The liver in uroporphyria : a biochemical and morphological study

The aim of the work described in this thesis was to examine further the mechanisms involved in the accumulation of uroporphyrins in the liver, i.e., the role of iron and an increased activity of one of the preceding enzymes in the heme biosynthetic pathway, PBG-D, in the porphyrinogenic process in experimental uroporphyria and in PCT. In the previous paragraphs, the proposed role of iron in the development of uroporphyria has been discussed. However, a study on the time-sequence relationship between iron accumulation and uroporphyrin production in the liver has not been performed. In addition, the nature of the iron pool involved in this process has not been established. The role of iron in uroporphyria has been explained by its ability to participate in peroxidative and free radical reactions. Desferrioxamine, an iron chelator, has been described to diminish uroporphyrin accumulation in the liver. At present, the specific effects of desferrioxamine on iron accumulation, free radical-mediated reactions, uroporphyrin accumulation and URO-D activity in the liver have not been studied in experimental uroporphyria. It has been reported that the activity of the enzyme PBG-D is increased in erythrocytes and livers of patients with PCT. It is not clear whether this increased PBG-D activity can be observed both in animals with experimental uroporphyria and in humans with sporadic and familial forms of PCT. An increased PBG-D activity could explain the absence of acute attacks in PCT. Moreover, an increased PBG-D activity could also provide an additional explanation for uroporphyrin accumulation in experimental and human uroporphyria

Штанги для горизонтально направленного бурения

В статті наведено технічні дані про конструкцію та експлуатаційні вимоги до бурових штанг горизонтально спрямованого буріння свердловин

Recurrence and survival after resection of adenocarcinoma of the gastric cardia

In a retrospective study, the results after resection of carcinoma of the gastric cardia in the era without neoadjuvant therapy or extended lymph node dissection were evaluated. All 184 patients who underwent resection between January 1983 and December 1993 were included. Recurrence of disease, survival and prognostic factors were determined. The overall cumulative 5-year recurrence rate was 71% and the survival rate 23%. Multivariate analysis identified locoregional lymph node and distant metastases as the crucial prognosticators of recurrence of disease and survival. These results were similar to those from a previous study concerning our patients operated during the years 1983-88. The prognosis of a resected cardiacarcinoma has remained unchanged in our hands over the past 10 years. These results stress the importance of exploring new ways, such as the use of new diagnostic tools, to optimize preoperative patient selection and more aggressive treatment regimens to improve final outcom

Protein energy malnutrition predicts complications in liver cirrhosis

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Ferritin accumulation and uroporphyrin crystal formation in hepatocytes of C57BL/10 mice: A time-course study

To establish the time-sequence relationship between ferritin accumulation and uroporphyrin crystal formation in livers of C57BL/10 mice, a biochemical, morphological and morphometrical study was performed. Uroporphyria was induced by the intraperitoneal administration of hexachlorobenzene plus iron dextran and of iron dextran alone. Uroporphyrin crystal formation started in hepatocytes of mice treated with hexachlorobenzene plus iron dextran at 2 weeks and in mice treated with iron dextran alone at 9 weeks. In the course of time, uroporphyrin crystals gradually increased in size. Uroporphyrin crystals were initially formed in hepatocytes in the periportal areas of the liver, in which also ferric iron staining was first detected. The amount and the distribution of the main storage form of iron in hepatocytes, ferritin, did not differ between the two treatment groups. Ferritin accumulation preceded the formation of uroporphyrin crystals in hepatocytes in both treatment groups. Moreover, uroporphyrin crystals were nearly always found close to ferritin iron. We conclude that uroporphyrin crystals are only formed in hepatocytes in which also iron (ferritin) accumulates. Hexachlorobenzene accelerates the effects of iron in porphyrin metabolism, but does not influence the accumulation of iron into the liver

Characterization of a new mutation (R292G) and a deletion at the human uroporphyrinogen decarboxylase locus in two patients with hepatoerythropoietic porphyria

A deficiency in the activity of uroporphyrinogen decarboxylase (UROD), the fifth enzyme of the haem biosynthetic pathway, is found in familial porphyria cutanea tarda (F-PCT) and hepatoerythropoietic porphyria (HEP). A new mutation (R292G) and a deletion have been found in a pedigree with two HEP patients (two sisters). The R292G mutation was not detected in 13 unrelated affected patients with F-PCT, so it appears to be uncommon. The possibility that the arginine 292 may participate at the active site of the enzyme is discussed. A summary of the 7 mutations/deletions found in the UROD gene with their frequency is presented

Allelic imbalance of 7q32.3-q36.1 during tumorigenesis in Barrett's esophagus

Malignant transformation of Barrett's esophagus is characterized by three distinct premalignant stages: intestinal metaplasia (MET), low- (LGD), and high-grade dysplasia (HGD). We reported recently an increase in the frequency of loss of 7q33-q35 between LGD and HGD as determined by comparative genomic hybridization (P. H. J. Riegman et al., Cancer Res., 61: 3164-3170, 2001). Now the 7q32.3-q36.1 region was additionally characterized by allelotype analysis with 11 polymorphic markers in 15 METs, 20 LGDs, 20 HGDs, and 20 Barrett's adenocarcinomas from different patients. Low percentages of imbalance were determined in METs and LGDs, 7% and 10%, respectively, whereas HGDs and Barrett's adenocarcinomas revealed high percentages of loss, 75% and 65%, respectively. This difference in frequency between LGDs and HGDs appeared highly significant: P = 0.00007. The majority of imbalances were found at D7S2439 and D7S483, located on 7q36.1. These data suggest that markers from this area can be used as a diagnostic tool in Barrett's esophagus, i.e., to distinguish between watchful waiting and active treatment