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Biomedical subjects

M Oketani

Publications and source records attributed to M Oketani.

12 recordsLinked to original sources
PubMed2001

Hepatic necrosis with cholestasis induced by long-term voglibose administration.

A 76-year-old woman admitted to our hospital for jaundice had been treated for diabetes mellitus with insulin for 9 years and voglibose had been added for the 39 months preceding admission. Elevated serum bilirubin and transaminase concentration began to normalize with initiation of corticosteroid treatment 1 week after discontinuation of voglibose. In the in vitro testing of the patient's peripheral blood, lymphocytes showed stimulation by voglibose. In dramatic contrast to an initial liver biopsy specimen that demonstrated cholestasis with submassive and zonal necrosis, the follow-up specimen was normal 1 year later. We believe that patients treated with voglibose should be monitored long-term with monthly determinations of transaminases and bilirubin in serum.

Aged↗
PubMed2000

[Hematological abnormalities of primary Sjogren's syndrome].

Sjogren's syndrome (SS) is an autoimmune disease characterized by a chronic inflammatory response mainly localized to the lacrimal and salivary glands. However, it sometimes involves extraglandular organs culminating in systemic disorders. Hematological abnormalities are not uncommon, although they rarely have clinical significance. In this study we examined 99 patients with primary SS who visited our hospital during 1989 to 1999. Patient's mean age was 54.1 years and 95 out of 99 were female. Lymphopenia and leukopenia was noted in 35 patients (35.3%) and 26 patients (26.2%) respectively, and 7 patients (7.1%) had thrombocytopenia. 43 patients (43.4%) had either of these hematological abnormalities. Patients with lymphopenia showed significantly low frequency of arthralgia and anti-SS-A/B antibody was more common in this group. Only one patient in this group required prednisolone therapy because of polyarthritis and general fatigue while others needed no specific therapy. Patients with thrombocytopenia were significantly younger and a male/female ratio was higher than those without this abnormality. They had higher tendency to accompany with skin eruption, positive anti-SS-B antibody, anti-nuclear antibody and rheumatoid factor. Three out of 8 patients with thrombocytopenia were treated with prednisolone according to the protocol for idiopathic thrombocytopenic purpura. All of 3 patients had positive PA-IgG and normocellular bone marrow. Autoimmune mechanism such as polyclonal B cell activation may play a role in the pathogenesis of thrombocytopenia.

Female↗
PubMed1999

Inhibition of hepatitis C virus-directed gene expression by a DNA ribonuclease.

BACKGROUND/AIMS: The aim of this study was to determine whether DNA analogs of ribozymes could be prepared to inhibit hepatitis C virus (HCV) gene expression. METHODS: Two DNA ribonucleases, Dz2 and Dz4, were designed with varying arm lengths, to cleave at the 5'-noncoding region (NCR) just upstream from the translation start site, and core region of HCV genome, respectively. A reporter vector was prepared to contain target HCV regulatory sequences controlling a downstream luciferase gene. DNA ribonucleases with normal phosphodiester, as well as with terminal phosphorothioate linkages, were administered to Huh7 cells, and luciferase activity was measured. RESULTS: DNA ribonucleases were highly active in cleaving HCV RNA targets. Enzymes with longer arms had consistently higher cleavage activity compared to enzymes with shorter arms under cell-free conditions. Furthermore, in Huh7 cells, terminal phosphorothioate derivatives, Dz2 and Dz4, significantly suppressed HCV-luciferase fusion gene expression up to 45% and 67% of controls, respectively. Interestingly, phosphorothioate-modified DNA ribonucleases had greater inhibitory effects on target gene expression than their unmodified counterparts. In contrast, DNA ribonucleases with point mutations in the catalytic domain had significantly lower inhibitory effects compared to wild-type DNA ribonucleases. However, activity was not eliminated, suggesting that some antisense contribution was present. CONCLUSIONS: DNA ribonucleases directed against the HCV genome can specifically cleave target HCV RNA. Modifications of the extreme 3'- and 5'-termini protect against nuclease degradation without appreciable reduction in inhibitory activity against viral gene expression under intracellular conditions.

Antisense Elements (Genetics)↗
PubMed1999

Effects of urinary metabolites of etodolac on diagnostic tests of bilirubin in urine.

Etodolac (CAS 41340-25-4) is a non-steroidal anti-inflammatory drug used clinically. The bilirubin levels in urine samples from patients treated with etodolac were determined with diagnostic tests (diazo and oxidized methods). The urine samples gave a positive reaction with a diazo method, but not with an oxidized method. The serum concentrations of bilirubin in the patients were also in the normal range. These results indicate that the positive reaction of the urine samples from patients treated with etodolac is false and caused by urinary metabolites of etodolac. To identify the false positive substance in the urine samples, the urinary metabolites of etodolac were extracted with ethyl acetate. The extract was injected into a high performance liquid chromatography (HPLC) column and the eluate was mixed with the diazo reagent. Three positive fractions were found. The retention times of the two metabolites in HPLC matched with those of the 6- and 7-hydroxylated metabolites of etodolac. In addition, authentic compounds of the 6- and 7-hydroxylated metabolites gave a positive reaction in the diazo methods. These results indicate that the 6- and 7-hydroxylated metabolites are mainly responsible for the false positive reactions of the urine sample from patients treated with etodolac.

Aged↗
PubMed1999

Complete response to twice-a-day interferon-beta with standard interferon-alpha therapy in acute hepatitis C after a needle-stick.

A 25-year-old male physician with acute hepatitis C after needle-stick injury was treated with combination therapy including twice-a-day interferon-beta (IFN-beta) and standard interferon-alpha (IFN-alpha). The infecting strain was of genotype 1b. Pretreatment hepatitis C virus (HCV) RNA levels were high. Because severe paresthesias occurred with initial daily administration of 5 million units (MU) of lymphoblastoid IFN-alpha, the dose was reduced to 3 to 6 MU of IFN-alpha2b three times a week. However, HCV RNA was not cleared from serum after 20 weeks of standard IFN-alpha2b treatment. A 4-week course with IFN-beta, at the dosage of 3 MU twice daily i.v. drip, was then started and followed by an 18-week course with IFN-alpha2b, 6 MU thrice weekly. After IFN-beta treatment, HCV RNA was cleared from serum without severe adverse effects, including paresthesias. Total amounts of IFN administered were 20 MU of lymphoblastoid IFN-alpha, 648 MU of IFN-alpha2b, and 252 MU of IFN-beta. Complete response and avoidance of chronic HCV infection were achieved. Thus, combination therapy with twice-a-day IFN-beta and standard IFN-alpha was effective in treating an acute hepatitis C patient with a high viral load and sensitivity to adverse effects of high-dose IFN-alpha.

Acute Disease↗
PubMed1999

Low level wild-type and pre-core mutant hepatitis B viruses and HBeAg negative reactivation of chronic hepatitis B.

A qualitative and a quantitative mutation-site specific polymerase chain reaction assay (MSSA) was used to detect low level wild-type and pre-core mutant hepatitis B virus (HBV)-DNA. Serum samples from 11 anti-hepatitis B e (anti-HBe)-positive asymptomatic HBV carriers (Group A) and 10 anti-HBe-positive chronic hepatitis B patients who achieved alanine transaminase (ALT) normalization after antiviral therapy (Group B) were tested. Eleven patients had both wild-type and pre-core mutant HBV-DNA (52%, 4 from Group A and 7 from Group B), whereas 3 patients had only pre-core mutant HBV-DNA (14%, 2 from Group A and 1 from Group B) by qualitative MSSA assay. During a 3-year follow-up period, relapses were observed in 3 patients from Group B and intermittent ALT elevation was observed in 4 patients from Group A and 3 patients from Group B. The wild-type HBV-DNA concentration in the patients with reactivation was 10(2.06+/-2.62) copies/ml, whereas that in all patients without reactivation was below 10(2) copies/ml (P < .05). The pre-core mutant HBV-DNA concentration in the patients with reactivation was also significantly higher than that in the patients without reactivation (10(3.94+/-2.25) vs. 10(0.65+/-1.45) copies/ml, P < .001). All patients with both HBV-DNA concentrations below 10(2) copies/ml did not exhibit reactivation. Our result suggest that a high prevalence of coexistence of low level wild-type and pre-core mutant HBV-DNA has the potential for reactivation in anti-HBe-positive patients. Furthermore, quantification of wild-type and pre-core mutant HBV-DNA was useful to predict the prognosis of anti-HBe-positive infection and evaluate the efficacy of antiviral therapy.

Adult↗
PubMed1999

[A case of Sjögren's syndrome with retrobulbar optic neuritis and cutaneous vasculitis].

A 52-year-old woman, diagnosed as having Sjögren's syndrome by parotid sialography and lip biopsy after a two years history of recurrent purpuric rashes on her lower extremities, was admitted to our hospital because of visual disturbance in March 1998. On presentation at the department of ophthalmology, her right visual acuity was light perception, and laboratory findings showed elevated levels of antinuclear antibody and anti-Ro/SS-A and anti-La/SS-B antibodies. Cerebrospinal fluid analysis showed mild pleocytosis and elevated levels of total protein and Q-albumin. The IgG-index was within normal level and no oligoclonal band was found. Magnetic resonance imaging showed increased signal intensity at the right optic nerve. After treatment with m-PSL pulse therapy, her visual acuity recovered to 0.08. When prednisolone was gradually tapered to the dose of 30 mg per day, she was transferred to our department because of high grade fever and pancytopenia. She also suffered from palpable purpura in her extremities extending the trunk, whose pathological diagnosis was leukocytoclastic vasculitis. The immunohistochemical examination showed depositions of IgG and C1q. After two additional cycles of mPSL pulse therapies, clinical improvement was achieved. The titers of von Willebrand factor and thrombomodulin correlated with her clinical improvement. Patients with Sjögren's syndrome can develop extra-grandular complications, including neurologic and cutaneus diseases, it is important to understand the role of SS-A-B antibodies in the immunopathogenesis of Sjögren's syndrome.

Female↗
PubMed1994

Hepatitis C virus RNA and anti-N14 antibody levels during interferon alpha therapy for chronic hepatitis C.

To investigate the markers useful for evaluating the long-term efficacy of interferon (IFN) therapy, the quantity of hepatitis C virus (HCV) RNA and two anti-HCV antibody titers (anti-N14 and anti-C-100-3 antibody) in 21 chronic hepatitis C patients were determined. In all complete responders, a sustained clearance of the virus and reductions in the anti-HCV antibody titers were observed during and after therapy. In most of the temporary responders, reductions in the HCV RNA levels and in both anti-HCV antibody titers were observed temporarily during the therapy, and relapse followed. In nonresponders, although the HCV RNA levels and anti-N14 antibody titer tended to remain unchanged or increased during and after therapy, the anti-C-100-3 antibody titers showed no tendency. These results demonstrate that the monitoring of the HCV RNA level and anti-N14 antibody titer is clinically useful for following the patient's response to IFN therapy for chronic hepatitis C.

Antigens, Viral↗
PubMed1993

Development of a specific enzyme-linked immunosorbent assay for the hepatitis C virus antibody using clone 14.

The authors isolated a specific cDNA clone (clone 14) for non-A, non-B hepatitis virus infection. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) using a synthetic oligopeptide encoded by clone 14 and examined its usefulness for detecting hepatitis C virus (HCV) antibody in 181 patients with chronic NANB hepatitis, 88 with cirrhosis and 24 with hepatocellular carcinoma associated with NANB hepatitis virus. Anti-clone 14 antibody was detected in 75% of patients with chronic NANB hepatitis, 57% of cirrhotic patients and 58% hepatocellular carcinoma patients. Anticlone 14 and anti-C-100 antibody assayed using a commercial kit were found in serum from 199 (69%) and 205 (70%) of these 294 patients, respectively. Approximately 85% of the patients showed the presence of anticlone 14 and/or anti-C-100 antibodies. We compared the presence of these antibodies and the second generation anti-HCV antibody using ELISA and HCV RNA by the polymerase chain reaction assay, in the same blood samples from 49 patients with chronic liver disease who had anti-clone 14 and/or anti-C-100 antibody. HCV RNA was detected in 38 of 40 (95%) plasma samples containing anti-clone 14 antibody, the prevalence of which was similar to that for anti-C-100 antibody (41/42, 98%) and the second generation anti-HCV antibody (46/47, 98%). Furthermore, 6 of 7 plasma samples containing anti-clone 14 antibody and lacking anti-C-100 antibody were positive for the second generation anti-HCV antibody and HCV RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Sarcoidosis with tumorous hepatic and bone lesions mimicking disseminated malignancy: a case report.

An asymptomatic 49-year-old woman with a diffuse abnormal shadow detected on a routine chest rentogenogram was referred for evaluation. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) revealed space-occupying lesions in the liver and spleen. Lymphadenopathy was observed in the mediastinum and abdomen on CT, and multiple lesions of low signal intensity were observed in the spine on MRI. Furthermore, the presence of multiple tumorous nodules in the liver suggesting metastatic hepatic cancer was demonstrated on laparoscopy. Biopsy of the liver tumors revealed sarcoidosis; transbronchial biopsy specimens showed identical histological features. After administration of prednisolone for one month, the space-occupying lesions in the liver, spleen and spine improved. This case of sarcoidosis exhibited hepatic tumorous nodules and space-occupying lesions in the spleen and the spine which mimicked the presence of metastatic hepatic cancer.

Diagnosis, Differential↗
PubMed1991

Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element.

A new B-cell-specific enhancer element has been identified 3' of E4 and the octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer. Tandem copies of this 67-bp MnlI-AluI fragment, when fused to the chloramphenicol acetyltransferase gene driven by the conalbumin promoter, stimulated transcription in B cells but not in Jurkat T cells or HeLa cells. Footprinting analysis revealed that the identical sequence CCGAAACTGAAAAGG, designated E6, was protected by nuclear extracts from B cells, T cells, or HeLa cells. Gel mobility shift assays using a synthetic E6 motif detected a B-cell-specific complex in addition to a ubiquitous band found also in T cells and HeLa cells. In agreement with the results of gel retardation assays, tandem copies of the E6 motif stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells. Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo enhancer activity. In striking contrast to the mouse Ig heavy-chain enhancer, in which the octamer motif acts as a B-cell-specific enhancer element, the human enhancer contains an octamerlike sequence with one base substitution which bound octamer-binding proteins with only very low affinity and showed no enhancer activity of its own. Interestingly, the MnlI-AluI fragment could suppress the basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells. Moreover, simian virus 40 enhancer activity was blocked by the MnlI-AluI fragment in HeLa cells but not in B cells. Thus, the novel enhancer element identified in this study is probably a target site for both positive and negative factors.

B-Lymphocytes↗