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Biomedical subjects

T Otsuka

Publications and source records attributed to T Otsuka.

At least 145 records · Page 8Linked to original sources

[CDw90 (Thy-1) expression on CD34 positive cells in peripheral blood stem cell harvest].

In this study, we investigated CDw90 (Thy-1) expression in CD34+ cells and hematopoietic colony-forming ability in purified CD34+ Thy-1+ and CD34+ Thy-1 fractions in the peripheral blood at the PBSCH. The high proliferative potential colony-forming cells (HPP-CFC), which are considered to be more primitive hematopoietic stem cells, were found more frequently in the purified CD34+ Thy-1+ fraction than in the purified CD34+ Thy-1- fraction. Thus, it is useful to decide the optimal time of PBSCH to measure the CD34+ Thy-1+ cells as well as CD34+ cells in the peripheral blood by flow-cytometry. In CD34+ acute myeloblastic leukemia (AML) cells, the co-expression rate of CD34 and Thy-1 was negative, suggesting that it may be possible to estimate the contamination of CD34+ AML cells by the Thy-1 expression rate in CD34+ cells at PBSCH.

Antigens, CD34↗

[Foscarnet therapy for ganciclovir-refractory cytomegalovirus hepatitis in a patient who underwent bone marrow transplantation from an unrelated donor].

Cytomegalovirus (CMV) hepatitis refractory to ganciclovir treatment occurred after prolonged administration of ganciclovir in a 36-year-old woman with chronic myelogeneous leukemia who had undergone allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor. The number of CMV antigen-positive leukocytes in blood were well correlated with the serum levels of transaminases and the antigenemia assay was useful in monitoring CMV hepatitis. The patient was treated with foscarnet, a potent inhibitor of CMV DNA-polymerase, which led to rapid improvement of the CMV antigenemia and the transaminase concentrations. Foscarnet therapy should be considered for ganciclovir-resistant CMV disease in the setting of BMT.

Adult↗

[Chronic pulmonary mucormycosis that developed in preexisting cavities caused by tuberculosis in a patient with diabetes mellitus and liver cirrhosis].

We describe a case of chronic pulmonary mucormycosis. The patient was a 44-year-old man with diabetes mellitus and alcoholic liver cirrhosis. He had been treated for pulmonary tuberculosis three years earlier and thin-walled cavities remained in the left upper lobe. He presented with coughing, sputum, and fever, and a chest radiograph and CT scan showed increased consolidation around the preexisting cavities in the left lung, along with a small round opacity in the right upper lobe. Transbronchial lung biopsy of the left upper lobe revealed pulmonary mucormycosis with necrosis. Treatment with amphotericin B for two months was not completely successful, particularly with regard to the lesion on the left, so surgery was done. A left upper lobectomy and a left S6 segmentectomy were successful, and the lesion in the right lung resolved after chemotherapy. Pathological examination showed that the resected lung had granulomas, infiltration of inflammatory cells, areas of necrosis, and a druse of Mucor in an abscess. We view this as a case of chronic necrotizing pulmonary mucormycosis.

Adult↗

[Cytomegalovirus disease after hematopoietic recovery in a patient with non-Hodgkin's lymphoma].

We report a case of marked cytomegalovirus (CMV)-antigenemia determined by direct immunoperoxidase staining using a peroxidase-labeled monoclonal antibody HRP-C7, after conventional chemotherapy for malignant lymphoma. A 65-year-old Japanese man suffered from unexplained fever, mild liver dysfunction and an abnormal shadow in the lung after hematopoietic recovery from intensive chemotherapy for T-cell non-Hodgkin's lymphoma in the leukemic phase. The assay for CMV-antigenemia revealed that he had an active CMV infection. After treatment with ganciclovir and gamma-globulin, his symptoms and signs improved with the decrease of CMV antigen-positive leukocytes. CMV disease should be considered in these situations, and the CMV antigen-detection assay is useful for rapid diagnosis of CMV infection.

Aged↗

Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a renotrophic agent, capable of stimulating renal regeneration after unilateral nephrectomy or acute kidney failure. However, evaluation of the therapeutic utility of HGF/SF requires thorough analysis of its effects in an appropriate in vivo model system. To this end, the renal structure and function in HGF/SF transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum demonstrated prominent tubular cystic disease and progressive glomerulosclerosis, and were susceptible to premature death from renal failure. The tubular phenotype appeared to result from HGF/SF-Met autocrine stimulation of the tubular epithelium and consequent hyperplasia. Electron microscopic examination of glomeruli, which also showed enhanced cellular proliferation, revealed ultrastructural features consistent with focal segmental glomerulosclerosis: an increase in mesangial matrix, effacement of foot processes, and thickening of basement membrane. These changes were not present at birth but developed progressively with age, which is consistent with the notion that HGF/SF may not be essential for the early stages of nephrogenesis, but may play an important role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice could be a useful model for dissecting the molecular mechanisms leading to polycystic disease and focal segmental glomerulosclerosis. Moreover, our results suggest that caution should be used when considering HGF/SF as a future therapeutic agent.

Animals↗

[Relationship between exercise-induced hypoxemia and long-term survival in patients with chronic obstructive pulmonary disease].

In patients with chronic obstructive pulmonary disease (COPD), exercise-induced hypoxemia (EIH) is an important limiting factor of exercise performance, but there are very few reports of the prognostic value of EIH. We therefore examined whether EIH is related to long-term outcome in patients with COPD. We gathered data on survival of 77 patients with COPD who had undergone three-minute incremental treadmill exercise tests between 1979 and 1988. A plastic catheter was placed percutaneously into a brachial artery to measure arterial blood gases at each stage of exercise. Expired gas was analyzed continuously during exercise with a Respiromonitor RM-300 (Minato Medical Science). As an index of the severity of EIH we used the delta PaO2/delta VO2 (mmHg/L/min), PaO2-slope. Patients were assigned to two groups according to PaO2-slope, and actuarial survival curves were plotted for the two groups. The survival data were analyzed by generalized Wilcoxon analysis. Survival was significantly better in the group with low PaO2-slopes (< 20 mmHg/L/min) than in the group with high PaO2-slopes (> or = 20 mmHg/ L/min) (p = 0.0031). Also, among the patients in whom PaO2 during exercise was less than 60 mmHg, there was a significant difference in survival between those who received home oxygen therapy and those who did not. We conclude that the degree of EIH can be used to predict survival in patients with COPD, and that the degree of EIH should be considered when prescribing continuous home oxygen therapy for these patients.

Aged↗

Breakpoint junction of interstitial homozygous deletion at chromosome 2q33 in a small cell lung carcinoma.

We have characterized the breakpoint junction of the homozygous deletion at chromosome 2q33 in a small cell lung carcinoma cell line. Cloning and sequencing of the genomic regions surrounding the breakpoint junction of the deletion revealed that the homozygous deletion was caused by a simple interstitial deletion of a 220-kb segment. An AT-dinucleotide of contributing germline sequences was overlapped at the junction. Since there were one or two nucleotide overlaps of germline sequences at breakpoint junctions in all four cases of interstitial deletions analyzed to date, this may reflect a common mechanism underlying the occurrence of chromosomal interstitial deletion.

Base Sequence↗

Hyperthermia induces apoptosis in malignant fibrous histiocytoma cells in vitro.

The effect of mild hyperthermia on a cultured rat malignant fibrous histiocytoma (MFH) cell line, MFH-2NR, was investigated. MFH cells in log-phase (growing phase) were heated at 41 degrees-44 degrees C for 1 hr. Hyperthermic treatment at 41 degrees C did not substantially affect cell proliferation and treatment at 44 degrees C caused necrosis. After hypothermic treatment at 42 degrees or 43 degrees C, proliferation of MFH cells was arrested and morphological changes characteristic of apoptosis, cell shrinkage accompanying apoptotic bodies and chromatin condensation, became apparent. Hyperthermia-induced apoptosis was further confirmed by terminal deoxynucleotidyl transferase staining and a ladder pattern on agarose gel electrophoresis. Flow cytometric analysis indicated that the population in the G1 phase of the cell cycle significantly decreased with a concomitant increase in apoptotic cells, indicating that apoptosis might occur mainly in the G1 phase population.

Animals↗

Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients.

Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The functional IL-4 receptor (IL-4R) consists of the IL-4R alpha chain (IL-4R alpha) and the IL-2R gamma chain (gamma c), which is shared by the IL-2, IL-7, IL-9, and IL-15 receptors. The functional IL-13R is thought to involve the IL-4R alpha but not gamma c. In this study, we have analyzed activation of members of the Janus tyrosine kinase (Jak) family and signal transducers and activators of transcription (STAT) 6 induced by IL-4 and IL-13 in Epstein-Barr virus-transformed B cells derived from two patients of X-linked severe combined immunodeficiency, who have mutations of the gamma c gene in the extracellular and intracellular domains. In these B cells, IL-4 failed to induce tyrosine phosphorylation of Jak3 and activation of STAT6, or activation of these molecules was significantly decreased compared with Epstein-Barr virus-transformed normal B cells. In contrast, IL-13 activated STAT6 in these cells as well as normal B cells. However, Jak3 was not activated by IL-13, even in normal B cells. These results clearly indicated that gamma c is essential for activation of Jak3 and STAT6 in the signal transduction pathway of IL-4 in human B cells and that IL-13 does not utilize gamma c but activates STAT6 through an alternative pathway, which is not impaired in B cells of X-linked severe combined immunodeficiency patients.

B-Lymphocytes↗

Chronic hepatitis A with persistent viral replication.

Hepatitis A virus (HAV) usually causes an acute self-limited illness. This report describes a patient with hepatitis A whose serum aminotransferase activities remained above normal and whose serum was persistently positive for immunoglobulin (Ig) M class anti-hepatitis A 31 months after the onset of hepatitis. Liver biopsy carried out 11 months after the onset of hepatitis showed histological changes consistent with chronic hepatitis of moderate severity. HAV RNA was detected by polymerase chain reaction (PCR) in feces collected at the time of the liver biopsy. Furthermore, the patient developed esophageal varices 25 months after the onset of hepatitis. We believe this to be the first reported case in which persistent replication of HAV is implicated in chronic hepatitis with the potential to develop into liver cirrhosis.

Hepatitis A↗

Deletion mapping of chromosome 2 in human lung carcinoma.

Sixty-three non-small cell lung carcinomas (NSCLCs) and 20 small cell lung carcinomas (SCLCs) were examined for loss of heterozygosity (LOH) on chromosome 2. Fifteen highly polymorphic dinucleotide markers spanning both the short and long arms of chromosome 2 were selected for a polymerase chain reaction (PCR)-based fine mapping. They included a DNA marker localized in the homozygously deleted region at 2q33, which we previously identified in an SCLC cell line. LOH on chromosome arm 2q was detected in 23/63 (37%) of NSCLC and 6/20 (30%) of SCLC, while LOH on 2p was observed in 14/56 (25%) and 4/17 (24%), respectively. There were two commonly deleted regions mapped to 2q32-q37 and 2p16-pter, and the homozygously deleted region at 2q33 was in the commonly deleted region on 2q. In NSCLC, the incidence of LOH on 2p and 2q was significantly higher in brain metastases than in primary tumors (P = 0.005 and 0.001, respectively). In addition, LOH on chromosome arm 2q occurred more frequently in moderately/poorly differentiated tumors than in well-differentiated tumors (P = 0.046). These results suggested that inactivation of tumor suppressor genes on chromosome 2 is involved in the phenotypic alterations of NSCLC cells into more aggressive ones.

Brain Neoplasms↗

Comparative allelotype of early and advanced stage non-small cell lung carcinomas.

To identify chromosomal loci of tumor suppressor genes involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), comparative allelotype analysis was performed in 23 stage I primary lung tumors and in 22 metastatic lung tumors to the brain. In total, 84 loci on all 22 autosomal chromosomes were examined for loss of heterozygosity (LOH) by restriction fragment length polymorphism (RFLP) analysis with 40 polymorphic DNA probes and polymerase chain reaction (PCR)-LOH analysis of 44 polymorphic loci. LOH on chromosome arms 3p, 13q, and 17p was detected frequently (> 60%) in both stage I primary lung tumors and brain metastases, whereas the incidence of LOH on chromosome arms 2q, 5q, 9p, 12q, 18q, and 22q was more than 60% only in brain metastases. In particular, the incidence of LOH on chromosome arms 2q, 9p, 18q, and 22q in brain metastases was significantly higher than that in stage I primary lung tumors (P < 0.05). These results indicate that tumor suppressor genes on chromosome arms 3p, 13q, and 17p are involved in the genesis of NSCLC, whereas those on several chromosome arms, especially on 2q, 9p, 18q and 22q, play an important role in the progression of NSCLC.

Brain Neoplasms↗

Effect of IL-10 on collagen-induced arthritis in mice.

In the present study we investigated the effect of a potent anti-inflammatory cytokine, interleukin (IL)-10, on the development of collagen-induced arthritis (CIA) in mice. Each DBA1/J mouse was immunized with 200 micrograms of native collagen and followed by booster injections at 3 weeks. rmIL-10 was injected i.p. daily at a dose of 100 ng/mouse. Mice were divided into four groups according to the administration period of rmIL-10. As a result, a 48-day course of IL-10 treatment significantly suppressed the severity of arthritis. Among the 4 groups, the most pronounced suppression was observed in the group in which IL-10 was given from day 0 to 21. On the other hand, there were no significant differences in the serum IgG anti-type II collagen (CII) titers between the four groups. Moreover, the production of cytokines (IL-6 and tumor necrosis factor-alpha (TNF-alpha)) and other mediators (prostaglandin E2 (PGE2) and nitric oxide (NO)) by peritoneal macrophages seemed to show no clear correlation with the severity of arthritis in mice. These results raise the possibility that IL-10 might be a useful agent for suppressing the progression and the development of CIA in mice.

Analysis of Variance↗

Immunophenotyping of peripheral blood mononuclear cells collected by cytotoxic and cytotoxic/G-CSF mobilization.

We investigated surface immunophenotypes of peripheral blood mononuclear cells (PBMC) collected by cytotoxic and cytotoxic/G-CSF mobilization of peripheral blood stem cells (PBSC) from 38 patients with haematological malignancies in complete remission who underwent consolidation chemotherapy. PBMC were collected by leucapheresis during the haematopoietic recovery phase after intensive chemotherapy. G-CSF was used for mobilization of PBSC in 19 cases. Surface immunophenotyping of frozen-thawed PBMC was performed by flow cytometry. Our findings showed that monocytes and T cells were the two major cell components of PBMC. There were very few B cells in PBMC. Expression of CD45RO and HLA-DR was elevated in lymphocytes, suggesting that T cells in PBMC were activated. The percentage of CD34 positive cells were significantly increased in PBMC collected by cytotoxic/G-CSF mobilization (group 1) compared with PBMC collected by cytotoxic mobilization (group 2). There were significantly higher percentages of CD14 and CD33 positive cells in group 1 than in group 2. The percentage of CD4 positive lymphocytes positive for HLA-DR was significantly higher in group 1 compared with group 2. These observations indicated that PBMC contained a large number of monocytes and activated T cells, especially in cytotoxic/G-CSF mobilization.

Adolescent↗