Enhancement of sensitivity to tumor necrosis factor alpha in non-small cell lung cancer cells with acquired resistance to gefitinib.

Tumor cells that have acquired resistance to gefitinib through continuous drug administration may complicate future treatment. To investigate the mechanisms of acquired resistance, we established PC-9/ZD2001, a non-small-cell lung cancer cell line resistant to gefitinib, by continuous exposure of the parental cell line PC-9 to gefitinib. After 6 months of culture in gefitinib-free conditions, PC-9/ZD2001 cells reacquired sensitivity to gefitinib and were established as a revertant cell line, PC-9/ZD2001R.

The combination of cisplatin and vinorelbine with concurrent thoracic radiation therapy for locally advanced stage IIIA or IIIB non-small-cell lung cancer.

Aims: The aims of this study were to assess the efficacy and toxicity of concurrent chemoradiotherapy with divided schedule of cisplatin and vinorelbine in patients with locally advanced non-small-cell lung cancer (NSCLC).

Methods: Patients with previously untreated, unresectable, and stage IIIA or IIIB NSCLC were eligible if they had a performance status of 0 or 1, were 75 years or younger, and had adequate organ function. Twenty-six patients (24 men and 2 women; median age, 66 years; age range, 42-75 years) were enrolled.

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C.

In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395).

Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load.

Patients with high viral load (> or =1.0 x 10(5) IU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve high sustained virological response rates to interferon (IFN)/ribavirin combination therapy. Previous studies suggested that pretreatment amino acid (aa) substitution patterns in the HCV core region could affect virological non-response especially in patients who could not achieve HCV-RNA negativity during treatment.

Cost-effectiveness of radiofrequency ablation and surgical therapy for small hepatocellular carcinoma of 3cm or less in diameter.

Background: Cost-effectiveness of radiofrequency ablation (RFA) was assessed in treatment of hepatocellular carcinoma (HCC).

Patients And Methods: During 5 years, 153 patients with HCC of 3cm or less received RFA, and 60 underwent surgery. Judgment after RFA therapy was classified into three grades: residual tumor (grade 1), necrotic area with a less safety margin of 5mm (grade 2), and necrosis with a safety margin of 5mm in all directions (grade 3).

Dynamics of lipid droplet-associated proteins during hormonally stimulated lipolysis in engineered adipocytes: stabilization and lipid droplet binding of adipocyte differentiation-related protein/adipophilin.

In mature adipocytes, triglyceride is stored within lipid droplets, which are coated with the protein perilipin, which functions to regulate lipolysis by controlling lipase access to the droplet in a hormone-regulatable fashion. Adipocyte differentiation-related protein (ADRP) is a widely expressed lipid droplet binding protein that is coexpressed with perilipin in differentiating fat cells but is minimally present in fully differentiated cultured adipocytes. We find that fibroblasts ectopically expressing C/EBPalpha (NIH-C/EBPalpha cells) differentiate into mature adipocytes that simultaneously express perilipin and ADRP.

Acetylacetoin synthase as a marker enzyme for detecting the 2,3-butanediol cycle.

Acetylacetoin synthase (AACSase) and acetylacetoin reductase (AACRase) are representative enzymes of the 2,3-butanediol cycle. After examining their induction conditions in various bacteria, the former was induced by acetoin and the latter by glucose. All strains carrying AACSase also had AACRase, but the reverse was not true.

Characterization of the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase gene from Bacillus cereus YUF-4.

A 1.4-kbp DNA fragment, including the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase (AACRII/BDH) gene from the chromosomal DNA of Bacillus cereus YUF-4, was cloned in Escherichia coli DH5alpha after its insertion into pUC119, and the resulting plasmid was named pAACRII119. The AACRII/BDH gene had an open reading frame consisting of 1047 bp encoding 349 amino acids.

Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection.

Background: Phlebotomy is performed to reduce excessive iron accumulation in hepatic tissue. We studied serum alanine aminotransferase (ALT) normalization rates and 50% reduction in initial serum ALT (ALT(50%) reduction rate) in patients with hepatitis C viral (HCV) infection and investigated the factors that influenced the response to phlebotomy therapy.

Methods: We evaluated 23 consecutive patients with HCV infection who underwent phlebotomy.

Anticarcinogenic impact of interferon on patients with chronic hepatitis C: a large-scale long-term study in a single center.

Background: The anticarcinogenic capacity of interferon (IFN) was assessed in a cohort of Japanese patients with chronic hepatitis C en masse.

Patients And Methods: The rate of hepatocarcinogenesis was analyzed in 2,166 patients with chronic hepatitis C, of whom 1,654 had received IFN therapy while 512 had not.

Results: Crude rates of hepatocarcinogenesis in treated and untreated patients were 2.

Long-term follow-up of interferon monotherapy in 454 consecutive naive patients infected with hepatitis C virus: multi-course interferon therapy may reduce the risk of hepatocellular carcinoma and increase survival.

Objective: The long-term effects of multi-course interferon (IFN) monotherapy in patients infected with hepatitis C virus (HCV) are still unclear.

Material And Methods: To evaluate the effects of multi-course IFN on hepatocarcinogenesis and survival, a follow-up study was conducted comprising 454 consecutively recruited non-cirrhotic naive patients infected with HCV, who had received IFN monotherapy between 1987 and 1992. The median follow-up was 11.

Usefulness of the serum KL-6 assay in patients with hepatitis C virus.

Objective: The aim of this study is to evaluate the serum level of KL-6 in hepatitis C virus (HCV)-positive patients with chronic liver disease.

Methods And Results: Subjects consisted of 502 HCV-positive patients. The serum samples of these patients stored at -80 degrees C were measured by enzyme-linked immunosorbent assay for KL-6 at the same time.

Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferon-ribavirin combination therapy.

Objective: Patients with high titer (>/=100 kIU/ml) of hepatitis C virus (HCV) genotype 1b do not achieve highly sustained virological response rates to combination therapy with interferon plus ribavirin. Non-virological responders (NVRs, namely ultimate resistant cases) who do not achieve HCV-RNA negativity during treatment are also encountered. We investigated the pretreatment virological features of NVRs.

[Infection control in a teaching hospital without a tuberculosis ward].

Approximately 30 cases of tuberculosis are diagnosed in our hospital each year. Because three of our nurses contracted tuberculosis in 1998, we implemented the following control measures for tuberculosis : (1) immediate examination, diagnosis, and treatment in suspected cases; (2) screening of all health-care workers with a two-step tuberculin skin test (TST); (3) examination of all persons exposed to tuberculosis-infected persons; and (4) greater awareness of tuberculosis. We offered prophylactic medications to all exposed persons with a TST reaction greater than 20 mm.

Virological differences between patients infected with subtypes Ba and Bj of hepatitis B virus genotype B.

Background: Hepatitis B virus (HBV) genotype B is classified into subtype Ba with the recombination with genotype C in the precore region plus core gene and subtype Bj without recombination. Virological and clinical differences between infections with subtypes Ba and Bj, however, are yet to be determined.

Methods: During 1976 through 2001, 224 patients visited Toranomon Hospital in Tokyo, Japan who were infected with HBV genotype B.

Virological and biochemical relapse after discontinuation of lamivudine monotherapy for chronic hepatitis B in Japan: comparison with breakthrough hepatitis during long-term treatment.

Objective: Comparison of virological and biochemical relapse in patients with chronic hepatitis B, based on continuation or discontinuation of lamivudine monotherapy.

Methods: In Japanese genotype C-dominant hepatitis B patients, 25 patients who stopped treatment at normal levels of alanine transferase (ALT) were retrospectively compared with 75 patients who continued treatment. Both groups were matched for age, sex, and observation period after start of treatment.

Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C.

Objective: The purpose of this clinical retrospective cohort study was to determine the most suitable ribavirin concentration on combination therapy of interferon (IFN)-ribavirin.

Methods: Entry criteria were serum HCV-RNA level >/=100 KIU/ml, HCV-genotype 1b, chronic hepatitis, and initial combination treatment of IFN-alpha-2b (6 million units daily for 2 weeks and then 3 times weekly for 6 weeks) and ribavirin (600-800 mg/day) for 8 weeks without stopping or decreasing the dosage of IFN and/or ribavirin. Sixty-eight consecutive patients who satisfied the above criteria were given maintenance therapy for another 16 weeks.

p115 Interacts with the GLUT4 vesicle protein, IRAP, and plays a critical role in insulin-stimulated GLUT4 translocation.

Insulin-regulated aminopeptidase (IRAP) is an abundant cargo protein of Glut4 storage vesicles (GSVs) that traffics to and from the plasma membrane in response to insulin. We used the amino terminus cytoplasmic domain of IRAP, residues 1-109, as an affinity reagent to identify cytosolic proteins that might be involved in GSV trafficking. In this way, we identified p115, a peripheral membrane protein known to be involved in membrane trafficking.

Hepatitis B virus-related hepatocellular carcinogenesis and its prevention.

To elucidate the influence of serum hepatitis B virus (HBV) load on hepatocellular carcinogenesis in cirrhotic patients, HBV-DNA was sequentially measured. In a nested, case-control study using 96 patients without antiviral therapy, high HBV-DNA (> or =10(3.7) copies/ml) in the last 3 years was significantly associated with carcinogenesis (a patient group without hepatocellular carcinoma (HCC) development; 0/48 vs.

Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan.

Among the 97 adult patients with acute hepatitis B who were admitted to the Toranomon Hospital in Metropolitan Tokyo during 28 years from 1976 to 2003, 31 (32%) were infected with hepatitis B virus (HBV) genotype A, nine (9%) with genotype B, 44 (45%) with genotype C, one (1%) each with genotypes E and F. HBV in the remaining 11 (11%) patients were untypeable. All the 31 patients with acute hepatitis B caused by HBV genotype A infection were male with a median age of 31 years, and 16 (52%) contracted infection through extramarital sexual contacts.

Lamivudine monotherapy for spontaneous severe acute exacerbation of chronic hepatitis B.

Background: Severe acute exacerbations of chronic hepatitis B virus (HBV) infection can spontaneously occur and rapidly progress to fatal hepatic failure. The purpose of the present paper was to identify factors that could influence the rapid progression of liver disease to hepatic failure, and assess the effects of lamivudine on serious disease.

Methods: Twenty-five patients with spontaneous severe acute exacerbation (accompanied by jaundice and coagulopathy) were consecutively treated with lamivudine.

Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility.

Problem: Preconception high peripheral natural killer (NK) cell activity in women with recurrent spontaneous abortion can predict subsequent miscarriages. We have examined prospectively, for the first time, the pregnancy rate in patients with unexplained infertility by measuring the peripheral NK activity.

Method Of Study: We tested the peripheral NK activity of 94 infertile women who despite treatment were unable to conceive for 6 or more months (mean; 2.

Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN-resistant cases with hepatocyte steatosis.

The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear, especially in patients infected with hepatitis C virus (HCV) genotype 2a. The present study was conducted in 364 consecutive non-cirrhotic naive patients infected with genotype 2a, who were evaluated for the severity of steatosis and response to IFN monotherapy after a 24-week median duration of therapy. The patients were examined for factors associated with steatosis and treatment efficacy according to the grade of steatosis.