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Biomedical subjects

Mitsuhiro Osame

Publications and source records attributed to Mitsuhiro Osame.

At least 37 records · Page 2Linked to original sources
PubMed2006

[A case of bronchiolitis obliterans syndrome successfully treated by Tiotropium bromide].

A 48-year-old woman was admitted with dyspnea on effort. She suffered from adult T-cell leukemia and received peripheral blood stem cell transplantation (PBSCT). Eight months after the PBSCT, she developed dyspnea on effort and was treated with bronchodilator, inhaled corticosteroid, anti-leukotriene drug, theophylline and oxytropium bromide. However her symptoms progressed and she was admitted. We diagnosed bronchiolitis obliterans syndrome (BOS) because of obstructive pulmonary dysfunction, diffuse patchy high density of the lung field on chest computed tomography and decreased ventilation with peripheral patchy accumulation on ventilation scintigraphy. She was treated with corticosteroid and cyclosporine A and her symptoms and her pulmonary function were improved. However, in parallel with corticosteroid tapering, her symptoms and pulmonary functions worsened. Treatment with Tiotropium bromide was started and her pulmonary function improved significantly. Her pulmonary function did not worsen and tapering steroid dose was successfully achieved. PBSCT was reported to up-regulate the muscarinic receptor activity in lung. Tiotropium bromide might become one additional option for the treatment of BOS.

Bronchiolitis Obliterans↗
PubMed2006

[Two lung adenocarcinoma patients with multiple brain metastasis treated with Gefitinib and surviving more than 2 years].

Case 1 is a 78-year-old woman in whom lung adenocarcinoma with multiple brain metastasis (cT2N3M1, stage IV) was diagnosed. She was treated with Gefitinib alone. Her lung tumor and metastatic brain lesions decreased 6 months after the start of therapy. She has no recurrence and is still alive with a good performance status after 25 months. Case 2 is an 80-year-old woman in whom lung adenocarcinoma with multiple brain (cT2N3M1, stage IV) was diagnosed. She was also treated with Gefitinib alone and her lung tumor and metastatic brain becomes improved 6 months after the start of therapy. She maintained a good performance status for more than 2 years (29 months). However, 29 months after beginning treatment, she had recurrence in bone and died 2 months later, 31 months after the start of therapy. The prognosis of non-small cell lung cancer with multiple brain metastasis is very poor and the efficacy of chemotherapy for the treatment of multiple brain metastases is limited, and longterm survival remains disappointing. We report two lung adenocarcinoma patients with multiple brain metastasis who survived more than 2 years by treatment with Gefitinib alone.

Adenocarcinoma, Papillary↗
PubMed2005

Chronic progressive sensory ataxic neuropathy associated with limited systemic sclerosis.

We report the case of a 33-year-old woman with limited systemic sclerosis and chronic progressive sensory ataxic neuropathy. Sural nerve biopsy showed loss of myelinated fibers mostly those of large diameter, axonal degeneration and infiltration of macrophages, but no signs of vasculitis. Physical examination, laboratory testing, neurophysiological and neuroradiological examinations suggested that the dorsal root was primarily affected in this patient. Cytokine analysis by multiplex bead array assay revealed that IL-1beta and GM-CSF were increased both in serum and CSF. Although her symptoms did not respond to corticosteroid therapy, intravenous immunoglobulin (IVIg) therapy resulted in marked improvement. IVIg could be effective in case of immune-mediated reversible neuronal dysfunction associated with collagen disease without vasculitis.

Adult↗
PubMed2005

A prospective uncontrolled trial of fermented milk drink containing viable Lactobacillus casei strain Shirota in the treatment of HTLV-1 associated myelopathy/tropical spastic paraparesis.

Ten patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were treated in an uncontrolled preliminary trial by oral administration of viable Lactobacillus casei strain Shirota (LcS) containing fermented milk. HTLV-1 provirus load, motor function, neurological findings, and immunological parameters were evaluated after 4 weeks. Although LcS did not change the frequencies or absolute numbers of all the examined cell surface phenotypes of peripheral blood mononuclear cells, NK cell activity was significantly increased after 4 weeks of oral administration of LcS preparation. Improvements in spasticity (modified Ashworth Scale scores) and urinary symptoms were also seen after LcS treatment. No adverse effect was observed in all the 10 patients throughout the study period. Our results indicated that LcS may be a safe and beneficial agent for the treatment of HAM/TSP; therefore randomized controlled studies are warranted.

Adult↗
PubMed2005

Involvement of discoidin domain receptor 1 in the deterioration of pulmonary sarcoidosis.

The prognosis of sarcoidosis with pulmonary infiltrates differs in each case, and several cytokines are reported to contribute to its deterioration. However, the detailed mechanism has not been fully elucidated. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen and associated with cytokine production from inflammatory cells. We previously reported the functional expression of DDR1 on CD14-positive bronchoalveolar lavage fluid (BALF) cells in vivo. In this study, we hypothesized that DDR1 might be associated with the deterioration of pulmonary sarcoidosis (PS), and investigated 33 patients with sarcoidosis with pulmonary infiltrates, prospectively. We found that patients with deteriorated PS showed significantly higher DDR1 expression in CD14-positive BALF cells predominant with DDR1b isoforms. Activation of DDR1 induced monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) production in a p38 mitogen-activated protein kinase-dependent manner from CD14-positive BALF cells of patients with deteriorated sarcoidosis. DDR1 activation also induced NF-kappaB nuclear translocation in CD14-positive BALF cells of patients with deteriorated PS. The inhibitor of NF-kappaB inhibited the production of MCP-1 and MMP-9. We propose that DDR1 is associated with the deterioration of pulmonary sarcoidosis.

Antibodies, Monoclonal↗
PubMed2005

Cellular immune response to HTLV-1.

There is strong evidence at the individual level and the population level that an efficient cytotoxic T lymphocyte (CTL) response to HTLV-1 limits the proviral load and the risk of associated inflammatory diseases such as HAM/TSP. This evidence comes from host population genetics, viral genetics, DNA expression microarrays and assays of lymphocyte function. However, until now there has been no satisfactory and rigorous means to define or to measure the efficiency of an antiviral CTL response. Recently, methods have been developed to quantify lymphocyte turnover rates in vivo and the efficiency of anti-HTLV-1 CTLs ex vivo. Data from these new techniques appear to substantiate the conclusion that variation between individual hosts in the rate at which a single CTL kills HTLV-1-infected lymphocytes is an important determinant, perhaps the decisive determinant, of the proviral load and the risk of HAM/TSP. With these experimental data, it is becoming possible to refine, parameterize and test mathematical models of the immune control of HTLV-1, which are a necessary part of an understanding of this complex dynamic system.

Animals↗
PubMed2005

Human T cell leukemia virus type I-infected patients with Hashimoto's thyroiditis and Graves' disease.

CONTEXT: Autoimmune thyroid diseases have been reported to be associated with human T cell leukemia virus type I (HTLV-I) infection. HTLV-I proviral load is related to the development of HTLV-I-associated myelopathy/tropical spastic paraparesis and has also been shown to be elevated in the peripheral blood of HTLV-I-infected patients with uveitis, arthritis, and connective tissue disease. OBJECTIVE: The objective of the study was to evaluate the proviral load in HTLV-I-infected patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) and ascertain the ability of HTLV-I to infect thyroid cells. PATIENTS AND METHODS: A quantitative real-time PCR assay was developed to measure the proviral load of HTLV-I in peripheral blood mononuclear cells from 26 HTLV-I-infected patients with HT, eight HTLV-I-infected patients with GD, or 38 asymptomatic HTLV-I carriers. Rat FRTL-5 thyroid cells were cocultured with HTLV-I-infected T cell line MT-2 or uninfected T cell line CCRF-CEM. After coculture with T cell lines, changes in Tax and cytokine mRNA expression were studied by RT-PCR. RESULTS: HTLV-I proviral load was significantly higher in the peripheral blood of patients with HT and GD than asymptomatic HTLV-I carriers. In the peripheral blood from HTLV-I-infected patients with HT, HTLV-I proviral load did not correlate with the thyroid peroxidase antibody or thyroglobulin antibody titer. After coculture with MT-2 cells, FRTL-5 cells expressed HTLV-I-specific Tax mRNA. These cocultured FRTL-5 cells with MT-2 cells expressed IL-6 mRNA and proliferated more actively than those cocultured with CCRF-CEM cells. CONCLUSION: Our findings suggest the role of the retrovirus in the development of autoimmune thyroid diseases in HTLV-I-infected patients.

Adult↗
PubMed2005

Fatigue and damage to the masseter muscle by prolonged low-frequency stimulation in the rat.

This study aimed to examine peripheral fatigue and the resultant damage to the masseter muscle due to prolonged low-frequency stimulation. Thirty male rats were divided into S1, S2, S4, Dantr and Sham groups. The left masseters were used as experimental muscles. A pair of stimulation electrodes was placed on the left masseter. A stimulating session included rectangular electric pulses of 18 Hz (5 mA, approximately 18 V, 0.7 ms) for 2 h with a 3 min rest period between sessions. One session was given to the S1 group, two sessions to the S2 group and four sessions to the S4 group. Four sessions were given to the Dantr group with administration of dantrolene to determine any artifacts of the electrical current. No electric stimulation was given to both side masseters in the Sham group or to the control (right) masseters in the other groups. In each session, jaw-closing force increased to a peak within 1 min and attenuated to the steady force. The peak force decreased as the session advanced in each group. Both side masseters were dissected after the stimulations and examined histologically. The experimental masseter was significantly heavier than that of the controls in the S1, S2 and S4 groups, and the muscle fibres showed irregularity of size and shape with enlargement of interstitial space and infiltration of mononuclear cells into the fibres. However, no such histological change was observed in the Dantr and Sham groups. It was confirmed that fatigue and damage to muscle fibres could be induced in masticatory muscles by prolonged low-frequency stimulation.

Animals↗
PubMed2005

ApaI polymorphism of vitamin D receptor gene is associated with susceptibility to HTLV-1-associated myelopathy/tropical spastic paraparesis in HTLV-1 infected individuals.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one outcome of human T-cell lymphotropic virus type-1 (HTLV-1) infection. It remains unknown why the majority of infected people remain healthy, whereas only approximately 2-3% of infected individuals develop the disease. The active form of vitamin D has immunomodulatory effects, and allelic variants of the vitamin D receptor (VDR) appear to be associated with differential susceptibility to several infectious diseases. To investigate whether VDR single nucleotide polymorphisms (SNPs) are associated with the development of HAM/TSP, we studied four VDR SNPs in a group of 207 HAM/TSP patients and 224 asymptomatic HTLV-1 seropositive carriers (HCs) in Kagoshima, Japan, by using PCR-RFLP analysis. We found that ApaI polymorphism of VDR is associated with the risk of HAM/TSP, although this polymorphism did not affect the provirus load of HTLV-1 in either HAM/TSP patients or HCs.

Adult↗
PubMed2005

Activation of discoidin domain receptor 1 on CD14-positive bronchoalveolar lavage fluid cells induces chemokine production in idiopathic pulmonary fibrosis.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. We previously reported the functional expression of DDR1 on human monocyte-derived macrophages in vitro; however, information regarding its role in diseases is limited. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, and the lesions contain an abundance of collagen. In this study, we examined DDR1 expression on bronchoalveolar lavage fluid (BALF) cells and investigated its functionality using samples obtained from 28 IPF patients, 13 chronic obstructive pulmonary disease patients, and 14 healthy volunteers. The DDR1 expression level in CD14-positive BALF cells was higher in IPF patients than in chronic obstructive pulmonary disease patients or healthy volunteers. The predominant isoform was DDR1b in the IPF group, while DDR1a was predominant in the other two groups. Using immunohistochemical analysis, we also detected DDR1 expression on infiltrating inflammatory cells in the IPF lesion. In IPF patients, DDR1 activation induced the production of MCP-1, IL-8, MIP-1 alpha, and matrix metalloproteinase-9 (MMP-9) from CD14-positive BALF cells in a p38 MAPK-dependent manner. In contrast, DDR1 activation of CD14-positive BALF cells in the other groups did not induce the production of these chemokines or MMP-9. These chemokines and MMP-9 contribute to the development of IPF and, therefore, we suggest that DDR1 might be associated with the pathogenesis of IPF in the tissue microenvironment.

Adaptor Proteins, Signal Transducing↗
PubMed2005

The origin of spontaneous discharges in acquired neuromyotonia. A Macro EMG study.

OBJECTIVE: To study the generator sites of spontaneous discharges in patients with immune-mediated neuromyotonia. METHODS: Macro EMGs triggered by both spontaneously and voluntarily activated single action potentials were recorded and the mean peak-to-peak amplitude and area of the macro motor unit potentials were compared in two patients with typical acquired neuromyotonia having positive antibodies against voltage-gated potassium channels. RESULTS: Mean peak-to-peak amplitude and area of Macro EMG motor unit potentials (macro MUPs) triggered by spontaneous discharges were significantly smaller than those triggered by voluntary activation in both patients. However, a few macro MUPs triggered by spontaneous discharges resembled those triggered by voluntary activation. CONCLUSIONS: Spontaneous discharges in two patients with immune-mediated neuromyotonia seem to be mostly generated at sites distal to the terminal axon branching points. SIGNIFICANCE: This finding may provide a new insight in the understanding of spontaneous discharges in immune-mediated neuromyotonia.

Action Potentials↗
PubMed2005

Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease observed only in 1-2 % of infected individuals. HTLV-1 provirus load, certain HLA alleles and HTLV-1 tax subgroups are reported to be associated with different levels of risk for HAM/TSP in Kagoshima, Japan. Here, it was determined whether these risk factors were also valid for HTLV-1-infected individuals in Mashhad in northeastern Iran, another region of endemic HTLV-1 infection. In Iranian HTLV-1-infected individuals (n=132, 58 HAM/TSP patients and 74 seropositive asymptomatic carriers), although HLA-DRB1*0101 was associated with disease susceptibility in the absence of HLA-A*02 (P=0.038; odds ratio=2.71) as observed in Kagoshima, HLA-A*02 and HLA-Cw*08 had no effect on either the risk of developing HAM/TSP or HTLV-1 provirus load. All Iranian subjects possessed tax subgroup A sequences, and the protective effects of HLA-A*02 were observed only in Kagoshima subjects with tax subgroup B but not in those with tax subgroup A. Both the prevalence of HTLV-1 subgroups and the host genetic background may explain the different risks levels for HAM/TSP development in these two populations.

Genetic Predisposition to Disease↗
PubMed2005

Effects of omega-3 polyunsaturated fatty acids on inflammatory markers in COPD.

BACKGROUND: COPD, the fifth-leading cause of death worldwide, is characterized by chronic inflammation. However, no available agent can effectively cure this inflammation. A dietary supplement containing omega-3 polyunsaturated fatty acids (PUFAs) has anti-inflammatory effects. In this study, we hypothesized that nutritional support with omega-3 PUFA-rich diets may be useful for treating COPD, and we compared the clinical features and inflammatory mediator levels between the COPD patients who received an omega-3 PUFA-rich supplement and those who received a nonrich supplement. METHODS: Sixty-four COPD patients received 400 kilocalories per day of an omega-3 PUFA-rich supplement (n-3 group) or an omega-3 PUFA-nonrich supplement (n-6 group) for 2 years. We prospectively investigated the clinical features of these patients and measured the levels of inflammatory mediators. RESULTS: In 6-min walk testing, the dyspnea Borg scale and decrease of arterial oxygen saturation measured by pulse oximetry significantly improved in the n-3 group. Leukotriene B4 levels in serum and sputum and tumor necrosis factor-alpha and interleukin-8 levels in sputum decreased significantly in the n-3 group, while there was no significant change in the n-6 group. Two patients in the n-3 group and three patients in the n-6 group had mild diarrhea, and three patients in the n-3 group and three patients in the n-6 group had nausea; however, their symptoms were controllable and they improved with treatment. With multiple regression analysis, it was proved that the omega-3 PUFA-rich diet significantly contributed to the change in cytokine levels in this study. CONCLUSION: We suggest nutritional support with an omega-3 PUFA-rich diet as a safe and practical method for treating COPD.

Aged↗
PubMed2005

Hyponatremia upon resumption of paroxetine therapy.

We present a 79-year-old woman with severe hyponatremia secondary to resumption of treatment with paroxetine, a selective serotonin-reuptake inhibitor antidepressant. Confusion and fatigue followed re-initiation of paroxetine after a 3-month hiatus. Hyponatremia, serum hypoosmolality, and urine hyperosmolality strongly suggested the syndrome of inappropriate secretion of antidiuretic hormone. Hyponatremia was quickly resolved after discontinuation of paroxetine and initiation of intravenous normal saline infusion together with oral fluid restriction. This case underscores the importance of monitoring serum sodium in elderly patients taking paroxetine, whether this represents a new prescription or reintroduction of the drug.

Aged↗
PubMed2005

Hermansky-Pudlak syndrome with a novel mutation.

We report a case of Hermansky-Pudlak syndrome (HPS) with a novel mutation in the HPS1 gene. This case showed oculocutaneous albinism and lysosomal ceroid accumulation, however platelet dysfunction was not observed. Histopathological findings of the biopsied lung tissue were compatible with HPS. Sequencing analysis showed the insertion of C in the codon 178 (739 bp) of the HPS1 gene forming a stop codon at codon 181. To the best of our knowledge, this is a novel HPS1 gene mutation.

Comorbidity↗
PubMed2005

Long-term follow-up study of health status in population living in methylmercury-polluted area.

At present, it is important to follow-up on the health condition of inhabitants living in a methylmercury-polluted area surrounding Minamata City, paying attention to subclinical disorders not only of the central nervous system, which have been concentrically studied for more than 40 years, but also to other health issues as well. We have performed annual follow-up multiple health examinations on about 1,500 persons of ages more than 40 years old in Tsunagi Town near Minamata City each summer from 1984 to 2004. Case-control studies were designed to estimate the role of risk factors for various health issues using geographical differences to compare the verified patients. The results of the study are summarized as follows: (1) There were no significant differences in the prevalence of diseases associated with Minamata disease (MD) (e.g., liver diseases, renal diseases). (2) Subjective complaints, which were related not only to neurological but also to general complaints were consistently much more common in the polluted area than in the control area. (3) Five percent of the inhabitants who were not certified as MD patients had a high predicting index of MD. They could be affected by methylmercury poisoning. It is important to make a differential diagnosis. (4) No significant differences with respect to ADL by residential area were observed. However, MD patients who stayed in their homes showed some impairments of instrumental ADL. (5) It is important to take into consideration mental distress not only from the physical effects but also from the secondary social damage experienced through MD in these area.

Adolescent↗