Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

Glycyrrhizin inhibits TNF-induced, but not Fas-mediated, apoptosis in the human hepatoblastoma line HepG2.

To determine the transaminase-lowering action of glycyrrhizin (GL) immunologically, the effect of GL on tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis was assessed using a human hepatoblastoma line, HepG2 cells. The HepG2 cells were resistant to TNF-alpha and anti-Fas antibody, but were rendered susceptible to TNF-alpha and anti-Fas antibody in the presence of actinomycin D (Act D), an inhibitor of RNA synthesis. The cytotoxicity induced by TNF-alpha/Act D or anti-Fas/Act D was accompanied by DNA fragmentation, indicating apoptotic death of HepG2 cells. GL partially prevented the apoptosis of HepG2 cells induced by TNF-alpha/Act D in a GL-dose dependent fashion. However, this protective effect of GL was not observed in the cytotoxicity of HepG2 caused by anti-Fas/Act D. Although the protection mechanism of GL, observed in a limited fashion against TNF-alpha-mediated apoptosis, is unclear, the present results provide an immunological explanation for the transaminase-lowering action of GL in the GL treatment of chronic liver diseases involving apoptotic hepatocyte death in their pathogenesis.

Disappearance of serum HCV-RNA after short-term prednisolone therapy in a patient with chronic hepatitis C associated with autoimmune hepatitis-like serological manifestations.

We report a 70-year-old woman with chronic hepatitis C associated with autoimmune hepatitis (AIH)-like serological manifestations, in whom elimination of hepatitis C virus (HCV) was observed after corticosteroid treatment. The patient was infected with HCV, genotype Ib, but had several laboratory findings, such as markedly elevated serum gamma-globulin and IgG, characteristic of AIH, as well as a high titer of an anti-nuclear antibody. An ultrasound (US)-guided liver biopsy disclosed chronic active hepatitis F3. Corticosteroid worsened her liver function test results and raised amounts of HCV-RNA in the serum. Withdrawal of the corticosteroid led to prompt normalization of transaminase levels and the disappearance of serum HCV-RNA, determined by reverse transcription-polymerase chain reaction (RT-PCR). For 4 years, up to the time of this study, her transaminase values have been normal and HCV viremia was not detected by repeated RT-PCR. We believe this to be the first reported case in which eradication of HCV was achieved by corticosteroid therapy alone, without the introduction of interferon.

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/platelet-derived endothelial cell growth factor and histological prognostic factor, and influences of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase levels. 5'-DFUR Joint Research Group in the Osaka Area for Gastric Cancer].

PURPOSE: Pyrimidine nucleoside phosphorylase (PyNPase), among which thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, is an enzyme to convert 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor, angiogenetic factor. Therefore, we expect that there is possibility of dThdPase being a prognostic factor. METHODS: We investigated for a possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, examined the influences of preoperative oral 5'-DFUR administration to PyNPase levels and investigated for a correlation between HPLC methods and ELISA methods in patients with gastric cancer. RESULTS: Higher levels of PyNPase were observed in patients with advanced t,n,v, and ly factors. PyNPase levels decreased by 5'-DFUR in patients with differentiated cases. A high correlation was found between HPLC and ELISA methods. CONCLUSION: This study suggests that we must investigate possibility of PyNPase being a prognostic factor in more detail.

Intragastric administration of ursodeoxycholic acid suppresses immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen or Peyer's patches in mice.

Ursodeoxycholic acid (UDCA) has been recognized as a therapeutic drug for primary biliary cirrhosis (PBC) and chronic viral hepatitis. As one of the mechanisms by which UDCA improves liver function tests in those patients, its immunomodulatory effect is currently considered important. Although the suppressive effects of UDCA on some cytokine productions, T-cell mediated cytotoxicity and immunoglobulin production were observed from in vitro studies, the immunomodulation in vivo by UDCA remains unclear. In the present study, we investigated the effect of UDCA administration on the number of immunoglobulin secreting cells in liver, peripheral blood, spleen and Peyer's patches in mice using the enzyme linked immunospot assay and assessed whether the UDCA-mediated immunomodulation is liver-specific. It was demonstrated that intragastric administration of UDCA reduced immunoglobulin secretion by lymphocytes from liver, but not from peripheral blood, spleen, or Peyer's patches. However, immunoglobulin production of those lymphocytes cultured in the presence of UDCA was suppressed, irrespective of their distribution sites, in a UDCA dose-dependent manner. When the concentrations of UDCA in portal and peripheral blood were measured using high performance liquid chromatography, UDCA was detectable in the portal blood in UDCA-treated mice, but not in peripheral blood, suggesting that the concentrations of UDCA in the environment surrounding lymphocytes may be an important factor for the modulation of lymphocyte functions.

[Combination therapy of high dose 5'-DFUR+MMC for advanced or recurrent gastric cancer. 5'-DFUR Joint Research Group in the Osaka District for Gastric Cancer].

We conducted multi-center clinical trials of 'Treatment with high dose 5'-DFUR+MMC' in order to evaluate the effects, the possibility for outpatient treatment and the survival effects in patients with advanced or recurrent gastric cancer. The treatment schedule was as follow; 5'-DFUR 1,600 mg/body/day was given orally for five consecutive days every week and MMC 6 mg/m2 was injected intravenously once every four weeks. Forty-eight patients were enrolled and 34 cases were evaluated for anti-tumor responses. The overall response rate was 29.4% (10/34 cases). Side effects were mainly diarrhea, but outpatient treatment was possible in most cases. The median survival period was 249 days, which is longer than with other treatments. This result suggests that this combination chemotherapy is useful in patients with advanced or recurrent gastric cancers.

Experimental study on the relapse of tuberculosis after the termination of antituberculous chemotherapy using immunodeficient nude mice.

The effect of cellular immunity induced by tuberculous infection on bacteriological relapse after the termination of antituberculous chemotherapy was studied experimentally using immunodeficient nu/nu mice and immunocompetent dd mice. The efficacy of intensive chemotherapy was excellent even in nu/nu mice; tubercle bacilli in the organs decreased below the detectable limit, but formidable regrowth of bacilli was seen after the termination of chemotherapy. On the other hand, in the case of dd mice that established antituberculous cellular immunity through tuberculous infection, bacteriological relapse was generally very slight. It was concluded that bacteriological relapse was related closely with the established cellular immunity induced by the infected tubercle bacilli.

Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine.

The antituberculous activity of 27753-RP (RP), a new semisynthetic derivative of griselimycine, was determined both in vitro and in vivo, and its activity against atypical mycobacteria was also studied in vitro. 1) The minimal inhibitory concentration of RP against H37Rv and its mutants resistant to streptomycin, isoniazide, kanamycin, rifampicin and enviomycin was 0.5 microgram/ml in liquid media, showing no cross-resistance. However, loss of potency occurred in Ogawa's egg media, and 50 micrograms/ml of RP were required for inhibition of growth. 2) In the therapeutic study of experimental tuberculosis in mice, RP was shown to have a remarkable effect. In particular, when treatment was started immediately after infection, RP showed a therapeutic efficacy comparable to that of rifampicin, although a double dose of the drug was required. When treatment was started 3 weeks after infection, RP was inferior to rifampicin in therapeutic efficacy. 3) RP also showed excellent antituberculous activity against experimental tuberculosis in guinea-pigs. Twice-a-week treatment had a therapeutic efficacy comparable to that obtained by daily treatment, but with an increased dosage. 4) Among atypical mycobacteria, RP showed some degree of activity against Mycobacterium kansasii in vitro, while its activity against M. intracellulare appeared to be extremely low.

[Study of lymphocytes blast transformation method by a small amount of whole blood cultivation with 125I-UdR (author's transl)].

Lymphocytes blast transformation method by a small amount of whole blood cultivation with 125I-UdR was studied. 1) It is suitable to take for 4 or 5 days as culture days. 2) It is suitable to add PHA-P in the concentration of 7.5 micrograms per ml of medium. 3) Addition of fetal calf serum in medium is not required. 4) The mean value of SI was 35.62 for the healthy persons, 31.23 for the patients of lung tuberculosis and 16.31 for the patients of lung cancer. The difference of SI between the healthy persons and the lung cancer was significant statistically.