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Biomedical subjects

P Devos

Publications and source records attributed to P Devos.

At least 55 records · Page 3Linked to original sources

Potentiating effect of metformin on insulin-induced glucose uptake and glycogen metabolism with Xenopus oocytes.

Xenopus laevis oocytes were chosen as the in vitro model for this study with the aim of reconsidering metformin action on the main insulin-responsive glucose pathway. Metformin alone, when present at a therapeutic dose (20 micromol/l) in the incubation medium, did not alter the basal rate of glucose uptake or of glycogen synthesis as measured by [U-14C] D-glucose incorporation. The drug had no effect on the main rate-limiting enzyme implicated in this pathway, i.e. glycogen synthase. In contrast, when combined with 2 micromol/l insulin, metformin led to a specific rise of both free and stored glucose, by 42.4 and 102.3% respectively. Moreover, a short-term preincubation of mature oocytes with metformin, but in the absence of glucose, enhanced significantly the amount of synthase a when stimulated by 50 nmol/l insulin (basal 17.4 +/- 5.7%, metformin 21.3 +/- 4.1%, insulin 31.2 +/- 4.6%, metformin together with insulin 62.7 +/- 4.2%, p < 0.005, n = 5). Interestingly, the microinjection of this biguanide, at a final concentration of 20 nmol/l, allowed a similar biochemical response. These data clearly suggest that metformin could act primarily at postreceptor steps which are thought to be key sites in controlling the cellular glucose homeostasis.

3-O-Methylglucose↗

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia.

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 x 10(9)/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18-90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0-15%) of the infants born to mothers who presented none of these antecedents (P=0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy (r=0.42, P=0.0075). These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.

Chronic Disease↗

[Modifications of heart rate and blood pressure during pregnancy].

The pathophysiology of pre-eclampsia, disease of the endothelium, placental ischaemia, and its consequences on blood pressure and heart rate variations are described. The methods of evaluation of heart rate and blood pressure during pregnancy, outpatient visit clinical measurement, self-measurement, ambulatory measurement, "Finapres", electrocardiogram and Holter ECG are reviewed; the practical implications of the nocturnal fall of vagal tone with tachycardia, demonstrated during pre-eclampsia, are discussed.

Blood Pressure↗

Insulin but not progesterone promotes the biosynthesis of glycogen in Xenopus laevis oocytes: implications on the control of glycogen synthase by phosphorylation, dephosphorylation.

Insulin, the well-known hypoglycemic hormone, mimics progesterone in promoting the resumption of meiosis within the oocyte of Xenopus laevis. Both hormones exert their action through the inhibition of protein kinases and the activation of protein phosphatases. Because glycogen synthase is an enzyme regulated by a kinases/phosphatases cascade, we investigated the effect of insulin and progesterone on the regulation of glycogen synthesis and glycogen synthase throughout the oogenesis of Xenopus laevis oocytes. In this framework the maximal activity of synthase "a" is concomitant with the vitellogenic period characterized by a drastic increase in the amount of glycogen. Oocyte glycogen synthase is inhibited by cAMP-dependent phosphorylation and stimulated by 20 mM Mg2+. The magnesium effect is inhibited by mu molar concentrations of okadaic acid and suggests that oocyte glycogen synthase is activated by dephosphorylation achieved by protein phosphatase-1. The okadaic acid effect is itself thwarted by the specific inhibitor of protein kinase A, confirming the role of this kinase in the regulation of glycogen synthase. Finally, working on intact ripe oocytes, we showed that insulin but not progesterone increases glycogen synthesis and glycogen synthase "a" activity and lowers the rates of phosphorylation, especially in the glycogen-bound proteins.

Animals↗

Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.

BACKGROUND: Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina. METHODS AND RESULTS: We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 < r < .72, .02 < P < .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction. CONCLUSIONS: A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.

Adult↗

Developmental extinction of liver lipoprotein lipase mRNA expression might be regulated by an NF-1-like site.

The molecular mechanism underlying the extinction of lipoprotein lipase (LPL) expression in rat liver during development was investigated. A mouse (BWTG3) and a rat (7777) hepatoma, both of which exhibit characteristics of fetal hepatocytes, were found to contain LPL mRNA, whereas the more differentiated human (Hep G2 and Hep 3B) or rat (Fa32) hepatoma cell lines did not. Somatic cell hybrids between LPL-producing hepatoma cells and non-LPL-producing cells, such as adult rat hepatocytes or fibroblasts, exhibited extinction of LPL gene expression. Assay of expression of nested deletions in the 5' regulatory sequences of the LPL gene in the Hep G2 cell line and in BWTG3 cells localized sequences involved in the suppression of LPL production to a region between -591 and -288 relative to the transcription initiation site. A site with sequence homology to a glucocorticoid responsive element (GRE) was shown not to play an important role in the extinction process. A novel transcription factor, termed RF-1-LPL, was shown to bind to an NF-1-like site in this region. In contrast to neonatal animals, in adult animals an additional protein complex (RF-2-LPL), was formed on the NF-1-like site, suggesting that this sequence might recruit a trans-acting factor involved in the extinction of LPL gene expression in adult rat liver.

Animals↗

Cobalamin absorption and serum homocysteine and methylmalonic acid in elderly subjects with low serum cobalamin.

We prospectively studied 41 consecutive elderly patients with serum cobalamin (vitamin B12) levels lower than 125 pmol/l. The protein-bound cobalamin absorption test (PBAT) was performed in 34 of them and in 27 selected elderly control patients. The lower decision limit was 0.18% and an abnormal test was detected in only 9 (26%) of the 34 patients with low serum cobalamin level. When the PBAT was compared to the Schilling (Dicopac method) test, a concordant result was found in 80%. Serum methylmalonic acid and/or total homocysteine concentrations were elevated in 75% (26/35) of the patients with low serum cobalamin levels but also in 30% (5/17) of the control patients. Of the 12 and 9 cobalamin-deficient patients with elevated serum levels of methylmalonic acid and homocysteine, normalization after cobalamin therapy was obtained in 11 and 5 respectively. In conclusion, determination of serum metabolites and their response to cobalamin therapy are a sensitive index of significant cobalamin deficiency and a useful means of distinguishing between cobalamin and folate deficiency. The PBAT offers little advantage over the Schilling test in diagnosing cobalamin malabsorption in elderly patients.

Aged↗

Alterations of the mineralization profile and osteocalcin concentrations in osteoarthritic cortical iliac crest bone.

The relation between bone mineralization and osteocalcin content was investigated in iliac crest cortical bone obtained at necropsy in young females and in two groups of elderly women with and without osteoarthritis of the hands evaluated by X-ray. Using density fractionation technique, the bone was separated into fractions of increasing density from 1.72 to 2.30 g/ml. The mineralization profile revealed a significant shift to higher densities in the osteoarthritis cases compared with young adults (P less than 0.005) and age-sex-matched controls (P less than 0.001). The ash, calcium, and phosphorus content of the bone increased with increasing density of the fractions whereas collagen content, measured as hydroxyproline, decreased. The osteocalcin concentration of each fraction was determined in the supernatants obtained after EDTA-extraction in the presence of protease inhibitors. In the young control and osteoarthritis group, the osteocalcin content in the lowest density fractions was higher compared with the older non-osteoarthritic group. Osteocalcin content of the high density fractions, representing highly mineralized osteons, was the same in the three groups studied. These findings support the hypothesis that quality differences in bone may explain the inverse relationship between osteoarthritis and osteoporosis.

Adult↗

Short-term course of 1,25(OH)2D3 stimulates osteoblasts but not osteoclasts in osteoporosis and osteoarthritis.

We investigated the effect of short-term, 1,25-dihydroxyvitamin D3 therapy (4 micrograms/day for 4 days) on calcium metabolism in 27 postmenopausal women (11 cases with osteoporosis and 16 cases with osteoarthritis). Bone mass at the axial and appendicular skeleton was higher in osteoarthritis than in osteoporosis. Initial values of calcium metabolism were similar. Osteoporotic and osteoarthritic patients responded with a similar significant increase in serum osteocalcin (+61% and +54%, respectively), fasting urinary calcium excretion (+178% and +124%, respectively) and 24 hour calcium excretion (+148% and +142%, respectively). Parathyroid hormone (PTH) levels decreased significantly in both groups (-30% and -18%, respectively). Osteoclastic bone resorption, evaluated by urinary hydroxyproline excretion, was not stimulated in either group. We conclude that in osteoporosis and also in osteoarthritis (1) 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) stimulation of osteoblast function is similar in production of osteocalcin; (2) the vitamin D target tissues react adequately to 1,25(OH)2D3 stimulation; (3) short-term high dose of 1,25(OH)2D3 does not stimulate bone resorption; and (4) the differences in bone mass between osteoarthritis and osteoporosis are not related to an alteration of the responsiveness to stimulation by 1,25 (OH)2D3.

Aged↗

Seasonal variation in bone metabolism in young healthy subjects.

Serum vitamin D metabolites and urinary calcium excretion; parameters of bone formation (serum alkaline phosphatase, serum osteocalcin); parameters of bone resorption (24 hour hydroxyprolinuria, 2 hour fasting urinary hydroxyproline/creatinine ratio); and parameters of cortical and trabecular bone density, parathyroid hormone (iPTH, COOH terminal assay), and serum minerals (calcium, phosphorus) were followed serially in 55 young adults (21 women and 34 men) from December 1985 until January 1987 at four different times during the year. The effect of a low-dose cyclooxygenase inhibitor (piroxicam 5 mg daily) on the same parameters of bone density and bone turnover when given from December until May, was also evaluated in this study. At the end of the treatment period parameters of bone turnover and bone density were comparable between placebo and piroxicam-treated groups. Therefore, the results of all subjects were pooled in order to investigate seasonal variation. In both sexes, seasonal variation was found not only for 250HD3 but also for 1,25(OH)2D3, serum calcium and phosphorus, urinary calcium excretion, and for bone density at the lumbar spine. Parameters of bone formation (serum osteocalcin and alkaline phosphatase), bone resorption (24 hour urinary hydroxyprolinuria and fasting urinary hydroxyproline/creatinine ratio) and PTH were influenced by this seasonal variation. We conclude that in young adults, a significant seasonal variation occurs, with low winter and high summer values, for serum 25 and 1,25(OH)2D3 for urinary calcium apparently without important influence on parameters of bone turnover or parathyroid activity and for lumbar spine density. Treatment with a low-dose cyclooxygenase inhibitor was without influence on the observed changes.

Adult↗

Electromagnetic extracorporeal shock wave lithotripsy in children.

Extracorporeal shock wave lithotripsy (ESWL) was performed for the treatment of urinary tract calculi in 28 children. All treatments were done with the standard Siemens Lithostar device in situ: no special adaptations for adequate positioning of children are required to target the stone precisely. A total of 42 calculi in 30 renal units was treated, requiring 50 ESWL sessions. The mean energy used was 16.4 kv. and the number of shock waves averaged 3,188. Mean fluoroscopy time per session was 1.5 minutes. In 26 of 50 sessions (52%) general anesthesia was needed for the child to remain perfectly still. A complete stone-free rate was achieved in 38 of 42 calculi (90.5%): after 1 session in 30 (71.4%), after 2 sessions in 6 (13.7%) and after 3 sessions in 2 (4.8%). Five staghorn calculi were treated with ESWL monotherapy. A complete stone-free result was obtained after 3 treatments in 2 patients, while 2 had residual fragments in the lower pole (5 mm. after 6 sessions and 11 months of followup in 1, and 7 mm. after 3 sessions and 3 months of followup in 1). A cystine staghorn stone necessitated open nephrolithotomy after 3 sessions without any fragmentation. One impacted sacroiliac ureteral stone required endoscopic laser lithotripsy. Except for these 2 failures no adjuvant procedures were needed. There were no intraoperative or postoperative complications and minor skin bruising at the coupling site after 3 treatments did not require any therapy. We conclude that electromagnetic ESWL with the standard Lithostar unit is a safe and effective method to treat calculi throughout the urinary tract in children.

Adolescent↗

Clinical significance of squamous cell carcinoma antigen in cancer of the human uterine cervix. Comparison with CEA and CA-125.

Serum squamous cell carcinoma antigen (SCCa) concentrations were determined by a radioimmunoassay kit before and during the treatment of 50 patients with cervical carcinoma: 44 with squamous cell carcinoma (SCC) and 6 with adenocarcinoma. The positivity rate of SCCa was 50% (52% for SCC and 33% for adenocarcinoma). The sensitivity of SCCa for SCC was twice as high as that of CEA and CA-125. Low serum concentrations were observed in early-stage carcinoma, indicating that SCCa is not useful for diagnosis. In advanced cases, serum levels were directly and significantly correlated with the stage of the disease.

Adenocarcinoma↗

Percutaneous interbody osteosynthesis in the treatment of thoracolumbar traumatic or tumoural lesions. A review of 51 cases.

The authors describe a technique of percutaneous interbody osteosynthesis applicable to the dorsal and lumbar spine. 51 patients were so treated for different aetiologies: traumatic conditions (35 cases) and tumoural lesions (16 cases). The material used consisted of special instruments that are positioned in double obliquity by a percutaneous posterolateral approach. A posterior approach limited to the pathological focus was used jointly whenever a graft or a decompression was necessary (19 cases). Several types of anaesthesia were used (local, local-regional, general, neuroleptanalgesia). The patients benefited by the advantages that usually accompany percutaneous techniques. The advantages and limitations of the method are discussed.

Adolescent↗

Sex- and age-related changes in bone and serum osteocalcin.

We measured bone osteocalcin concentrations in EDTA extracts from iliac crest cortical bone specimens obtained postmortem from 63 men and 71 women (age range 19-90 years), and serum osteocalcin levels in healthy blood donors, 49 men and 49 women (age range 21-65 years). Bone and serum osteocalcin concentrations were higher in men than in women, and an age-related decline was observed in both sexes. In women, however, a temporary increase in serum (P less than 0.05) osteocalcin was seen in the sixth decade. This study shows sex- and age-related changes in bone osteocalcin consistent with changes in serum osteocalcin, confirming that serum measurement of osteocalcin reflects bone levels. As osteocalcin reflects osteoblastic activity and thus bone formation, the overall decline in bone and serum osteocalcin in men and women, and the increase in serum osteocalcin in the sixth decade in women, indicate that aging is associated with a decrease in bone formation and turnover and that osteoblastic activity and bone turnover are stimulated at the menopause.

Adult↗

Background correction in factor analysis of dynamic scintigraphic studies: necessity and implementation.

In factor analysis, structures are separated on the basis of their temporal behaviour, even if there is a partial overlap. Usually, the temporal behaviour of the system under study cannot be sampled in its true form due to a total overlap by the background. In the ROI (region of interest) method, background subtraction is used as a means to correct the problem. In factor analysis, this problem has been ignored for a long time. We prove that the factor analysis method gives incorrect results when there is a total overlap of a structure. By assuming a local homogeneity of the overlapping structure, we can greatly improve the solution found. Compared with the classical ROI method, our method is operator independent and organ specific.

Biophysical Phenomena↗

Binding properties of monoclonal antibodies against human fragment D-dimer of cross-linked fibrin to human plasma clots in an in vivo model in rabbits.

Two (MA-15C5 and MA-8D3) out of approximately 500 monoclonal antibodies, obtained by fusion of P3X63-Ag8-6.5.3 myeloma cells with spleen cells of mice immunized with purified fragment D-dimer from human fibrin, demonstrated a more than 1,000-fold higher affinity for fragment D-dimer than for native fibrinogen. MA-15C5 was directed against a neoantigenic determinant only expressed in fragment D-dimer. MA-8D3 reacted equally well with fragment D-dimer of crosslinked fibrin and with fragment D of non-crosslinked fibrin but not with fragment D of fibrinogen. Both monoclonal antibodies did not crossreact with rabbit fibrin and its degradation products. The binding of 125I-labeled Fab fragments to human plasma clots, introduced and aged for 1 hr in the jugular vein of heparinized rabbits was studied. Following injection of an equimolar mixture of Fab fragments derived from MA-15C5 and MA-8D3, the clot to blood ratios of radioactivity increased from 3.2 +/- 1.2 (mean +/- SD) at 4 hr to 7.2 +/- 1.4 at 17 hr. The binding of Fab fragments of MA-15C5 and MA-8D3 was independent of the age (1 to 72 hrs) of the clot and of heparin anticoagulation and was only slightly decreased (by 20%) in the presence of circulating human fibrinogen (90 mg/kg body weight) and of human cross-linked fibrin degradation products at a plasma concentration of 10 micrograms/ml. The binding of Fab fragments of MA-15C5 and MA-8D3 to occlusive human plasma clots in the femoral artery of rabbits was comparable to that of the non-occlusive human plasma clots in the jugular vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗