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Biomedical subjects

P Geoffroy

Publications and source records attributed to P Geoffroy.

At least 19 recordsLinked to original sources
PubMed1994

Molecular characterization of a novel tobacco pathogenesis-related (PR) protein: a new plant chitinase/lysozyme.

A new PR (pathogenesis-related) protein was isolated from tobacco leaves (Nicotiana tabacum cv. Samsun NN), reacting hypersensitively to tobacco mosaic virus (TMV), by zinc chelate chromatography and was therefore named Pz. Its reactivity toward several lectins indicated the presence of bound sugar residues. From the amino acid sequence of tryptic peptides, Oligonucleotide primers were derived which allowed the synthesis of Pz cDNA by PCR. Using this cDNA as probe, near full-length clones were isolated from a library made from poly(A)+ RNA purified from TMV-infected leaves. Sequence analysis revealed similarities with chitinases/lysozymes of various origins and the purified protein was, indeed, shown to hydrolyse different N-acetylglucosamine-containing substrates. Comparison of peptide and cDNA sequences indicated that Pz protein is synthesized as a pre-pro-protein, a seven-amino acid C-terminal peptide probably being involved in the vacuolar targeting of the protein. Pz mRNA and protein were demonstrated to accumulate strongly in TMV-infected tobacco leaves. Pz transcripts were also found in various tissues of healthy plants, indicating that Pz gene expression is developmentally regulated.

Amino Acid Sequence↗
PubMed1993

Molecular cloning and expression of a new class of ortho-diphenol-O-methyltransferases induced in tobacco (Nicotiana tabacum L.) leaves by infection or elicitor treatment.

In tobacco (Nicotiana tabacum L. cv Samsun NN), three distinct enzymes account for ortho-diphenol-O-methyltransferase (OMT) activity. OMT I is the major enzyme of healthy leaves, whereas enzymes OMT II and III are preferentially induced during the hypersensitive reaction to tobacco mosaic virus (TMV). Using an anti-OMT III antiserum, we isolated a partial OMT III cDNA clone by immunoscreening an expression library made from mRNA of TMV-infected tobacco leaves. Using this OMT III clone as a probe, we isolated a full-length clone with a deduced amino acid sequence encompassing all of the sequences obtained by Edman degradation of both purified proteins II and III. Thus, OMT II and III of tobacco are likely to be encoded by the same genes and to arise from different posttranslational modifications. Sequence analysis showed that this OMT clone represents a new class of OMT enzymes (class II) with a low level of similarity (53-58%) to OMTs cloned previously from other dicotyledonous plants. Southern analysis indicated that a small family of class II OMT genes inherited from ancestors related to Nicotiana sylvestris and Nicotiana tomentosiformis occurs in the tobacco genome. RNA blot analysis demonstrated that class II OMT genes, unlike class I OMT genes, are not expressed at a high constitutive level in lignified tissues of tobacco. Class II OMT transcripts were found to accumulate in tobacco leaves infected with TMV or treated with megaspermin, a proteinaceous elicitor from Phytophthora megasperma, but not in leaves treated with salicylic acid, a molecule known to trigger many defense genes. In TMV-infected or elicitor-treated tissues, a marked increase in catechol-methylating activity accompanied the accumulation of class II OMT gene products.

Amino Acid Sequence↗
PubMed1989

Route of delivery of phenylalanine influences its effect on short-term food intake in adult male rats.

The effect of phenylalanine (Phe) on plasma and brain Phe and tyrosine (Tyr) levels and on short-term food intake in male rats was measured after intragastric (i.g.), subcutaneous (s.c.) and intraperitoneal (i.p.) administration. Compared to equimolar alanine (Ala), which served as the control, Phe significantly suppressed feeding at a dose of 90 mg/kg body wt when given i.p., but doses up to 720 mg/kg body wt had no effect when given i.g. or s.c. The high doses of Phe given by the i.g. or s.c. route resulted in higher levels of Phe in both plasma and brain than those following i.p. injection (90 mg/kg body wt). Furthermore, brain Tyr levels after i.g. Phe (720 mg/kg body wt) were equal to or higher than after i.p. Phe (90 mg/kg body wt). We conclude that the route of administration is an important variable influencing the effects of Phe on feeding behavior, and that these effects are not readily explained by plasma or brain Phe and Tyr concentrations.

Alanine↗
PubMed1988

Nadolol for prophylaxis of gastrointestinal bleeding in patients with cirrhosis. A randomized trial.

This controlled trial was designed to evaluate the prophylactic effect of nadolol on gastrointestinal bleeding in cirrhotic patients with large oesophageal varices who had never bled. Nadolol or placebo was given randomly to two groups of 53 patients. The percentage of patients free of gastrointestinal bleeding 1 year after inclusion in the study was 83 +/- 6% (mean +/- S.D.) in the nadolol group and 80 +/- 6% in the placebo group. In the nadolol and placebo groups, 40 and 47 patients, respectively, were compliant, i.e., took nadolol or placebo continuously. The percentage of patients who were free of bleeding 1 year after inclusion was 97 +/- 3% in the subgroup of compliant nadolol patients. This percentage was significantly higher than that of patients who were free of bleeding in the placebo group (P less than 0.03) as well as in the subgroup of compliant placebo patients (77 +/- 6%; P less than 0.02). We concluded that, although there was no overall significant effect of nadolol on the risk of bleeding in cirrhotic patients in good condition with large oesophageal varices, this study suggests that nadolol reduced the risk of bleeding in compliant patients.

Clinical Trials as Topic↗
PubMed1988

Comparative haemodynamic effects of betaxolol and propranolol in patients with cirrhosis.

The acute effects of betaxolol (10 mg, intravenously), a new cardioselective beta-blocker, and propranolol (15 mg, intravenously) on splanchnic and systemic circulations were studied in two matched groups of six patients with portal hypertension due to cirrhosis. Similar decreases in hepatic venous pressure gradient and azygous blood flow--an estimation of superior portosystemic shunts--were observed after both drugs, whereas hepatic blood flow was not modified. The decreases in heart rate and cardiac index were also similar after betaxolol and propranolol. Both drugs induced a significant decrease in the fraction of cardiac output flowing through superior portosystemic shunts. These findings confirm that the marked effect of beta-adrenoceptor blocking agents on splanchnic circulation results both from the reduction in cardiac output and from a vasoconstriction of the portal vein territory, and demonstrate that this vasoconstriction of the portal vein area does not necessitate a beta 2-blocking activity of the drug. The similar efficiency of the two agents in decreasing the hyperkinetic circulation suggests that betaxolol merits further long-term study in the pharmacologic treatment of portal hypertension.

Adrenergic beta-Antagonists↗
PubMed1987

Enzymatic synthesis of lignin: purification to homogeneity of the three O-methyltransferases of tobacco and production of specific antibodies.

Three o-diphenol-O-methyltransferases (OMTs; EC 2.1.1.6) involved in the biosynthesis of lignin have been purified to homogeneity from tobacco leaves. Seven different fractionation steps which included (NH4)2 SO4 precipitation, conventional low-pressure chromatography on Ultrogel AcA34 and DEAE-cellulose columns, high-performance liquid chromatography (HPLC) on three different supports (Mono Q, Mono P, and TSK G-3000 SW columns), and finally preparative electrophoresis were necessary. At each step of purification, the protein content of the enzymatic fractions was analyzed by electrophoresis on polyacrylamide gels under denaturing conditions. Purified OMT I appeared on sodium dodecyl sulfate-polyacrylamide gel as a doublet with electrophoretic mobilities corresponding to molecular weights of 38,500 +/- 2000 and 39,500 +/- 2000. The other two enzymes migrated as single but rather broad bands with molecular weights of 42,000 (OMT II) and 43,000 (OMT III). Polyclonal antibodies were raised in rabbits. The titers of antibodies were measured by an indirect enzyme-linked immunosorbent assay method, and their specificity was demonstrated by immunoblotting enzyme preparations at different stages of purification. Immunodetection of the three enzymes with a specific antiserum suggested serological relationships between the three OMTs of tobacco.

Animals↗
PubMed1987

Reversal of adrenaline-induced increase in azygos blood flow in patients with cirrhosis receiving propranolol.

In patients with cirrhosis, endogenous catecholamines may influence the circulatory effects of propranolol. We intended to evaluate the interaction of adrenaline and propranolol on azygos blood flow, an estimate of blood flow in the superior portosystemic collateral circulation. We investigated 6 patients with cirrhosis, 5 with good liver function, receiving an intravenous infusion of adrenaline (50 ng/kg/min) before and after administration of propranolol. The median value for baseline azygos blood flow was increased from 700 ml/min (range 340-1 470 ml/min) to 1 050 (range 570-1 840 ml/min) with adrenaline alone (P less than 0.05), and decreased to 610 ml/min (range 260-1 190 ml/min) with propranolol alone (P less than 0.05). The infusion of adrenaline given after propranolol further reduced azygos blood flow to a median value of 530 ml/min (range 200-730 ml/min) (P less than 0.05). Thus, following beta-adrenergic blockade, there is a reversal of the effects of adrenaline on azygos blood flow, which corresponds to a potentiation of the effects of propranolol. Similar endogenous adrenaline-propranolol interactions may play a role in preventing recurrent variceal bleeding in cirrhotic patients.

Adult↗
PubMed1987

Effects of propranolol and sucralfate on ethanol-induced gastric mucosal damage in chronic portal hypertensive rats.

In a rat model of chronic portal hypertension we studied ethanol-induced gastric mucosal damage and the effects of pretreatment by propranolol and sucralfate. Susceptibility to ethanol was increased in chronic portal hypertensive rats compared with sham-operated rats (55 +/- 8% vs. 25 +/- 4%). Both acute pretreatment (10 min) and chronic pretreatment (3 weeks) with propranolol reduced gastric mucosal injury induced by ethanol in portal hypertensive rats, compared with saline-treated rats. Acute and chronic pretreatment with propranolol had no protective effect in sham-operated rats. In portal hypertensive rats, sucralfate in two different doses (500 and 125 mg/kg) protected the gastric mucosa against ethanol-induced gastric injury compared with animals receiving saline (2 +/- 1% and 3 +/- 2% vs. 25 +/- 3%). Sucralfate at the higher dose did not reduce portal pressure in portal hypertensive rats. We conclude that: (1) chronic portal hypertension increases ethanol-induced gastric damage; (2) acute and chronic propranolol treatment reduces ethanol-induced gastric injury in portal hypertensive rats, probably by decreasing portal hypertension; (3) sucralfate has a cytoprotective effect in portal hypertensive rats without reducing portal pressure. These results suggest a potential application of sucralfate in patients otherwise treated by sclerotherapy.

Animals↗
PubMed1986

Circulatory actions of vasopressin in anaesthetized rats with portal hypertension subjected to haemorrhage.

To assess the influence of vasopressin on splanchnic and renal circulatory changes induced by haemorrhage in portal hypertension, we studied 4 groups of 7 rats with chronic portal vein stenosis. Two groups received saline (C and H) and two groups vasopressin, 0.01 IU/kg/min (VP and VP-H). Ten minutes after starting drug infusion, group H and VP-H animals were allowed to bleed from the superior mesenteric vein. Both haemorrhage and vasopressin alone, decreased portal venous tributary blood flow and pressure but their association was not additive (as reflected by comparable bleeding rate in groups H and VP-H). By contrast, vasopressin increased renal perfusion in bleeding and non-bleeding animals whereas haemorrhage alone decreased renal perfusion. These results indicate that the effects of vasopressin on the splanchnic circulation in bleeding anaesthetized animals differ from the effects observed when blood volume is normal. Therefore, in patients with cirrhosis the effects of vasopressin during bleeding might also differ from those observed in patients in stable condition.

Anesthesia↗
PubMed1986

Haemodynamic rebound phenomena after abrupt cessation of propranolol therapy in portal hypertensive rats.

The haemodynamic effect of sudden termination of propranolol therapy was studied in sham-operated and portal hypertensive rats. All animals were injected with propranolol (20 mg/kg/day) or saline i.p. for 10 days, then had an isoproterenol infusion test performed 48 h or 72 h after cessation of injections. The dose of isoproterenol required to increase the heart rate by 50 beats/min (CD50), was significantly lower in both sham-operated and portal hypertensive rats at 48 h after propranolol withdrawal. Maximum chronotropic response (Rmax), was significantly higher only in portal hypertensive rats at 48 h after propranolol withdrawal. These results show the existence of a transient beta-adrenergic hypersensitivity state following propranolol withdrawal in normal and portal hypertensive rats.

Animals↗
PubMed1986

Influence of the degree of liver failure on systemic and splanchnic haemodynamics and on response to propranolol in patients with cirrhosis.

Systemic and splanchnic haemodynamics were studied in patients with cirrhosis who had been classified in three groups (A, B, and C) according to the degree of liver failure (modified Pugh's classification). In patients of group A, cardiac index was significantly lower than that of group C and systemic vascular resistance was higher, but not significantly so, than that of patients with liver failure. Wedged hepatic venous pressure was significantly lower in the former group than in the latter. In patients in group B, corresponding values fell between those of groups A and C. Azygos blood flow averaged 0.477 +/- 0.242 l/min (mean +/- SD) in group A and it was significantly lower than in groups B and C (0.642 +/- 0.224 and 1.061 +/- 0.476 l/min, respectively). In the three groups, acute administration of propranolol induced statistically significant changes in systemic and splanchnic haemodynamics. In patients of group C but not of group B, the mean value of azygos blood flow after propranolol remained significantly higher than in group A. Moreover, the fraction of azygos blood flow to cardiac output decreased in groups A and B while slightly increased in group C. This study shows that in patients with cirrhosis, the degree of liver failure may be a determinant for the haemodynamic responses to drugs acting on portal hypertension.

Female↗
PubMed1985

Effects of pentobarbital sodium anesthesia on splanchnic hemodynamics of normal and portal-hypertensive rats.

To determine the effect of pentobarbital sodium anesthesia on the rat with portal hypertension due to portal vein stenosis, four groups of rats were studied. Cardiac output and regional blood flow were measured by radioactive microspheres in anesthetized and conscious sham-operated and portal-hypertensive rats. Anesthesia markedly decreased cardiac output in both sham-operated (109.7 +/- 4.6 vs. 77.8 +/- 1.4 ml/min, P less than 0.001) and portal-hypertensive rats (130.1 +/- 7.6 vs. 93.8 +/- 5.3 ml/min, P less than 0.01). In spite of this diminution in cardiac output, pentobarbital did not significantly change absolute blood flow values of splanchnic organs in either group. However, the fractions of cardiac output perfusing the splanchnic organs were significantly increased by pentobarbital in both groups because of the decrease in cardiac output: sham operated, anesthetized, 22.86 +/- 1.19% vs. conscious, 14.83 +/- 1.02%, P less than 0.001; and portal hypertensive, anesthetized, 26.67 +/- 0.71% vs. conscious, 19.07 +/- 1.44%, P less than 0.001. The hyperdynamic circulation of the portal vein-stenosed rat compared with the sham-operated rat continued to manifest itself with significantly increased portal pressure, cardiac output, and splanchnic blood flow, whether the animal was anesthetized or awake. We conclude that, despite marked hemodynamic changes induced by pentobarbital, the rat with portal vein stenosis remains a useful experimental model of portal hypertension.

Anesthesia, General↗
PubMed1984

[Acute hepatitis due to carbamazepine (Tegretol). Study of a case and review of the literature].

The case of a 28-year-old epileptic woman, treated for 3 months with carbamazepine and who developed jaundice, fever and exfoliative dermatitis is reported. Biological investigations showed an increase in the activity of serum transaminases and alkaline phosphatases as well as in the blood eosinophilic count. Liver biopsy revealed centrolobular necrosis and cholestasis with portal inflammatory infiltrate. Drug challenge was followed by the rapid recurrence of clinical and biological signs. The definitive outcome was favorable. The analysis of the 12 previously published cases, and particularly the frequency of granulomatous hepatitis, suggests an immunoallergic mechanism for the development of carbamazepine hepatitis.

Acute Disease↗
PubMed1980

A controlled field trial of liver oral typhoid vaccine Ty21a.

A controlled field trial of a live oral typhoid vaccine was carried out in Alexandria, Egypt, in 1978-79. A total of 32 388 children were included in the study. They were divided in two comparable groups, one given 3 doses of the vaccine and the other 3 doses of the placebo. Each active dose contained 1 x 10(9)-8 x 10(9) live Ty21a bacteria. From March 1978 to March 1979, the population studied was followed up and suspected typhoid cases were investigated bacteriologically and serologically. The effectiveness of the vaccine was assessed by analysis of the incidence of typhoid fever in the two groups. The results of the follow-up indicate that, in the dosage schedule used, the Ty21a mutant strain, found previously to be stable and safe, is protective against typhoid fever for at least one year.

Child↗