pharmacology and pharmacokinetics of stereoisomers in radiopharmacy.

Nowadays stereochemistry and biologic stereospecificity are involved in the search for new radiopharmaceuticals. This article reviews: 1) The factors involved in selective distribution of stereoisomers: first-pass effect, binding to plasma proteins, enzyme effect and membrane transport; 2) the distinction between pharmacologic specific receptors and acceptor sites; recognition of stereoisomer ligands by specific receptors of opioids, neuroamines, steroids; 3) the ligands labeled with positron emitter radionuclides useful for tomography: dopaminergic, opiate, serotonergic, benzodiazepine ligands and muscarinic ligands; these ligands are labeled with 11C, 18F or 75Br. The balance between the benefit of using a stereoisomer and the burden of sophistication in its chemical preparation is discussed. In conclusion, there is not a clearcut position in favor of a systematic choice of an enantiomer radiopharmaceutical.

Carbon Radioisotopes↗

PubMed1990

Experience in the treatment of epithelial ovarian carcinoma with cisplatinum-containing combination chemotherapy and dose intensity calculation.

Twenty-six patients with epithelial ovarian carcinoma, were treated by cisplatinum--containing combination chemotherapy following initial laparotomy. The mean number of treatment cycles was 7.8 (median: 9). The mean dose intensity (DI) and mean relative dose intensity (RDI) respectively were for cyclophosphamide: 108 mg/m2/week and 0.65, for doxorubicin: 8.6 mg/m2/week and 0.51, and for cisplatinum: 9.8 mg/m2 week and 0.59. The mean average relative dose intensity (ARDI) was 0.53. The three-year survival for all patients was 43%. No statistically significant difference in the three-year survival between patients receiving RDI's and ARDI of less than median dose and those receiving RDI's and ARDI of more than median dose could be demonstrated. Larger series are needed to test whether, and to what extent, dose intensity contributes to outcome, independently of the total amount of drug given.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats.

We evaluated the temporal and anatomic relationships between changes in diffusion-weighted MR image signal intensity, induced by unilateral occlusion of the middle cerebral artery in cats, and tissue perfusion deficits observed in the same animals on T2-weighted MR images after administration of a nonionic intravascular T2 shortening agent. Diffusion-weighted images obtained with strong diffusion-sensitizing gradient strengths (5.6 gauss/cm, corresponding to gradient attenuation factor, b, values of 1413 sec/mm2) displayed increased signal intensity in the ischemic middle cerebral artery territory less than 1 hr after occlusion, whereas T2-weighted images without contrast usually failed to detect injury for 2-3 hr after stroke. After contrast administration (0.5-1.0 mmol/kg by Dy-DTPA-BMA, IV), however, T2-weighted images revealed perfusion deficits (relative hyperintensity) within 1 hr after middle cerebral artery occlusion that corresponded closely to the anatomic regions of ischemic injury shown on diffusion-weighted MR images. Close correlations were also found between early increases in diffusion-weighted MR image signal intensity and disrupted phosphorus-31 and proton metabolite levels evaluated with surface coil MR spectroscopy, as well as with postmortem histopathology. These data indicate that diffusion-weighted MR images more accurately reflect early-onset pathophysiologic changes induced by acute cerebral ischemia than do T2-weighted spin-echo images.

Acute Disease↗

PubMed1989

[Treatment of large cell lymphoma].

During 1977-1985, 50 patients with Stages III and IV large cell lymphoma (diffuse histiocytic [DH] and diffuse mixed [DM] types, Rappaport classification) were treated with the CHOP regimen (cyclophosphamide, adriamycin, Oncovin and prednisone). The male:female ratio was 1:1, the mean age at treatment 57 years, and mean follow-up 37 months. 80% had the DH type and 20% the DM type. 46% were in Stage III and 54% in Stage IV. The average relative dose intensity of CHOP was 0.68, which was well tolerated. In 68% a complete response was achieved after a mean of 4 treatment cycles. The average number of cycles for all patients was 7.2. The 5-year survival for those in Stage III was 50% and in Stage IV, 34%. Females survived better than males (60% vs 23%, respectively; p less than 0.02). The 5-year survival of the complete responders was 60% and their relapse-free survival 44%. In our experience, CHOP is a useful combination in the treatment of DH and DM lymphoma; it has yet to be proved in a randomized fashion that the current third generation of combinations is superior to it.

Antineoplastic Combined Chemotherapy Protocols↗