Search PubMed⌕ Search

Biomedical subjects

Yoichi Nakamura

Publications and source records attributed to Yoichi Nakamura.

At least 55 records · Page 3Linked to original sources
PubMed2004

Significance of the level of monocyte chemoattractant protein-1 in human atherosclerosis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, plays an important role in the earliest events of atherogenesis. However, direct evidence of the effects of MCP-1 on atherosclerosis in chronic hemodialysis (HD) patients has not been reported. METHODS AND RESULTS: The serum MCP-1 concentrations and the intimal - medial thickness (IMT) in the carotid arteries were measured in 42 non-diabetic chronic HD patients and 20 age-matched controls. The expression of MCP-1 was examined immunohistochemically in radial arterial tissues obtained from the HD patients. IMT and the serum concentration of MCP-1 in the HD patients were both significantly greater than in controls. Multiple regression analysis revealed that the serum concentration of MCP-1 was an independent factor influencing IMT. Tissue immunostaining showed that MCP-1 is expressed in both endothelial and smooth muscle cells and that its level of expression correlates with the serum concentration of MCP-1. CONCLUSIONS: An increase in MCP-1 may be an important factor in the progression of atherosclerosis in non-diabetic HD patients.

Adult↗
PubMed2004

A small outbreak of pulmonary tuberculosis in non-close contact patrons of a bar.

Four habitual drinking and smoking patients with pulmonary tuberculosis who were thought to have had no contact with one another were admitted to our hospital. During admission, we found that they were regular visitors of the same bar. To investigate the possibility of outbreak, we analyzed the tuberculosis isolates from them by restriction fragment length polymorphism. Such analysis showed identical chromosomal DNA restriction patterns of these 4 culture isolates. We concluded that these patients were considered to represent a mini-outbreak of pulmonary tuberculosis, although there was little, if any, contact among them while in or out of the bar.

Alcohol Drinking↗
PubMed2004

Anatomical study of meandering and functions of human intralaryngeal artery.

In recent years, partial laryngectomy and partial reconstruction are increasingly intended for conservation of functions of phonation and swallowing. In partial reconstruction, it is important to comprehend morphological characteristics of the blood vessels distributed in the larynx, but there have been only few reports discussing detailed information about them. Previous reports on laryngeal blood vessels have shown that branches of some arteries show remarkable "meandering". In the present study, we devised a method for objectively determining the morphological nature, "meandering" and assessed functions of the arteries. Intralaryngeal arteries were excised from the larynx of cadavers prepared for practice in anatomy, and images of the "meandering" artery were analyzed with NIH Image. The extent of "meandering" was expressed mainly as the ratio of the total length of the blood vessel to the distance between the starting point and the end point of meandering. The results showed that there was a significant difference in the extent of meandering between superior posterior and medial posterior branches of superior laryngeal artery. These arteries, which were distributed in the arytenoid region, were found to be of primary importance in partial laryngectomy and partial reconstruction of the larynx.

Aged↗
PubMed2004

Relationship between cathepsin B and thrombin in rheumatoid arthritis.

OBJECTIVE: To investigate the pathophysiological significance of cathepsin B and thrombin in synovial fluid (SF) from patients with rheumatoid arthritis (RA). METHODS: Thrombin and cathepsin B activities of samples from patients with RA and osteoarthritis (OA) were measured using fluorogenic synthetic substrates. The concentration of interleukin 8 (IL-8) in SF was measured by ELISA. The effect of thrombin on the proliferation of synovial fibroblast-like cells (SFC) was examined by measuring 3H-thymidine incorporation. The effect of thrombin on the release of IL-8 and cathepsin B from SFC was investigated. The expression of IL-8 mRNA in SFC after stimulation with thrombin was evaluated using real-time quantitative RT-PCR. The effect of recombinant IL-8 on the activation of cathepsin B was examined using the knee joints of rabbits. RESULTS: In SF supernatants, cathepsin B and thrombin-like activity was significantly higher in RA than in OA, and there was a significant correlation between them. Cathepsin B activity was also significantly higher in SF cells and synovial tissue extracts from RA patients than in those from OA patients. There was a significant correlation between cathepsin B activity and the concentration of IL-8 in RA SF. Thrombin enhanced the proliferation of SFC in a dose-dependent manner. Thrombin significantly enhanced the release of IL-8 from SFC as well as the expression of IL-8 mRNA in SFC. IL-8 induced activation of cathepsin B in the knee joints of rabbits. However, thrombin did not directly increase cathepsin B activity in SFC. CONCLUSION: In RA, thrombin was found to be related to the enhanced growth of SFC and the release of IL-8 from these cells; thus thrombin is probably related to worsening of inflammation through the recruitment of leukocytes (neutrophils), which release cathepsin B into the SF. Thrombin can induce activation of cathepsin B in SFC via increased expression of IL-8.

Adult↗
PubMed2004

[Case of multi-drug resistant tuberculosis complicated with bronchoesophageal fistula].

A 71-year-old man visited the surgical department of our hospital due to back pain in November, 1999. Esophagogram showed bronchoesophageal fistula and a plain chest radiograph showed a nodular shadow in the left upper area with left pleural effusion. As the symptom disappeared on treatment with an antimicrobial agent, he was followed up as an outpatient. In August, 2001, he presented to the Respiratory Department of our hospital with low-grade fever and productive cough. Since tubercle bacilli were detected in a sputum culture, combined treatment with antituberculous chemotherapy was started. But, none of the symptoms were improved. These bacilli were identified as being multi-drug-resistant. After the chemotherapy regimen was changed, the symptoms disappeared and the esophagorespiratory fistula was closed. We report a rare case of esophagorespiratory fistula with multi-drug resistant tuberculosis, which was improved by chemotherapy.

Aged↗
PubMed2004

[Microglial cell death induced by polyamines].

Pathological activation of microglia, which quiescently reside in physiological CNS, causes various neurodegenerative diseases. Endogenous polyamines, spermidine (SPD) and spermine (SPM) are known to be activators of cell proliferation and differentiation. We examined the effect of polyamines on microglial activation in culture. Cultured microglia prepared from the whole brains of newborn rats produced nitric oxide (NO) by the stimulation with lipopolysaccharide (LPS). LPS-induced NO production was remarkably inhibited by SPD and SPM. Cell viability assessed by total mitochondrial activity decreased by the incubation with SPD and SPM for 24 h. In astrocyte culture, on the other hand, polyamines showed no significant effect on either LPS-induced NO production or cell viability. After the treatment with SPM for 24 h, the cells changed into small round shapes, and were markedly stained with propidium iodide. By the staining with Hoechst33342, condensation and fragmentation of the nucleus were often observed. Semiquantitative analysis of fragmented DNA with the ELISA technique revealed that a large amount of fragmented DNA appeared in cytosol prior to disruption of the cell membrane, suggesting that polyamines induced apoptosis. Fragmented DNA in cytosol increased dose dependently with SPM. These results suggest that particular polyamines induce cell death through apoptosis at low concentrations in cultured microglia

Animals↗
PubMed2004

The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells.

Histone deacetylase inhibitors modulate the transcription of target genes and represent a new class of anticancer agents. The histone deacetylase inhibitor FR901228 has been reported to show antiproliferative and apoptotic effects in various malignancies including small cell lung cancer (SCLC) in vitro; however, the underlying mechanism is not fully understood. BCL-2 and BCL-XL are antiapoptotic proteins, of which overexpression has been reported to confer resistance to anticancer agents. High levels of BCL-2 and BCL-XL are frequently expressed in SCLC tumors. The present study was designed to clarify the apoptotic pathway of FR901228 in SCLC cells in vitro. FR901228 induced apoptosis in three SCLC cell lines after 24 hours of treatment. FR901228 activated caspase-9 and caspase-3 but not caspase-8, and the caspase-3 inhibitor Z-DEVD-fmk blocked the cytotoxicity of FR901228. FR901228 down-regulated the expression of bcl-2 and bcl-xL mRNA through de novo protein synthesis and suppressed the expression of BCL-2 and BCL-XL proteins. In addition, the combination of bcl-2 antisense oligonucleotides with FR901228 enhanced FR901228-induced caspase-3 activity and cytotoxicity. These findings suggest that FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway rather than the death receptor pathway. Considering the possible contributions of BCL-2 and BCL-XL to multidrug resistance, FR901228 is a promising agent in the treatment of refractory as well as primary SCLC tumors.

Apoptosis↗
PubMed2003

Stimulation of human bronchial epithelial cells by IgE-dependent histamine-releasing factor.

An IgE-dependent histamine-releasing factor (HRF p23; also known as translationally controlled tumor protein or p23) stimulates the release of histamine, IL-4, and IL-13 from a subpopulation of highly allergic donor basophils. It has also been shown to act as a chemoattractant for eosinophils. To elucidate novel functions of HRF p23 in airway inflammation, we examined the effects of human recombinant HRF p23 (hrHRF) on bronchial epithelium and found that hrHRF stimulated the secretions of IL-8 and granulocyte/macrophage colony-stimulating factor by both primary cultures of human bronchial epithelial cells and BEAS-2B cells. In response to hrHRF, these cells induced IL-8 mRNA expression within 4 h. H2O2, but not IL-1 beta or tumor necrosis factor-alpha, stimulated secretion of HRF p23 by BEAS-2B cells, suggesting that oxidative stress may trigger the release of HRF p23 from bronchial epithelial cells. Bronchoalveolar lavage (BAL) from healthy volunteers contained only trivial or undetectable amounts of HRF p23. Significantly higher amounts of HRF p23 were recovered from BAL fluid taken from asthmatic patients, and the amounts of HRF p23 were further elevated in patients with idiopathic eosinophilic pneumonia. Our results demonstrate for the first time that HRF p23 can stimulate nonimmune epithelium. HRF p23 derived from bronchial epithelial cells may regulate complex cytokine networks in eosinophil-dependent inflammation of the human airway.

Biomarkers, Tumor↗
PubMed2003

Adenosine triphosphate inhibits cytokine release from lipopolysaccharide-activated microglia via P2y receptors.

Microglial proliferation and activation have been reported to occur after several central nervous system injuries. In this study, we tested the effects of adenosine triphosphate (ATP) on cultured microglia obtained from the spinal cord of rat embryos. The amounts of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta and interleukin 6 released from the microglia, which were stimulated by lipopolysaccharide (LPS; 100 ng/ml), were inhibited by the simultaneous addition of ATP in a dose dependent manner (10-300 microM). We examined the effect of several endogenous purines (ATP, ADP, CTP, UDP, UTP) and P(2)y receptor agonists (ADPbetaS and 2-methylthio-ATP) on LPS-induced TNF-alpha release. The rank order of inhibitory potency of endogenous purines on TNF-alpha release was: ATP>ADP>>UTP>UDP>CTP. The latter three were much less potent than the former two. The addition of 10 microM 2-methylthio-ATP showed a potency similar to 100 microM ATP. The addition of ADPbetaS, however, showed less effect. These endogenous purines and selective ATP receptor agonists showed a similar inhibitory effect in their rank order on LPS-induced interleukin 6 release. We demonstrate that ATP inhibits cytokine release from LPS-activated microglia via metabotropic receptors. The application of P(2)y receptor agonists might be considered as a pharmacological treatment of several pathological conditions of the spinal cord, including toxic immunoreactions.

Adenosine Diphosphate↗
PubMed2003

Expression and functional analyses of breast cancer resistance protein in lung cancer.

PURPOSE: Breast cancer resistance protein (BCRP/ABCG2), an ATP binding cassette half-transporter, confers resistance to mitoxantrone, doxorubicin, and topoisomerase I inhibitors of irinotecan and topotecan. Recently, we reported that BCRP efficiently transported SN-38 (the active metabolite of irinotecan) with a high affinity in lung cancer cells in vitro (K. Nakatomi et al., Biochem. Biophys. Res. Commun., 288: 827-832, 2001). The aim of this study is to explore the role of BCRP in the drug resistance of lung cancer. EXPERIMENTAL DESIGN: The BCRP mRNA expression in lung cancer cells and 23 untreated non-small cell lung cancer (NSCLC) tissues was quantitated by real-time reverse transcription-PCR. To evaluate the drug-efflux function of BCRP, the intracellular topotecan accumulation and drug sensitivity were measured in lung cancer cells with various levels of the BCRP mRNA expression by flow cytometric and tetrazolium dye assay, respectively. RESULTS: The levels of BCRP mRNA expression in the cell lines were significantly correlated with the BCRP function and the sensitivity to SN-38 and topotecan. In NSCLC tissues, the BCRP mRNA expression levels were widely dispersed. Five (22%) of 23 tissues expressed higher levels of the BCRP mRNA than that in NCI-H441 cells with active BCRP function conferring high resistance to topotecan in vitro. CONCLUSIONS: Some NSCLC tissues expressed sufficient levels of the BCRP mRNA to confer drug resistance in vitro.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2003

Antiproliferative effects of the histone deacetylase inhibitor FR901228 on small-cell lung cancer lines and drug-resistant sublines.

FR901228 is a novel histone deacetylase (HDAC) inhibitor, and its antiproliferative effects on non-small cell lung cancer cells have been shown in vitro. However, there have been no reports concerning the effects on small-cell lung cancer (SCLC). We have recently demonstrated that the HDAC inhibitors trichostatin A and sodium butyrate inhibit expression of the catalytic subunit of telomerase (hTERT) mRNA and telomerase activity in prostate cancer cells. The present study was designed to evaluate the effects of FR901228 on proliferation and telomerase activity in SCLC cells in vitro. FR901228 at 5 to 10 nM increased the fraction of cells in the G(2)/M and sub-G(1) phases of the cell-cycle, and inhibited the growth of H69, H526 and H82 cell lines. The expression of hTERT mRNA was inhibited 6 hr after treatment, prior to obvious inhibition of cell growth or cell-cycle distribution shifts. The inhibition of hTERT mRNA expression and telomerase activity was not a consequence of cell-growth arrest or apoptosis. Cycloheximide blocked the suppression of hTERT mRNA induced by FR901228, and the inhibition of hTERT mRNA by FR901228 required newly synthesized proteins. FR901228 also effectively inhibited growth of etoposide-resistant UMCC-1/VP-16, irinotecan-resistant PC-6/SN2-5H and cisplatin-resistant H526/CDDP cells having decreased expression of hTERT mRNA and telomerase activity, as well as their parental cells. This implies that SCLC resistant to these key drugs are not cross-resistant to FR901228. The present study suggests that FR901228 may be a promising drug for chemotherapy of cancers including SCLC, even for refractory or relapsing tumors after conventional chemotherapy.

Anti-Bacterial Agents↗
PubMed2003

Involvement of protein kinase C in glutamate release from cultured microglia.

Glutamate release from microglial cells may cause neuronal damage. To elucidate the mechanism of glutamate release, we examined the possible regulation by nitric oxide and protein kinase C. Cultured microglia prepared from the whole brains of newborn rats released glutamate by the stimulation with lipopolysaccharide (LPS) dose dependently. The time course study revealed that glutamate release showed a long lag time about 6 h after LPS stimulation, whereas about 3 h lag time was observed in LPS-induced NO production. An inhibitor for NO synthase, N(G)-nitro-L-arginine, could effectively inhibit the glutamate release. Glutamate release induced by LPS was enhanced by 1 nM phorbol myristate acetate (PMA). Furthermore, high concentrations of PMA (>10 nM) induced glutamate release even without LPS stimulation. Glutamate release stimulated either by 100 ng/ml LPS or 100 nM PMA was inhibited by staurosporine, and also by alpha-aminoadipate. These results provide insight into the pathways regulating microglial pathological activation by protein kinase C and may be a base for the protection against microglia-evoked neurotoxicity.

Analysis of Variance↗
PubMed2003

Induction of complete remission of hypoplastic leukemia with antithymocyte globulin.

A 13-year-old boy was admitted to a local hospital because of pancytopenia. A bone marrow aspiration and biopsy revealed severely hypocellular marrow with no obvious leukemic cells. The diagnosis was severe aplastic anemia, and the patient was treated with antithymocyte globulin and cyclosporin A. A trilineage response was obtained, and the patient became transfusion-independent within 2 weeks. Two months later, the peripheral blood count normalized with an increased bone marrow cellularity. However, the patient was readmitted 5 months later for recurrence of the pancytopenia. A bone marrow aspiration revealed hypocellular marrow with morphologically blastoid cells. A surface marker study revealed the presence of a single clone that was positive for CD7, CD33, CD34, and HLA-DR. A diagnosis of hypoplastic leukemia was made on the basis of morphology and the surface marker studies. Retrospectively, the laboratory findings were the same as those seen at the onset of the disease. The patient did not respond to combination chemotherapy consisting of vincristine, prednisolone, cyclophosphamide, L-asparaginase, and doxorubicin, but administration of etoposide resulted in complete remission. An in vitro study revealed that >95% of the leukemic cells of this patient could be lysed after an incubation with antithymocyte globulin and human AB serum or baby rabbit serum. These findings suggest the efficacy of antithymocyte globulin in treating certain hypoplastic leukemias.

Adolescent↗
PubMed2003

Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis.

INTRODUCTION: Tissue factor plays a key role in the extrinsic coagulation pathway and is induced by inflammatory cytokines. Atrial myocarditis has been detected recently in some patients with lone atrial fibrillation. Virchow's triad of low blood flow, hypercoagulability, and endothelial dysfunction, enhances thrombus formation. The present study was designed to elucidate the role of endothelial dysfunction in thrombogenesis associated with nonvalvular atrial fibrillation. MATERIAL AND METHODS: We investigated tissue factor expression in the endothelia of left atrial appendages obtained from seven patients with nonvalvular atrial fibrillation and cardiogenic thromboembolism. Tissues were divided into 7-13 sections and compared with control specimens from four patients who died of noncardiac events. Expression of tissue factor, von Willebrand factor and tissue factor pathway inhibitor was evaluated by immunohistochemistry. RESULTS: Histopathologically, inflammatory cells infiltrated the endocardium and all seven patients showed features of persistent myocarditis. Activated T cells [15.3+/-9.4 cells/high power field (HPF, mean+/-S.D.) vs. control 2.2+/-4.4/HPF (P=0.0294)] and a few macrophages [5.1+/-8.4 cells/HPF vs. control 2.4+/-3.5 cells/HPF (P=NS)] infiltrated the endocardium. Tissue factor was overexpressed in the endothelia particularly in tissues containing inflammatory cells and denuded matrix of the endocardium, compared with the control group. Von Willebrand factor, but not tissue factor pathway inhibitor, was also overexpressed in these tissues. CONCLUSION: Tissue factor expression induced by local inflammation is involved in the pathogenesis of thrombosis in patients with nonvalvular atrial fibrillation.

Aged↗
PubMed2003

Anatomical study of distribution of valves of the cutaneous veins of adult's limbs.

Since the cutaneous veins of the four limbs have been used as autogenous grafts in the treatment of cardiovascular disorders, knowledge of distribution of the valves is increasingly required depending upon the use. In the gross anatomical study of distribution of valves of the trunci venae, there has been argument about locational relationships between the venous roots and the valves in the vicinity of the roots and the inter-valvular distance. However, there have been only few reports discussing detailed information about valves of the cutaneous veins of the four limbs. The authors observed patterns of distribution of the cutaneous venous valves of the four limbs of cadavers prepared for practice in anatomy. The following parts were excised from each cadaver: the cephalic, basilic, and the great saphenous veins, which originate from the acral venous network and flow into the proximal deep veins, and the venous roots communicating with these veins. An incision was made on each excised vein in the direction of the long axis under observation with a stereoscopic microscope, and the inter-valvular distance and the distance between the valve and the orifice of venous root in the vicinity of the valve were measured. The inter-valvular distance varied with type of the truncus venae, and it varied according to area even in the same truncus venae.

Aged↗
PubMed2003

Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis.

We studied the effects of exogenously administered recombinant murine interleukin (IL)-10 on the development of experimental autoimmune orchitis (EAO) in C3H/He mice. IL-10 significantly augments histological signs of EAO when administered for 6 consecutive days from days 15 to 20 after primary immunisations with testicular germ cells. These data demonstrate that IL-10, in addition to its well-known antiinflammatory property, also has proinflammatory functions capable of up-regulating testicular immunoinflammatory processes in vivo.

Animals↗
PubMed2003

Toluene diisocyanate exposure induces laryngo-tracheal eosinophilia, which can be ameliorated by supplementation with antioxidant vitamins in guinea pigs.

OBJECTIVE: Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational lung disease. In addition, a sore throat is one of the complaints of TDI-exposed workers. The aim of the present study was to determine whether TDI exposure induces laryngeal and/or tracheal lesions in experimental animals. MATERIAL AND METHODS: Guinea pigs underwent naris application of TDI three times, and their respiratory tracts were then examined using light and electron microscopy. Some animals simultaneously received vitamins C and E. which function as antioxidant agents. RESULTS: When TDI-treated animals showed the clinical sign of labored breathing, many eosinophils had appeared in the lamina propria and mucosa of both the larynx and trachea, which finally infiltrated the tract lumen through the ruptured epithelium. Laryngo-tracheal inflammation was more severe than that observed in the lungs. However, supplementation with antioxidant vitamins in TDI-treated animals ameliorated the respiratory eosinophilia. CONCLUSION: Naris application of TDI induced laryngotracheitis. which was significantly suppressed by the antioxidant vitamins, This implies a preventive effect of the vitamins on this occupational disease.

Animals↗