Prevalence of hepatitis C virus antibody in an area endemic for hepatitis B virus and human T cell leukaemia virus

To clarify the prevalence of concurrent infection with hepatitis C virus (HCV), hepatitis B virus (HBV) and human T cell leukaemia virus (HTLV), we measured HCV antibody in the population of a district endemic for HBV and HTLV infection. Blood samples were collected in June 1990 from 579 inhabitants of four islands of Uwa Bay in the southwest of Ehime Prefecture in Japan. Anti-HCV antibody against C100-3 protein was detected using an enzyme-linked immunosorbent assay kit (Ortho Diagnostics). Thirteen of the 579 inhabitants (2.2%) were positive for anti-HCV, and this prevalence rate was not significantly different from the frequency of anti-HCV in Tokyo blood donors. A total of 11% (64 of 579) of the subjects were positive for HBsAg and 3.3% (19 of 579) were positive for anti-HTLV. These frequencies of HBsAg and anti-HTLV positivity were distinctly higher than the respective means of Japanese. All anti-HCV positive individuals were negative for HBsAg and anti-HTLV, while 54% (7 of 13) had increased alanine aminotransferase levels. These data suggest that the prevalence of HCV infection is not high even in an area endemic for HBV and HTLV infection.     

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.     

Protective antibodies against Taenia taeniaeformis in rats infected with eggs or injected with non-viable oncospheres or recombinant antigens of oncospheres

Antibody responses against Taenia taeniaeformis in rats infected with eggs or injected with non-viable oncospheres or recombinant antigens of oncospheres were analysed by passive transfer of serum and Western blotting. When recipient rats were injected with 1 ml serum from donors infected with eggs (infected serum), they all showed complete resistance to oral egg challenge, whereas those injected with 1 ml serum from donors injected with either oncospheres or recombinant antigens (vaccinated serum) showed no resistance. IgG and IgG subclass responses detected by Western blotting revealed that antibody responses to oncosphere antigens in infected serum thoroughly differed from those in vaccinated serum. It is suggested that IgG_2a responses in infected serum should be used for screening of epitopes for candidate vaccine.     

Acute myeloblasts leukaemia without Philadelphia chromosome developing after interferon therapy for chronic myelocytic leukaemia with Philadelphia chromosome

Summary. We report a patient who developed Philadelphia chromosome negative acute myeloblastic leukaemia with trisomy 8 and trisomy 11 after receiving treatment with alkylating agents and interferon for chronic myelocytic leukaemia positive for Philadelphia chromosome. Leukaemic cells were positive for myeloperoxidase and expressed CD13, CD33 and DR; some expressed CD2, CD4 and CD34. The fluorescence in situ hybridization method revealed that bcr-abl fusion genes were absent from > 90% of the bone marrow cells. The major bcr rearrangement was not detected by Southern blot analysis. We conclude that the leukaemic cells negative for Philadelphia chromosome may have developed as a result of treatment with alkylating agents and interferon in the present case.     

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.     

Three-year results of treatment for prostate cancer with low-dose rate temporary iridium-192 brachytherapy

AIM: To report the 3-year treatment results of definitive irradiation by using a temporary interstitial implant with low-dose rate iridium-192 with or without external beam radiotherapy in the treatment of localized prostate cancer. METHODS: One-hundred and forty-three patients with pathologically defined prostate carcinoma were treated from December 1997 to April 2003. The patients were classified into a low-risk group (T2, PSA20 ng/mL or Gleason score>or=7). Low-risk patients were treated with low-dose-rate iridium brachytherapy as monotherapy delivering 70 Gy. High-risk patients were treated with the combination of brachytherapy and external beam radiotherapy delivering 40 Gy and 36 Gy, respectively. Kaplan-Meier estimates of prostate-specific antigen (PSA) progression-free survival rate were analysed. To assess the treatment quality in different periods, PSA progression-free survival rates in late era (year of 2000 and after) and in early era (before 2000) were compared. Morbidity was graded according to the Radiation Therapy Oncology Group grading scale. RESULTS: One hundred and nineteen patients were analysed, of which 86 patients underwent monotherapy with an iridium implant, and 33 were treated with the combination of external beam radiotherapy. Twenty-four patients were excluded from the analysis because the classification of risk group did not suit the criteria. The total (n=119) PSA progression-free survival rate at 3 years was 80.3%. The PSA progression-free survival rate at 3 years for the monotherapy group (n=86) and the combination therapy group (n=33) were 78.2% and 86.9%, respectively. There were 23 patients who were followed for more than 36 to 63 months, and, during this period, only 1 patient who received the monotherapy was diagnosed as PSA failure at 50 months. The 3-year PSA progression-free survival rate of monotherapy in late era was significantly higher than that in early era; however, no significant difference was seen in the combination treatment. Morbidity for the combination treatment was low; however, for the monotherapy, three patients developed severe rectal ulcers, and colostomies were made. CONCLUSIONS: The PSA progression-free survival rate after low-dose rate iridium-192 brachytherapy with or without external beam radiotherapy can be satisfactory and longer follow up is necessary to compare the efficacy of other treatments.     

Combined hepatocellular-cholangiocarcinoma associated with dermatomyositis

A 56 year old female developed combined hepatocellular cholangiocarcinoma associated with dermatomyositis. Serum tumour markers except for carbohydrate antigen (CA 19-9; 6400 ng/ml) were within normal range. Despite extensive chemotherapy, no clinical response was obtained and the patient's course deteriorated after 4 months. Macroscopically, the liver was mainly occupied by hepatocellular carcinoma but cholangiocarcinoma was found in the hilum. This is the first case of a rare association of combined hepatocellular-cholangiocarcinoma and dermatomyositis.     

The role of OX22− helper T cells in protective immunity to reinfection with Taenia taeniaeformis in rats

Spleen cells (SpC) and mesenteric lymph node cells (MLNC) from F344 donor rats actively immunized by oral inoculation with Taenia taeniaeformis eggs were syngeneically transferred into previously uninfected recipient rats by intravenous injection. Recipient rats were challenged with eggs after cell transfer. The degree of immunity was assessed by counting the number of growing metacestodes (MC) in the liver and compared with that in controls. Transfer of 2 × 10⁸ SpC, obtained from donors immunized for ten or more (but not for three or five) days before cell transfer inhibited the establishment of most of MC. There were approximately 86–88% reductions in MC recoveries. SpC (2 × 10⁸) obtained from donors immunized for ten days inhibited the establishment of most of MC in recipient rats when transferred nought, two, or 24 h (but not 48 h) before egg challenge. Functional cells in the immune SpC were helper T cells W3/25⁺, OX8⁻ and OX22⁻. However, immune MLNC obtained from donors immunized for three to ten days before cell transfer had no effect on transferring immunity.