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Biomedical subjects

B Guibert

Publications and source records attributed to B Guibert.

At least 37 records · Page 2Linked to original sources

[Long-term outcome of 72 patients surgically treated for stage II non-small cell bronchial cancer, between 1982 and 1989].

We report a 72 patients trial, who had surgical treatments for non small cell lung cancer, stage II (T1N1, T2N1). In our retrospective study, the overall 5-years survival is 44%, with a 24-month median survival. 45% of the patients have recurrence mainly due to distant metastasis. State II appears to be an heterogeneous group. As shown in other studies, the presence of hilar nodes (N1H) seems to be linked with a pejorative outcome. In our series, the survival associated with Lobar N1 (N1L) disease is the same as the survival of Hilar N1 disease, but the initial sites of recurrence differ. The interest of a postchirurgical treatment is controversial. The postoperative radiotherapy reduces the local recurrence without increasing the survival. The chemotherapy treatment is debatable and several studies are under way. We reviewed the different causes of death. The appearance of second cancer in the cured patients is very frequent.

Adult↗

Antihistamines and production of granulocyte-macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro: evaluation of the effects of loratadine and cetirizine.

1. In this study, we compared the effects of two antihistamine drugs on the production of granulocyte-macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro. 2. Cytokine production was assessed by the use of an enzyme-linked immunosorbent assay. 3. Epithelial cells spontaneously released both cytokines and tumor necrosis factor alone induced a significant increase in this production but loratadine and cetirizine had no effect at the various concentrations studied. 4. The antihistamines have no effect and this suggests that histamine plays no role in cytokine production under these conditions.

Adult↗

RU 41740 (Biostim) stimulates the production of granulocyte macrophage colony-stimulating factor and interleukin-8 by human bronchial epithelial cells in vitro.

1. In this study, we observed the effects of RU 41740 (Biostim) on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) in human bronchial epithelial cells in vitro. 2. Cytokine production was assessed by enzyme-linked immunosorbent assay. 3. We report that epithelial cells spontaneously released both cytokines and that RU 41740 induced a significant increase in production of IL-8 and GM-CSF. 4. This is the first observation of a stimulatory effect of an immunostimulating compound used in humans on cytokine production by epithelial cells.

Adjuvants, Immunologic↗

[Spontaneous hydro-pneumothorax disclosing malignant mesothelioma. Apropos of 2 cases].

We report the cases of two males who presented with spontaneous complete unilateral pneumothorax with ipisilateral liquid effusion. Neither had a history of previous respiratory disease. In both cases chest tube drainage resulted in recurrence of pneumothorax with chronic illness requiring surgical exploration. The surgery revealed a malignant pleural mesothelioma by histological examination. Thus, spontaneous pneumothorax, particularly with abondant effusion can be a revealing symptom of malignant pleural mesothelioma.

Adult↗

[Malignant mesothelioma of the pleura following radiotherapy of Hodgkin disease].

Second neoplasms following chemotherapy and radiotherapy for Hodgkin's disease have been extensively described, including acute myeloblastic leukemia, non Hodgkin's lymphomas and various solid tumors. We report malignant pleural mesothelioma occurring 17 years after mantle radiotherapy and MOPP chemotherapy for Hodgkin's disease. According to Cahan's criteria, this mesothelioma may be considered as treatment-related. Fourteen similar cases have been previously published. Post-radiation mesothelioma might be characterised by limited stage at diagnosis and might be surgically removed at presentation.

Antineoplastic Combined Chemotherapy Protocols↗

Direct in vivo comparison of two mechanisms releasing dopamine in the rat striatum.

A push-pull cannula supplied with artificial CSF was implanted in the striatum of anaesthetized rats, and the basal extracellular DA and DOPAC was assayed in the superfusates using HPLC and electrochemical detection. Simultaneously, a carbon fibre electrode was implanted in close proximity of the cannula and the evoked DA release was detected by differential pulse amperometry during stimulation of the DA axons. Local treatments with cadmium (100 microM) blocked the evoked DA release (-90%), but substantially increased the basal extracellular DA (+125%). The effects of glutamate agonists NMDA (1 mM) and kainate (0.1 mM), known to increase basal extracellular DA were confirmed (+150% and +60% respectively). It was, however, simultaneously observed that the evoked DA release was inhibited (-80% and -50%, respectively). Amphetamine (1 microM) released DA (+150%) and produced also an increase (+100%) of the evoked DA release. These results, apparently conflicting, show that the two mechanisms releasing dopamine (firing-dependent and not) can be directly and simultaneously observed. These two releasing processes appear to be not strictly antagonist. They are also differently and independently modulated by calcium and by local influences such those conveyed by glutamate.

3,4-Dihydroxyphenylacetic Acid↗

Acute stimulatory effect of estradiol on striatal dopamine synthesis.

The acute effect of physiological doses of estradiol (E2) on the dopaminergic activity in the striatum was studied. In a first series of experiments, ovariectomized rats were injected with 17 alpha or 17 beta E2 (125, 250, or 500 ng/kg of body weight, s.c.), and in situ tyrosine hydroxylase (TH) activity (determined by DOPA accumulation in the striatum after intraperitoneal administration of NSD 1015) was quantified. A dose-dependent increase in striatal TH activity was observed within minutes after 17 beta (but not 17 alpha) E2 treatment. To examine whether E2 acts directly on the striatum, in a second series of experiments, anesthetized rats were implanted in the striatum with a push-pull cannula supplied with an artificial CSF containing [3H]tyrosine. The extracellular concentrations of total and tritiated dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured at 20-min intervals. Addition of 10(-9) M 17 beta (but not 17 alpha) E2 to the superfusing fluid immediately evoked an approximately 50% increase in [3H]DA and [3H]DOPAC extracellular concentrations, but total DA and DOPAC concentrations remained constant. This selective increase in the newly synthesized DA and DOPAC release suggested that E2 affects DA synthesis rather than DA release. Finally, to determine whether this rapid E2-induced stimulation of DA synthesis was a consequence of an increase in TH level of phosphorylation, the enzyme constant of inhibition by DA (Ki(DA)) was calculated. Incubation of striatal slices in the presence of 10(-9) M 17 beta (but not 17 alpha) E2 indeed evoked an approximate twofold increase in the Ki(DA) of one form of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

TH mRNA over-expression in rats with chronic excitotoxic striatal lesions.

Twenty weeks after ibotenic acid lesions of the striatum, the amount of tyrosine hydroxylase (TH) in this structure was markedly increased. This was accompanied by a 3-fold increase in TH mRNA levels in the ipsilateral subtantia nigra (SN). Striatal levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were markedly reduced. In the nucleus accumbens, spared by the lesion, DA neurotransmission was also altered, as evidenced by a reduction of DA and DOPAC, but no increase in TH could be detected. TH mRNA levels were moderately enhanced in the ventral tegmental area (VTA). Thus, lesioning in the striatum induces TH gene activation in both SN and VTA neurones, not strictly related to DA function at the terminal level.

3,4-Dihydroxyphenylacetic Acid↗

Regulation of tyrosine hydroxylase gene expression in mesencephalic dopamine neurons: effect of imipramine treatment.

The effects of a chronic imipramine treatment on the mesoamygdaloid pathway of rats were examined. Using semiquantitative immunocytochemical techniques, it was observed that the level of TH mRNA was decreased in the ventral tegmental area (VTA). In contrast, the TH protein was increased in both the VTA and amygdala. The TH activity was decreased in the amygdala when assessed under normal conditions but increased after a preincubation to phosphorylate the enzyme, suggesting a lowering of the protein-specific activity in the terminals. These results show that TH protein turnover in the mesoamygdaloid neurons can be reduced by chronic imipramine treatments, thereby producing an accumulation of inactive TH protein in the neurons while also decreasing TH gene activity in the cell bodies.

Amygdala↗

Evidence for protein kinase C involvement in the short-term activation by prolactin of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons.

The mechanism of the short-term activation by prolactin (PRL) of tyrosine hydroxylase (TH) in tuberoinfundibular dopaminergic neurons was examined in vitro on hypothalamic slices from ovariectomized rats. TH activity (determined by 3,4-dihydroxyphenylalanine accumulation in the median eminence after blockade of decarboxylase with NSD 1055) showed a dose-dependent increase within 2 h of incubation of the hypothalamic slices with PRL. To determine whether a phosphorylation process was involved in this increase in TH activity, we studied the sensitivity of the enzyme to dopamine (DA) feedback inhibition. In control median eminences, two kinetically different forms of TH coexisted, one exhibiting a Ki(DA) value of 29.92 +/- 0.49 microM, the other being approximately 15-fold more sensitive to DA inhibition with a Ki(DA) of 1.96 +/- 0.09 microM, likely corresponding to a phosphorylated and active form and to a nonphosphorylated and less active form, respectively. After PRL treatment, the TH form of low Ki(DA) remained unaffected, whereas the Ki(DA) of the purported active form of TH increased to 62.6 +/- 0.8 microM, suggesting an increase in the enzyme phosphorylation. This increase in the Ki(DA) of TH was selectively prevented by GF 109203X, a potent and selective inhibitor of protein kinase C, but not by a specific inhibitor of protein kinase A or calmodulin. Finally, this action of PRL could be mimicked by 12-O-tetradecanoylphorbol 13-acetate (a direct activator of protein kinase C). These results suggest that PRL, at the median eminence level, activates TH by increasing the enzyme phosphorylation and that this action may involve an activation of protein kinase C.

Animals↗

Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone.

Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis). Confluent monolayers of HBEC cultured on collagen were incubated for 24 h in a medium without study drugs (spontaneous production) or containing cefodizime or ceftriaxone at the clinically relevant concentrations of 1, 10 and 100 mg/l, with or without tumor necrosis factor alpha (TNF alpha, 100 U/ml). GM-CSF and IL-8 were measured in supernatant by ELISA technique. TNF alpha alone led to a significant (p < 0.005) increase in both GM-CSF and IL-8 production. Cefodizime induced a significant (p < 0.05), dose-dependent increase in GM-CSF release. No additive effect of cefodizime with TNF alpha was observed. Cefodizime did not affect IL-8 production and ceftriaxone had no influence on cytokine production. This is the first report of a stimulatory effect of a beta-lactam antibiotic on cytokine production by epithelial cells. GM-CSF production by epithelial cells is an important immunological step for neutrophil and monocyte recruitment and cell priming during lung defence. Previous studies with cefodizime in immunodepressed subjects have shown activation of phagocytosis and phagocytosis-related functions in non-lung phagocytes. An indirect mechanism of action, similar to that indicated by our results, may have been responsible for these stimulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Recurrent hemothorax due to pleural endometriosis].

We report a case of a 31 year old woman with recurrent hemothorax at the beginning of mens. Pleural biopsy confirmed the diagnosis of pleural endometriosis. Medical treatment with a Gn-RH analogue failed to cure and we realised surgical pleurodesis.

Adult↗

Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis.

Intraperitoneal chemo-hyperthermia with mitomycin C was used to treat 28 patients with far advanced digestive adenocarcinoma and histologically confirmed peritoneal carcinomatosis. Surgical resection of the primary tumor was possible in 17 cases. After closure of the abdominal wall, intraperitoneal chemo-hyperthermia was performed for 90 to 120 minutes under general anesthesia and 32 degrees C hypothermia, through 3 intraperitoneal drains forming a closed circuit, using 10 mg/l of mitomycin C in 6 liters of peritoneal dialysate heated to an inflow temperature of 46-49 degrees C. No mortality occurred, and there were 2 post-operative complications, with transitory biological side effects. In 9 out of 10 patients with preoperative malignant ascites, the ascites cleared after treatment. One-year survival rate was 54.2%. These encouraging preliminary results show that intraperitoneal chemohyperthermia with mitomycin C is a safe and reliable treatment for peritoneal carcinomatosis in far advanced digestive cancers.

Adenocarcinoma↗

Analysis of the human dopamine beta-hydroxylase promoter: transcriptional induction by cyclic AMP.

We have analyzed some functional aspects of the promoter of the human dopamine beta-hydroxylase (DBH) gene. A fragment of 1,247 bp directly 5' to the transcriptional start was progressively shortened, placed in front of a reporter gene, and tested in a human neuroblastoma cell line expressing DBH (SK-N-SH-TFM) and in a monkey kidney cell line (CV-1). A remarkably short region (267 bp), directly upstream from the transcription start, was sufficient to confer activity and tissue-specific expression. Furthermore, the expression of the DBH gene was shown to be inducible by cyclic AMP in SK-N-SH-TFM cells. This effect was demonstrated to occur at the transcriptional level, as shown by run-on assays, and was due to the presence of a near-consensus cyclic AMP-responsive element located in the untranscribed 5' regulatory region of the gene.

Animals↗

Short-term inhibitory effect of estradiol on tyrosine hydroxylase activity in tuberoinfundibular dopaminergic neurons in vitro.

The short-term inhibition by estradiol of tyrosine hydroxylase (TH) in tuberoinfundibular dopaminergic neurons was examined in vitro on hypothalamic slices from ovariectomized rats. TH activity (determined by L-3,4-dihydroxyphenylalanine accumulation in the median eminence after blockade of decarboxylase with NSD 1055) showed a 30-40% decrease within 1 h of incubation with estradiol. To determine whether a dephosphorylation process was involved in this decline in TH activity, we studied the sensitivity of the enzyme to dopamine (DA) feedback inhibition: In controls, we observed that two kinetically different forms of TH coexisted, with one exhibiting a Ki(DA) of 26.4 +/- 2 microM and the other being approximately 10-fold more sensitive to DA inhibition, with a Ki(DA) of 2.56 +/- 0.17 microM, likely corresponding to a phosphorylated and active form and to a nonphosphorylated and poorly active form, respectively. Conversely, after estradiol treatment all TH molecules exhibited the same Ki(DA) of 2.5 +/- 0.3 microM. This effect was stereospecific, because 17 alpha-estradiol could not promote it, whereas with 17 beta-estradiol, it could be observed at only 10(-11) M and after a short delay (30 min). Finally, this decrease in the Ki(DA) of the purported active form of TH could be prevented by okadaic acid (an inhibitor of protein phosphatases). These results suggest that estradiol can act directly on the mediobasal hypothalamus to trigger a rapid decline in TH activity and that this action may involve a decrease in TH phosphorylation.

Animals↗

GnRH-associated peptide (GAP) is present in the rat striatum and affects the synthesis and release of dopamine.

A possible interference of the GnRH-associated peptide (GAP) with the metabolism of dopamine in the rat striatum was investigated. The presence of the precursor of the peptide in this central region of dopaminergic terminals was first evidenced using specific RIA. The action of GAP on dopamine release was investigated in the caudate nucleus using the local superfusion with a push-pull cannula supplied with an artificial CSF containing the tritiated precursor of dopamine [( 3H]tyrosine). Addition of GAP (1 microM) to the superfusing fluid resulted in an increase of the release of the newly synthesized dopamine without a significant modification of the total amine release. In situ neutralization of GAP by addition in the CSF of a rabbit serum containing antibodies directed against the GAP produced opposite effects evidencing a tonic function for this peptide. In addition to the increased specific activity of the dopamine released during GAP treatment, the alterations observed in the efflux (and the specific activity) of dihydroxyphenyl acetic acid and the activation of dopamine synthesis obtained in vitro in striatal slices in the presence of GAP led us to conclude that the GAP system could be considered as a positive control of dopamine synthesis.

3,4-Dihydroxyphenylacetic Acid↗

Noradrenergic hyperactivity after partial fornix section: role in cholinergic dependent memory performance.

Rats with unilateral or bilateral partial section of the fornix were impaired on an eight arm radial maze task. Neurochemical analysis of hippocampal tissue four weeks after the lesions revealed a 50% reduction of choline acetyltransferase (ChAT) activity. The cholinergic marker was correlated negatively with the number of errors in the maze; the lower the ChAT activity, the higher the error score. The fornix lesion also induced a 50% reduction in norepinephrine (NE), but no change in the noradrenergic metabolite methylhydroxyphenylglycol (MHPG), suggesting a net increase in turnover of NE in these animals. Additional lesion of the noradrenergic system with the neurotoxin DSP4 reduced both MHPG and NE levels by more than 90%, compared to nonlesioned controls, and reversed the behavioral deficit. This treatment had no further effect on cholinergic markers. There was a significant negative correlation between ChAT activity and the index of NE turnover, suggesting that hyperactivity in the noradrenergic system after fornix section inhibits the spared cholinergic function and thus exacerbates the cognitive deficit. The pattern of neurochemical results bear a striking resemblance to those seen in some Alzheimer's patients and suggest that an equilibrium among neurotransmitters is important to cognitive function.

Alzheimer Disease↗