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Keiichi Nagao

Publications and source records attributed to Keiichi Nagao.

18 recordsLinked to original sources

State of hepatitis C viral replication enhances activation of NF-kB- and AP-1-signaling induced by hepatitis B virus X.

We examined the effect of hepatitis B virus X (HBx) on NF-kB- and AP-1- mediated transcription in human hepatocellular carcinoma cell lines, Huh-7 with or without subgenomic hepatitis C virus (HCV) RNA. Expression of HBx in Huh-7 cells with HCV resulted in 4.9 times increased NF-kB-activation and 3.8 times AP-1-activation whereas that without HCV resulted in 2.4 times increased NF-kB-activation and 2.3 times AP-1-activation. Interestingly, the expression of the matured form of HCV core protein, Core173, did not activate NF-kB- or AP-1-transcription in either Huh7 with or without HCV replicon. HBx protein might play an important role in HCV-related hepatocarcinogenesis.

Blotting, Western↗

Amantadine inhibits hepatitis A virus internal ribosomal entry site-mediated translation in human hepatoma cells.

The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal entry site (IRES) was investigated using a bicistronic reporter construct containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives were transfected with in vitro transcripts, and the reporter gene activity was determined. IFN suppressed both cap-dependent and HAV IRES-dependent translation, while amantadine specifically inhibited HAV IRES-dependent translation. In contrast to IFN, by reporter assay, amantadine did not activate the interferon-stimulated response element (ISRE) or interferon gamma-activated sequence (GAS)-associated pathways. Immunoblot analysis revealed that amantadine had no effect on PKR and on IFN-regulatory factor-1 (IRF-1) expression. These findings demonstrated a novel antiviral effect of amantadine against HAV with or without HCV infection.

Amantadine↗

5-aza-2'-deoxycytidine sensitizes hepatoma and pancreatic cancer cell lines.

Hepatocellular carcinoma (HCC) and pancreatic cancer are at the forefront of chemotherapy-resistant tumors with poor prognosis. Even with innovative treatment regimens, response rates remain low and the duration of response is short. We examined whether the suppression of DNA methylation was capable of enhancing the sensitivity of hepatoma and pancreatic cancer cell lines to 5-fluorouracil (5-FU). 5-aza-2'-deoxycytidine (5-aza-dC) at 2 microM, a specific DNA methylation inhibitor, did not induce cell death in Huh-7 with or without HCV, HLE, HepG2 and MIA PaCa-2 cells. However, a combination of 5-aza-dC with 5-FU showed a reduction in cell viability and induction of apoptosis in these cell lines to a greater degree than with 5-FU only. These findings underline the fact that DNA methylation plays a key role in conferring chemoresistance to hepatoma and pancreatic cancer, and the combination of DNA methylation inhibitor with chemotherapy could be a novel and highly effective tool for future targeted therapy of chemoresistant tumors.

Antimetabolites, Antineoplastic↗

Individually different "weights" of quality of life assessment in patients with advanced nonsmall-cell lung cancer.

BACKGROUND AND OBJECTIVE: The structure of quality of life (QOL) assessment was investigated by estimating subject-specific as well as population-averaged "weights" for four domains (functional, physical, mental, and psychosocial) relative to global QOL. METHODS: Among 583 eligible patients with advanced nonsmall-cell lung cancer in two phase III trials, 377 completed QOL questionnaires at baseline, and during treatment. A random coefficients model was applied, using the global QOL score and scores for the four domains as response and explanatory variables, respectively. RESULTS: A large diversity in subject-specific weights was found for the physical and psychosocial domains during treatment and for the psychosocial and functional domains after treatment. The population-averaged weights of all domains were significant during treatment (especially the physical domain), as well as after treatment (except the functional domain). CONCLUSION: Thus, all four domains were associated with global QOL, and the associations varied among individual patients as well as among the domains.

Aged↗

[Pulmonary toxisity].

Pulmonary toxicities, with special reference to interstitial pneumonia, due to cancer chemotherapy and/or chest irradiation were reviewed. Two sorts of mechanism of development of the interstitial pneumonia are considered; one is directly cytotoxic action to pneumocytes and/or pulmonary capillary endothelium and the other is an allergic mechanism against anticancer drug or its derivatives. The risk factors of cancer therapy induced interstitial pneumonia are an aged, poor performance status, and underlying interstitial pulmonary diseases. Recently some new serum markers involving KL-6 for interstitial pneumonia have been reported and further studies are needed to clarify whether these markers are predictive of subsequent pulmonary damage by anti-cancer treatments.

Antineoplastic Agents↗

Peripheral pulmonary diseases: evaluation with endobronchial US initial experience.

Endobronchial ultrasonography (US) with 4.5-F small-caliber US probes, combined with bronchoalveolar lavage technique, was evaluated in autopsied lungs and 22 patients with various pulmonary interstitial or alveolar diseases. Several different echoic patterns were found that may reflect changes due to pathologic alteration of lung parenchyma. This technique may have potential for evaluation and diagnosis of peripheral lung diseases.

Adult↗

[The current status and problems of the intestinal tuberculosis through a review of the Annual of the Pathological Autopsy Cases in Japan].

From 1997 to 1999 the incidence rate of tuberculosis increased and extrapulmonary tuberculosis has also increased during the same period. Among various types of extrapulmonary tuberculosis, intestinal tuberculosis is one of the diseases difficult to diagnose. Recently doctors could not make appropriate diagnosis of intestinal tuberculosis because they did not pay much attention to tuberculosis. With a background described above, we reviewed the Annual of the Pathological Autopsy Cases in Japan in previous five years 1994-1998, in order to investigate a current status of intestinal tuberculosis. Out of 140,358 autopsied cases, the number of cases with active and old tuberculosis was 5,103 (3.6%), in which the intestinal tuberculosis was accompanied in 80 (0.057%). The 80 cases were consisting of 45 males and 35 females and their mean age was 72.7 years old ranging from 28 to 96. Of the 80 intestinal tuberculosis cases, 71 were seen in pulmonary tuberculosis cases and six cases were considered to be intestinal tuberculosis alone. In terms of the location of intestinal tuberculosis the most commonly affected site was ileocecum which occupied 72.7% of all intestinal tuberculosis. Among the 80 cases, 14 cases were complicated with malignant tumor and only 30 cases (37.5%) were diagnosed clinically as intestinal tuberculosis before their death. Clinical diagnosis of other cases were ileus, simple constipation, severe diarrhea, malignant tumor or its tumor. The delay in diagnosing intestinal tuberculosis may result in fatal outcome in the aged persons, so that in general practice much attention should be paid not only to pulmonary but also extrapulmonary tuberculosis including intestinal tuberculosis.

Adult↗

[Problems about tuberculin skin test raised from consultations and countermeasures--influence to the interpretation of tuberculin skin test in case of the stoppage of BCG revaccination abolition and the introduction of induration measurement].

Since people have very limited access to informations on TB, Chiba Anti-TB Association started "Chiba Kekkaku Dial 110", free TB consultation service through telephone, fax and e-mail, since October 1997. We received 1453 consultations during three years by September 2000. The most frequent consultations was about tuberculin skin test (TST) that amounted to 383, 26.4% of the all consultations. We reviewed the consultations on TST to know why consultations on TST are so frequent and what are problems clients want to know. We categorized the consultations according to the professions of clients and three periods of TST, that is, before testing, during testing and reading, and post reading. There were 178 (46.5%) consultations from health professionals, 134 (35.0%) from general citizens and the rest of them were from those unknown job. The health professionals were 94 physicians, 34 public health nurses, 23 school nurses, 19 nurses, 2 medical technicians, 2 radiographers and 4 others. Consultation after tuberculin reading was the most frequent: 93 out of 178 consultations from health professionals and 97 out of 134 from general citizens. Especially, difficulty in the interpretation of the reading result was common reason of the consultations in both health professionals (69/93) and general citizens (89/97). They feel difficulties in TST result because of widely practiced BCG revaccination and booster phenomenon due to the repetition of TST. Furthermore, TST reading results vary very much between readers especially in double redness (erythema), and it sometimes affects the diagnosis of tuberculosis infection. Therefore, if repeated TST and BCG revaccination practices in children are abolished, most of those consultations might be solved. When induration measurement is used in TST according to the international standard, the complexity of the classifications of the result seems to be dissolved. Considering the current practices in Japan, we recommend that the size of TST induration should be measured and recorded as we measure and record erythema. And induration should be referred in interpretation when they diagnose TB infection with TST.

BCG Vaccine↗

Prevalence of obesity in patients with acute hepatitis; is severe obesity a risk factor for fulminant hepatitis in Japan?

BACKGROUND/AIMS: The prevalence of obesity in acute convalescent hepatitis and fulminant hepatitis has not been reported. The aim of this study was to investigate whether obesity affected the disease severity in Japanese patients with acute hepatitis. METHODOLOGY: 31 non-severe acute hepatitis (NS-AH) and 24 severe acute hepatitis and 14 fulminant hepatitis patients (S-AH) between January 1995 and December 2001 were analyzed retrospectively. Height and weight were used to calculate the body mass index (BMI) in these 69 patients. RESULTS: Mean height, weight and BMI were not significantly different between S-AH and NS-AH patients. Two severely obese (BMI greater than 35kg/m2) patients had developed S-AH. CONCLUSIONS: Severe obesity may be one of the prognostic factors in acute hepatitis. Further studies are needed.

Acute Disease↗

Acute-onset autoimmune hepatitis resembling acute hepatitis: a case report and review of reported cases.

We report a 54-year-old Japanese man, whose ALT level was 1689 IU/L, without increased gamma-globulin level or autoantibodies. He could not be diagnosed as autoimmune hepatitis (AIH) using scoring systems, and his liver function became normalized after steroid treatment. Recently, AIH with acute presentation of disease and acute-onset AIH without bridging fibrosis have been increasingly reported but cases without the character of increasing gamma-globulin level or autoantibodies before immunosuppressive treatment are extremely rare. This is the third such case report in the literature.

Acute Disease↗