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Biomedical subjects

Hiroyuki Nakamura

Publications and source records attributed to Hiroyuki Nakamura.

142 records · Page 8Linked to original sources

[Comparative study of bone resorption markers for the diagnosis of bone metastasis in lung cancer].

NTx and I CTP, a metabolite of type I collagen, were compared as to their usefulness as indicators of bone metastasis in lung cancer. The NTx level was significantly higher in lung cancer patients with bone metastasis (107.9 +/- 56.1 nM BCE/mM) than in those without it (p < 0.0001), as was the I CTP level (10.0 +/- 6.5 ng/ml; p < 0.0001). The Z scores of NTx and I CTP were 2.37 and 2.04, respectively, indicating that NTx is superior to I CTP in sensitivity to bone metastasis because of its higher Z score and its higher area under the ROC curve. The cutoff values of these markers were set to produce the highest accuracy/sensitivity rates and to make possible the highest diagnostic efficiency, and then the odds ratios at these cutoff values were calculated. The odds ratios of NTx and I CTP at cutoff values for the highest accuracy were 66.3 and 12.6, respectively; those offering the highest diagnostic efficiency were 46.5 and 10.0, respectively. These results indicated that NTx offers better prediction of bone metastasis in lung cancer than does I CTP.

Biomarkers, Tumor↗

[A case of infective endocarditis accompanied with pulmonary complications in a drug addict].

A 21-year-old man who had a history of intravenous drug addiction was admitted with complaints of high fever and a productive cough. Chest CT on admission showed multiple consolidations, and pneumonia was initially diagnosed and treated. Because echocardiography after admission showed vegetation, with no bacteriological findings, attached to the tricuspid valve, right-sided infective endocarditis was diagnosed. After antibiotic therapy was changed, his fever was reduced and the inflammatory findings were eliminated. In the western world, most cases of right-side infective endocarditis are caused by drug addicts, but in Japan, this disease is very rare. Right-side infective endocarditis in drug addicts causes a high rate of pulmonary complications, in particular, septic pulmonary embolism. Many drug addicts suffering from pulmonary complications may consult doctors, but if the latter are not well-informed about this disease, it may not be possible to give an accurate diagnosis or proper treatment.

Adult↗

[A case of immotile-dyskinetic cilia syndrome responding to clenbuterol hydrochloride and azithromycin].

In this case, a 30-year-old man had been treated for chronic sinusitis and bronchiectasis since 2000, and presented at our outpatient clinic in May 2001 with chief complaints of massive yellow sputum expectoration and dyspnea. After he was admitted by our hospital, Pseudomonas aeruginosa bacteria were isolated at the rate of 10(8)/ml from his sputum culture. In electron-microscopic observation, the cilia of the bronchial epithelium were found to lack dynein arms. Semen examination revealed decreased sperm motility. Thus, the following diagnosis was made: diffuse bronchiectasis associated with the immotile-dyskinetic cilia syndrome, complicated with a P. aeruginosa infection. After the airway infection was ameliorated, 40 mg/day of clenbuterol hydrochloride was administered in combination with 250 mg of azithromycin, which was given twice a week, and which led to a markedly decreased frequency of exacerbation of airway infection. Moreover, chest CT scanning and respiratory function testing also indicated improvements. It was hypothesized that the decreased cilia motility due to P. aeruginosa-produced pyocyanin would be ameliorated with a b2 stimulant, and the inhibitory effect of a macrolide on the P. aeruginosa biofilm and production of pyocyanin would also be involved in the improvement of this case.

Adult↗

[A case of diffuse malignant mesothelioma of the pleura with bilateral chylothorax].

We describe a case of bilateral chylothorax with malignant pleural mesothelioma. A 41-year-old woman was admitted to our hospital because of dyspnea. She had no history of exposure to asbestos. A chest radiograph and chest computed tomogram (CT) on admission revealed massive bilateral pleural effusion and a large tumor with pleural thickening in the left lateral and anterior parts of the pleura and mediastinum. Biochemical tests of pleural fluid revealed chyle. Two years before, she had been diagnosed through histological and histochemical examinations as having diffuse malignant pleural mesothelioma of the epithelial type. Chest-tube drainage was performed, and pleurodesis was induced by the intrathoracic injection of OK-432 at 10 KE per dose. The chylothorax disappeared after pleurodesis. To date, reports of malignant mesothelioma with nontraumatic chylothorax have been rare.

Adult↗

[A case of hemophagocytic syndrome caused by tuberculosis].

A 59-year-old woman was admitted to our hospital with a picture of high fever and dyspnea. Pneumonia was diagnosed by chest CT scan and was treated. Laboratory findings showed pancytopenia and examination of aspirated bone marrow showed mature histiocytes with marked hemophagocytosis. She was treated with prednisolone, but her respiratory condition worsened, so she was ventilated. An acid-fast bacterial smear of bronchoalveolar lavage fluid from the left lingula showed Gaffky's scale No. 5, and so tuberculosis was diagnosed. Though anti-tuberculosis therapy was started, she died after eight days of hospitalization. Infection-associated hemophagocytic syndrome is caused by various infections. Until now, 26 cases of tuberculosis-associated hemophagocytic syndrome have been reported, and many of these diseases were caused by severe tuberculosis. If a patient with severe tuberculosis presents with leucocytopenia or thrombocytopenia, investigations should serve a differential diagnosis that takes into account disseminated intravascular coagulation, tuberculous granuloma of the bone marrow, side effects of anti-tuberculous drugs, and hypersplenism from hemophagocytic syndrome.

Female↗

[A case of post-traumatic bilateral eosinophilic pleural effusion].

A 58-year-old man was admitted to our hospital with chest pain caused by chest trauma. After admission, his chest pain decreased and he was discharged. Later, he was admitted again with a high fever and dyspnea. Laboratory findings on second admission showed a leukocyte count of 7,900/microliter (9% eosinophils) and a C-reactive protein of 17.0 mg/dl. Chest radiography and chest CT scanning on second admission showed moderate bilateral pleural effusion. Close examination showed an increase of eosinophils in the pleural effusion (14% of total cell counts on the right and 27% of total cell counts on the left) that was exudate. Post-traumatic bilateral eosinophilic pleural effusion was diagnosed. The patient was treated with antibiotic therapy and his condition improved. A chest CT scan afterwards showed improvement of the bilateral pleural effusion. The eosinophil count in the peripheral blood was 1% at chest trauma, 15% in the hospital to the max and decreased to 3% with the decrease of pleural effusion. Post-traumatic eosinophilic pleural effusion may be accompanied with inflammatory findings, and the mechanism is guessed by immunological reaction.

Eosinophilia↗

Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis.

Vascular endothelial growth factor (VEGF) is a strong angiogenic mitogen and plays important roles in angiogenesis under various pathophysiological conditions. The in vivo angiogenic activity of secreted VEGF may be regulated by extracellular inhibitors, because it is also produced in avascular tissues such as the cartilage. To seek the binding inhibitors against VEGF, we screened the chondrocyte cDNA library by a yeast two-hybrid system by using VEGF165 as bait and identified connective tissue growth factor (CTGF) as a candidate. The complex formation of VEGF165 with CTGF was first established by immunoprecipitation from the cells overexpressing both binding partners. A competitive affinity-binding assay also demonstrated that CTGF binds specifically to VEGF165 with two classes of binding sites (Kd = 26 +/- 11 nM and 125 +/- 38 nM). Binding assay using deletion mutants of CTGF indicated that the thrombospondin type-1 repeat (TSP-1) domain of CTGF binds to the exon 7-coded region of VEGF165 and that the COOH-terminal domain preserves the affinity to both VEGF165 and VEGF121. The interaction of VEGF165 with CTGF inhibited the binding of VEGF165 to the endothelial cells and the immobilized KDR/IgG Fc; that is, a recombinant protein for VEGF165 receptor. By in vitro tube formation assay of endothelial cells, full-length CTGF and the deletion mutant possessing the TSP-1 domain inhibited VEGF165-induced angiogenesis significantly in the complex form. This antiangiogenic activity of CTGF was demonstrated further by in vivo angiogenesis assay by using Matrigel injection model in mice. These data demonstrate for the first time that VEGF165 binds to CTGF through a protein-to-protein interaction and suggest that the angiogenic activity of VEGF165 is regulated negatively by CTGF in the extracellular environment.

Animals↗

Electroporation-mediated gene transfer that targets glomeruli.

Electroporation has been applied to introducing DNA into several organs; however, gene expression was localized around the injected area. Examined was the efficiency of intrarenal injection of DNA followed by in vivo electroporation, using FITC-labeled oligodeoxynucleotides (FITC-ODN) and plasmid DNA expressing beta-galactosidase or luciferase. FITC-ODN or expression vectors were injected into the left renal artery; thereafter, the left kidney was electroporated between a pair of tweezer-type electrodes. FITC-ODN were transferred into all glomeruli, and transfected cells were identified as mesangial cells. Four d after transfection of the pCAGGS-LacZ gene, beta-galactosidase expression was observed in 75% of glomeruli. To compare the transfection efficacy by electroporation with that by the hemagglutinating virus of Japan (HVJ) liposome method, a luciferase reporter gene, pActLuc, was transferred into glomeruli by either electroporation or the HVJ liposome method. On day 4, electroporation resulted in higher glomerular luciferase activity than did the HVJ liposome method. We also observed that co-transfection of pcEBNA, an expression vector for Epstein-Barr virus nuclear antigen, and poriP-cLuc, oriP-harboring vector, resulted in an eightfold higher luciferase gene expression than simple poriP-cLUC: No histologic damages were seen in glomeruli or tubular epithelial cells. In conclusion, gene transfer into renal artery followed by electroporation was an effective and simple strategy for gene transfer that targets glomerular mesangial cells.

Animals↗

Thyroid Carcinoma in Japan and the West: Similarities and Differences.

Geographic or ethnic differences in the incidence of thyroid carcinoma, as well as in the histologic distribution of thyroid carcinoma between Japan and Western countries, have been described but are still unclear. The recent establishment of histologic criteria for the diagnosis of thyroid carcinoma by the WHO committee has facilitated the comparison of clinicopathological data of patients with thyroid carcinoma all over the world. The aim of the present review article is to clarify the epidemiological and clinicopathological differences of thyroid carcinoma between Japan and Western countries. We found recently no significant differences in the incidence, mortality, and histologic distribution of thyroid carcinoma between Japan and Western countries; this was contrary to our expectation. This is likely attributable to westernization of the Japanese diet, standardized medical levels, and international standardization of histologic criteria of thyroid carcinoma.

Journal Article↗

Induction of myeloperoxidase and nitrotyrosine formation in a human eosinophilic leukemia cell line, EoL-1.

The human eosinophilic leukemia cell line, EoL-1, differentiated with butyrate as an eosinophilic cellular model was evaluated for peroxidase-dependent tyrosine nitration. Butyrate suppressed cell growth and induced eosinophilic granules in EoL-1 cells after 9 days of culture. Peroxidase activity was detected biochemically and histochemically from 3-day cultures and it increased in a time dependent manner. This peroxidase activity was inhibited by cyanide. Nitrotyrosine formation catalysed by peroxidase using hydrogen peroxide and nitrite was detected at a high level similar to that of mature eosinophils. However, no expression of eosinophil peroxidase (EPO) was detected by RT-PCR or immunocytochemistry. In contrast, the induction of myeloperoxidase (MPO) by butyrate was clearly detected by RT-PCR, Northern blot, and immunocytochemical staining. These results suggest that butyrate induces MPO rather than EPO in EoL-1 cells and that the formation of nitrotyrosine in butyrate-induced cells is dependent on MPO.

Butyrates↗

Acute-phase treatment in general hospitals: clinical psychopharmacologic evaluation in first-episode schizophrenia patients.

A case-control study was conducted to investigate possible predictors of response to antipsychotic treatment in acute schizophrenic patients. During a 14-month period, 13 female first-episode schizophrenic patients were included. According to their antipsychotic treatment response 8 weeks after admission, they were placed in either a good-response group (n = 8) or poor-response group (n = 5). Scores of the two groups differed on several items of the Positive and Negative Syndrome Scale (PANSS) at baseline and during the following 8 weeks. At baseline, the maximum scores for Conceptual disorganization, Poor rapport, Passive/apathetic social withdrawal, and Stereotyped thinking in the good-response group were lower than the corresponding minimum scores in the poor-response group. Furthermore, minimum improvements after 1 week in scores for excitement in the good-response group were higher than the maximum improvements in the corresponding scores of the poor-response group. These PANSS items might serve as simple and rapid predictors of treatment resistance. In addition, Lack of judgment and insight significantly improved by 1 week, and further improved by 5 weeks in the good-response group. This suggests that treatment in the good-response group will be optimal if provided during a hospital stay of appropriate length.

Acute Disease↗

Nonthermal effects of mobile-phone frequency microwaves on uteroplacental functions in pregnant rats.

Exposure to high-density microwaves can cause detrimental effects on the testis, eye, and other tissues, and induce significant biologic changes through thermal actions. To examine nonthermal effect of continuous wave (CW) 915MHz microwaves used in cellular phones, we compared the effects of microwaves with those of heat. Thirty-six pregnant rats were assigned to six groups: rats exposed to microwaves at 0.6 or 3mW/cm(2) incident power density at 915MHz for 90min, rats immersed in water at 38 or 40 degrees C, which induces about the same increase in colonic temperature of 1.0 or 3.5 degrees C as 0.6 or 3mW/cm(2) microwaves, respectively; rats immersed in water at 34 degrees C, which is considered to be thermoneutral; and control rats. We identified significant differences in the uteroplacental circulation, and in placental endocrine and immune functions between pregnant rats immersed in water at 34 and 38 degrees C, but not between rats immersed at 38 degrees C and those exposed to microwaves at 0.6mW/cm(2). By contrast, we observed significant decreases in uteroplacental blood flow and estradiol in rats exposed to microwaves at 3mW/cm(2) as compared with those immersed in water at 40 degrees C. These results suggest microwaves at 0.6mW/cm(2) at 915MHz, equal to a specific absorption rate (SAR) of 0.4W/kg, which is the maximum permissible exposure level recommended by the American National Standards Institute (ANSI), do not exert nonthermal effects on blood estradiol and progesterone, on splenic natural killer cell activity, on the uteroplacental circulation.

Animals↗

Transferrin-loaded nido-carborane liposomes: tumor-targeting boron delivery system for neutron capture therapy.

The nido-carborane lipid 2 as a double-tailed boron lipid was synthesized from heptadecanol in five steps. The lipid 2 formed stable liposomes at 25% molar ratio toward DSPC with cholesterol. Transferrin was able to be introduced on the surface of boron liposomes (Tf(+)-PEG-CL liposomes) by the coupling of transferrin to the PEG-CO(2)H moieties of Tf(-)-PEG-CL liposomes. The biodistribution of Tf(+)-PEG-CL liposomes, in which (125)I-tyraminyl inulins were encapsulated, showed that Tf(+)-PEG-CL liposomes accumulated in tumor tissues and stayed there for a sufficiently long time to increase tumor/blood concentration ratio, although Tf(-)-PEG-CL liposomes were gradually released from tumor tissues with time. A boron concentration of 22 ppm in tumor tissues was achieved by the injection of Tf(+)-PEG-CL liposomes at 7.2 mg/kg body weight boron in tumor-bearing mice. After neutron irradiation, the average survival rate of mice not treated with Tf(+)-PEG-CL liposomes was 21 days, whereas that of the treated mice was 31 days. Longer survival rates were observed in the mice treated with Tf(+)-PEG-CL liposomes; one of them even survived for 52 days after BNCT.

Animals↗

Sustained tyrosine-phosphorylation of FAK through Rho-dependent adhesion to fibronectin is essential for cancer cell migration.

BACKGROUND: Co-stimulation with lysophosphatidic acid (LPA) and fibronectin (FN) is essential for migration of rat ascites hepatoma MMI cells. We examined the roles of LPA and FN in Rho-FAK pathway to migration. MATERIALS AND METHODS: We evaluated the morphology, phagokinetic motility and the status of Rho activation and tyrosine-phosphorylation of FAK after stimulation of MMI or HT-1080 cells with LPA + FN or each alone. RESULTS: On FN-coated dishes without LPA, MM1 cells could not migrate and harbored undetectable levels of activated RhoA. Stimulation with LPA + FN enabled the MM1 cells to migrate and bear active RhoA and sustained tyrosine-phosphorylation of FAK. To the contrary, HT-1080 cells could migrate and harbored a significant amount of active RhoA accompanied by sustained tyrosine-phosphorylation of FAK even without LPA. CONCLUSION: Rho-dependent adhesion to FN leading to sustained tyrosine-phosphorylation of FAK is essential for cancer cell migration.

Animals↗