Bile acids inhibit tumour necrosis factor α-induced interleukin-8 production in human colon epithelial cells

To clarify the regulatory mechanism of the production of various inflammatory mediators by intestinal epithelial cells, the effect of bile acids (tauroursodeoxycholate, TUDC; taurochenodeoxycholate, TCDC; and taurocholate, TC) on the cytokine-induced production of interleukin (IL)-8 in a human colon epithelial cell line (HT-29) was examined. HT-29 cells were incubated for 24 h in a culture medium containing tumour necrosis factor α (TNFα; 1 ng/mL) and/or interleukin (IL)-1 β (1 ng/mL) in the presence or absence of bile acids. The IL-8 concentration in the medium was measured by an enzyme-linked immunosorbent assay. The binding assay of TNFα was performed using [125I]-TNFα (100 pmol/L). Interleukin-8 production during incubation with TNFα was markedly reduced in the presence of 0.5 and 1 mmol/L TUDC, 0.5 and 1 mmol/L TCDC and 0.5 and 1 mmol/L TC, by 56, 85, 86, 91, 37 and 70%, respectively. The IL-8 production during incubation with IL-1ß was not significantly reduced in the presence of these bile acids. The specific binding of TNFα to cells was inhibited 33, 47, and 14% by 1 mmol/L TUDC, TCDC and TC, respectively. These findings suggest that bile acids inhibit TNFα-induced IL-8 production by the colonic cells. The suppression may be partly due to inhibition of TNFα binding to the cells by bile acids.     

Amino acid residues of core region of hepatitis B virus. Asymptomatic carriers versus patients with liver disease

Recent molecular biological studies have shown that mutations of hepatitis B virus (HBV) genes may have an important role in the pathogenesis of HBV-induced liver diseases. It has been suggested that the core antigen of HBV could be an immunologic target of cytotoxic T lymphocytes. In this study, nucleotide sequences encoding 183 amino acid residues of the core region of HBV were analysed in 4 asymptomatic healthy carriers and in 5 patients with chronic liver disease, in whom serum aminotransferase levels were fluctuating. A cluster of amino acid substitutions were found from codon 87 to 97 of the core region of HBV in all 5 patients with liver diseases. Such changes were not found in any of the asymptomatic carriers. These data suggest that the peptide sequence spanning 11 amino acid residues in this particular region may play an important role in the pathogenesis of B-viral liver disease, and could be an immunologic target of cytotoxic T lymphocytes.     

Portal hypertension and Budd–Chiari syndrome: intervention

Abstract   Due to the progressive nature of the etiologic diseases of portal hypertension, medical, surgical and endoscopic therapy for the associated symptoms become difficult. For their treatment, interventional radiology plays an important role. In this lecture, the vascular interventional procedures useful for the treatment of portal hypertension and its associated diseases, Budd–Chiari syndrome, portal vein thrombosis, and portal vein stricture will be discussed.     

Stage specific follow-up strategy after cystectomy for carcinoma of the bladder

BACKGROUND: Follow-up strategies after cystectomy for carcinoma of the bladder should be determined according to the risk of recurrence, which is stage dependent. We aimed to develop follow-up protocol for monitoring patients with carcinoma of the bladder for tumor recurrence and diverted urinary tract complications after radical cystectomy. METHODS: The records of 351 patients with carcinoma of the bladder who underwent cystectomy between 1979 and 1999 were reviewed for dates and presenting symptoms of local and distant recurrences. The results of imaging studies and blood tests were also reviewed. Based on the division of patients into pathological stages of pT1 and lower, pT2, and pT3 and higher groups, we proposed a new follow-up schedule for carcinoma of the bladder. RESULTS: The risk of metastasis was related to the pathological stage of the primary tumor. Recurrence developed in 10 of 124 patients (8%) with pT1 or lower, 17 of 101 patients (17%) with pT2, and 55 of 101 patients (54%) with pT3 or higher disease at a median of 11 (range 6-186), 10 (1-40) and 7 (1-76) months, respectively. Recurrences in patients with pT3 or higher were found earlier and more frequently than those with pT2 or lower. Of 82 patients with metastases, 54 initially were symptomatic, and three of pT1 or lower, six of pT2, and 19 of pT3 or higher were asymptomatic. Based on these results we proposed a stage specific follow-up protocol. CONCLUSIONS: A stage-driven follow-up strategy for monitoring patients after radical cystectomy can reduce medical expenses while efficiently detecting recurrences and complications.     

Macrocytosis Resulting from Early Denucleation of Erythroid Precursors

In an attempt to elucidate the mechanism of production of macrocytosis inacute anemia, we studied changes in red cell volume and hemoglobin content, the RNA level of normoblasts and reticulocytes and RNA synthesis inreticulocytes of rabbits made anemic by blood loss or phenylhydrazine administration. The results were as follows:

(1) In severe phenylhydrazine anemia, red cell volume and hemoglobincontent per cell increased to twice the normal values.

(2) The RNA level of normoblasts decreases with the maturation of thecells and reaches a minimum at the orthochromatic stage. The decrease issimilar in the normal and anemic rabbits.

(3) The RNA level of reticulocytes in the bone marrow is higher in anemicthan in normal rabbits. In general, the RNA level of reticulocytes of anemicrabbits is comparable to that of the polychromatic normoblasts, while in normal rabbits this value is comparable to that of orthochromatic normoblasts.

(4) Autoradiographs of reticulocytes incubated with H³-uridine indicatethat the increased level of reticulocyte RNA of anemic rabbits is not due tonewly synthesized RNA.

From these results, we conclude that in an "emergency" situation of erythropoietic stimulation denucleation of normoblasts occurs at the polychromaticstage of red cell maturation, with skipping of the terminal cell division toorthochromatic cells and formation of macrocytic reticulocytes and red cells.

Submitted on August 28, 1963 Accepted on April 30, 1964