Severe exacerbation of hepatitis after short-term corticosteroid therapy in a patients with "latent" chronic hepatitis B

We present a case of severe exacerbation of hepatitis after short-term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with "latent" chronic hepatitis B showing no HBV-related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)-related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G-to-A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Diagnostic usefulness of transbronchial aspiration and bronchial lavage for pulmonary tuberculosis

Fiberoptic bronchoscopy is a well established methods as a useful tool in the diagnosis of pulmonary tuberculosis with smear negative cases. In order to get the early and definite diagnosis of pulmonary tuberculosis, we performed transbronchial aspiration and bronchial lavage by a fiberoptic bronchoscope in 97 patients. All patients (1) were clinically suspected of having active tuberculosis; (2) showed abnormal chest roentgenogram suggesting tuberculosis; (3) showed negative sputum smears of acid-fast bacilli, or had no sputum. The results of the study were summarized as follows: 1) Final diagnosis of study subjects were 90 patients of active pulmonary tuberculosis, and 7 patients of pulmonary atypical mycobacteriosis. 2) Sputum culture of acid-fast bacilli was positive in 22 out of 90 patients with active pulmonary tuberculosis. 3) Smear and culture examination of acid-fast bacilli of transbronchial aspirates were positive in 9 and 28, respectively out of 90 patients. 4) Smear and culture examination of acid-fast bacilli of bronchial lavage were positive in 12 and 39, respectively out of 90 patients. 5) A rapid and definite diagnosis was made in 16 out of 90 patients by transbronchial aspirates or bronchial lavage. 6) Atypical mycobacteria were detected in 7 out of 97 patients by transbronchial aspirates or bronchial lavage. 7) There were no serious complications such as pneumonia and exacerbation of pulmonary tuberculosis. These results suggested that transbronchial aspiration and bronchial lavage were useful procedures for rapid and definite diagnosis of pulmonary tuberculosis.     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

A boy with fatal infectious mononucleosis suspected as the first Japanese case of X-linked lymphoproliferative syndrome

We report a case of a 10-month-old boy who died of severe hepatic failure after a prolonged course of infectious mononucleosis. He also presented interstitial pneumonitis, meningoencephalitis and aplastic anaemia. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte (CTL) activity had not been detected in his peripheral blood during the course of the illness. Studies of his mother revealed a severe reactivation pattern of anti-EBV antibodies and decreased EBV-specific CTL activity. An X-linked familial susceptibility to EBV infection such as X-linked lymphoproliferative syndrome (XLP) might be associated with his fatal EBV infection.     

Evaluation of the cell survival curve under radiation exposure based on the kinetics of lesions in relation to dose-delivery time

We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric–kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate.     

Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.     

Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome

Summary. A cell line designated SKM-1 was newly established from leukaemic cells of a 76-year-old Japanese male patient with monoblastic leukaemia following myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of the patient when he lost multiple point mutations of ras genes with acquisition of chromosomal abnormalities during disease progression in MDS. The cells grew as a single floating cell, and have been continuously growing with the morphological characteristics of immature monoblasts by serial passages during the past 42 months with a doubling time of about 48 h. By cytochemical analysis. the cloned cells were positive for butyrate esterase, but negative for the Epstein-Barr virus associated nuclear antigen. Phenotypic analysis revealed the expression of myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA-DR. Cells from the primary peripheral blood and those from SO passages of the SKM-1 cell line both possessed no activated ras genes but showed karyotype abnormalities with 46.XY, del(9)(q13;q22), der(17) t(17:?)(p13:?). The SKM-1 cells have two mutations in p53 gene and overexpress the pS3 products. This cell line may contribute to a better understanding of molecular mechanisms in the progression from MDS to myelogenous leukaemia.     

Celecoxib inhibits production of MMP and NO via down-regulation of NF-κB and JNK in a PGE2 independent manner in human articular chondrocytes

The purpose of this study was to examine the effects of celecoxib on matrix metalloproteinases (MMP-1 and MMP-3), nitric oxide (NO), and the phosphorylation of nuclear factor-κB (NF-κB) and three mitogen-activated protein kinases (MAPKs), (p38, JNK and ERK) in human articular chondrocytes from normal, osteoarthritis, and rheumatoid arthritis cartilages. Celecoxib at 100 nM reduced the IL-1β-induced productions of MMP-1, MMP-3, iNOS, and NO, whereas indomethacin at 100 nM showed no effect. The additional stimulation of prostaglandin E2 (PGE2) failed to restore those productions, while the production of PGE2 were reduced by 1 and 10 μM but not 100 nM of celecoxib. The inhibitors of NF-κB, JNK and p38, but not ERK, decreased IL-1β-enhanced MMP-1, MMP-3 and NO production, respectively, and 100 nM celecoxib down-regulated the phosphorylation of NF-κB and JNK but has no effect on either p38 or ERK. Celecoxib has inhibitory effects on MMP-1, MMP-3 and NO productions, suggesting the protective roles directly on articular chondrocytes. Despite the COX-2 selectivity, celecoxib affects those productions via not PGE2 but NF-κB and JNK MAPK.