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T Gauthier

Publications and source records attributed to T Gauthier.

At least 37 records · Page 2Linked to original sources
PubMed1993

The effect of gamma-aminobutyric acid on hepatic regenerative activity following partial hepatectomy in rats.

BACKGROUND: gamma-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter with growth-regulatory properties. In fulminant hepatic failure, a condition in which hepatic regeneration may be impaired, systemic serum GABA concentrations are markedly elevated. The present study was designed to determine whether increased amounts of circulating GABA interfere with hepatic regenerative activity. METHODS: Exogenous GABA or isotonic saline was administered to adult male rats (n = 6-12/group) 16 hours before partial hepatectomy and twice daily for 1-3 days thereafter. The hypertrophic and hyperplastic components of hepatic regeneration were determined by calculation of the restitution of liver mass, [14C]leucine incorporation into protein (protein synthesis), and [3H]thymidine incorporation into hepatic DNA (DNA synthesis). RESULTS: Exogenous GABA impaired restitution of liver mass (GABA vs. controls, day 3: 76% +/- 7% vs. 90% +/- 9%, mean +/- SD) (P < 0.005) and the rate of protein synthesis (GABA vs. controls, day 1: 379 +/- 39 dpm/mg protein vs. 564 +/- 67 dpm/mg protein) (P < 0.01) without interfering with DNA synthesis. Supplemental administration of corticosterone and putrescine restored protein synthesis rates to normal in GABA-treated rats. CONCLUSIONS: These results indicate that elevated serum GABA concentrations interfere with the hypertrophic component of hepatic regeneration following partial hepatectomy in rats.

Animals↗
PubMed1993

Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates.

Compounds possessing neurotrophic properties may represent a possible treatment for neurodegenerative disorders such as Alzheimer's disease. SR 57746A, 1-[2-(naphth-2-yl)ethyl]-4-(3-trifluoromethylphenyl)-1,2,5,6- tetrahydropyridine hydrochloride, is a new compound with neurotrophic activity in a number of in vitro preparations. The neurotrophic effects of this compound have been evaluated in vivo using four distinct rat models of neurodegeneration: transient global ischaemia produced by a four-vessel occlusion; septohippocampal lesion produced by injection of vincristine sulphate into the medial septum; sciatic nerve crushing; and acrylamide-induced peripheral neuropathy. Rats were administered vehicle or 2.5-10 mg/kg p.o. SR 57746A, after initiation of the degenerative process, then once daily for 10 days in the first two models, 16 days in the third and 26 days in the fourth model. Median scores for ischaemia-induced neuronal damage were reduced by 30-40% by SR 57746A treatment in hippocampal CA1, CA2, and CA3 regions, and in the dorsal striatum. Twelve days after intraseptal vincristine administration, there was a marked loss of septohippocampal cholinergic neurons, as indicated by reduced choline acetyltransferase activity in both the septum and hippocampus. SR 57746A dose-dependently reversed this reduction in both areas. These results were confirmed by histoenzymological evaluation of hippocampal acetylcholinesterase content. SR 57746A also reversed the loss of hippocampal choline acetyltransferase induced by intraseptal vincristine in marmosets. Behavioral deficits in these models (exploratory behaviour in the former and short-term social memory in the latter) were also significantly reduced by SR 57746A treatment. In the sciatic crush model, sensorimotor function improved more rapidly in rats treated with 10 mg/kg SR 57746A. In this same model, SR 57746A (10 mg/kg/day) also significantly increased the length of regenerated nerve eight days after the crush, as measured using the pinch test. Finally, SR 57746A retarded the onset, reduced the amplitude and accelerated the recovery of acrylamide-induced peripheral neuropathy. Thus, SR 57746A possesses notable neurotrophic activity in a variety of neurodegenerative models in vivo, suggesting that the compound may possess therapeutic potential for the treatment of neurodegenerative diseases.

Acetylcholinesterase↗
PubMed1993

Cerebral metabolic and histological effects of thioacetamide-induced liver failure.

Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.

Animals↗
PubMed1993

Hepatic fibrosis as a predictor of hepatic regenerative activity after partial hepatectomy in the rat.

Liver regeneration is an essential component of the recovery period after partial hepatectomy. Unfortunately, tests that accurately predict regenerative activity in the postoperative period have yet to be described. This study was designed to determine whether the extent of hepatic fibrosis correlates with liver regeneration activity after partial hepatectomy in rats with carbon tetrachloride-induced liver disease. Two groups of adult male Sprague-Dawley rats (12 to 30/group) were treated for 20 to 22 wk with weekly intragastric doses of carbon tetrachloride or vehicle. All rats then underwent 70% hepatectomy while under ether anesthesia. Liver regeneration activity was determined at 24 and 48 hr by [3H]thymidine incorporation into DNA. Hepatic fibrosis was calculated at the time of partial hepatectomy by automated image analysis on Van Gieson-stained liver tissue. Although a significant inverse correlation was found between the extent of hepatic fibrosis and DNA synthesis when all rats were considered (carbon tetrachloride-treated and vehicle-treated) at 24 and 48 hr after partial hepatectomy (r = -0.4943 and -0.7396, respectively; p < 0.05), no such correlation existed when carbon tetrachloride-treated rats were considered independently (r = -0.3231 and -0.0910 at 24 and 48 hr, respectively). In conclusion, we believe that in diseased livers, preoperative quantitation of hepatic fibrosis on automated image analysis does not serve as a useful predictor of liver regeneration activity.

Animals↗
PubMed1992

Human fusion proteins between interleukin 2 and IgM heavy chain are cytotoxic for cells expressing the interleukin 2 receptor.

We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans.

Base Sequence↗
PubMed1992

Differential expression of the CD44 molecule in human brain tumours.

Expression of the CD44 molecule was examined in a variety of human brain tumours, brain metastases and normal brain. Immunohistological staining with several CD44 antibodies demonstrated differential expression of the CD44 molecule among different brain tumour types. CD44 was strongly expressed in high-grade gliomas and weakly expressed in meningiomas, medulloblastomas and normal brain. Northern blot analysis revealed the presence of 3 major CD44 mRNAs of 1.6, 2.2, and 5.0 kb in glioblastomas and a mRNA of 5.6 kb in meningiomas. CD44 expression was also detected by flow cytometric analysis on cultured cells derived from a variety of human brain tumours including glioblastomas and meningiomas.

Brain Neoplasms↗
PubMed1992

Effects of partial hepatectomy on hepatic insulinlike growth factor binding protein-1 expression.

Insulinlike growth factor binding proteins modulate the action of the insulinlike growth factors in various bioassays and may regulate the bioavailability of the insulinlike growth factors in vivo. Because the insulinlike growth factors may influence hepatic regeneration, we have examined the effect of partial hepatectomy on serum insulinlike growth factor binding proteins and on the abundance of insulinlike growth factor binding protein-1 messenger RNA in the liver. All rats were fasted before and after partial hepatectomy or sham operation to avoid the confounding effects of difference in food intake. Using a conventional protocol, 70% of the liver was removed, and groups of four or five rats were killed at different intervals after partial hepatectomy. Sham-operated rats served as controls. Pooled sera from each group of rats were analyzed by ligand blotting with 125I-insulinlike growth factor-I. Liver RNA from individual rats was analyzed by slot-blot and Northern-blot hybridization. A small decrease in the 39- to 42-kD insulinlike growth factor binding protein was apparent in sera from both the sham-operated and partial hepatectomized rats. In contrast, a dramatic increase (fivefold) in the 29-kD serum insulinlike growth factor binding protein (insulinlike growth factor binding protein-1) was apparent only in the partial hepatectomized rats. Hepatic insulinlike growth factor binding protein-1 messenger RNA abundance was significantly increased (1.99 +/- 0.18-fold; p less than 0.05) at 1 hr, reached a peak of 2.32 +/- 0.22-fold (p less than 0.01) at 3 hr after partial hepatectomy and returned to basal levels over the subsequent 6 to 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Liver regeneration and the effect of exogenous putrescine on regenerative activity after partial hepatectomy in cirrhotic rats.

There are conflicting data regarding the ability of the liver to regenerate after partial hepatectomy in animals and humans with cirrhosis. The purpose of this study was to document liver regeneration after partial hepatectomy in a carbon tetrachloride rat model of cirrhosis and to determine whether exogenous putrescine, a polyamine that has been reported to stimulate liver regeneration in animal models of acute liver failure, enhances regenerative activity in cirrhosis. Liver fibrosis and cirrhosis were produced by weekly intragastric gavage with carbon tetrachloride in 130 adult male rats. Vehicle-gavaged rats (n = 12) served as healthy controls. At surgery and at 4 and 8 hr after 70% hepatectomy, rats received normal saline solution or 1 or 10 mg/kg putrescine by intraperitoneal injection. Another group (n = 32) of carbon tetrachloride-treated rats was given putrescine (100 mg/kg) or normal saline solution twice daily for 10 days before partial hepatectomy and at 0, 4 and 8 hr after partial hepatectomy. Liver regeneration was documented 24 and 48 hr after partial hepatectomy on the basis of restitution of liver mass, ornithine decarboxylase activity and [3H]thymidine incorporation into liver DNA. Automated image analysis of the resected liver specimens separated carbon tetrachloride-treated rats into two subgroups: those with bridging fibrosis (fibrotic group) and those with micronodular cirrhosis (cirrhotic group). Restitution of liver mass and ornithine decarboxylase activity at 24 and 48 hr after partial hepatectomy were similar to carbon tetrachloride-treated rats (both fibrotic and cirrhotic) and vehicle-treated healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Adhesion molecules and malignant gliomas: implications for tumorigenesis.

Adhesion molecules, a family of cell-surface molecules, are likely to be of central importance in mediating cell-extracellular matrix and specific cell-cell interactions within both neoplastic and inflammatory sites. The recently discovered expression of adhesion molecules on glioma cells, tumor-infiltrating lymphocytes, and endothelial cells within the tumor offers insight into the molecular basis of the interactions both between the glioma cell and surrounding heterologous cell types within the tumor environment, and between the tumor cell and the extracellular matrix. Such interactions suggest that these molecules may play roles in the homing of immune cells to these tumors and in regulating the extent of local tumor invasion. The ability to modulate adhesion molecule expression on either immune cells or their respective ligands on gliomas provides an approach to modify cell-cell interactions that may be used to increase tumor kill by the immune system. A similar approach in the modulation of adhesion molecules involved in tumor cell adhesion to the extracellular matrix or endothelial cells may be a method to limit local invasion in these lesions.

Cell Adhesion Molecules, Neuronal↗
PubMed1992

A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis.

Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/- SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis.

Acyclovir↗
PubMed1992

Selective bowel decontamination does not alter hepatic regeneration in rats.

The purpose of the present study was to determine whether changes to the gut flora that occur following norfloxacin-induced selective bowel decontamination alter hepatic regenerative activity. Adult rats (n = 6 per group) were treated with norfloxacin (10 mg/day) or vehicle for 10 days before 70% partial hepatectomy. Hepatic regenerative activity was determined 24 hours after surgery by documenting restitution of liver mass, [3H]thymidine incorporation into DNA, and ornithine decarboxylase activity in the liver. The results of the study revealed that hepatic regeneration was unaffected by norfloxacin therapy. Thus, selective bowel decontamination with norfloxacin does not alter hepatic regenerative activity following partial hepatectomy in the rat.

Animals↗
PubMed1991

Enhancement of neurite outgrowth from central nervous system neurons in primary culture by thrombin inhibitors.

Previous studies have shown that serine protease inhibitors promote neurite outgrowth from neuroblastoma cells, sympathetic neurons and sensory ganglia in culture. In the present study, a neurite promoting activity of thrombin inhibitors such as hirudin, D-Phe,Pro,Arg-CH2Cl, and paraamidinophenylalanine derivatives, was found in rat embryo (E17) septal neurons in primary culture. In contrast, no effect was shown on choline acetyltransferase activity of septal fragments in culture. These results suggest that thrombin inhibitors might interact with a thrombin-like protease involved in the control of neurite outgrowth.

Amidines↗
PubMed1991

Angiographic contrast media interference with laser-induced fluorescence excitation and detection in atherosclerotic human coronary arteries.

Laser-induced fluorescence has been used in conjunction with angiography for laser angioplasty guidance. The effect of radiopaque contrast media on the excitation and detection of arterial fluorescence has not been previously reported. Accordingly, fluorescence emission spectra from human coronary artery necropsy specimens (n = 7) during excitation with pulsed excimer laser excitation (308 nm) was examined before and after the addition of three different contrast media, sodium and meglumine diatrizoate, sodium and meglumine ioxaglate, and iopamidol. A decrease in overall fluorescence intensity was observed at all wavelengths for each contrast agent examined. The decrease in intensity of fluorescence emission was more marked at wavelengths less than 410 nm than at wavelengths above 425 nm. Similar effects were observed for contrast media diluted with whole blood. Absorption spectra for all three contrast media demonstrated absorption in the ultraviolet centered around 240 nm. We conclude that preferential absorption in the ultraviolet range by contrast media interferes with the excitation and detection of laser-induced fluorescence; use of visible light excitation may obviate interference with laser-induced fluorescence analysis of plaque.

Angioplasty, Laser↗
PubMed1991

The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats.

Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline-treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure.

Animals↗
PubMed1991

The effect of long-term, voluntary ethanol consumption on hepatic regeneration in rats.

Previous studies have reported conflicting results regarding the effect of ethanol on hepatic regeneration. The purpose of the present study was to determine whether long-term, voluntary consumption of ethanol, within the range reported in humans, has an effect on hepatic regenerative activity in rats following partial hepatectomy. Ninety-four adult male Sprague-Dawley rats (n = 3-9/group) were studied. Based on the amount of 9% ethanol consumed over a 50-day period, low ethanol intake (0.1-1.9 g.kg-1.d-1) and high ethanol intake (2.0-4.0 g.kg-1.d-1) groups were identified. Control groups consisted of rats provided with propylene glycol in equivalent caloric amounts to the ethanol consumed by high ethanol intake rats (isocaloric group) and rats served water only (ad libitum group). An additional two groups from which ethanol was removed 5 days prior to surgery were also studied (low ethanol grace and high ethanol grace). Hepatic regeneration was determined by restitution of liver weight, [3H]thymidine incorporation into DNA, and [14C]leucine incorporation into protein 24, 48, and 72 h following partial (70%) hepatectomy. The results of the study revealed no significant differences in the rate of hepatic regeneration between low and high ethanol consuming rats or between either of these groups and isocaloric or ad-libitum fed control groups. Regeneration in low ethanol grace and high ethanol grace groups were also similar to each other and controls. Moreover, there was no correlation between mean ethanol consumption per rat and restitution of liver weight, [3H]thymidine incorporation into DNA, or [14C]leucine incorporation into protein by the regenerating liver (r = 0.0716, -0.1637, and 0.1395, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1990

Phosphofructokinase 2 and glycolysis in HT29 human colon adenocarcinoma cell line. Regulation by insulin and phorbol esters.

Kinetic properties of phosphofructokinase 2 (PFK2) and regulation of glycolysis by phorbol 12-myristate 13-acetate (PMA) and insulin were investigated in highly glycolytic HT29 colon cancer cells. PFK2 was found to be inhibited by citrate and, to a lesser extent, by phosphoenolpyruvate and ADP, but to be insensitive to inhibition by sn-glycerol phosphate. From these kinetic data, PFK2 from HT29 cells appears different from the liver form, but resembles somewhat the heart isoenzyme. Fructose 2,6-bisphosphate (Fru-2,6-P2) levels, glucose consumption and lactate production are increased in a dose-dependent manner in HT29 cells treated with PMA or insulin. The increase in Fru-2,6-P2 can be related to an increase in the Vmax. of PFK2, persisting after the enzyme has been precipitated with poly(ethylene glycol), without change in the Km for fructose 6-phosphate. The most striking effects of PMA and insulin on Fru-2,6-P2 production are observed after long-term treatment (24 h) and are abolished by actinomycin, cycloheximide and puromycin, suggesting that protein synthesis is involved. Furthermore, the effects of insulin and PMA on glucose consumption, lactate production, Fru-2,6-P2 levels and PFK2 activity are additive, and the effect of insulin on Fru-2,6-P2 production is not altered by pre-treatment of the cells with the phorbol ester. This suggests that these effects are exerted by separate mechanisms.

Adenocarcinoma↗
PubMed1990

Changes in serum and hepatic polyamine concentrations after 30%, 70% and 90% partial hepatectomy in rats.

Polyamines have been reported to play an important role in stimulating hepatic regeneration after partial hepatectomy. To determine whether changes in systemic or hepatic polyamine concentrations correlate with the extent of the regenerative stimulus, serum and tissue putrescine, spermidine and spermine concentrations were determined in groups of adult male rats (n = 6 to 12/group) 0, 24, 48, and 72 hr after 30%, 70% or 90% partial hepatectomy. Serum putrescine levels were variably increased after partial hepatectomy and did not correlate with hepatic regenerative activity. Serum spermidine levels remained unaltered and spermine levels were undetectable both before and after partial hepatectomy. In hepatic tissue, only putrescine concentrations increased in proportion to the extent of hepatic resection. Moreover, there was a significant correlation between hepatic putrescine concentrations and restitution of liver mass (r = 0.778), DNA synthesis (r = 0.8026) and protein synthesis (r = 0.7034) (p less than 0.05). No significant correlations existed between hepatic spermidine or spermine concentrations and these parameters of hepatic regeneration. The results of this study support the hypothesis that hepatic putrescine plays an important role in stimulating hepatic regeneration after partial hepatectomy.

Animals↗