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Biomedical subjects

M Nakajima

Publications and source records attributed to M Nakajima.

At least 361 records · Page 20Linked to original sources
PubMed1998

Encephalitis in mice inoculated intranasally with an influenza virus strain originated from a water bird.

Five-week-old ddY mice were inoculated intranasally with a low virulent (4e) or highly virulent (24a5b) avian influenza virus strain originated from a water bird. None of mice in the 4e group showed clinical signs and brain lesions. Of the 24a5b group, two mice died and one mouse was killed at a moribund state at day 7 post-inoculation (PI). Four mice of the 24a5b group necropsied at day 5 or 7 PI had mild to severe encephalitis in the brain stem and the cerebellar white matter. Influenza virus antigen was detected in neurons, glial cells and vascular endothelium in the lesions. The distribution of the lesions seems to indicate the transneuronal invasion of the virus via cranial nerve fibers into the brain.

Animals↗
PubMed1998

Chlamydia pneumoniae infection in patients with diffuse panbronchiolitis and COPD.

STUDY OBJECTIVES: To determine the possible association of Chlamydia pneumoniae infection with diffuse panbronchiolitis (DPB) and with COPD. DESIGN: Prospective case-control study. SETTING: Division of Respiratory Diseases, Kawasaki Medical School Hospital. PARTICIPANTS: Fifteen DPB and 77 COPD patients who had acute exacerbations of respiratory conditions and 35 and 120 control subjects, respectively, matched for age, sex, and smoking status. MEASUREMENTS AND RESULTS: Nasopharyngeal swabs and paired serum samples were obtained from all patients and control subjects for isolation and antibody testing of C pneumoniae. C pneumoniae was isolated from one DPB patient and from no COPD patients or control subjects. Serologic evidence of acute C pneumoniae infection was observed in one DPB patient (6.7%) and six COPD patients (7.8%). The prevalence and mean titer of C pneumoniae IgG and IgA antibodies were significantly higher in COPD patients than in control subjects (p<0.001). However, no such differences were observed between DPB patients and control subjects. CONCLUSIONS: This study showed that C pneumoniae infection may be associated with acute exacerbations of COPD and that chronic C pneumoniae infection is common in COPD but not in DPB.

Adult↗
PubMed1998

Nicotine metabolism in liver microsomes from rats with acute hepatitis or cirrhosis.

Nicotine exerts a number of physiological effects. Nicotine is absorbed through the lungs with smoking and is rapidly metabolized in humans. Although it is mainly metabolized in the liver, the effects of liver injuries on nicotine metabolism are not clear. The purpose of this study was to clarify the effects of liver injuries on nicotine metabolism. Rats were treated with D-galactosamine (GalN) or thioacetamide (TA), to induce acute hepatitis or liver cirrhosis, respectively. Serum transaminase levels were significantly elevated in model rats with both types of liver injury. Cytochrome P450 (CYP) and cytochrome b5 contents in liver microsomes were decreased significantly in TA-treated cirrhotic rats but not in GalN-treated hepatitic rats. The major metabolic pathways of nicotine, i.e. cotinine formation catalyzed by CYP and nicotine-1'-N-oxide formation catalyzed by flavin-containing monooxygenase, were investigated in these rat liver microsomes. Formation of cotinine and nicotine-1'-N-oxide from nicotine was not changed in GalN-treated hepatitic rats, in comparison with the controls, but was significantly decreased in TA-treated cirrhotic rats. By immunoblotting, decreases in CYP1A2, CYP2B2, CYP2C, and CYP2E1 protein were recognized in liver microsomes from TA-treated cirrhotic rats. It was also shown that the maximal velocity values for nicotine-1'-N-oxide formation in TA-treated cirrhotic rats were significantly decreased, compared with the controls. These results suggested that the reduction of nicotine metabolism in cirrhosis was due to decreases in CYP and flavin-containing monooxygenase protein expression levels.

Acute Disease↗
PubMed1998

Cytochrome P450 2C9 catalyzes indomethacin O-demethylation in human liver microsomes.

Indomethacin is a widely used nonsteroidal anti-inflammatory drug. We studied the human cytochrome P450 (CYP) isoform responsible for indomethacin O-demethylation, the major metabolic pathway for indomethacin. For indomethacin O-demethylase activities, the KM value was 34.6 +/- 5.4 muM and the Vmax value was 14.1 +/- 3.9 pmol/mg/min in human liver microsomes (N = 4). Indomethacin O-demethylase activity in human liver microsomes was competitively inhibited by sulfaphenazole, (S)-warfarin, and tolbutamide and was not affected by alpha-naphthoflavone, (S)-mephenytoin, or erythromycin. Indomethacin O-demethylase activities in microsomes from nine human livers were significantly correlated with tolbutamide hydroxylase activities (r = 0.750, p < 0.05) and not with (S)-mephenytoin 4'-hydroxylase activities. When the capacity for indomethacin O-demethylation in microsomes of B lymphoblastoid cells expressing human CYPs was investigated at an indomethacin concentration of 5 microM, cDNA-expressed CYP2C9 exhibited 6-fold greater activity than did CYP2C19. At an indomethacin concentration of 50 microM, cDNA-expressed CYP1A2 and CYP2D6 also exhibited slight activities. The KM values were 9.9 +/- 1.2 and 117.1 +/- 13.8 microM and the Vmax values were 0.33 +/- 0.05 and 0.24 +/- 0.04 pmol/min/pmol CYP in microsomes with cDNA-expressed CYP2C9 and CYP2C19, respectively (N = 4). Considering the 16-fold higher intrinsic clearance of CYP2C9, compared with that of CYP2C19, and these expression levels in human livers, the contribution of CYP2C19 to indomethacin O-demethylation was considered to be negligible. Indomethacin appears to be O-demethylated exclusively by CYP2C9 in humans.

Alkylation↗
PubMed1998

[Late phase II study of TAT-59 (miproxifene phospate) in advanced or recurrent breast cancer patients (a double-blind comparative study with tamoxifen citrate)].

The efficacy and safety of TAT-59 (miproxifene phospate) were compared with tamoxifen citrate (TAM) in ER-positive or ER-unknown patients with advanced or recurrent breast cancer, using the double-blind method. TAT-59 and TAM were both given 20 mg/body orally for over 12 weeks in daily doses. Eligible cases were 93 in the TAT-59 group and 102 patients in the TAM group. The response rate was shown to be 30.1% (28/93) in the TAT-59 group and 26.5% (27/102) in the TAM group. Statistical equivalence between both treatments was proven at 90% confidence interval (-8.5% < or =, < or = 12.8%). Adverse reactions observed in the patients receiving TAT-59 were hot flush, nausea and vomiting, sweating, anorexia, abnormal values in liver function tests, and anemia, showing no differences from the TAM group. Leukopenia (4.9%) and thrombopenia (2.9%) reactions were found only in the TAM group. Two patients in the TAT-59 group and three in the TAM group discontinued treatment due to adverse reactions. However, these adverse reactions were reversible in both groups. In conclusion, TAT-59 was showed comparable efficacy and safety with TAM in ER-positive or ER-unknown patients with advanced or recurrent breast cancer.

Administration, Oral↗
PubMed1998

[Sulbactam/ampicillin-induced pneumonitis].

We report on two patients with sulbactam/ampicillin (SBT/ABPC)-induced pneumonitis. Both patients were being treated with SBT/ABPC for respiratory-tract infections. Following the initiation of SBT/ABPC chemotherapy, however, chest X-ray films showed a shift of shadow in patient 1 and new pulmonary infiltration shadows in patient 2. Bronchoalveolar lavage fluid (BALF) findings showed a marked increase in the total cell count and percentage of eosinophils in patient 1 and of lymphocytes in patient 2. The results of lymphocyte stimulation tests were SBT/ABPC positive for both patients. SBT/ABPC therapy was therefore discontinued and corticosteroid therapy started. Both patients were subsequently relieved of their symptoms demonstrated significantly lower and pulmonary infiltrate levels. Based on these findings, both patients were given a diagnosis of SBT/ABPC-induced pneumonitis. It has been widely reported that CD 4/CD 8 ratio in BALF decreases in cases of drug-induced pneumonitis. However, some reports have cited increase in the CD 4/CD 8 ratio. In our two patients as well, the CD 4/CD 8 ratio increased. These results, together with the findings from several other case reports, indicate that the CD 4/CD 8 ratio may not be good basis for diagnosing drug-induced pneumonitis. Recently, the incidence of drug-induced pneumonitis has been rising. To our knowledge this is the first report documenting cases of SBT/ABPC-induced pneumonitis.

Aged↗
PubMed1998

[Evaluation of serum KL-6 levels in summer-type hypersensitivity pneumonitis].

A high level of serum KL-6 is a known feature of active pulmonary fibrosis. Some researchers have suggested that KL-6 is produced and secreted by type II pneumocytes. The present study evaluated serum KL-6 levels in patients with summer-type hypersensitivity pneumonitis (summer-type HP) (n = 6, 7 episodes), Mycoplasma pneumoniae pneumonia (n = 16), Chlamydia psittaci pneumonia (n = 3), Chlamydia pneumoniae pneumonia (n = 9), and bacterial pneumonia (n = 12). In addition, transbronchial lung biopsy (TBLB) specimens were examined pathologically in order to identify the site of production and secretion of KL-6. In patients with summer-type HP, the serum KL-6 levels exceeded 500 U/ml (2.996 +/- 2.016 U/ml), but was below 500 U/ml (302 +/- 126 U/ml, p < 0.001) in the patients with other infectious pneumonias, with the exception of two. One of these two patients with a high serum KL-6 level had adult respiratory distress syndrome due to Mycoplasma pneumoniae. The other had organizing pneumonia due to Chlamydia pneumoniae. TBLB specimens showed proliferative type II pneumocytes in all summer-type HP cases. We believe that the high serum KL-6 levels were produced by type II pneumocytes, and may provide a useful indicating serum marker for HP. Although serum LDH, serum CRP and PaO2 are known as monitoring markers in summer-type HP, our findings demonstrated no manifest correlations among these markers. However, serum KL-6 levels showed a strong positive correlation with serum LDH levels and an inverse correlation with serum CRP levels. These results suggest that serum KL-6 may be a better marker of the degree of disease activity than serum LDH, CRP, or PaO2 in summer-type HP.

Adolescent↗
PubMed1998

[Acetaminophen-induced pneumonitis].

We report a case of drug-induced pneumonitis caused by acetaminophen taken for headache. The patient was a 49-year-old woman who had been taking a common cold drug (Benza BlockSP) containing acetaminophen and an anti-gastritis drug for headache. Seven days after she began taking acetaminophen, fever, dry cough, and dyspnea developed. The patient was admitted to our hospital on December 6,1996. Chest X-ray films and computed tomography scans revealed ground-glass and reticulonodular opacities. All chemotherapy was discontinued under a presumptive diagnosis of drug-induced pneumonitis. Transbronchial lung biopsy specimens revealed infiltration of lymphocytes and eosinophils into the alveolar walls and interstitum, with granulomotous lesions and macrophages in the alveolar spaces. The patient's chest X-ray findings improved and her symptoms subsided after the medications were stopped. However, she was given oral prednisolone (30 mg/day) because shadows were still evident on chest X-ray films. Prednisolone was effective in removing those shadows. A lymphocyte stimulation test was positive for acetaminophen. Based on the above findings, acetaminophen-induced pneumonitis was diagnosed. To our knowledge, acetaminophen-induced pneumonitis is rare. However, when drug-induced pneumonitis is suspended, common cold drugs containing acetaminophen should be kept in mind.

Acetaminophen↗
PubMed1997

Partial purification and characterization of a gibberellin-binding protein from seedlings of Azukia angularis.

Little is known about mechanisms for the perception of gibberellin (GA), a phytohormone, by plants. A GA-binding protein (GBP) with receptor-like characteristics was partially purified from azuki bean (Azukia angularis) seedlings. Gibberellins that caused much elongation of azuki epicotyl sections showed strong binding affinity for the GBP, and their biosynthetic precursors and inactive metabolites had weak affinity for it. The apparent Kd value for GA4 was calculated to be 7 x 10(-10) M from Scatchard plots. The molecular weight of the GBP in the native state was estimated to be 25,000 by high-performance liquid chromatography with a gel-permeation column. The GBP may be one of the receptor candidates for GAs.

Carrier Proteins↗
PubMed1997

Detection of sarin hydrolysis products from sarin-like organophosphorus agent-exposed human erythrocytes.

A sarin-like organophosphorus agent, [bis(isopropyl methyl)phosphonate; BIMP], was synthesized. This agent has the same phosphonate group as sarin and also has the same anti-acetylcholinesterase activity potency as sarin. The ID50 and LD50 values of BIMP in mice after intravenous injection were 3.9 nM and 0.8 mg/kg, respectively. The AChE activities of their red blood cells and brains were dose-dependently reduced by intravenous BIMP. After preparation of experimental BIMP-exposed human red blood cells, BIMP-bound acetylcholinesterase (AChE) was solubilized from erythrocyte membranes, purified by immunoaffinity chromatography, digested with trypsin, and the sarin hydrolysis products bound to AChE were released by alkaline phosphatase digestion. The digested sarin hydrolysis products were subjected to trimethylsilyl (TMS) derivatization and detected by gas chromatography-mass spectrometry. Isopropyl methylphosphonic- and methylphosphonic acids, which are the sarin hydrolysis products, were detected in experimental BIMP-exposed human red blood cells. This new method, which enables sarin's hydrolysis products to be detected in BIMP-exposed erythrocytes, is a useful tool for studying sarin-poisoning victims.

Acetylcholinesterase↗
PubMed1997

Major co-localization of the extracellular-matrix degradative enzymes heparanase and gelatinase in tertiary granules of human neutrophils.

The expression of cell-surface adhesion proteins and the release of extracellular-matrix degradative enzymes constitute crucial processes for the attachment of neutrophils to the endothelium and for the subsequent extravasation of these cells through the endothelial layer. We have analysed in resting human neutrophils the subcellular localization of heparanase, a heparan-sulphate-degrading endoglycosidase that can degrade basement-membrane components, thereby facilitating neutrophil passage into the tissue during an inflammatory reaction. By subcellular fractionation of postnuclear supernatants from resting human neutrophils on continuous sucrose gradients, we have found that heparanase activity was mainly located in gelatinase-containing tertiary granules. Using a specific antibody, the 96-kDa heparanase protein was further located in the gelatinase-rich subcellular fractions. Following immunoblotting and immunoprecipitation analysis in the distinct subcellular fractions, we also found co-localization of heparanase and Mo1 (CD11b/CD18), a leucocyte integrin involved in the attachment of neutrophils to the endothelium, in the fractions enriched in gelatinase-containing tertiary granules. Treatment of human neutrophils with tumour necrosis factor or granulocyte/macrophage colony-stimulating factor induced an increase in the CD11b/CD18 cell-surface expression, as well as the release of both gelatinase (matrix metalloproteinase-9) and heparanase, but not of other granule markers, indicating a major co-localization of gelatinase, heparanase and CD11b/CD18 in the same organelle. Furthermore, confocal laser scanning microscopy using specific antibodies against gelatinase and heparanase revealed a major co-localization of both enzymes in intracellular cytoplasmic granules. The major localization of heparanase and CD11b/CD18 in the gelatinase-containing tertiary granule supports the notion that mobilization of this organelle can regulate extravasation of human neutrophils.

CD18 Antigens↗
PubMed1997

Enzymatic treatment to eliminate the extracellular ATP for improving the detectability of bacterial intracellular ATP.

A novel and effective treatment of biological samples with a combination of adenosine phosphate deaminase and apyrase was developed for reducing extracellular ATP, which has been a major problem encountered in improving the sensitivity of assays for intracellular ATP by the firefly luciferin-luciferase (L-L) method. Under the enzymatic reaction conditions, ATP and the related adenosine derivatives were converted to IMP, which are not active to the L-L system. In the model system (3.2 x 10(-8) M ATP in 1% yeast extract solution) the treatment with adenosine phosphate deaminase resulted in the reduction of ATP to 1.3 x 10(-11) M, and the concomitant use of apyrase lowered the concentration to 3.3 x 10(-13) M. The treatment (0.05 U/ml of adenosine phosphate deaminase and apyrase) was applied to the detection of bacteria in broth by the L-L method, affording the detection of 42 colony-forming unit (CFU)/ml of Escherichia coli and 10 CFU/ml of Staphylococcus aureus in the broth.

Adenosine Deaminase↗
PubMed1997

Development of flexible ventriculoscope (Yamadori-type VII) and its application to experimental animals.

We developed a new ventriculoscope (Yamadori-type VII), a 2.1 mm calibrated fiberscope with a monopolar coagulator, that can be inserted from the cisterna cerebellomedullaris into the third cerebral ventricle of experimental animals, like dogs. With the improved performance of the neuroendoscope compared to its prototype, Yamadori III, it was possible to inspect clearly and to produce electrocoagulative lesions accurately on any part of the intraventricular structures with minimal injury to nearby vital brain areas.

Animals↗
PubMed1997

Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to endothelial cells of the target tissue.

We studied the role of glycosphingolipids expressed on the cell surfaces of a metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic murine lymphosarcoma cell line RAW117-P and its sub-line, RAW117-H10, which shows higher metastatic potential for the liver than P cells, were compared. Both types of cells had LacCer, Gg3Cer, and Gg4Cer as the major neutral glycosphingolipids and GM1b and GD1alpha as the gangliosides. There are differences in glycosphingolipid contents, the neutral glycosphingolipid contents in the parental cells being 1.5-fold higher than that in the variant ones. In contrast, the level of GD1alpha in H10 cells was twice as much as that in the P cells; however, the expression of other gangliosides was down-regulated. On the basis of the results of glycosphingolipid analysis, we investigated the functional role of GD1alpha in H10 cells in the adhesion of the tumor cells to the target tissue by using hepatic sinusoidal endothelial (HSE) cells. GD1alpha and GM1b inhibited the adhesion when HSE cells were incubated prior to coculture with the tumor cells. This inhibitory effect by GD1alpha and GM1b was observed within 30 min after addition of H10 cells to HSE cells and was dose dependent. GD1alpha showed a higher inhibitory effect on the adhesion than GM1b, whereas other glycosphingolipids showed no inhibitory effect. Anti-GD1alpha monoclonal antibody also inhibited the adhesion between the H10 and HSE cells. When cultured without fetal bovine serum for 30 min in a various glycosphingolipids-coated dish for bacterial culture, HSE cells adhered to the area coated with GD1alpha but not to areas coated with other glycosphingolipids. HSE cell adhesion depended on the amount of GD1alpha coated on the plate. These data indicate that GD1alpha functions as an adhesion molecule in the process of metastasis of H10 cells.

Animals↗
PubMed1997

Lead-induced alteration of heparan sulfate proteoglycans in cultured vascular endothelial cells.

We investigated the alterations of heparan sulfate proteoglycans produced by vascular endothelial cells after exposure to lead. Bovine aortic endothelial cells were cultured and metabolically labeled with [3H]glucosamine and [35S]sulfate in the presence of lead chloride at 10 microM. Radiolabeled HSPGs were separated by ion-exchange chromatography and either their hydrodynamic size or the length of heparan sulfate chains were characterized by gel filtration. It was found that lead markedly suppresses the incorporation of the radioactive precursors into HSPGs in the cell layer; the incorporation into chondroitin/dermatan sulfate proteoglycans was decreased by the metal only slightly. The suppression by lead occurred in the low molecular weight subclass of HSPGs rather than the high molecular weight subclass. However, the length of heparan sulfate chains was not changed by the metal. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]methionine-labeled proteoglycans after heparitinase digestion showed that there were slightly more HSPG core proteins without a change of the size in lead-treated cell layer. It was, therefore, suggested that vascular endothelial cell layer after exposure to lead has more HSPG core proteins with fewer heparan sulfate chains without a change in length.

Animals↗
PubMed1997

Formation of leukotoxin (9,10-epoxy-12-octadecenoic acid) during the autoxidation of phospholipids promoted by hemoproteins.

Myoglobin (Mb) and cytochrome c (Cyt c) are known to promote lipid peroxidation when mixed with certain types of phospholipids. In the presence of phospholipids such as cardiolipin (CL), ferrous Mb and Cyt c were converted to ferric hemoproteins, and autoxidation of the phospholipids and the oxidation of free linoleic acid (LA) added to the reaction mixture were observed. When the reaction mixture comprising 0.01 mM Cyt c, 0.2 mM CL and 0.1 mM LA was incubated, 92.7% of LA was consumed, and the LA products included 2.49 microM 9,10-epoxy-12-octadecenoic acid (leukotoxin) and its isomer which are potent inhibitors of mitochondrial respiration and have toxic effects on cardiac function. Hemoglobin (Hb) could promote almost no lipid peroxidation in the presence of any kinds of phospholipids. The experiments using some scavengers of active oxygen species revealed that tocopherol and ascorbic acid could strongly reduced LA oxidation caused by Cyt c or Mb. As LTx production was also observed when LA was mixed with Fe2+, LTx may be a common product where non-enzymatic lipid peroxidation occurs.

Cardiolipins↗