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Biomedical subjects

Y Guigoz

Publications and source records attributed to Y Guigoz.

28 records · Page 2Linked to original sources
PubMed1993

Type 1 plasminogen activator inhibitor is not an acute phase reactant in rats. Lack of IL-6- and hepatocyte-dependent synthesis.

The contributing role of hepatocytes and IL-6 in the acute phase-like elevation of plasma type 1 plasminogen activator inhibitor (PAI-1) in vivo is not known. We addressed this question by comparing the effects of two inflammatory stimuli known to increase plasma concentrations of IL-6 on the plasma concentrations and site of synthesis of PAI-1 and cysteine proteinase inhibitor (CPI) in rats. Subcutaneous injection of turpentine results in a sustained increase in plasma IL-6 and CPI Ag levels over a 24-h period. In contrast, plasma PAI-1 activity was not altered by turpentine treatment. Northern blot analysis of poly(A)+ mRNA extracted from freshly isolated hepatocytes of saline- or turpentine-treated animals demonstrated induction of CPI mRNA expression but failed to detect basal or induced PAI-1 or IL-6 mRNA expression. However, PAI-1 mRNA was detected in rat hepatocytes in primary culture for 24 h and was induced by dexamethasone. Intravenous infusion of bacterial LPS (4 mg/kg) induced a sustained increase in plasma CPI Ag and transient increases in plasma IL-6 and PAI-1. Northern blot analysis of freshly isolated, fractionated liver cells indicated that LPS treatment (3 h) induced PAI-1 mRNA expression most significantly in the endothelial and Kupffer cell fractions. IL-6 mRNA expression was induced in Kupffer cells and CPI mRNA was induced in hepatocytes. Immunocytochemical analysis revealed LPS-induced accumulation of PAI-1 Ag associated with the vascular endothelium, subendothelial matrix, and sinusoidal lining cells. Our results indicate that PAI-1 mRNA is not significantly expressed by rat hepatocytes in vivo and that plasma PAI-1 levels are not influenced by increased IL-6 expression in Kupffer cells or in plasma.

Acute-Phase Proteins↗
PubMed1992

Serum T-kininogen levels increase two to four months before death.

We have reported an accumulation of T-kininogen mRNA in the liver of aging Sprague-Dawley rats. T-kininogen is a cysteine proteinase inhibitor. Since a disruption of the intracellular protein degradation machinery is known to occur during senescence, we wished to further define the role of this protein in the aging process. As a first step, we have measured T-kininogen levels both in serum and within the liver. We have found that serum protein levels are indeed augmented during senescence, although not as dramatically as the mRNA (2.5-fold versus 8.3-fold). Immunocytochemistry, as well as Western blot analysis suggests that this is due to the presence of T-kininogen within hepatic cells in aged rats. Life-long dietary restriction, a known age-prolonging treatment, decreases the overexpression of the protein in 24-month-old rats. Later, diet-restricted animals still show an increased expression from the gene, the effect being delayed but not abolished by dietary manipulation. Interestingly, a longitudinal study indicated the existence of a positive correlation between the time of increase of serum T-kininogen and the time of death of the animal. Serum T-kininogen was found to increase 2.5-4 months before death.

Aging↗
PubMed1989

T-kininogen gene expression is induced during aging.

We have constructed a cDNA library from senescent (24-month-old) rat liver mRNA and, by differential screening, have selected clones corresponding to mRNA species with increased abundance in aging rats. Direct sequencing of the inserts indicated that most of the clones (9 of 10) contained sequences coding for T-kininogen, also called major acute-phase protein, cysteine protease inhibitor, or thiostatin. Nuclear elongation experiments showed that the increase in mRNA concentration was controlled at the transcriptional level. RNase mapping and S1 analysis indicated that the age-dependent induction operated preferentially at one of the three transcriptional start sites of the gene(s). The acute-phase reaction (inflammation) is known to also induce these genes at the level of transcription; however, two of the three start sites are induced by inflammation. Transcription from one of these sites was induced by both phenomena, aging and inflammation.

Acute-Phase Proteins↗
PubMed1987

Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression.

Rotation-mediated aggregate cultures of foetal rat liver cells were prepared and grown in a chemically defined medium. Their capacity for cellular organisation and maturation was studied over a culture period of 3 wk by using both morphologic and biochemical criteria. It was found that within each aggregate, distinct liver cell types were present and attained their normal, differentiated phenotype. Parenchymal cells formed small acini with a central lumen. Within the first 2 wk in culture, albumin and ferritin mRNA levels were maintained, while the alpha-fetoprotein mRNA levels decreased, and tyrosine aminotransferase (TAT) gene expression increased. No significant response to glucocorticoids was observed in early cultures, whereas after 3 wk a marked increase in TAT mRNA levels was elicited by dexamethasone and glucagon (additive stimulatory effects). The results show that foetal rat liver cells cultured in a chemically defined medium are able to rearrange themselves into histotypic structures, and display a developmental pattern of gene expression comparable to that of perinatal rat liver in vivo. This culture system offers therefore a useful model to study the development and function of liver cells.

Albumins↗
PubMed1986

The effect of age on the induction of tyrosine aminotransferase and tryptophan oxygenase genes by physiological stress.

Expression of the genes coding for tyrosine aminotransferase and tryptophan oxygenase in rats is induced in response to cold stress. We have studied the effect of ageing on this induction. The induction of tyrosine aminotransferase activity in young adult rats (10 months) was about twice that observed with old rats (25 months). This difference between the two age groups was also observed when the steady-state level of tyrosine aminotransferase mRNA was measured by hybridization with a specific DNA probe. However, when the transcription rate of the gene was measured by in vitro elongation of nascent RNA in isolated nuclei, no difference was detected. In contrast to the results with tyrosine aminotransferase, induced tryptophan oxygenase enzyme and mRNA levels did not show an age-dependent difference. These results suggest that there is, with ageing, an impairment in post-transcriptional regulation of the synthesis of tyrosine aminotransferase. The regulation of tryptophan oxygenase, on the other hand, is similar in the two age groups.

Aging↗
PubMed1985

Pretranslational regulation of tyrosine aminotransferase and phosphoenolpyruvate carboxykinase (GTP) synthesis by glucagon and dexamethasone in adult rat hepatocytes.

The regulation of synthesis of the gluconeogenic cytosolic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and of tyrosine aminotransferase (TAT) by glucagon and glucocorticoid hormones was studied in hepatocytes maintained in suspension culture for 7 h. Specific antibodies were used to measure relative rates of enzyme synthesis after pulse-labelling of the cells with [3H]leucine or [35S]methionine. Concomitantly, amounts of mRNA were quantified after translation in vitro in a reticulocyte lysate and specific immunoprecipitation of the proteins. Glucagon stimulated the rate of synthesis of PEPCK by 4-6-fold and that of TAT by 6-8-fold in 2h. In contrast, dexamethasone had little effect on PEPCK synthesis, whereas it increased TAT synthesis by 5-9-fold. When used in combination, the two hormones displayed additive effects on TAT synthesis, whereas the glucocorticoid hormone strongly potentiated stimulation of PEPCK synthesis by glucagon. In every instance, changes in rates of synthesis of the two enzymes were totally accounted for by increases in amounts of the corresponding functional mRNA, suggesting a pretranslational site of action for both glucagon and dexamethasone.

Animals↗
PubMedDate not supplied

Overview of the MNA--Its history and challenges.

The Mini Nutritional Assessment (MNA) is a simple tool, useful in clinical practice to measure nutritional status in elderly persons. From its validation in 1994, the MNA has been used in hundreds of studies and translated into more then 20 languages. It is a well-validated tool, with high sensitivity, specificity, and reliability. An MNA score > or = 24 identifies patients with a good nutritional status. Scores between 17 and 23.5 identify patients at risk for malnutrition. These patients have not yet started to lose weight and do not show low plasma albumin levels but have lower protein-calorie intakes than recommended. For them, a multidisciplinary geriatric intervention is needed, which takes into account all aspects that might interfere with proper alimentation and, when necessary, proposes therapeutic interventions for diet or supplementation. If the MNA score is less than 17, the patient has protein-calorie malnutrition. It is important at this stage to quantify the severity of the malnutrition (by measuring biochemical parameters like plasma albumin or prealbumin levels, establishing a 3- day record of food intake, and measuring anthropometric features like weight, BMI, arm circumference and skin folds). Nutritional intervention is clearly needed and should be based on achievable objectives established after a detailed comprehensive geriatric assessment. The MNA has been shown to be useful for nutritional intervention follow-up as well. The MNA can help clinicians design an intervention by noting where the patient loses points when performing the MNA. Moreover, when a nutritional intervention is successful, the MNA score increases. The MNA is recommended by many national and international clinical and scientific organizations. It can be used by a variety of professionals, including physicians, dietitians, nurses or research assistants. A short screening version (MNA-SF) has been developed, which, if positive, indicates the need to complete the full MNA. It takes less than 4 minutes to administer the MNA-SF and between 10 and 15 minutes for the full MNA.

Aged↗
PubMedDate not supplied

The Mini Nutritional Assessment (MNA) review of the literature--What does it tell us?

To review the literature on the MNA to Spring 2006, we searched MEDLINE, Web of Science and Scopus, and did a manual search in J Nutr Health Aging, Clin Nutr, Eur J Clin Nutr and free online available publications. VALIDATION AND VALIDITY: The MNA was validated against two principal criteria, clinical status and comprehensive nutrition assessment using principal component and discriminant analysis. The MNA shortform (MNA-SF) was developed and validated to allow a 2-step screening process. The MNA and MNA-SF are sensitive, specific, and accurate in identifying nutrition risk. NUTRITIONAL SCREENING: The prevalence of malnutrition in community-dwelling elderly (21 studies, n = 14149 elderly) is 2 +/- 0.1% (mean +/- SE, range 0- 8%) and risk of malnutrition is 24 +/- 0.4% (range 8-76%). A similar pattern is seen in out-patient and home care elderly (25 studies, n = 3119 elderly) with prevalence of undernutrition 9 +/- 0.5% (mean +/- SE, range 0-30%) and risk of malnutrition 45 +/- 0.9% (range 8-65%). A high prevalence of undernutrition has been reported in hospitalized and institutionalized elderly patients: prevalence of malnutrition is 23 +/- 0.5% (mean +/- SE, range 1- 74%) in hospitals (35 studies, n = 8596) and 21 +/- 0.5% (mean +/- SE, range 5-71%) in institutions (32 studies, n = 6821 elderly). An even higher prevalence of risk of malnutrition was observed in the same populations, with 46 +/- 0.5% (range 8-63%) and 51 +/- 0.6% (range 27-70%), respectively. In cognitively impaired elderly subjects (10 studies, n = 2051 elderly subjects), detection using the MNA, prevalence of malnutrition was 15 +/- 0.8% (mean +/- SE, range 0-62%), and 44 +/- 1.1% (range 19-87%) of risk of malnutrition. CHARACTERISTICS: The large variability is due to differences in level of dependence and health status among the elderly. In hospital settings, a low MNA score is associated with an increase in mortality, prolonged length of stay and greater likelihood of discharge to nursing homes. Malnutrition is associated with functional and cognitive impairment and difficulties eating. The MNA(R) detects risk of malnutrition before severe change in weight or serum proteins occurs. NUTRITIONAL INTERVENTION: Intervention studies demonstrate that timely intervention can stop weight loss in elderly at risk of malnutrition or undernourished and is associated with improvements in MNA scores. The MNA can also be used as a follow up assessment tool. CONCLUSION: The MNA is a screening and assessment tool with a reliable scale and clearly defined thresholds, usable by health care professionals. It should be included in the geriatric assessment and is proposed in the minimum data set for nutritional interventions.

Aged↗