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Biomedical subjects

A Muller

Publications and source records attributed to A Muller.

At least 73 records · Page 4Linked to original sources
PubMed1997

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.

Adult↗
PubMed1997

Retinoic acid and N-(4-hydroxy-phenyl) retinamide suppress growth of esophageal squamous carcinoma cell lines.

Retinoids are vitamin A analogs that regulate growth and differentiation of squamous epithelial cells in vitro and in vivo. We examined the effects of retinoic acid (RA) and N-(4-hydroxy-phenyl) retinamide (HPR) on the growth properties of esophageal squamous carcinoma cell lines, and found that both RA and HPR induce morphological changes and inhibit growth. Immunofluorescence studies suggest alterations in keratins as a result of treatment with RA or HPR. In order to determine underlying molecular mechanisms, we found that RA or HPR did not induce arrest of cells in the G1 phase nor did treated cells undergo apoptosis. However, RA and HPR treatment did result in the downregulation of epidermal growth factor receptor (EGFR) which is known to bind key proproliferative ligands, such as epidermal growth factor and transforming growth factor alpha.

Antineoplastic Agents↗
PubMed1997

Free radicals in rabbit retina under ocular hyperpressure and functional consequences.

Pharmacological experiments have suggested that ocular ischemia, induced by high intraocular pressure in the rabbit, provokes an oxidative stress responsible for functional alteration of the retina. However, the nature of the oxidant chemical species and their mode of generation were not elucidated. The aim of the present studies was to characterize the oxygen-derived free radicals produced during and/or after the hyperpressure period. The technique used was based on electron spin resonance spin trapping analysis of the signals obtained in microdialysates of the retina perfused with the nitrone 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO). The oxidative stress was also evaluated under ischemia and reperfusion periods by measuring the level of ascorbate in the retina via electron spin resonance detection of the ascorbyl free radical-dimethyl sulfoxide (AFR-DMSO) complex. Electroretinograms were recorded to determine the functional consequences of high intraocular pressure and free radical generation. Our results show that superoxide dismutase-inhibitable DEPMPO/hydroxyl radical adducts were generated during the high intraocular pressure period and that the oxidative stress was not increased at reperfusion as assessed by spin trapping and AFR-DMSO measurements. Functional protection provided by free radical scavengers (superoxide dismutase+catalase, TEMPO nitroxide+catalase and dimethylthiourea) against high intraocular pressure-induced electroretinogram alteration confirmed these observations. In conclusion, these experiments demonstrate for the first time by direct measurement that oxygen-derived free radicals are produced by the retina during acute ischemia. This generation could be the explanation for electroretinogram alteration.

Animals↗
PubMed1997

New Aspects of Spin Diffusion and Cross Relaxation in Solid-State NMR

Theoretical models for motionally driven spin diffusion are compared and applied to spins S = (1/2) and S = 1. Their predictions are quantitatively corroborated by experiments on a single crystal of deuterated biphenyl. In this system, a molecular flip process drives spin diffusion and makes it strongly temperature dependent. In the second part, it is shown how spin diffusion of quadrupolar order degenerates into cross relaxation. A single crystal of partially deuterated durene provides a clear-cut example of cross relaxation in a dipolar coupled pair of spins S = 1. This observation explains why, in solids, the relaxation time of quadrupolar order, T 1Q , is often much shorter than T 1 .

Journal Article↗
PubMed1997

[Extra-digital glomus tumor: a rare cause of neuralgia].

We report three cases of extradigital glomus tumor mimicking neuralgia. The delay between the onset of symptoms and diagnosis ranged from 6 months to more than 10 years. None of the patients had spontaneous pain. Only palpation of a trigger-zone and movements elicited local pain and a sharp neuralgic pain (greater occipital nerve, medial antebrachial cutaneous nerve, obturator nerve). Albeit atypical, such pain features must suggest the diagnosis of glomus tumor, the confirmation of which is only obtained by histologic examination. Complete excision was fully effective in all three cases.

Arm↗
PubMed1997

Pituitary adenylate cyclase-activating polypeptide triggers dual transduction signaling in CATH.a cells and transcriptionally activates tyrosine hydroxylase and c-fos expression.

We used a catecholaminergic neuron-like cell line (CATH.a cells) as a model system to investigate the likelihood that pituitary adenylate cyclase-activating polypeptide (PACAP) may participate in the regulation of specific gene expression in catecholaminergic neurons. Analysis by reverse transcriptase-PCR amplification revealed the presence in these cells of type I PACAP receptors, with a short isoform, together with a heavier so-called Hop splice variant. PACAP38 and PACAP27 enhanced, in a dose-dependent manner, both cyclic AMP formation and phosphoinositide breakdown, with EC50 values of, respectively, 0.6 x 10(-10) and 2 x 10(-9) M. These peptides, in addition, also elevated [Ca2+]i by mobilizing intracellular calcium pools. Vasoactive intestinal peptide (VIP) was approximately 1,000-fold less potent in stimulating cyclic AMP (with EC50 = 2 x 10(-7) M) and failed to change the turnover of phosphoinositides and to alter [Ca2+]i. Both forms of PACAP, as well as forskolin, stimulated transcriptional induction of tyrosine hydroxylase (TH) and c-fos promoters fused to a chloramphenicol acetyltransferase (CAT) reporter gene in transiently transfected cells (p < 0.01 vs. controls). Induction of CAT activity linked to both TH and c-fos promoters was obliterated upon coexpression of a dominant inhibitory mutant (Mt-RAB) of cyclic AMP-dependent protein kinase. We conclude that CATH.a cells do express functional PACAP type I receptors, the activation of which impinges on TH and c-fos transcription according to a process that is primarily dependent on the cyclic AMP-PKA pathway.

Adenylyl Cyclases↗
PubMed1997

Modulation of SERCA2 expression by thyroid hormone and norepinephrine in cardiocytes: role of contractility.

Decreased expression of the cardiac slow-twitch sarcoplasmic reticulum Ca2+-adenosinetriphosphatase (SERCA2), a major determinant of Ca2+ homeostasis, contributes to the abnormal intracellular Ca2+ handling in the failing heart. We investigated the contractility dependence of the effects of norepinephrine (NE) and thyroid hormone (T3) on SERCA2 expression in cultured neonatal heart cells under serum-free conditions. NE and T3 are associated with pathological and physiological forms of hypertrophy, respectively, whereas both hormones increase contractility. In contracting cultures, T3 increased SERCA2 protein and mRNA levels by 35 and 110%, respectively. The same stimulatory effects of T3 on SERCA2 expression were found in contraction-arrested cells. In contracting cultures, NE induced a decrease of SERCA2 protein and mRNA levels by 40 and 60%, respectively. In contrast, SERCA2 protein and mRNA levels were not decreased by NE in contraction-arrested cells, indicating that contractility is a prerequisite for the negative influence of NE on SERCA2 expression. Electrical stimulation at a fixed frequency in the presence and absence of NE demonstrated that the NE-induced increase in contraction frequency is unlikely to account for the decreased SERCA2 expression induced by NE. The results suggest that the effect of contractility on SERCA2 expression depends on the signal transduction pathways that are activated by NE and T3.

Animals↗
PubMed1997

Indications for combined orthodontic and surgical (orthognathic) treatments of dentofacial deformities in cleft lip and palate patients and their impact on velopharyngeal function.

Malformations, deformations and abnormal intermaxillary relationships varying in severity can be found in cleft lip and/or palate children. Such multiple deformities have an influence on speech resonance and articulation, as well as on masticatory, auditive and respiratory functions. Therefore, a multidisciplinary team should monitor these patients from birth on to adulthood. This article describes our treatment protocol, discusses the limitations of dental orthopedic action and the indications for orthognathic surgery. Timing and techniques of different surgical interventions are presented and the impact of these procedures on velopharyngeal function is evaluated.

Cephalometry↗
PubMed1997

Synthesis and biochemical/pharmacological profile of the novel leukotriene B4 receptor antagonist sodium (1S*, 3S*)-1-hydroxy-3-[(3 R*S*,E)-3-hydroxy-7-phenyl-1-hepten-1-yl]-1-cyclohexane acetate.

A novel series of leukotriene B4 (LTB4) antagonists is reported. These compounds present a cyclohexane ring in their chemical structure, which mimics the three conjugated double bonds of LTB4. The biochemical/pharmacological profile of the leader compound, PH-163 (sodium (1S*,3S*)-1-hydroxy-3-[(3R*S,E)-3-hydroxy-7-phenyl-1-hepten-1-yl]- 1 -cyclohexane acetate, CAS 163251-41-0) is described. This compound competes with [3H]LTB4 binding to its receptor in human neutrophils and guinea pig lung membranes with IC50's of 0.8 mumol/l and 0.2 mumol/l, respectively, i.e. relative binding affinities of 1% as compared to LTB4. PH-163 does not elicit any agonist activity, but inhibits leucocyte chemotaxis induced by LTB4 (pKB = 6.57) and lung parenchymal strip contraction (IC50 = 0.1 mumol/l). In conclusion, PH-163 or derivatives could be useful in the treatment of inflammatory diseases where LTB4 seems to be involved.

Animals↗
PubMed1996

Expression of MyoD in cultured primary myotubes is dependent on contractile activity: correlation with phenotype-specific expression of a sarcoplasmic reticulum Ca(2+)-ATPase isoform.

Myogenic determination factors (MDF) have been implicated in the establishment and maintenance of the fast or slow phenotype in skeletal muscle, with MyoD favoring the fast and myogenin favoring the slow phenotype. Accordingly, contractility-induced changes in muscle phenotype should be accompanied by a change in the MyoD/myogenin ratio. Some reports show such changes, but limitations inherent to in vivo studies complicate interpretation of these data. Here we tested whether a relationship can be found between contractility, MDF expression, and the expression of phenotype-specific muscle proteins in a simple in vitro system of cultured primary myotubes. We show that contractions reduce the MyoD/myogenin ratio by specifically repressing MyoD mRNA expression. This is accompanied by a selective repression at a pretranslational level of the expression of fast-type sarcoplasmic reticulum Ca(2+)-ATPase. These in vitro results support a phenotype-determining role of MDFs as a function of contractile activity and show that cultured myotubes can be a useful model for the analysis of the molecular mechanism of such regulation of muscle phenotype.

Animals↗
PubMed1996

Characterisation of complete responders to combination chemotherapy for advanced breast cancer: a retrospective EORTC Breast Group study.

This retrospective study was undertaken to characterise the natural history of women achieving complete response (CR) following standard dose combination chemotherapy for metastatic breast cancer (MBC), and to analyse the significance of various patient, disease and treatment characteristics in determining survival and time to disease progression. 75 patients achieving a CR following standard dose combination chemotherapy or combined chemoendocrine therapy for MBC have been studied. At a median follow-up of 6 years, 28% of patients are still alive, with 18 of 21 patients showing no evidence of disease. 15 (20%) patients, with median follow-up of 61 months from start of chemotherapy, have never experienced relapse. Median overall survival is 32.5 months. Multivariate analysis for survival identified inclusion of anthracyclines and WHO performance status as significant predictors of good long-term outcome. Concomitant hormonotherapy almost reached statistical significance in our multivariate analysis. Neither dominant site of disease nor disease-free interval were significant determinants of complete remission. With conventional dose combination chemotherapy, approximately 20% of women with MBC who have achieved a clinical CR have been shown to be expected to remain alive and free of disease at 5 years. Inclusion of an anthracycline appears to be an important determinant of durability of CR and patient survival.

Adult↗
PubMed1996

[Cancer pain: beneficial effect of ketamine addition to spinal administration of morphine-clonidine-lidocaine mixture].

OBJECTIVE: To assess the benefit of ketamine addition to a morphine-clonidine-lidocaine mixture administered continuously by the intrathecal route for the treatment of cancer pain. STUDY DESIGN: Case series analysis. PATIENTS AND METHOD: Four patients experiencing cancer pain with nociceptive and neuropathic components were treated with a continuous intrathecal administration of a mixture of ketamine (10 mg)-morphine (1-20 mg)-clonidine (30 micrograms)-lidocaine (20 mg) in 12 mL of normal saline, injected daily with an infusor (Baxter) pump. This treatment, associated with oral administration of sustained release morphine (SRM), was extended over 35 to 58 days, until the death of the patients. RESULTS: Either the secondary addition of ketamine to the morphine-clonidine-lidocaine mixture after the 40th and 15th days of treatment in patients no 1 and 2 respectively, because of a loss of efficiency of the mixture, or the immediate administration of the association of the four agents in patients no 3 and 4 provided efficient analgesia, unchanged over time, without significant adverse effects and allowed a decrease of the SRM doses. CONCLUSION: Ketamine by intrathecal route potentiates analgesia obtained with morphine-clonidine and lidocaine, while impeding the development of a tolerance vis-à-vis the former.

Aged↗
PubMed1996

[Treatment of unstable fractures of the distal extremity of the radius by Hoffmann's external fixation. Report of 68 cases].

Sixty-eight fractures of the distal extremity of the radius, mostly unstable, homogeneously treated by Hoffmann's radio-metacarpal external fixation, were reviewed in terms of functional, objective and radiological criteria. Mean follow-up was 4 years, with a range of 6 months to 10 years. Overall, this treatment achieved 56% of satisfactory results, 26% moderate results and 18% poor results. Open and comminuted fractures give the worst overall results, mostly in terms of functional parameters. From this study, it is clear that external fixation is effective for the treatment of unstable fractures, as it provides good restitution of anatomical integrity of the radius, ensures better stabilization and allows immediate physiotherapy, leading to restoration of a good range of movement. Moreover, compliance with certain technical aspects such as minimal distraction, limits the disadvantages of this technique.

Adolescent↗
PubMed1996

Differential effect of ischemia/reperfusion on pigmented and albino rabbit retina.

The purpose of the study was to compare the retinal sensitivity of pigmented and albino rabbits to ischemia/reperfusion-induced electroretinogram (ERG) alterations and optic nerve morphological changes. High intraocular pressure (HIOP) was induced by applying a suction-cup on the eye and a depression with an ophthalmodynamometer. HIOP was maintained for lengths of time (30-75 min). Flash ERGs were recorded in dark-adapted animals for ischemia and 2 h reperfusion periods. Two weeks later, histological examination of the retinas and optic nerves was done. Albino rabbits submitted to 45 min HIOP failed to recover b-wave ERG amplitude after 2 h reperfusion, whereas pigmented animals presented a total ERG recovery even if ischemia was maintained as long as 75 min. Intravenous treatment of albino animals with Lazaroid U74389G led to significant ERG recovery at reperfusion. Histological studies show that pigmented rabbit optic nerves suffered less damage than the albino ones. These results emphasize the role of the pigmentary status of the animals in the retinal sensitivity to ischemia. Neuroprotection afforded by the antioxidant U74389G suggests that ocular pigments could also protect the retinal functional integrity through a free radical scavenging activity.

Albinism, Ocular↗