Search PubMed⌕ Search

Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 181 records · Page 10Linked to original sources
PubMed1998

The effect of a high partial pressure of carbon dioxide environment on metabolism and immune functions of human peritoneal cells-relevance to carbon dioxide pneumoperitoneum.

OBJECTIVE: Our purpose was to evaluate in vitro the effect of a high partial pressure of carbon dioxide environment used in laparoscopy on metabolic and immune response of various human peritoneal cells. STUDY DESIGN: Polymorphonuclear leukocytes were obtained from 5 healthy volunteers, peritoneal macrophages were obtained from the effluent of 8 patients undergoing continuous ambulatory peritoneal dialysis, and human peritoneal mesothelial cell cultures were prepared from omentum derived from 5 patients undergoing elective surgery. The cells were exposed to a laparoscopy-like environment (1 atmosphere carbon dioxide and 0.2 atmosphere oxygen), to a control gas mixture (1 atmosphere helium and 0.2 atmosphere oxygen), or air for 3 hours. After exposure to gas mixtures, cell functions were tested at various recovery periods. RESULTS: Three hours of exposure to a high partial pressure of carbon dioxide had no effect on viability of peritoneal macrophages and human peritoneal mesothelial cells, tested by trypan blue dye uptake and lactate dehydrogenase release. A high partial pressure of carbon dioxide decreased the mitochondrial dehydrogenases activity of peritoneal macrophages and human peritoneal macrophage cells by 60%, assayed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction. High partial pressure of carbon dioxide blocked the superoxide release from activated polymorphonuclear leukocytes and the secretion of interleukin 1beta from stimulated peritoneal macrophages, and human peritoneal macrophage cells were decreased by 15% and 30% and the secretion of tumor necrosis factor-alpha from peritoneal macrophages was suppressed by 85%. Mitochondrial activity, polymorphonuclear leukocyte function, and interleukin 1beta and tumor necrosis factor-alpha secretion returned to normal after a recovery period of 12 to 24 hours, 4.5 hours, and 24 hours, respectively. In the control experiments exposure of cells to helium had no suppressive effect. CONCLUSIONS: Exposure of cells to a high partial pressure of carbon dioxide environment suppresses the inflammatory and metabolic responses of peritoneal cells. We suggest that this suppressive effect may contribute to the low postsurgery adhesion formation and the reduction in postoperative pain observed in laparoscopy. Nevertheless, the suppression of the immune response should also be taken into account for operations involving a high risk of bacterial dissemination.

Ascitic Fluid↗
PubMed1998

Spatio-temporal working memory and frontal lesions in man.

The delayed-response paradigm is thought to be a marker of the activity of the dorsolateral convexity of primates' prefrontal cortex, as this procedure requires the activation of working memory processes. Although the role of the dorsolateral prefrontal cortex (DLPC) in working memory seems to be well established, much remains to be understood about the processes this structure actually controls: encoding domain-specific information, its retention in short-term memory, its monitoring in working memory, or its selection and retrieval when a specific response program is required. To clarify the role of the DLPC in delayed-response tasks in humans, a set of sequencing paradigms was designed which incorporates the dissociation of (1) spatial and temporal parameters, (2) recall and recognition processes, and (3) the presence or absence of a delay. Performance of a group of patients with DLPC lesions (n = 8) was compared to that of age-matched normal subjects (n = 8). To verify the specificity of the results obtained for the DLPC lesioned patients, the performance of patients with a temporal lobotomy was also studied (n = 10). A significant effect of the delay was observed only in patients with DLPC lesions, affecting both their spatial and spatio-temporal recall, whereas their spatio-temporal recognition was normal. These findings suggest that the DLPC plays a role in the retrieval of visuospatial information for guiding a response program.

Brain Injuries↗
PubMed1998

Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension.

Oxidative stress and inflammation have recently been linked to endothelial damage in essential hypertension (EH). Activated peripheral polymorphonuclear leukocytes (PMN) damage surrounding tissue by releasing reactive oxygen species (ROS) and proteolytic enzymes before self-necrosis. PMN necrosis further exacerbates inflammation and promotes chemotaxis and PMN recruitment. The number and properties of PMN from untreated EH patients is the focus of the present study. Oxidative stress was assessed by measuring the rate of superoxide anion release from separated, phorbol ester-stimulated PMN and the redox state of plasma glutathione. Inflammation was estimated indirectly by determining PMN number and their in vitro survival. PMN from EH patients (n = 37) released superoxide anion faster (P < .0001) than those of normotensives (NC, n = 37), 17.7 +/- 1.14 v 9.54 +/- 0.51 nmol/10 min/10(6) cells. The redox state of glutathione was twofold higher in EH plasma (P < .02) indicating systemic oxidative stress. PMN survival in vitro correlates linearly with the rate of superoxide release (r2 = 0.60, P < .02) and PMN count of EH patients, although in the normal range, were significantly higher (P < .0001), indicating necrosis and recruitment. Hypertensive plasma significantly reduced NC PMN viability, whereas normal plasma significantly increased EH PMN viability. What our studies show is that EH is accompanied by a primed state PMN that does not correlate with the levels of blood pressure. PMN priming in EH patients reflects an in vivo exposure to a constant stimulus ending in oxidative stress, increased self-necrosis, and cell recruitment. Oxidative stress and inflammation will result in endothelial damage and atherosclerosis in the long run.

Adult↗
PubMed1998

Laser scanning confocal imaging of abnormal or arrested human preimplantation embryos.

PURPOSE: The improved resolution and optical sectioning of a confocal microscope make it an ideal instrument for extracting three-dimensional information, especially from extended biological specimens such as human embryos. The staining of actin together with chromatin allowed us to specify the architecture of the embryo and the appearance of the nucleus. METHODS: F-Actin and chromatin distributions were visualized using laser scanning confocal microscopy in "fresh" and "cryopreserved" human preimplantation embryos obtained by in vitro fertilization. RESULTS: The current study revealed a high rate of multinucleation in arrested or poor-quality embryos (89%, in grade IV embryos). CONCLUSIONS: Confocal microscopy revealed high levels of multinucleated blastomeres, suggesting that the probable cause of arrested development in these embryos was due to multinucleation of blastomeres.

4-Chloro-7-nitrobenzofurazan↗
PubMed1998

Opioid modulation of extracellular signal-regulated protein kinase activity is ras-dependent and involves Gbetagamma subunits.

Although it is well-established that G protein-coupled receptor signaling systems can network with those of tyrosine kinase receptors by several mechanisms, the point(s) of convergence of the two pathways remains largely undelineated, particularly for opioids. Here we demonstrate that opioid agonists modulate the activity of the extracellular signal-regulated protein kinase (ERK) in African green monkey kidney COS-7 cells transiently cotransfected with mu-, delta-, or kappa-opioid receptors and ERK1- or ERK2-containing plasmids. Recombinant proteins in transfected cells were characterized by binding assay or immunoblotting. On treatment with corresponding mu- ([D-Ala2,Me-Phe4,Gly-ol5]enkephalin)-, delta- ([D-Pen2,D-Pen5]enkephalin)-, or kappa- (U69593)-selective opioid agonists, a dose-dependent, rapid stimulation of ERK1 and ERK2 activity was observed. This activation was inhibited by specific antagonists, suggesting the involvement of opioid receptors. Pretreatment of cells with pertussis toxin abolished ERK1 and ERK2 activation by agonists. Cotransfection of cells with dominant negative mutant N17-Ras or with a betagamma scavenger, CD8- beta-adrenergic receptor kinase-C, suppressed opioid stimulation of ERK1 and ERK2. When epidermal growth factor was used to activate ERK1, chronic (>2-h) opioid agonist treatment resulted in attenuation of the stimulation by the growth factor. This inhibition was blocked by the corresponding antagonists and CD8- beta-adrenergic receptor kinase-C cotransfection. These results suggest a mechanism involving Ras and betagamma subunits of Gi/o proteins in opioid agonist activation of ERK1 and ERK2, as well as opioid modulation of epidermal growth factor-induced ERK activity.

Animals↗
PubMed1998

Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes.

Two cannabinoid receptors belonging to the superfamily of G protein-coupled membrane receptors have been identified and cloned: the neuronal cannabinoid receptor (CB1) and the peripheral cannabinoid receptor (CB2). They have been shown to couple directly to the G(i/o) subclass of G proteins and to mediate inhibition of adenylyl cyclase upon binding of a cannabinoid agonist. In several cases, however, cannabinoids have been reported to stimulate adenylyl cyclase activity, although the mechanism by which they did so was unclear. With the cloning of nine adenylyl cyclase isozymes with various properties, including different sensitivities to alpha(s), alpha(i/o), and betagamma subunits, it became important to assess the signaling pattern mediated by each cannabinoid receptor via the different adenylyl cyclase isozymes. In this work, we present the results of cotransfection experiments between the two types of cannabinoid receptors and the nine adenylyl cyclase isoforms. We found that independently of the method used to stimulate specific adenylyl cyclase isozymes (e.g., ionomycin, forskolin, constitutively active alpha(s), thyroid-stimulating hormone receptor activation), activation of the cannabinoid receptors CB1 and CB2 inhibited the activity of adenylyl cyclase types I, V, VI, and VIII, whereas types II, IV, and VII were stimulated by cannabinoid receptor activation. The inhibition of adenylyl cyclase type III by cannabinoids was observed only when forskolin was used as stimulant. The activity of adenylyl cyclase type IX was inhibited only marginally by cannabinoids.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Low values on 50 gram glucose challenge test or oral 100 gram glucose tolerance test are associated with good perinatal outcome.

We set out to reevaluate the hypothesis that high normal (negative) results of 50 g oral glucose challenge test or high normal glucose level on 100 g oral glucose tolerance test are associated with complications of pregnancy and delivery. This was a prospective study involving 735 nondiabetic women. The first group (n=352) was made up of pregnant women with normal 50 g oral glucose challenge test without previous history of diabetes mellitus or gestational diabetes. The second group (n=383) was made up of pregnant women without previous history of diabetes mellitus or gestational diabetes with an abnormal 50 g oral glucose challenge test and with normal 100 g oral glucose tolerance test and not more than one previous delivery. In nondiabetic women, we demonstrated a positive correlation between high normal 50 g glucose challenge test values and the incidence of preeclampsia, caesarean section rate, macrosomia, neonatal hyperlipidaemia and minor congenital abnormalities. We failed to confirm any relationship to any pregnancy complication in pregnant women with 2-hour glucose levels in the range 6.7-9.1 mmol/l on the 100 g oral glucose tolerance test. We have demonstrated a positive relationship between the incidence of premature rupture of membranes and 1-hour glucose level, caesarean section rate and maternal 1-hour glucose level or 1-hour glucose level minus fasting glucose level of 4.2 mmol/l, instrumental delivery rate and maternal 3-hour glucose level, incidence of neonatal macrosomia and 1-hour glucose level, and incidence of neonatal hyperlipidaemia and at least one high but normal glucose level on the 100 g oral glucose tolerance test. With regard to pregnancy and delivery complications there were no significant difference if the high normal value is on the 50 g glucose challenge test or on the 100 g oral glucose tolerance test. It is concluded that one high normal 100 g oral glucose tolerance test or high normal 50 g glucose challenge test are associated with adverse pregnancy and delivery outcome. Nondiabetic women with 50 g glucose challenge test value of 6.1 mmol/l and/or 100 g oral glucose tolerance test values of 5 mmol/l have a favourable pregnancy and delivery outcome.

Journal Article↗
PubMed1998

Annexin V labelling and terminal transferase-mediated DNA end labelling (TUNEL) assay in human arrested embryos.

Confocal laser scanning microscopy was used to observe human arrested and fragmented preimplantation embryos obtained by in-vitro fertilization. Observation of the cellular actin cortex and chromatin showed a high frequency of embryos with blastomeres exhibiting two or more nuclei, while others had nuclei displaying chromatin condensation and fragmentation patterns. Many of the abnormal chromatin images could be due to the process of programmed cell death (apoptosis). The possible link between abnormalities of the blastomeres and apoptosis was investigated using two detection methods for cells undergoing apoptosis. Detection of phosphatidylserine exposure was performed using annexin V; the chromosomal breakdown preceding the nuclear collapse of apoptotic nuclei was tested using the terminal transferase-mediated DNA end labelling (TUNEL) assay. Annexin V staining was observed in all arrested and/or fragmented human embryos, but not in cryopreserved embryos which continued to develop normally after thawing. The TUNEL assay was positive in 30% (15/50) of arrested embryos, all of which had cytoplasmic fragments. In contrast, embryos showing regular size blastomeres without fragments were TUNEL negative.

Actins↗
PubMed1998

Inhibition of adenylyl cyclase isoforms V and VI by various Gbetagamma subunits.

An intriguing development in the G-protein signaling field has been the finding that not only the Galpha subunit, but also Gbetagamma subunits, affect a number of downstream target molecules. One of the downstream targets of Gbetagamma is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhibited or stimulated by Gbetagamma subunits. Until now, adenylyl cyclase type I has been the only isoform reported to be inhibited by free Gbetagamma. Here we show by transient cotransfection into COS-7 cells of either adenylyl cyclase V or VI, together with Ggamma2 and various Gbeta subunits, that these two adenylyl cyclase isozymes are markedly inhibited by Gbetagamma. In addition, we show that Gbeta1 and Gbeta5 subunits differ in their activity. Gbeta1 transfected alone markedly inhibited adenylyl cylcase V and VI (probably by recruiting endogenous Ggamma subunits). On the other hand, Gbeta5 produced less inhibition of these isozymes, and its activity was enhanced by the addition of Ggamma2. These results demonstrate that adenylyl cyclase types V and VI are inhibited by Gbetagamma dimers and that Gbeta1 and Gbeta5 subunits differ in their capacity to regulate these adenylyl cyclase isozymes.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Regulation of adenylyl cyclase isozymes on acute and chronic activation of inhibitory receptors.

Adenylyl cyclase superactivation, a phenomenon by which chronic activation of inhibitory Gi/o-coupled receptors leads to an increase in cAMP accumulation, is believed to play an important role as a compensatory response of the cAMP signaling system in the cell. However, to date, the mechanism by which adenylyl cyclase activity is regulated by chronic exposure to inhibitory agonists and the nature of the adenylyl cyclase isozymes participating in this process remain largely unknown. Here we show, using COS-7 cells transfected with the various AC isozymes, that acute activation of the D2 dopaminergic and m4 muscarinic receptors inhibited the activity of adenylyl cyclase isozymes I, V, VI, and VIII, whereas types II, IV, and VII were stimulated and type III was not affected. Conversely, chronic receptor activation led to superactivation of adenylyl cyclase types I, V, VI, and VIII and to a reduction in the activities of types II, IV, and VII. The activity of AC-III also was reduced. This pattern of inhibition/stimulation of the various adenylyl cyclase isozymes is similar to that we recently observed on acute and chronic activation of the mu-opioid receptor, suggesting that isozyme-specific adenylyl cyclase superactivation may represent a general means of cellular adaptation to the activation of inhibitory receptors and that the presence/absence and intensity of the adenylyl cyclase response in different brain areas (or cell types) could be explained by the expression of different adenylyl cyclase isozyme types in these areas.

Adenylyl Cyclase Inhibitors↗
PubMed1998

Prospective study to determine clinical relevance of detection of pneumococcal DNA in sera of children by PCR.

We undertook a prospective study to evaluate the accuracy of PCR of serum (aimed at the pneumococcal pneumolysin gene) at detecting pneumococcal infections in infants and children. The assay was positive for all blood and cerebrospinal fluid culture-positive samples and for 38 and 44% of patients with lobar pneumonia and acute otitis media, respectively. It was positive for 17% of healthy controls. There was a marked effect of age on the rate of positivity among healthy controls, with the highest rate (33%) being in 2-year-old children, the age group with the highest rate of nasopharyngeal (NP) carriage; the lowest rate was found among infants <2 months of age (13%) and adults ages 18 to 50 years (0%), age groups with the lowest NP pneumococcal carriage rates. Carriers of pneumococci in the nasopharynges had a higher rate of positivity than noncarriers of pneumococci in the nasopharynges for all groups. Our results suggest that although PCR of serum is a sensitive test for the detection of Streptococcus pneumoniae in sterile fluids, its high rate of positivity for healthy controls, related to NP pneumococcal carriage, might exclude it from being useful in detecting deep-seated pneumococcal infections.

Adolescent↗
PubMed1998

Coupled temporal memories in Parkinson's disease: a dopamine-related dysfunction.

Dysfunction of the basal ganglia and the brain nuclei interconnected with them leads to disturbances of movement and cognition, including disordered timing of movement and perceptual timing deficits. Patients with Parkinson's disease (PD) were studied in temporal reproduction tasks. We examined PD patients when brain dopamine (DA) transmission was impaired (OFF state) and when DA transmission was reestablished, at the time of maximal clinical benefit following administration of levodopa + apomorphine (ON state). Patients reproduced target times of 8 and 21 sec trained in blocked trials with the peak interval procedure, which were veridical in the ON state, comparable to normative performance by healthy young and aged controls (Experiment 1). In the OFF state, temporal reproduction was impaired in both accuracy and precision (variance). The 8-sec signal was reproduced as longer and the 21-sec signal was reproduced as shorter than they actually were (Experiment 1). This "migration" effect was dependent upon training of two different durations. When PD patients were trained on 21 sec only (Experiment 2), they showed a reproduction error in the long direction, opposite to the error produced under the dual training condition of Experiment 1. The results are discussed as a mutual attraction between temporal processing systems, in memory and clock stages, when dopaminergic regulation in the striatum is dysfunctional.

Aged↗
PubMed1998

Culturally sensitive validation of screening questionnaires for depression in older African-Caribbean people living in south London.

BACKGROUND: We tested the validity of two screens for depression in older African-Caribbean adults, the 15-item Geriatric Depression Scale (GDS) and a new Caribbean Culture-Specific Screen for emotional distress (CCSS). Two independent criteria were used for validity: (a) a psychiatric diagnosis derived from GMS-AGECAT, and (b) a culturally sensitive assessment of mental disorder, derived from a tool developed with local African-Caribbean religious healers. METHOD: One hundred and sixty-four consecutive African-Caribbean primary care users, aged 60 years or older, were screened with the GDS and the CCSS. Diagnostic interviews were carried out on 80% of high scorers and 20% of low scorers. RESULTS: The number of cases detected by the two separate diagnostic approaches was similar. However, the agreement between who was and who was not a case was only modest. At a cut-off of > or = 5, the GDS was an adequate case detector for psychiatric depression, and, at a cut-off of > or = 4, for 'depressed/lost spirit', as defined by culture-specific criteria. It performed as well as the new CCSS. CONCLUSIONS: At a cut-off of > or = 4 the 15-item GDS can be recommended as a case detector for significant forms of depression in older African-Caribbean people living in south London.

Aged↗
PubMed1998

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

Adult↗
PubMed1998

[Malignant pleural mesotheliomas].

An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p < 0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.

Adult↗