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M Tomas

Publications and source records attributed to M Tomas.

15 recordsLinked to original sources
PubMed2003

RhoA and lysophosphatidic acid are involved in the actin cytoskeleton reorganization of astrocytes exposed to ethanol.

Astroglial cells play an important role in maintaining neuronal function in the adult and in the developing nervous system. Ethanol exposure induces profound alterations in the astrogliogenesis process, affecting important cell functions, including intracellular protein trafficking. Because the actin cytoskeleton plays a crucial role in intracellular protein transport, the aim of the present study was to analyze the effects of ethanol on actin cytoskeleton organization and the involvement of the RhoA signaling pathway in these effects. We show that RhoA and lysophosphatidic acid (LPA), an upstream activator of RhoA, stimulate the formation of stress fibers and focal adhesion in cortical astrocytes in primary culture. Exposure of cultured astrocytes to different concentrations of ethanol profoundly disorganizes the actin cytoskeleton, leading to the formation of actin rings at the cell periphery and decreasing the content of focal adhesion proteins. Furthermore, LPA treatment or RhoA transfection revert the ethanol-induced actin alterations in astrocytes, whereas transfection with an inactive mutant of RhoA is unable to revert the actin ring organization. In addition, inhibition of endogenous RhoA by C3 exoenzyme effectively blocks ethanol-induced actin ring formation. These results suggest that the effects of alcohol on actin cytoskeleton organization are mediated by the RhoA signaling pathway. Disruptions in actin organization may impair important astrocyte functions, participating in ethanol-induced astroglial and brain damage during development.

Actins↗
PubMed2001

Neural cell adhesion molecule is endocytosed via a clathrin-dependent pathway.

Neural cell adhesion molecule (NCAM) constitutes a group of cell surface glycoproteins that regulate cell-cell interactions in the developing and adult brain. Endocytosis is a mechanism which dynamically controls the amount of cell surface NCAM expression and may involve the rapid changes occurring in NCAM expression under certain physiological or pathological conditions. However, the endocytic pathway of NCAM is presently unknown. Using astrocytes in culture and immunofluorescence we show that NCAM is internalized and that the immunolabelling presents a high degree of colocalization with clathrin, alpha-adaptin and transferrin, suggesting that NCAM is endocytosed by a clathrin-dependent pathway. Potassium depletion which disrupts clathrin-mediated endocytosis, inhibited internalization of NCAM. Electron microscopy and immunogold studies also demonstrate that the surface of clathrin-coated vesicles are also immunolabelled for both alpha-adaptin and PSA-NCAM, the highly sialylated isoform of NCAM. Furthermore, immunoprecipation studies demonstrate that NCAM is associated with both clathrin and alpha-adaptin, a component of adaptor complex AP-2, in brain, neurons and astrocytes. These findings indicate that NCAM is mainly endocytosed via clathrin-coated vesicles, suggesting a possible mechanism that may contribute to the rapid changes in NCAM expression at the cell surface.

Adaptor Protein Complex alpha Subunits↗
PubMed2000

Posttranslational modification of the glycosylation inhibiting factor (GIF) gene product generates bioactive GIF.

Glycosylation inhibiting factor (GIF) and macrophage migration inhibitory factor (MIF) share an identical structure gene. Here we unravel two steps of posttranslational modifications in GIF/MIF molecules in human suppressor T (Ts) cell hybridomas. Peptide mapping and MS analysis of the affinity-purified GIF from the Ts cells revealed that one modification is cysteinylation at Cys-60, and the other is phosphorylation at Ser-91. Cysteinylated GIF, but not the wild-type GIF/MIF, possessed immunosuppressive effects on the in vitro IgE antibody response and had high affinity for GIF receptors on the T helper hybridoma cells. In vitro treatment of wild-type recombinant human GIF/MIF with cystine resulted in preferential cysteinylation of Cys-60 in the molecules. The cysteinylated recombinant human GIF and the Ts hybridoma-derived cysteinylated GIF were comparable both in the affinity for the receptors and in the immunosuppressive activity. Polyclonal antibodies specific for a stretch of the amino acid sequence in alpha2-helix of GIF bound bioactive cysteinylated GIF but failed to bind wild-type GIF/MIF. These results strongly suggest that cysteinylation of Cys-60 and consequent conformational changes in the GIF/MIF molecules are responsible for the generation of GIF bioactivity.

Amino Acid Sequence↗
PubMed2000

Long-term effects of clinical outcome with low and high dose in the Captopril in Heart Insufficient Patients Study (CHIPS).

BACKGROUND: Although angiotensin-converting enzyme inhibitors are recommended as first line therapy in patients with chronic heart failure, the target doses proven to be effective in major morbidity and mortality trials (e.g. captopril 50 mg b.i.d), are generally not used in daily practice in Belgium. AIM: The objective of this study (CHIPS, Captopril in Heart Insufficient Patients Study) was to compare the long-term effects of a low dose (25 mg b.i.d.) and a high dose (50 mg b.i.d.) of captopril in mild to moderate heart failure. After a titration period of at least 10 days, patients who tolerated 50 mg b.i.d., were randomly assigned to receive either the low dose or the high dose of captopril and followed up to 2 years. RESULTS: 298 patients were included and were followed up for a mean of 12 months. Progression in heart failure seems to be favourably influenced by therapy with high dose in comparison to low dose; a relative difference of 29% in the rates of heart failure worsening was observed between the two doses, 31.5% and 22.4% for low and high dose (p = 0.088), respectively. Treatment with high dose showed also a trend to benefit as compared to low dose in reducing the number of hospitalizations for all causes from 22.4 to 14.5% (p = 0.1) and for congestive heart failure from 14.7 to 7.2% (p = 0.06); moreover, the incidence of fatal and nonfatal cardiac events showed a trend in favour of the high dose of 22% (p = 0.142). The total number of adverse events was comparable for both doses, but dizziness and hypotension were a little more frequently reported in the high-dose group. Serum creatinine values showed no significant changes either in the low-dose or in the high-dose group. CONCLUSION: In the CHIPS-study, in comparison to a low dose, therapy with a high dose of captopril tends to improve the long-term clinical outcome of patients with mild to moderate heart failure without significantly more toxicity.

Adolescent↗
PubMed1996

[Cardiological fitness examination of the athlete and prevention of sudden death].

Sudden death happening to an athlete is a frightening tragedy. Epidemiological data are quite controversial but sudden death occurring during sporting activity is probably not a rare occurrence. Beside drug abuse and accidental causes, cardiovascular abnormalities represent the principal origin of sudden death. Cardiomyopathy in young athletes and coronary artery disease in older athletes are the underlying pathologic substrates for most incidences. A certain proportion of sudden death in apparently healthy athletes was preceded by symptoms of exercise intolerance; pre participation evaluation directed to detect the cardiovascular abnormalities is probably of more value to reduce sudden cardiac death in athletes than detailed and routine sophisticated investigations.

Adolescent↗
PubMed1994

Belgian multicenter clinical study of alfuzosin, a selective alpha 1-blocker, in the treatment of benign prostatic hyperplasia. The Alfuzosin Belgian Group.

The effects of alfuzosin, a potent alpha 1-blocker, were assessed in patients with benign prostatic hyperplasia, in a double-blind, multicenter, placebo-controlled, cross-over study. Treatment duration was 4 weeks for both alfuzosin and placebo. A significant beneficial effect of alfuzosin (7.5 to 10 mg a day) on clinical subjective and objective criteria was observed as compared to placebo: total Boyarsky score decreased by 1.63 points, peak urinary flow improved by 2.03 ml/sec. Alfuzosin was well tolerated, the observed adverse events corresponded to the pharmacological properties of this compound, and resolved rapidly.

Adrenergic alpha-Antagonists↗
PubMed1994

Non-fistulous idiopathic coronary artery aneurysm. Report of three cases and literature review.

Non-fistulous idiopathic aneurysm of coronary arteries is a rare anomaly, often localized on the left coronary trunk and diagnosed in young patients following myocardial ischemia. Diagnosis before death is only possible since advent of selective coronary angiography. Idiopathic etiology can be inferred when the aneurysm is found in the absence of atherosclerosis and calcification of other arteries and if there is an absence of risk factors for atherosclerosis. Inflammatory etiology is excluded by a negative clinical history and lack of histologic inflammatory features. However, cumulating observations suggest that angeitis or other acquired process cannot definitely be disapproved. Advances in coronary artery surgery have permitted resection of aneurysms and grafting of involved coronary artery since the early seventies. Three cases of non-fistulous idiopathic aneurysms of coronary arteries are presented. The literature has been reviewed and the clinical, anatomic, angiographic findings and management are discussed.

Adult↗
PubMed1990

Phase II trial of carboplatin and tegafur (Ftorafur) as induction therapy in squamous-cell carcinoma of the head and neck.

Cisplatin and 5-fluorouracil by continuous infusion combination produces a high response rate in squamous-cell carcinoma of the head and neck (SCCHN). Carboplatin (CBDCA) is a cisplatin analogue with lower emetic potential and nephrotoxicity, although the myelosuppression potential is higher. Tegafur (ftorafur, FT) is an analogue of 5-fluorouracil. It is absorbed well in its oral form and has moderate gastrointestinal and hematologic toxicity. This clinical trial tested the association of CBDCA i.v. plus FT p.o. in patients with SCCHN who had not been previously treated. Twenty-one patients were evaluable for response; the overall response was 62% (33% complete response, 29% partial response). Toxicity was moderate in most of the patients, although there was a treatment-related death.

Administration, Oral↗
PubMed1990

Phase II trial of cisplatin and tegafur (Ftorafur) as initial therapy in squamous-cell carcinoma of the head and neck.

Cisplatin and 5-fluorouracil infusion combination produces a high response rate in squamous-cell carcinoma of the head and neck. Tegafur (Ftorafur) is an analog of 5-fluorouracil, and its oral form is well absorbed. This agent has a moderate toxicity. We report a study to determine the efficacy of the cisplatin (100 mg/m2, day 1) and tegafur (1,000 mg/m2 daily for 21 days) combination. Thirty-nine patients entered the study; 36 were evaluable for response. Overall response was 94%, with a 22% complete response. Toxicity was moderate. We conclude that the cisplatin and tegafur combination is active in untreated patients with head and neck cancer.

Administration, Oral↗