Tryptophan--niacin and tryptophan--serotonin pathways in weaning pigs with porphyria experimentally induced.
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Biomedical subjects
Publications and source records attributed to P Calandra.
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The urinary excretion of metabolites of the tryptophan leads to niacin pathway after an L-tryptophan load in patients with potential and latent diabetes, and in a third of those with chemical diabetes, was normal. In the remaining subjects with chemical diabetes and in those with clinical diabetes it was altered and characterized by an increase of xanthurenic acid and by a reduction of kynurenines and 3-hydroxyanthranilic acid. The thin-layer chromatographic pattern of tryptophan metabolites in the epidermis of patients with potential, latent, chemical, clinical diabetes was characterized by the kynurenine pathway metabolites that were also present in the epidermis of healthy subjects. Morevoer, the above pattern was characterized by the appearance of 5-hydroxytrptamine, and in patients with chemical and clinical diabetes by the appearance of xanthurenic acid.
PURPOSE: To analyze the genetic variability in a variable number of tandem repeats (VNTR) in the thymidylate synthase (TS) enhancer promoter region and assess the influence of functional alterations in mismatch repair genes by analyzing constitutional and tumoral DNA from patients with colorectal adenocarcinoma with a high microsatellite instability (MSI-H) or microsatellite stability (MSS) status. PATIENTS AND METHODS: Patients who underwent surgery for colorectal adenocarcinoma were selected from the colorectal database of our institute and, on the basis of MSI status, assigned to a study group and a control group: group A, MSI-H; group B, MSS. Microsatellite status was investigated using the Bethesda recommended panel (BAT-26, BAT-25, D2S123, D5S346, D17S250). In MSI-H patients an additional analysis was made of the microsatellite loci D18S61 and D18S58, both mapping in the region containing the TS gene (18p11.2-11.32). Based on the number of altered microsatellites (> or = 2, 1, or 0), tumors were considered as having high (MSI-H) or low (MSI-L) instability or microsatellite stability (MSS), respectively. Genotyping for thymidylate synthase promoter polymorphism was carried out on constitutional and tumor DNA of each patient by PCR amplification of the polymorphic region. RESULTS: MSI-H was found in 55 patients (group A) and MSS in 50 patients (group B). In none of the MSI-H patients was microsatellite instability found in the additional D18S61 and D18S58 loci. In five group A and ten group B cases the analysis was not performed because constitutional DNA and/or tumoral DNA were not amplifiable. Homozygotes for the triple repeat variant (3R/3R) displayed only the large PCR product, homozygotes for the double repeat variant (2R/2R) displayed only the smaller PCR product, while heterozygotes (2R/3R) displayed both the larger and smaller PCR products. In 3/50 (6%) group A patients and 5/40 (12%) group B patients repeat variations were found in tumoral DNA. CONCLUSION: Our findings demonstrate that there is genetic homogeneity between constitutional and tumoral DNA but do not support the hypothesis that mismatch repair genes are involved in VNTR recombinant events in TS gene variability.
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