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Biomedical subjects

N Mousseau

Publications and source records attributed to N Mousseau.

At least 19 recordsLinked to original sources
PubMed1999

Expression of matrix metalloproteinases and their inhibitors in human brain tumors.

Sixty human brain tumors, classified according to the New World Health Organization (WHO) classification including, grade I schwannomas, meningiomas and pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astrocytomas, grade IV glioblastomas, grade III anaplastic oligodendrogliomas and grade IV glioblastomas and lung and melanoma metastases were analyzed for the expression of three matrix metalloproteinases (MMPs), two tissue inhibitors of MMPs (TIMPs) and for MMP activity. Some correlation was found between MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) than of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. MMP-9 levels were found to be significantly higher in grade III anaplastic astrocytomas and anaplastic oligodendrogliomas than those in grade I schwannomas and meningiomas. Anaplastic astrocytomas and Grade IV glioblastomas expressed significantly higher levels MMP-12 than grade I meningiomas. All sixty tumors showed a similar pattern of activity in zymography, proMMP-9 being the major species detected. Interestingly, TIMP-1 and TIMP-2 expression levels were especially low in tumors of grade II and grade III but significantly higher in tumors of grade I, particularly in schwannomas. Taken together, these data suggest that: 1) a balance between MMPs and TIMPs has an important role to play in human brain tumors; 2) TIMP expression may be valuable markers for tumor malignancy.

Astrocytoma↗
PubMed1999

Matrix metalloproteinases and their inhibitors in human pituitary tumors.

OBJECTIVE: To determine the expression of matrix metalloproteinases (MMP)-1, -2, and -3 and the tissue inhibitors of metalloproteinases (TIMP)-1, -2, and -3 in 12 tissue samples from normal pituitary glands and in 28 human pituitary tumors ranging from Grade 0 to Grade IV, and to establish a correlation between the level of expression of MMPs and TIMPs and the tumor grade. METHODS: The expression of MMPs and TIMPs was determined by Western blotting. MMP activity was detected by gelatin zymography. RESULTS: MMPs were expressed in the majority of tumors, and their levels of expression were unrelated to tumor grade or to their invasive phenotype. Some correlation was observed between MMP activity detected by zymography and tumor grade. TIMP-2 and TIMP-3 were poorly expressed in high-grade tumors and strongly expressed in normal pituitary glands and in the majority of low-grade tumors. CONCLUSION: No correlation could be established between the invasive potential of tumors and MMP-1, -2, and -3 expression levels. Some correlation was observed between MMP activity detected by zymography and tumor grade. A good inverse correlation was observed between TIMP-2 and TIMP-3 expression levels and tumor grade. These data suggest that monitoring the expression of TIMP-2 and TIMP-3 or gelatinolytic activity could be of prognostic value.

Adenoma↗
PubMed1999

Expression of matrix metalloproteinases and their inhibitors in human brain tumors.

Sixty human brain tumors, including grade I meningiomas, schwannomas, and pilocytic astrocytomas, grade II astrocytomas, grade III anaplastic astrocytomas and oligodendrogliomas, and grade IV glioblastomas and lung and melanoma metastases were analyzed for expression of four matrix metalloproteinases (MMPs), two tissue inhibitors of MMPs (TIMPs), and MMP activity. No marked correlation was found between MMP expression and the degree of malignancy. Western blotting analysis revealed a more uniform pattern of distribution of MMP-2 (gelatinase A) than of MMP-9 (gelatinase B) and MMP-12 (metalloelastase) among tumors. All 60 tumors showed a similar pattern of activity in zymography, MMP-2 being the major species detected. Interestingly, TIMP-1 and TIMP-2 expression levels were low in tumors of grade III but significantly higher in tumors of grade I, particularly schwannomas. Altogether, these data suggest that: (1) the balance between MMP-2 and TIMP-2 is important in human brain tumors; and (2) TIMP expression may be a valuable marker for tumor malignancy.

Blotting, Western↗
PubMed1997

Differences in caffeine 3-demethylation activity among inbred mouse strains: a comparison of hepatic Cyp1a2 gene expression between two inbred strains.

The 3-demethylation of caffeine can be used as an index of cytochrome P450 CYP1A2 activity in vivo. We compared the plasma levels of caffeine and the 3-demethylated metabolite. 1,7-dimethylxanthine, in six common inbred strains (A/J, P/J, BALB/cJ, C3H/HeJ, AKR/J, and SWR/J) and one inbred strain (APN) derived in our laboratory from outbred Swiss-Webster mice on the basis of its relative susceptibility to acetaminophen-induced hepatotoxicity. We found significant variations between a number of the common strains, all of which produced significantly higher caffeine 3-demethylation indices than our APN strain. In three of the six common strains, there was a significant difference between males and females, with the females having consistently lower 1,7-xanthine/caffeine ratios. Hepatic Cyp1a2 expression was compared between APN and C3H/HeJ males. Microsomal methoxyresorufin O-demethylation, acetanilide 4-hydroxylation, and CYP1A2 immunoreactive protein levels were significantly higher in C3H/HeJ relative to APN mice, as were hepatic CYP1A2 mRNA levels. These results indicate the importance of strain and gender to the outcome of pharmacological or toxicological studies involving CYP1A2-mediated metabolism, as well as the suitability of the plasma 1,7-dimethylxanthine/caffeine ratio as a marker of CYP1A2 activity in the mouse. The striking differences observed between the APN and C3H/HeJ mice suggest that these strains may be suitable for a genetic analysis of the regulation of the basal expression of CYP1A2, a key enzyme in procarcinogen activation.

Acetaminophen↗
PubMed1997

Increased basal expression of hepatic Cyp1a1 and Cyp1a2 genes in inbred mice selected for susceptibility to acetaminophen-induced hepatotoxicity.

Susceptibility to acetaminophen-induced hepatotoxicity was found to vary widely in an outbred colony of Swiss Webster mice. Some acetaminophen-treated male mice showed a significant elevation in serum levels of the hepatic enzyme alanine aminotransferase at a normally non-hepatotoxic oral dose. A selective breeding program over 17 generations produced inbred mice which were either susceptible or nonsusceptible to the hepatotoxic effects of acetaminophen. Liver microsomes from the susceptible group showed a statistically significant increase in the ability to metabolize acetaminophen to a reactive intermediate which covalently binds N-acetylcysteine. Microsomal cytochrome P450 activities associated with CYP1A2 (acetanilide 4-hydroxylation and methoxyresorufin O-demethylase) were significantly increased in the susceptible group. Ethoxyresorufin O-deethylase activity, associated with both CYP1A1 and CYP1A2, was also significantly elevated in this group. Further examination of both CYP1A isoforms revealed that hepatic CYP1A1 and CYP1A2 mRNA and protein levels were significantly elevated in animals from the susceptible group. In vivo caffeine 3-demethylation, which is associated with CYP1A2 activity, co-segregated with acetaminophen susceptibility and showed a significant positive correlation (r = 0.626, p < 0.005) with CYP1A2 mRNA expression in animals from both the susceptible and nonsusceptible groups. The co-segregation of elevated basal Cyp1a1 and CYP1a2 gene expression levels in animals selected for susceptibility to acetaminophen-induced hepatotoxicity suggested a common heritable basis for regulation of basal expression of both of these CYP1A isoforms. This was supported by the correlated expression of both CYP1A mRNAs within individual mice (r = 0.644, p < 0.02).

Acetaminophen↗
PubMed1991

Chromatographic and spectroscopic characterization of sulphur-bound dimetridazole and ranidazole derivatives.

The 5-nitroimidazoles, dimetridazole and ronidazole, two important veterinary drugs, were reacted under reductive conditions with the sulfhydryl-containing substrates cysteine and glutathione to yield 5-amino-4-S-substituted imidazoles. After purification by reversed-phase liquid chromatography (RP-LC), the four adducts were characterized by RP-LC with photodiode array detection using conditions where their parent drugs were not eluted from the column. Structural identification was conducted by spectroscopic techniques, mainly 1-dimensional and 2-dimensional NMR. While the dimetridazole adducts were found to be monosubstituted at the C-4 position, the two ronidazole products contained two units of the sulfhydryl substrate, located at the C-4 and C-6 positions.

Chromatography, Liquid↗
PubMed1988

High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma: evaluation of their stability.

A rapid, specific and reproducible high-performance liquid chromatographic method was developed for the simultaneous determination of diltiazem and four of its metabolites in plasma. The method involves extraction with methyl tert.-butyl ether, back-extraction into 0.017 M phosphoric acid followed by reversed-phase chromatography on a 3-micron particle, 15-cm ODS column with UV detection at 237 nm. Overall the recovery of each compound was reproducible and greater than 85%. Calibration curves were linear over the concentration range 10-250 ng/ml, with within-day or between-day coefficients of variation not exceeding 12%. A stability study indicates that while diltiazem is stable for at least six weeks in frozen plasma, more than 30% degradation of the major metabolite, N-monodesmethyldiltiazem, was observed after four weeks at -20 degrees C. The assay procedure has been applied to monitoring of plasma levels in patients receiving chronic oral therapy.

Biotransformation↗