Bcl-2 and Bax expression on rat ischemic kidney.
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Animals↗
Biomedical subjects
G Benoit
Publications and source records attributed to G Benoit.
Expression of alpha 1 adrenoceptor subtypes in rat corpus cavernosum.
Norepinephrine mediates the antierectile role of the sympathetic nervous system. It binds to postsynaptic alpha 1 adrenoceptors present on smooth muscle fibers of the corpus cavernosum. Receptor cloning studies have evidenced three alpha 1 adrenoceptor subtypes: alpha 1A, alpha 1B and alpha 1D. We searched for the presence of these three alpha 1 adrenoceptor subtypes in the rat corpus cavernosum using in situ hybridization with specific oligonucleotide probes. Brain tissue was used as the reference of probes specificity. Autoradiographic films were studied with light illumination and computer-assisted densitometry using an image analyser. We provide evidence that the three alpha 1 adrenoceptor subtypes are expressed in the rat corpus cavernosum. These three subtypes appear to be more expressed in the trabecular smooth muscle fibers than in vascular smooth muscle fibers. Further experiments are needed to determine whether the proportion of alpha 1 adrenoceptor subtypes changes according to the etiology of erectile dysfunction. This morphological approach provides a basis for future pharmacological research of specific alpha 1 adrenoceptor subtypes blocking agents designed to treat erectile dysfunction.
Animals↗
Expression patterns of the JEM-1 gene in normal and tumor cells: ubiquity contrasting with a faint, but retinoid-induced, mRNA expression in promyelocytic NB4 cells.
The JEM-1 gene, recently identified in acute promyelocytic leukemia (APL) cells, codes for a novel nuclear factor (Duprez et al Oncogene 1997; 14: 1563-1570). JEM-1 is kept silent in the APL cell line NB4, but up-regulated (3 kb transcript) during cell maturation. Here, we show that retinoic acid (RA)-induced JEM-1 expression is biphasic (peaks at 6 h and 48 h) and associated with the later stages of maturation. Retinoids, which cooperates with cAMP to induce maturation, also cooperates with cAMP to up-regulate JEM-1, either in maturation-responsive NB4 cells or in NB4-R1 resistant subclones. APL patients showed a low, yet variable, level of JEM-1 mRNA in bone marrow. RA treatment induced an increase in the level of JEM-1 mRNA, as detected by a semi-quantitative PCR. This increase can result from both gene up-regulation or replacement of leukemia cells by differentiated ones. Analysis of JEM-1 expression patterns in normal and tumor cells revealed that JEM-1 expression was ubiquitous. Cell lines derived from monocytic and erythroid leukemias, expressed low and high amounts of JEM-1 mRNA, respectively. Using a JEM cDNA probe, distinct profiles of expression and different transcript sizes (4 kb, 3 kb and 2 kb) were also identified in tumour and normal non-hematopoietic tissues, while interestingly only the 3kb transcript was up-regulated in NB4 cells. This work identifies JEM-1 as a novel ubiquitous gene whose expression is low in APL cells, but can be restored by RA treatment, concomitant with cell maturation.
Adult↗
Surgical aspects of kidney transplantation in France in 1997.
In France the number of procurements and transplantations has declined since 1991. Procurement and surgical transplantation are generally performed by the urologist using a transplantation surgical technique similar to the one René Küss described in 1951. The urinary and vascular complication rate has decreased with procurement and transplantation technique improvement--procurement with a Carrel patch, with the inferior vena cava for the right kidney, and transplantation with an extravesical urinary anastomosis. The surgical complications are now generally treated by endourological techniques, celioscopy, or percutaneously with a good overall result for the patient and kidney.
Adult↗
[Von Hippel-Lindau disease and renal cancer: 10 years of genetic progress. GEFVHL (French-Speaking Study Group on von Hippel-Lindau disease)].
Von Hippel-Lindau (VHL) disease is a genetic disease predisposing to the development of various tumours (haemangioblastomas of the neuraxis and retina, tumours of the membranous labyrinth, renal clear cell carcinomas or cysts, phaeochromocytomas, pancreatic cysts or tumours, epididymal cystadenomas), affecting one in 36,000 people. Renal cancer constitutes one of the main causes of death. The VHL gene, situated at 3p25-26, is a tumour suppressor gene which plays a major role in regulation of VEGF transcription and expression. The germ cell mutation can be identified in 70% of patients. Somatic mutations of the VHL gene are also responsible for sporadic clear cell carcinomas. In the urological setting, any patient presenting with "sporadic" bilateral clear cell renal cancer or detected at an early age, or bilateral epididymal cystadenomas, should be investigated for the presence of VHL disease.
Adenocarcinoma, Clear Cell↗
[Pachydermoperiostosis with extramedullary hematopoiesis without myelofibrosis].
BACKGROUND: In three previous reports of primary hypertrophic osteoarthropathy, an associated extramedullary hematopoiesis was related to myelofibrosis. CASE REPORT: A 44-year-old male patient with primary hypertrophic osteoarthropathy diagnosed when he was 34-year-old was referred to our hospital with an abdominal mass fortuitously detected. DISCUSSION: The present case is unique for the patient developed an extramedullary hematopoïesis without associated myelofibrosis. It suggests the possible intervention of growth factors common to the skin fibroblasts and the blood progenitor cells in the pathogenesis of primary osteoarthropathy.
Abdomen↗
MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas.
Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.
CD3 Complex↗
Long-term results of combined kidney and liver transplantation at one center.
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Adult↗
Kinetics of permeation of 2,3-butanediol on isolated perfused rat kidney model assessed by proton nuclear magnetic resonance spectroscopy.
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Animals↗
Expression of aldehydic lipid peroxidation products in rat kidneys during warm ischemia.
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Aldehydes↗
Evidence of sympathetic fibers in the male rat pelvic nerve by gross anatomy, retrograde labeling and high resolution autoradiographic study.
Several arguments exist in various animal species and man for the presence of a sympathetic component in the pelvic nerve, classically regarded as parasympathetic. We tested this hypothesis in the male rat. Nerve bundles issued from the sacral region of the paravertebral sympathetic chain and reaching the S1 spinal nerve were identified. Neurons in the sacral parasympathetic nucleus of the L6-S1 spinal cord and in the L2-S1 paravertebral sympathetic chain were retrogradely labeled from the pelvic nerve. Radioautography evidenced labeling of unmyelinated fibers in the pelvic nerve following in vitro incubation with 3H-noradrenaline. A population of sympathetic fibers issued from the lumbosacral sympathetic chain exists in the pelvic nerve of the male rat. This qualitative study provides a morphological basis to uncover the role of the sympathetic outflow present in the pelvic nerve.
Animals↗
Erectile response to hypothalamic stimulation in rats: role of peripheral nerves.
The role of peripheral parasympathetic and sympathetic pathways was explored in erectile responses elicited by hypothalamic medial preoptic area (MPOA) stimulation in adult male anesthetized rats. Under control conditions, MPOA stimulation reliably elicited erectile responses evidenced by an increase of the intracavernous pressure-to-blood pressure ratio. The erectile response was abolished by 1) acute bilateral section of cavernous or pelvic nerves or cauda equina and 2) chronic lesions of pelvic nerves or cauda equina. Acute section of the hypogastric nerve did not significantly decrease the erectile response. The erectile response was significantly depressed after acute or chronic sections of the paravertebral sympathetic chain at the L4-L5 level or chemical sympathectomy with 6-hydroxydopamine. The decrease due to acute sympathetic chain lesion was reversed by bilateral ligation of the external iliac arteries. Accordingly MPOA stimulation elicits erectile responses via 1) activation of the parasympathetic outflow conveyed by the pelvic and cavernous nerves and 2) activation of neural fibers conveyed by the sympathetic pathways. We propose that sympathetic fibers running in the paravertebral sympathetic chain are responsible for vasoconstriction of nonpenile areas to divert blood to the penis, allowing the dramatic increase of penile arterial inflow required for erection.
Animals↗
Is matching for sex and age beneficial to kidney graft survival? Société Française de Transplantation and Association France Transplant.
A total of 6889 cadaver kidney grafts carried out in the French transplant network from 1 January 1989 to 31 December 1992 were analyzed using single and multifactorial methods in order to evaluate the impact on graft survival of matching for sex and age between donors and recipients. The mean graft survival rate was 75% at 3 yr with donors between 10 and 50 yr of age compared to 65% for donors under 10 yr of age and 67% at 3 yr for donors over 50 yr of age (p < 0.000001). For child recipients there were no significant differences in graft survival whatever the difference in age with the donor (+/- 10 yr). For young adults (17-49 yr of age) the prognosis at 3 yr was the same (75%) whether the donor was in the same age category or older than the recipient. For older adults (> 50 yr of age) a poorer prognosis was obtained when the donor was 10 yr or more older than the recipient (61% at 1 yr, p = 10(-4)). The grafts performed with male donors had a better prognosis (76% at 3 yr) than those using female donors (71% at 3 yr, p < 0.0002). The poorest results were obtained with female donors when the recipient was male (70% at 3 yr). The results of the multivariate analysis of seven parameters involved in graft survival show that the main parameters significantly controlling graft survival are preimmunization before the graft (p = 10(-6)), HLA-DR incompatibility (p = 0.004), retransplantation (p = 0.008), donor sex (p = 0.003), and matching for age between donor and recipient (p = 0.1). These results suggest that age and sex should be considered as criteria in the choice of donors and recipients in organ allocation.
Adolescent↗
[Central nervous system control of erection].
Relaxation of arterial and cavernous smooth muscle fibers, leading to the filling of the sinusoidal spaces with blood, are the local mechanisms of erection. Smooth muscle relaxation results from activation of parasympathetic neural pathway and probably simultaneous inhibition of the sympathetic outflow. Reflexive erection elicited by recruitment of penile afferents conveyed by the dorsal penile nerve involves both autonomic and somatic efferents. This reflex is mediated at the spinal cord level and modulated by supraspinal influences. Serotonergic pathways originating in the raphe nuclei mediate inhibitory control on reflexive erection. Several hypothalamic areas such as the medial preoptic area and the paraventricular nucleus are the source of descending pathways and/or represent important integrating centers. Dopamine acting at the medial preoptic area level may regulate penile erection. Neuroendocrine regulation may vary depending on the context in which erection occurs, for example, coitus, in response to extrinsic or psychogenic stimuli, and rapid eye movement sleep.
Afferent Pathways↗
[The peripheral pharmacology of erection].
The peripheral control of local mechanisms of erection and detumescence has now been more clearly elucidated. This knowledge has been acquired as a result of the recent development of pharmacological research designed to study the regulation of erectile smooth muscle tone. Smooth muscle fibres of the corpora cavernosa and arteries supplying the penis relax in response to a reduction of intracellular calcium. This relaxation allows both an increase of the blood flow to the penis and opening of sinusoid spaces. Cyclic nucleotides, cAMP and cGMP, are intracellular messengers of the mediators acting on smooth muscle fibres and regulating these intracellular calcium movements. Gap-junctions, greatly facilitating rapid ion exchanges between smooth muscle fibres, make erectile tissue a real functional syncytium. Nonadrenergic, noncholinergic neurotransmitters, mainly nitric oxide (NO), are synthesized by parasympathetic neurons present in cavernous nerves and act directly on smooth muscle fibres. NO increases the intracellular cGMP concentration. Other proerectile mediators, such as acetylcholine, CGRP or substance P, act via endothelial cells by promoting the synthesis and release of NO by these cells. In contrast, neurotransmitters of the sympathetic nervous system, norepinephrine and neuropeptide Y, and endothelin, secreted by endothelial tissues, induce contraction of cavernous smooth muscle fibres, thereby opposing erection. Oxygenation of the cavernous tissue is also an important factor in the regulation of local mechanisms of erection. Poor oxygenation prevents the synthesis of cGMP and predisposes to cavernous fibrosis due to increased synthesis of collagen via TGF beta. A better understanding of the peripheral pharmacology of erection opens the way to new pathophysiological and therapeutic prospects in the broad symptomatic context of erectile dysfunction.
Acetylcholine↗
[No relationship between tacrine cytotoxicity and its metabolisation by cytochrome P4501A2].
It has been suggested that tacrine (THA) induced hepatotoxicity was related to its metabolic pathway involving cytochrome P4501A2 (CYP1A2). Using a model of genetically modified cells we have demonstrated that THA induced a marked decrease in cell viability and a strong inhibition of RNA and protein synthesis. However, these cytotoxic effects did not differ in parental Chinese hamster V79 cells and variant cells expressing human or rat CYP1A2 as well in human HepG2 and Chang Liver cells despite their notable metabolism ability to metabolize THA to hydroxylated metabolites. These results strongly suggest that THA-induced cytotoxicity is not mediated by CYP1A2 indicating that THA could be toxic by direct inhibition at the ribosomial level.
Analysis of Variance↗
Stimulation of the medial preoptic area of the hypothalamus in the rat elicits increases in intracavernous pressure.
Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of the male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering L-glutamate. An erectile response, assessed by an increase of intracavernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of L-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.
Analysis of Variance↗
Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases.
We have generated mouse models of human Tay-Sachs and Sandhoff diseases by targeted disruption of the Hexa (alpha subunit) or Hexb (beta subunit) genes, respectively, encoding lysosomal beta-hexosaminidase A (structure, alpha) and B (structure, beta beta). Both mutant mice accumulate GM2 ganglioside in brain, much more so in Hexb -/- mice, and the latter also accumulate glycolipid GA2. Hexa -/- mice suffer no obvious behavioral or neurological deficit, while Hexb -/- mice develop a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor and ataxia. The Hexb -/- but not the Hexa -/- mice have massive depletion of spinal cord axons as an apparent consequence of neuronal storage of GM2. We propose that Hexa -/- mice escape disease through partial catabolism of accumulated GM2 via GA2 (asialo-GM2) through the combined action of sialidase and beta-hexosaminidase B.
Animals↗