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Biomedical subjects

G Michel

Publications and source records attributed to G Michel.

At least 343 records · Page 19Linked to original sources

In vitro studies with the stabilized epoprostenol analogue taprostene. Effect on platelets and erythrocytes.

In vitro, the oxacyclic epoprostenol (prostacyclin) analogue taprostene like the native epoprostenol inhibited platelet aggregation and adhesion and induced deaggregation. Antiaggregatory action of taprostene was demonstrated towards arachidonic acid-, ADP-, thrombin- and norepinephrine-induced aggregations of human platelet rich plasma with IC50 values between 17 and 34 nmol/l. ADP-induced aggregations of human, dog or rabbit platelets were inhibited with an equivalent efficacy. Under the present conditions taprostene was about 3fold less active than epoprostenol. The deaggregatory effect, measured in arachidonic acid-induced aggregates of human PRP, could be detected only in concentrations from 1 mumol/l taprostene. The adhesion-inhibiting effect towards glass beads, measured in whole blood, appeared at comparable high concentrations (IC50 value: 2.4 mumol/l) and likewise the antihaemolytic effect on rat erythrocytes, which was exerted with a threshold concentration of 10 mumol/l. Heparin in a concentration range of 0.1-1000 micrograms/ml increased thrombocyte adhesion and this effect was prevented by 1 mumol/l taprostene.

Alprostadil↗

In vivo studies with the stabilized epoprostenol analogue taprostene. Effects on platelet functions and blood clotting.

Like the native epoprostenol (prostacyclin, PGI2), the oxacyclic epoprostenol analogue taprostene affects platelet functions. In the rat taprostene inhibited in vivo induced ADP aggregation after i.v. bolus injection, i.v. infusion, s.c. and p.o. application with ED50 values of 4.6 micrograms/kg, 0.36 microgram/kg/min, 190 micrograms/kg and approximately 760 micrograms/kg, respectively. In vivo induced collagen aggregation was inhibited with an ED50 value of 17.1 micrograms/kg i.v. Referring to both bolus injection and i.v. infusion, taprostene was about 3 times less active than the native prostacyclin, but the antiaggregatory effect of taprostene was longer lasting. 5,6-Dihydroepoprostenol inhibited ADP-induced aggregation with an ED50 value of 3 micrograms/kg/min, being 10 fold less active than taprostene. Whereas epoprostenol induced a rebound effect by increasing in vivo aggregation after the end of infusion, no such effect could be seen after taprostene. In the mouse s.c. and p.o. application of taprostene inhibited aggregation with the same efficacy as in the rat. Intra-arterial infusion of taprostene into the rabbit inhibited ADP-induced aggregation ex vivo with an ED50 value of 0.49 micrograms/kg/min. An increased bleeding time was observed in rats in doses of 2.15 micrograms/kg i.v. and higher, corresponding to the antiaggregatory dose range of taprostene. Administered alone, taprostene did not prolong the clotting time in rats. However, in heparinized rats, the heparin-induced prolongation of clotting time was further increased by taprostene with a threshold dose of 21.5 micrograms/kg (= heparin sparing effect).

Adenosine Diphosphate↗

[Imaging of cancer of the uterine cervix].

Recently, magnetic resonance imaging (MRI) and transrectal or transvaginal ultrasound (TRUS, TVUS) had an important place in imaging techniques of cervical carcinomas and raise the question of modifying the imaging strategies. For the diagnosis of primitive tumor, those techniques cannot take the place of clinical examination and gross examination. In the assessment of parametrial involvement, TRUS which has better accuracy than clinical examination, and MRI which is considered as the most accurate technique, have an important role to play. In the follow-up and the detection of recurrences, MRI is actually considered as the best imaging technique. The authors, according to recent data in literature and their own experience, present basic concepts of imaging strategies for staging and follow-up of cervical carcinomas.

Evaluation Studies as Topic↗

[An epidemiological study of hypercholesterolemia in the Grand Duchy of Luxembourg].

Epidemiology of hypercholesterolemia in the Grand Duchy of Luxembourg was studied by the mean of a questionnaire filled out by 17 physicians. 113 patients (50 men and 63 women) were recruited. 43 patients had an isolated hypercholesterolemia (type IIa) and 63 patients had a type IIb. Analysis of associated risk factors showed large variations (13.2% of patients had diabetes, 61% were sedentary). However, 33.5% of patients had at least one associated risk factor. The nutritional assessment showed the well-known dietary errors. A two month's treatment with ciprofibrate has shown a 20% decrease of total cholesterol and a 32% decrease of triglycerides. No serious adverse events were reported.

Adult↗

Allogeneic or autologous bone marrow transplantation for acute lymphoblastic leukemia in first complete remission.

Forty-seven patients with high risk acute lymphoblastic leukemia (ALL) received an allogeneic (allo) or autologous (auto) bone marrow transplant (BMT). Patients in both groups were comparable in terms of age, initial presentation of ALL and induction chemotherapy. Allo patients were transplanted earlier (median 3 months after CR) than auto patients (median 6.5 months after CR). Auto patients received more consolidation chemotherapy before BMT. All patients received total body irradiation 2.2 Gy/day x 5 days after cyclophosphamide 60 mg/kg x 2 (18 allo and five auto) or melphalan 140 mg/m2 (seven allo and 17 auto). Prevention of graft-versus-host disease (GVHD) was by conventional immunosuppression in 17 patients and T cell depletion in eight. Seven patients (28%) developed moderate to severe acute GVHD. Auto marrow was treated in vitro in each case. Seven patients died in CR from BMT complications (five allo and two auto). The probability of relapse was 9% for patients receiving allo BMT and 52% for patients receiving auto BMT (p less than 0.01). The disease-free survival was 71% for allo BMT and 40% for auto BMT (p = NS). Early BMT is an effective form of consolidation for high risk patients with ALL in first CR. An allogeneic anti-leukemia effect was demonstrated in this study.

Adolescent↗

[Anatomo-pathologic ovarian cancers].

Ovarian cancers constitute a group of tumours characterized by a variety of histological patterns. The classification used is that of the W.H.O. Common épithelial account for two-thirds of all ovarian cancers. In this group, tumours of borderline malignancy should be distinguished from adenocarcinomas. Since these lesions are associated with an unusually good prognosis, it is of major importance to rule out an infiltration of the ovarian stroma. Extra-ovarian spread of borderline tumours probably results from a multifocal process which is not associated with the poor prognosis of metastatic involvement. Tumours of the mesenchyma and sex cords are less frequent, as are germ cell tumours. For the latter, preoperative assays of serum markers can be of help in the diagnosis and management of the cases.

Adenocarcinoma↗

Treatment of high-risk gestational trophoblastic disease with chemotherapy combinations containing cisplatin and etoposide.

The authors have treated 22 patients with high-risk gestational trophoblastic disease (GTD) by cisplatin-etoposide-containing combinations. Sixteen patients were treated with dactinomycin, platinum, and etoposide combination (APE regimen) and six patients had platinum and etoposide combination (PE regimen). Fourteen patients were treated for resistant or relapsing GTD after first-line therapy, and eight patients initially. All 22 patients were high risk according to the World Health Organization prognostic score values. Sustained complete remission was achieved in 19 patients (86%). All eight patients who received treatment as initial therapy were cured (100%) whereas only 11 patients were cured among the 14 patients who failed prior chemotherapy (78%). Hematologic and renal toxicities were limited and no treatment-related deaths occurred in this group of patients. Cisplatin and etoposide could be more widely used in chemotherapeutic combinations for high-risk gestational trophoblastic disease.

Adult↗

Structure and activity of proteins from pathogenic fungi Phytophthora eliciting necrosis and acquired resistance in tobacco.

The phytopathogenic fungi Phytophthora cryptogea and Phytophthora capsici cause systemic leaf necrosis on their non-host tobacco; in culture they release proteins, called cryptogein and capsicein, which elicit similar necrosis. In addition, both proteins protect tobacco against invasion by the pathogen Phytophthora nicotianac, the agent of the tobacco black shank, that is unable to produce such an elicitor. Cryptogein causes visible leaf necrosis starting at about 1 microgram/plant, whereas 50-fold as much capsicein is required for the same reaction. Capsicein induces protection even in near absence of leaf necrosis. The activities of both elicitors are eliminated upon pronase digestion. They are proteins of similar Mr (respectively 10,323 and 10,155) and their complete amino acid sequences were determined. They consist of 98 residues, with some internal repetitions of hexapeptides and heptapeptides. 85% identity was observed between both sequences: only two short terminal regions are heterologous, while the central core is entirely conserved. Secondary structure predictions, hydropathy and flexibility profiles differ only around position 15 and at the C-terminus; these modifications could play a role in the modulation of their biological activities. After a search of the sequence data bases, they appear to be novel proteins.

Algal Proteins↗

Particular processing of pro-opiomelanocortin in Xenopus laevis intermediate pituitary. Sequencing of alpha- and beta-melanocyte-stimulating hormones.

alpha- and beta-melanocyte-stimulating hormones (alpha-MSH and beta-MSH) have been isolated from Xenopus laevis neurointermediate pituitary and microsequenced. Intracellular alpha-MSH is not N-acetylated after proteolytic processing of pro-opiomelanocortin in contrast to mammalian alpha-MSHs. There is a high preservation of the melanotropic amino acid sequence common to all MSHs although in Xenopus beta-MSH a histidine residue replaces the glutamic acid residue found in position 8 of mammalian beta-MSHs.

Acetylation↗

Fatty acid and beta-amino acid syntheses in strains of Bacillus subtilis producing iturinic antibiotics.

Iturinic antibiotics, produced by different strains of Bacillus subtilis, contain long-chain beta-amino acids (beta-AA). The regulation of the synthesis of fatty acids (FA) and beta-AA was studied by modifying the culture medium. Addition of possible precursors, branched-chain alpha-amino acids, to the medium affected the FA and beta-AA compositions. According to this, the B. subtilis strains can be divided into two groups. The first contains the producers of mycosubtilin and bacillomycin F which synthesize a high level of iso C16 chains; the second contains the producers of bacillomycin D, bacillomycin L and iturin which synthesize a high level of n carbon chains. The incorporation of radioactive sodium acetate into FA and beta-AA showed rapid FA synthesis followed by a second synthetic step. Although the detailed mechanism has not yet been elucidated, this second step, corresponding to the beta-AA synthesis, seemed to be a key step in determining the alkyl chain of beta-AA.

Amino Acids↗

Whole abdominal irradiation following chemotherapy in patients with minimal residual disease after second look surgery in ovarian carcinoma.

From January 1981 through December 1985, 65 patients with epithelial carcinoma of the ovary were treated with the following protocol: surgery, combination chemotherapy, second-look surgery documenting tumor less than or equal to 2 cm, and whole abdominal irradiation. Chemotherapy consisted of a combination of cyclophosphamide, adriamycin, and cisplatinum in 89% of the patients. The median number of cycles was eleven. Second-look surgery documented no residual tumor in 23 patients, microscopic disease in three patients, and macroscopic disease less than or equal to 2 cm in 39 patients. Whole abdominal irradiation was given with an open field technique up to 20 Gy without renal or hepatic shield. A pelvic boost of 15-30 Gy was subsequently added in 17 patients with macroscopic disease in the pelvis at the time of second-look surgery. Fifteen patients received complementary chemotherapy mostly hexamethylmelamine. All but two patients completed whole abdominal irradiation: one refused further radiotherapy after 3 Gy and one developed disease progression with bowel obstruction after 1 Gy. The median follow-up was 69 months. The 3-year and 6-year no evidence of disease survival rates were 60% (95% CI: 48-71) and 33% (95% CI: 21-46), respectively. The 3-year and 6-year recurrence rates were 33% (95% CI: 22-45) and 54% (95% CI: 40-67), respectively. The 3-year and 6-year metastasis rates were 22% (95% CI: 13-34) and 43% (95% CI: 30-58), respectively. A multivariate analysis showed that residual disease after second-look surgery was the only significant prognostic factor with a relative risk of death or local or distant failure of 4.2 (95% CI: 1.9-9.5, p less than 10(-4)). Two patients developed mean-term gastrointestinal complications (small bowel obstructions requiring surgery). Survival remains poor with high level of failure even with aggressive multimodal treatment.

Adult↗

Hydrins, hydroosmotic neurohypophysial peptides: osmoregulatory adaptation in amphibians through vasotocin precursor processing.

From neurointermediate pituitary glands of Xenopus laevis and Rana esculenta, previously unreported peptides termed hydrins, active on water permeability of frog urinary bladder and frog skin (Brunn or "water-balance" effect), have been isolated and sequenced. These peptides seem to be derived from the pro-vasotocin-neurophysin precursor. Hydrin 1, found in Xenopus, has been identified as vasotocin C-terminally extended with the Gly-Lys-Arg sequence; hydrin 2, found in Rana, has been identified as vasotocin C-terminally extended with glycine. Hydrin 2 has been detected in several Ranidae (R. esculenta, Rana temporaria, Rana pipiens) and Bufonidae (Bufo bufo, Bufo ictericus) and appears to have a large distribution in terrestrial or semiaquatic anurans. Hydrins, in contrast to vasotocin, are not active on rat uterus or rat blood pressure. They are absent from other vasotocin-bearers such as birds and could be involved specifically in water-electrolyte regulation of amphibians.

Acclimatization↗

Liquid culture and cryopreservation of marrow cells of leukaemic patients prior to autologous bone marrow transplantation.

The feasibility of marrow cryopreservation for autologous bone marrow transplantation after 7 d in liquid culture was assessed in 10 leukaemic patients. A median of 0.17 x 10(8) nucleated cells/kg and 0.4 x 10(4) CFU-GM/kg could be collected after the complete procedure, with overall a consistent cell loss. Long-term cultures could be established from these cultured and frozen marrows, showing the persistance of precursors of haematopoietic and stromal cells. In vitro a significant decrease in the proportion of leukaemic cells could be observed in only one out of nine evaluable patients. This patient, with refractory AML, received an autologous transplant and is alive in continuous complete remission after 600 d. One patient with chronic myeloid leukaemia in acute phase underwent an autologous BMT with a marrow collected and cultured while in chronic phase and failed to engraft. These results show the feasibility of cryopreservation of cultured marrow cells for autologous bone marrow transplantation. The procedure is associated with poor cell recovery and must be improved to have a more general clinical application. This technology may have a major application with the emergence of modulators of growth and differentiation of haematopoietic cell lines.

Adolescent↗

Study of the metabolism of flucytosine in Aspergillus species by 19F nuclear magnetic resonance spectroscopy.

The metabolism of flucytosine (5FC) in two Aspergillus species (Aspergillus fumigatus and A. niger) was investigated by 19F nuclear magnetic resonance spectroscopy. In intact mycelia, 5FC was found to be deaminated to 5-fluorouracil and then transformed into fluoronucleotides; the catabolite alpha-fluoro-beta-alanine was also detected in A. fumigatus. Neither 5-fluoroorotic acid nor 5-fluoro-2'-deoxyuridine-5'-monophosphate was detected in perchloric acid extracts after any incubation with 5FC. 5FC, 5-fluorouracil, and the classical fluoronucleotides 5-fluorouridine-5'-mono-, di-, and triphosphates were identified in the acid-soluble pool. Two hydrolysis products of 5-fluorouracil incorporated into RNA, 5-fluorouridine-2'-monophosphate and 5-fluorouridine-3'-monophosphate, were found in the acid-insoluble pool. No significant differences in the metabolic transformation of 5FC were noted in the two species of Aspergillus. The main pathway of 5FC metabolism in the two species of Aspergillus studied is thus the biotransformation into ribofluoronucleotides and the subsequent incorporation of 5-fluorouridine-5'-triphosphate into RNA.

Alkaline Phosphatase↗

Action of mycosubtilin on erythrocytes and artificial membranes.

Mycosubtilin has a strong lytic action upon erythrocytes. The haemolytic effect of the antibiotic is inhibited by free cholesterol as well as cholesterol included in liposomes of phosphatidylcholine-cholesterol. The antibiotic binding on artificial membranes was studied with radioactive bilayer vesicles of dipalmitoylphosphatidylcholine (DPPC), and DPPC-cholesterol:mycosubtilin destroyed both kinds of vesicles. The inhibition of the haemolytic effect of mycosubtilin by liposomes is a result of an interaction which diminishes the concentration of free cholesterol.

1,2-Dipalmitoylphosphatidylcholine↗

[The occurrence and behavior of the goblet cells in the intestinal canal of swine].

After a short survey of the literature the form, distribution and histochemistry of the goblet cells in the duodenum, jejunum and colon were investigated on pigs of different age. There are much goblet cells in the colon than in the parts of the intestine. The goblet cells occur in a great number in the crypts of Lieberkühn, but their evidence is relatively rare in the superficial epithelium. Histochemically the goblet cells are alcian blue- and PAS-positive, where by the alcian blue reaction is dominant, therefore the secret contains more acid than neutral glycoproteins.

Animals↗