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Biomedical subjects

M Ohtsuka

Publications and source records attributed to M Ohtsuka.

At least 73 records · Page 4Linked to original sources

Immunohistochemical measurement of cell proliferation as replicative DNA synthesis in the liver of male Fischer 344 rats following a single exposure to nongenotoxic hepatocarcinogens and noncarcinogens.

We aimed to modify an in vivo/in vitro hepatocyte replicative DNA synthesis (RDS) test using autoradiography of [3H]methylthymidine (3HTdR) into a nonradioactive in vivo version by applying 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. The effects of 12 nongenotoxic hepatocarcinogens and 4 noncarcinogens on RDS induction and histological changes in the liver of male Fischer 344 (F344) rats were investigated 24 or 48 hrs after a single oral administration at diverse dose levels. A statistically significant, dose-related elevation in BrdU labeling indices (LI) was obtained for all of the 12 nongenotoxic hepatocarcinogens with only one exception of D,L-ethionine at relatively lower dose levels. No increase was observed in LI for any of the four noncarcinogens examined. From the results of histopathological evaluation, the increase in hepatocyte proliferation by carbon tetrachloride (CCl4), chloroform (CHCl3), and thioacetamide (TAA) was confirmed to be a regenerative liver response following cytotoxicity. Conversely, safrole, tannic acid, and urethane yet hepatotoxicants did not show inflammatory reaction or necrosis under the condition of the present study, and hence their mode of action by which they induce proliferative response was not obvious. The results of this study showed that the in vivo version of RDS test efficiently discriminated nongenotoxic hepatocarcinogens from noncarcinogens, while it did not well clarify the induction mode of cell proliferation.

Animals↗

Curved chest tube for drainage of malignant pleural effusion.

Thoracentesis with a chest tube insertion and drainage of large pleural effusion is widely performed in patients with malignant lung diseases. One potential problem with a conventional chest tube placement is occasional incomplete evacuation of effusion owing to inappropriate position of the tip where the drainage holes opened. We have developed a curved chest tube and evaluated the position of tip placement just after the placement and before removal on plain chest X-ray in 20 patients with massive pleural effusions due to lung cancer. In 15 of the 20 patients, the tip of the tube was successfully positioned at the paravertebral gutter in posterobasal with higher drainage efficacy compared with other patients whose tube tips happened to be positioned at other sites. There were no significant complications. This study suggested that the curved chest tube would be safe and useful in completing drainage of pleural effusion.

Adult↗

Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38.

The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a camptothecin derivative, were evaluated in four human cultured cell lines derived from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to SN-38 followed by TNP-470 produced synergistic effects in the four cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Routes of hepatic metastasis of gallbladder carcinoma.

This clinicopathologic study aims to clarify routes of hepatic metastasis of gallbladder carcinoma. Nineteen liver specimens obtained by extensive hepatectomy performed for the treatment of advanced gallbladder carcinoma were analyzed. We defined hepatic metastasis as a discrete hepatic lesion separate from the primary tumor and paid special attention to portal tracts at the margins of direct hepatic invasion. Eleven early metastatic foci were demonstrated histologically in 6 cases, most commonly in segments adjacent to the gallbladder. All cases with hepatic metastasis had direct hepatic invasion. Nine of the 11 metastatic lesions were located within the portal tracts or accompanied by invasion into the portal tracts. Because they are in continuity with areas of direct hepatic invasion, the portal tracts at the invasive margin often were involved by cancer cells that spread along these tracts. These results suggest that the most important route in development of hepatic metastasis from gallbladder carcinoma is along the portal tracts after direct hepatic invasion.

Aged↗

Vibrio halioticoli sp. nov., a non-motile alginolytic marine bacterium isolated from the gut of the abalone Haliotis discus hannai.

Six alginolytic, facultatively anaerobic, non-motile marine bacteria were isolated from the gut of abalone Haliotis discus hannai. DNA-DNA hybridization data showed that the six strains constituted a single genospecies. Phylogenetic analyses of 16S rDNA sequences indicated that the isolates should be assigned to the genus Vibrio. The phenotypic features of the isolates were closely related to Vibrio fischeri and Vibrio pelagius biovar I, but 13 traits (motility, luminescence, alginase production, lipase production, lysine decarboxylase, indole production, growth in 1 and 6% NaCl and assimilation of five carbon compounds) distinguished these strains from V. fischeri, and 17 traits (motility, growth at 37 degrees C, lipase production, indole production, growth in 1 and 6% NaCl, acid from sucrose and D-sorbitol, and assimilation of nine carbon compounds) distinguished these strains from V. pelagius. The G + C content of the isolates was 41.6-43.1 mol%. According to DNA-DNA hybridization data and 16S rDNA phylogenetic analyses, it was concluded that the six isolates constitute a new species different from any other Vibrio species. The name Vibrio halioticoli sp. nov. (type strain IAM 14596T) is proposed. A set of phenotypic features which enables differentiation of the new species from other species of the Vibrionaceae family is described.

Animals↗

Cloning of rat eotaxin: ozone inhalation increases mRNA and protein expression in lungs of brown Norway rats.

The C-C chemokine eotaxin is thought to be important in the selective recruitment of eosinophils to the site of inflammation in guinea pigs, mice, and humans. We isolated the rat eotaxin gene to determine whether a similar molecule might play a role in the pulmonary infiltration of eosinophils during acute inflammation in the rat. The cDNA for rat eotaxin encoded a 97-amino acid protein containing a 74-amino acid mature eotaxin protein with 97.3% identity to mouse eotaxin. The recombinant protein encoded by this gene displayed specific chemotactic activity for eosinophils when analyzed with a microchemotactic chamber. The expression of eotaxin mRNA increased approximately 1.6-fold immediately after exposure to ozone and was 4-fold higher after 20 h. The number of lavageable eosinophils at the same time points were 3- and 15-fold greater, respectively, than control eosinophils. Immunocytochemistry revealed that alveolar macrophages and bronchial epithelial cells were positive for eotaxin. These results suggest that eotaxin may be involved in the recruitment of eosinophils into the air spaces during certain inflammatory conditions in rats.

Administration, Inhalation↗

Elevated serum sialyl Lewis X-i antigen levels in non-small cell lung cancer with lung metastasis.

To evaluate the relationship between serum levels of sialyl Lewis X-i antigen and lung metastasis in patients with non-small cell lung cancer (NSCLC), we measured the serum level of the antigen in 299 patients with untreated locally advanced or metastatic NSCLC. Before treatment, serum levels of sialyl Lewis X-i antigen were significantly higher in patients with lung metastasis than in those without lung metastatis (p = 0.0001). Of 201 patients without lung metastasis at the time of primary diagnosis, 121 patients died between July 1987 and December 1995. Serum levels of sialyl Lewis X-i antigen in 21 patients who developed lung metastasis during the period were significantly higher than those in 100 patients who did not develop lung metastasis (p = 0.0171). Our results suggested that sialyl Lewis X-i antigen might be a good indicator for the presence or development of lung metastasis, and it might provide clinical information about the management of patients with NSCLC.

Aged↗

Circadian rhythms in the incorporation and secretion of 3H-proline by odontoblasts in relation to incremental lines in rat dentin.

Circadian incremental lines are universally found in the dentin of animals. They are believed to be caused by functional changes in odontoblasts over 24 hrs. However, the mechanism of rhythmic dentin formation has not yet been elucidated. In the present study, we investigated whether there is a 24-hour rhythm in the collagen-synthetic and secretory activities of odontoblasts by radioautography with 3H-proline as a tracer. Six different groups of rats were injected with 3H-proline at 0000, 0400, 0800, 1200, 1600, or 2000 after the animals had become acclimated to a 12/12-hour light-dark illumination cycle for 2 wks. One hour after the injection, the maxillary incisors were removed and processed for radioautographic study. The silver grains of 3H-proline were most intense over odontoblasts and predentin during the environmental light period, while the nadir occurred during the dark period. The peak value was approximately two-fold higher than the minimum value. Moreover, in the dentin from rats that had been infused with 3H-proline continuously for 10 days by means of osmotic minipumps, silver grains of 3H-proline were heavily distributed over the dark hematoxylin-stained incremental lines. Thus, we demonstrated that odontoblasts show circadian rhythm with regard to collagen synthesis and secretion. These rhythms in odontoblastic function may be responsible for circadian incremental lines in dentin.

Analysis of Variance↗

[Biological response modifier activity of Lactococcus lactis 332].

The biological response modifier (BRM) activity of a preparation of heat killed cells of Lactococcus lactis 332 which can produce large amount of lactate in culture, was investigated in C3H/He and ICR mice. Intraperitoneal injection of Lactococcus lactis 332 caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice, similarly to BRMs used clinically. As a parameter of the activation of macrophages, the effect of the Lactococcus lactis 332 preparation on the production of tumor necrosis factor (TNF) was examined. The Lactococcus lactis 332 preparation was revealed to have both priming and triggering activities for the production of TNF. The TNF level in the sera reached about 1000 IU/ml in mice 2 h after the triggering injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro. Intratumoral injection of the Lactococcus lactis 332 preparation regressed MM46 tumor cells in C3H/He mice. These results suggest that the Lactococcus lactis 332 preparation is a biological response modifier (BRM) with various activities on phagocytes similarly to a streptococcal antitumor agent, OK432, used clinically.

Animals↗

Skin sensitization and photosensitization studies of hydrophobically modified hydroxypropyl methylcellulose in guinea pigs.

Skin sensitization and photosensitization tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, were conducted using guinea pigs. An aqueous dispersion of HM-HPMC (3 w/v %) was applied in the tests. Skin reaction was not observed in any animal in the HM-HPMC-treated group or control group. In the photosensitization test, no skin reaction was found in any animal in the test-preparation group or the control group. It was concluded that HM-HPMC dispersion does not exhibit skin sensitizing or photosensitizing activity under the condition of this test.

Adjuvants, Pharmaceutic↗

[A case of thymoma with pleural dissemination which was treated by pleurectomy with patient survival without recurrence for more than five years].

A 46-year-old woman was admitted to our hospital with chest pain. Chest X-ray and CT revealed an anterior mediastinal mass as well as several small masses attached to the left chest wall. Thymoma was diagnosed by percutaneous biopsy. The serum level of anti-acetylcholine receptor antibody was 30.3 pmol/ml. At operation, the thymoma was found left in the anterior mediastinum, extending to the upper lobe of the lung. There were also numerous tumors of various size in the left parietal pleura. Thymectomy, partial resection of the upper lobe of the lung and pleurectomy were performed. One month later, she developed myasthenia gravis. After a complete remission of myasthenia gravis brought about by anti-choline esterase therapy, the patient was treated with irradiation. She has been well for more than five years after the operation but her serum anti-acetylcholine receptor antibody level is still higher than normal.

Combined Modality Therapy↗

[Lymphocyte chemotactic factor in tuberculous pleural effusion].

To evaluate whether lymphocyte chemotactic factor is involved in the accumulation of lymphocytes in tuberculous pleurisy, we measured lymphocyte chemotactic activity in tuberculous pleural effusions, and compared with that in malignant pleural effusions and transudate. The lymphocyte chemotactic activity was measured in vitro with chemotactic chamber. The cells suspended in the culture medium was added to the upper well and the effusions, normal human serum (NHS), or culture medium were placed below nitrocellulose filter. The lymphocyte migration was quantified by counting the number of cells migrating beyond a distance of 70 microns from top of the filter in 5 selected fields. The chemotactic activity of the effusions was expressed as a percentage of the control migration in the culture medium. When we used the freshly isolated peripheral blood lymphocytes as responding cells, the chemotactic activity was 176.0 +/- 41.3% in tuberculous effusions, 115.1 +/- 53.8% in malignant effusions, 87.1 +/- 16.1% in transudate, and 113.3 +/- 24.2% in NHS, respectively. The activity of tuberculous effusions was significantly higher than that of transudate and NHS. When we used PHA-activated lymphocytes, the activity was 284.4 +/- 159.3% in tuberculous effusions, 123.1 +/- 77.6% in malignant effusions, 75.8 +/- 10.3% in transudate, and 52.6 +/- 10.1% in NHS, respectively. The activity of tuberculous effusions was significantly higher than that of malignant effusions, transudate and NHS. The chemotactic activity of tuberculous effusions to PHA-activated lymphocytes was significantly higher than that to freshly isolated lymphocytes. The activity was specific for T lymphocytes, and showed both chemotaxis and chemokinesis by checkerboard analysis. Gel filtration performed with Sephacryl S-200 revealed that the chemotactic activities in a tuberculous fluid had three peaks located in the regions between blue dextran and immunoglobulin G, near to human albumin and cytochrome c marker. The most potent activity was found at the region near human albumin. Lymphocyte chemotactic factor in tuberculous effusion may stimulate the migration of T lymphocytes, especially the activated T lymphocytes to the pleural spaces.

Chemokines, C↗

[Sixty percent lidocaine tape alleviates pain on injection of propofol after diminishing venipuncture pain].

We evaluated the efficacy of the 60% lidocaine tape in alleviating pain associated with intravenous propofol administration in 71 gynecological patients. Thirty-eight women had the tape applied for 2.5 h before venipuncture, with the remaining patients acting as the control. A 20 gauge cannula was inserted into the cephalic vein. Propofol at room temperature was injected at a rate of 1200 ml.hr-1. The statistical significance of differences was established with the Mann-Whitney's U test and the chi 2 test. The median level of pain intensity resulting from venipuncture among the patients treated with the tape was smaller than that in the control group (16.5, vs 34, P = 0.006). Thereafter, cannulation was successfully achieved with reduced or no pain (VAS at cannulation < or = 25, n = 39), and only 16% of the treatment group complained of pain on injection as compared with 53.8% of the control group (P = 0.02). Moreover, the pain intensity was decreased with lidocaine tape (P = 0.006). The cost of the lidocaine tape is covered by medical insurance for reducing pain on venipuncture. Thus, as the tape also alleviates the pain on injection of propofol through its anesthetic action, it can be a safe, easy and cost-effective method as "it kills two pains with one tape".

Adult↗

[The coexistence of pulmonary tuberculosis and thymoma a case report].

A 33-year-old male was admitted with complaints of cough, dysphagia, and swelling of face and upper extremities. Chest X-ray and CT scan revealed a large mediastinal mass and infiltrates in the right upper lobe. Percutaneous biopsy proved the mediastinal tumor as thymoma with cellular atypia. After irradiation, the tumor was surgically removed. Caseous epitheloid granulomas were found in the dissected mediastinal lymph nodes. AFB (Acid fast bacillus) stain of the patient's gastric fluid was positive for Mycobacterium. The coexistence of these two diseases was incidental, however, this case suggested that clinicians should perform careful evaluation of lung parenchyma as well as mediastinum on chest X-ray to identify occult diseases including pulmonary tuberculosis in patients with mediastinal mass lesion.

Adult↗

Novel alginate lyases from marine bacterium Alteromonas sp. strain H-4.

A bacterium Alteromonas sp. strain H-4 isolated from Laminaria fronds produced extra- and intra-cellular alginate lyases and utilized alginate as its sole carbon source. An extracellular alginate lyase was purified from the culture supernatant of the strain and its substrate specificity was characterized. The estimated molecular mass of the enzyme was 32 kDa and the isoelectric point was 4.7. Both polyM and polyG block degrading activities were observed using the substrate-containing gel overlay technique after isoelectric focusing of the enzyme. By analyzing the reaction products from the polyM block, polyG block, MG random block and intact alginate, three major peaks containing unsaturated tri-uronide through octa-uronide were detected for each substrate. The results indicate that the enzyme of Alteromonas sp. H-4 can degrade both polyM and polyG blocks with a K(m) in mg/mL 20-times higher for the polyM block.

Alginates↗

Neutrophil-mediated sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats.

The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL)-8 family, and a major neutrophil chemotactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP)/alanine transaminase (ALT) ratio as a marker of sinusoidal endothelial cell (SEC) injury showed no significant differences between the two groups. Intercellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both groups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.

Alanine Transaminase↗