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Biomedical subjects

A Tanaka

Publications and source records attributed to A Tanaka.

At least 145 records · Page 8Linked to original sources
PubMed2001

Detection of the exogenous hGDNF in gerbils under the treatment with AxCAhGDNF adenoviral vector.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent neurotrophic factors and promotes survival in many populations of cells. We examined the neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia [Brain Res. 885 (2000) 273-282]. Gerbils received AxCAhGDNF or an adenoviral vector encoding bacterial beta-galactosidase gene (AxCALacZ) through administration into the lateral ventricle. Two days later, occlusion of the common carotid arteries for 5 min bilaterally using aneurysm clips produced transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by the adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA-1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. In this paper, we describe in detail the techniques for the detection of the exogenous gene of hGDNF under the treatment with AxCAhGDNF.

Adenoviridae↗
PubMed2001

4-(Methylthio)-3-butenyl isothiocyanate, a principal antimutagen in daikon (Raphanus sativus; Japanese white radish).

The antimutagenic activity of n-hexane extracts from eight strains of daikon (Raphanus sativus; Japanese white radish) have been examined using the UV-induced mutation assay of Escherichia coli B/r WP2. A correlation was found between the potency of antimutagenicity and the amount of 4-(methylthio)-3-butenyl isothiocyanate (MTBITC) in their n-hexane extracts. Because the pure MTBITC also showed antimutagenicity, MTBITC is presumably the active antimutagen principle in n-hexane extracts of daikon. Among the eight strains of daikon studied, Aokubi, the improved common strain in Japan, contained 71.0 micromol of MTBITC in 100 g of fresh daikon. In contrast, Karami and Momoyama, which are original wild strains, contained much more MTBITC (363.5 and 168.0 micromol/100 g, respectively). In addition, phenethyl isothiocyanate was found in a lesser amount (5-33 nmol/100 g) in eight strains of daikon, and allyl isothiocyanate and benzyl isothiocyanate were not detectable in any strains (<3 nmol/100 g). The amount of total isothiocyanate in grated daikon was 7.0 times higher than that in cut daikon measured after 30 min of cooking. Through eating habits, humans might be able to consume substantial amounts of the antimutagen MTBITC from dishes using the grated form of wild strains of daikon. Therefore, it is possible to substantially increase the intake of the antimutagenic ingredient of daikon (i.e., MTBITC) by changing food preferences and preparation procedures (i.e., using the grated form of the wild strains).

Antimutagenic Agents↗
PubMed2001

Isolation and characterization of a Na+/H+ antiporter gene from the halophyte Atriplex gmelini.

With a homologous gene region we successfully isolated a Na+/H+ antiporter gene from a halophytic plant, Atriplex gmelini, and named it AgNHX1. The isolated cDNA is 2607 bp in length and contains one open reading frame, which comprises 555 amino acid residues with a predicted molecular mass of 61.9 kDa. The amino acid sequence of the AgNHX1 gene showed more than 75% identity with those of the previously isolated NHX1 genes from glycophytes, Arabidopsis thaliana and Oryza sativa. The migration pattern of AgNHX1 was shown to correlate with H+-pyrophosphatase and not with P-type H+-ATPase, suggesting the localization of AgNHX1 in a vacuolar membrane. Induction of the AgNHX1 gene was observed by salt stress at both mRNA and protein levels. The expression of the AgNHX1 gene in the yeast mutant, which lacks the vacuolar-type Na+/H+ antiporter gene (NHX1) and has poor viability under the high-salt conditions, showed partial complementation of the NHX1 functions. These results suggest the important role of the AgNHX1 products for salt tolerance.

Amino Acid Sequence↗
PubMed2001

Effect of carbohydrate structure on biological activity of artificially N-glycosylated eel calcitonin.

To reveal the function of the carbohydrate portion of glycopeptides and glycoproteins, we chemo-enzymatically synthesized artificially N-glycosylated derivatives of eel calcitonin and studied their three-dimensional structure and biological activity. The CD and NMR spectra in trifluoroethanol-H(2)O solution showed that the glycosylation did not change the three-dimensional structure. All the derivatives retained the strong in vivo hypocalcemic activity of calcitonin. However, the relative activity was dependent on the structure of the attached carbohydrate. The single GlcNAc attachment best enhanced the activity, while larger carbohydrates decreased the activity. This relative activity order of compounds could be partly explained by their calcitonin-receptor binding affinity, though the affinity of the GlcNAc derivative did not exceed that of calcitonin. The enhanced hypocalcemic activity of the GlcNAc derivative was explained by its altered biodistribution. The GlcNAc attachment caused calcitonin to escape from the trap at the liver during the early circulation. Thus, the glycosylation was shown to modulate the biological activity of calcitonin depending on the carbohydrate structure without a change in the peptide backbone conformation.

Amino Acid Sequence↗
PubMed2001

E-cadherin expression in wound healing of mouse skin.

BACKGROUND: E-cadherin has been studied extensively in other systems but little attention has been paid to its role in wound healing. We investigated E-cadherin expression in epithelial wound healing in vivo by focusing on the migrating cells in the epithelial tongue and the mitotic cells in the non-injured side apart from the original wound edge. METHODS: Round full-thickness excisional wounds (6 mm in diameter) and full-thickness incisional wounds were prepared dorsally in mice. On various days after the operation, E-cadherin expression was examined by immunohistochemical staining using a monoclonal antibody specific for E-cadherin. RESULTS: In both models, the level of E-cadherin expression did not decrease on the 1st postoperative (P.O.) day. After the 2nd P.O. day, E-cadherin expression decreased in cells at a site 500 microm apart from the original wound edge. After the 3rd P.O. day, decreased expression was also observed in cells at the top and in the basal layer of the epithelial tongue. This decreased expression continued for 1 or 2 days after the meeting of the epithelial tongue. There was no significant difference in the expression of E-cadherin between two models. CONCLUSIONS: The results suggested that E-cadherin expression decreases in epithelial cells. This decrease may depend on the activity of migration and mitosis. In addition, the change was similar in both the excisional and incisional wounds.

Animals↗
PubMed2001

Expression of matrix metalloproteinase-2 and -9 in synovial fluid of the temporomandibular joint accompanied by anterior disc displacement.

The purpose of this study was to determine whether or not matrix metalloproteinases (MMPs) in synovial fluid are helpful in the biochemical diagnosis of temporomandibular joint (TMJ) disorder (TMD). We examined the synovial fluid from 38 TMD patients with disc displacement and 20 volunteers by gelatin zymography and immunoblotting analysis to clarify the involvement of the joint pathology from the viewpoint of expression of MMPs. Two gelatinolytic enzymes, MMP-2 and -9, were detected in the samples. The incidences of expression, except for pro-MMP-2, in anterior disc displacement (ADD) without reduction (ADD w/o R) were significantly higher than in ADD with reduction (ADD w R) (P<0.05). Quantitative analysis showed that the degree of MMP-2 and -9 expression in ADD w/ o R were higher than in ADD w R. These data suggest that the presence or absence of disc reduction is a major turning point in the process of joint destruction, and these MMPs are useful as biochemical markers for TMD diagnosis.

Adolescent↗
PubMed2001

Effects of YM471, a nonpeptide AVP V(1A) and V(2) receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells.

YM471, (Z)-4'-[4,4-difluoro-5-[2-(4-dimethylaminopiperidino)-2-oxoethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl]-2-phenylbenzanilide monohydrochloride, is a newly synthesized potent vasopressin (AVP) receptor antagonist. Its effects on binding to and signal transduction by cloned human AVP receptors (V(1A), V(1B) and V(2)) stably expressed in Chinese hamster ovary (CHO) cells, and oxytocin receptors in human uterine smooth muscle cells (USMC) were studied. YM471 potently inhibited specific [(3)H]-AVP binding to V(1A) and V(2) receptors with K(i) values of 0.62 nM and 1.19 nM, respectively. In contrast, YM471 exhibited much lower affinity for V(1B) and oxytocin receptors with K(i) values of 16.4 microM and 31.6 nM, respectively. In CHO cells expressing V(1A) receptors, YM471 potently inhibited AVP-induced intracellular Ca(2+) concentration ([Ca(2+)](i)) increase, exhibiting an IC(50) value of 0.56 nM. However, in human USMC expressing oxytocin receptors, YM471 exhibited much lower potency in inhibiting oxytocin-induced [Ca(2+)](i) increase (IC(50)=193 nM), and did not affect AVP-induced [Ca(2+)](i) increase in CHO cells expressing V(1B) receptors. Furthermore, in CHO cells expressing V(2) receptors, YM471 potently inhibited the production of cyclic AMP stimulated by AVP with an IC(50) value of 1.88 nM. In all assays, YM471 showed no agonistic activity. These results demonstrate that YM471 is a potent, nonpeptide human V(1A) and V(2) receptor antagonist which will be a valuable tool in defining the physiologic and pharmacologic actions of AVP.

Animals↗
PubMed2001

Lack of small intestinal ulcerogenecity of nitric oxide-releasing indomethacin, NCX-530, in rats.

AIM: To evaluate the intestinal ulcerogenic property of nitric oxide-releasing indomethacin (NCX-530) in the rat, in comparison with indomethacin. METHODS: Animals were given indomethacin or NCX-530 subcutaneously and killed 24 h later for macroscopic examination of the small intestine. RESULTS: A single administration of indomethacin (10 mg/kg) provoked damage, mainly in the jejunum and ileum, accompanied by an increase in myeloperoxidase and inducible nitric oxide synthase activities as well as bacterial translocation. NCX-530 at an equimolar dose (14.2 mg/kg) caused no gross damage in the small intestine, nor any significant change in inducible nitric oxide synthase and myeloperoxidase activities or bacterial translocation. NOR-3, the nitric oxide donor (6.0 mg/kg), when administered subcutaneously together with indomethacin, significantly prevented the occurrence of intestinal lesions and other mucosal changes. Indomethacin reduced mucus and fluid secretions in the small intestine, while both NCX-530 and NOR-3 enhanced these secretions. NCX-530 reduced the mucosal prostaglandin E2 contents and exhibited an anti-inflammatory action against carrageenan-induced paw oedema, with equal effectiveness to indomethacin. CONCLUSION: NCX-530 does not cause intestinal damage, despite inhibiting cyclooxygenase activity. The reduced intestinal toxicity of NCX-530 may be attributable to inhibition of enterobacterial translocation, partly by increasing the mucus and fluid secretions mediated by nitric oxide released from this compound.

Acetates↗
PubMed2001

Overexpression of chlorophyllide a oxygenase (CAO) enlarges the antenna size of photosystem II in Arabidopsis thaliana.

The light-harvesting efficiency of a photosystem is thought to be largely dependent on its photosynthetic antenna size. It has been suggested that antenna size is controlled by the biosynthesis of chlorophyll b. To verify this hypothesis, we overexpressed the enzyme for chlorophyll b biosynthesis, chlorophyllide a oxygenase (CAO), in Arabidopsis thaliana by transforming the plant with cDNA for CAO under the control of the 35S cauliflower mosaic virus promoter. In the early de-etiolation phase, when the intrinsic CAO expression is very low, the chlorophyll a: b ratio was drastically decreased from 28 to 7.3, indicating that enhancement of chlorophyll b biosynthesis had been successfully achieved. We made the following observations in full-green rosette leaves of transgenic plants. (1) The chlorophyll a : b ratio was reduced from 2.85 to 2.65. (2) The ratio of the peripheral light-harvesting complexes (LHCII) to the core antenna complex (CPa) resolved with the green-gel system increased by 20%. (3) The ratio of the light-harvesting complex II apoproteins (LHCP) to 47-kDa chlorophyll a protein (CP47), which was estimated by the results of immunoblotting, increased by 40%. These results indicated that the antenna size increased by at least 10-20% in transgenic plants, suggesting that chlorophyll b biosynthesis controls antenna size. To the best of our knowledge, this is the first report on enlargement of the antenna size by genetic manipulations.

Apoproteins↗
PubMed2001

A case of autoimmune hepatitis with a high titer of antimitochondrial antibody and normal gamma-globulinemia.

We report here a patient with chronic active hepatitis who had no markers for hepatitis viruses and no hyper-gamma-globulinemia, but had high titers of antimitochondrial antibody. Serum levels of alkaline phosphatase were normal, and antinuclear antibody, antismooth muscle antibody, and antiliver kidney microsome antibody tested negative. The titers of antimitochondrial antibody exceeded 1:640, and the positivity for anti-M2 was ascertained by using both ELISA and immunoblot with beef-heart mitochondria and a recombinant pyruvate dehydrogenase E2 subunit as antigens. This patient responded to ursodeoxycholic acid (UDCA) therapy in the beginning, but her hepatitis flared up during UDCA therapy. In contrast, she responded completely to corticosteroid therapy. The clinical course and histological findings of this patient strongly suggest that this patient has autoimmune hepatitis.

Aged↗
PubMed2001

Protective effect of rebamipide on indomethacin-induced intestinal damage in rats.

BACKGROUND AND AIM: We evaluated the effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid), a novel anti-ulcer drug, on indomethacin-induced small intestinal lesions in rats. METHODS: The animals were administered indomethacin (10 mg/kg, s.c.), and they were killed 24 h later. Rebamipide (30-300 mg/kg) was administered p.o. twice, 30 min before, and 6 h after indomethacin. RESULTS: Indomethacin caused hemorrhagic lesions in the rat small intestine, accompanied by an increase in enterobacterial translocation, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) activities, as well as thiobarbituric acid (TBA) reactants, and these changes were significantly prevented by the supplementation with 16,16-dimethyl prostaglandin E2 (dmPGE2; 10 microg/kg, i.v.) or the pretreatment of animals with the antibiotic ampicillin. Treatment of the animals with rebamipide dose-dependently prevented the development of intestinal lesions, and this effect was mimicked by i.v. administration of superoxide dismutase (SOD: 3000 U/kg) + catalase (CAT: 5000 U/kg). The protection by rebamipide was accompanied by a significant suppression of the increase in both MPO and iNOS activities, and a complete inhibition of the increase in TBA reactants, while SOD + CAT significantly inhibited the increase of MPO activity and TBA reactants, but not iNOS activity. The bacterial translocation following indomethacin was also significantly decreased by either rebamipide or SOD + CAT. CONCLUSION: These results confirmed the importance of enterobacteria and iNOS/NO in the pathogenesis of indomethacin-induced small intestinal lesions, and suggested that rebamipide prevents the development of these lesions, probably by its radical scavenging action.

Alanine↗
PubMed2001

Morphological differences between glomerular epithelial cells (GEC) excreted during chemotherapy with antineoplastic drugs and GEC excreted in renal diseases.

BACKGROUND: To better understand the mechanisms of glomerular epithelial cell (GEC) injuries in various diseases, we compared GEC excreted during chemotherapy (antineoplastic drugs) and GEC excreted in renal diseases. METHODS: For 19 patients undergoing chemotherapy (85 courses), 69 patients with IgA nephropathy and 16 patients with Henoch-Schölein purpura nephritis, the number of excreted GEC and GEC casts were counted by an immunofluorescent study. The morphological features of GEC were also studied in an immunofluorescent study combined with Hoechst stain. RESULTS: Glomerular epithelial cells were detected in 78% of the chemotherapy courses and in 94% of the patients with renal diseases. The GEC casts were observed in 2% of chemotherapy courses, while in renal diseases GEC casts were observed in 60% of the patients. Proteinuria (>30 mg/dL) and hematuria were not identified in any of the chemotherapy courses. The morphology and size of GEC were more variable than that in patients with nephropathy. Furthermore, GEC in patients undergoing chemotherapy often showed small nuclei and fragmented nuclei, which were rarely observed in patients with nephropathy. CONCLUSIONS: These results showed that the detachment of podocytes was not directly associated with proteinuria or hematuria. The findings also suggest that GEC are damaged via an apoptotic process by chemotherapy. On the contrary, GEC may be detached through a non-apoptotic process in renal diseases.

Adolescent↗
PubMed2001

Automatic detection and classification of abnormalities for artificial hearts using a hierarchical self-organizing map.

A hierarchical self-organizing map (SOM) has been developed for automatic detection and classification of abnormalities for artificial hearts. The hierarchical SOM has been applied to the monitoring and analysis of an aortic pressure (AoP) signal measured from an adult goat equipped with a total artificial heart. The architecture of the network actually consists of 2 different SOMs. The first SOM clusters the AoP beat patterns in an unsupervised way. Afterward, the outputs of the first SOM combined with the original time-domain features of beat-to-beat data are fed to the second SOM for final classification. Each input vector of the second SOM is associated with a class vector. This class vector is assigned to every node in the second map as an output weight and learned according to Kohonen's learning rule. Some experimental results revealed that a certain abnormality caused by breakage of sensors could be identified and detected correctly and that the change in the state of the circulatory system could be recognized and predicted to some extent.

Animals↗
PubMed2001

Recent progress on the vibrating flow pump as a totally implantable ventricular assist device.

This study describes the present state of progress in the development of the vibrating flow pump (VFP) ventricular assist system. We have proceeded with development aiming at a totally implantable ventricular assist system with smaller size and lighter weight appropriate for Asians like the Japanese by increasing the drive frequency. An actuator is important for the development of the miniature sized and lightweight artificial heart. We applied a linear motor for the mechanical part at first. The step motor was applied after that. This form may be best if we want the lightweight small sized motor for an actuator. The cross slider form is applied at present. It succeeded in the miniaturization compared with the linear motor. In the VFP-type ventricular assist system, the blood contact parts are a central vibration tube with inflow and outflow chambers. We designed round diaphragms to prevent thrombus formation. In addition, we developed an energy transmission system for total implantation. The VFP creates a high frequency oscillated blood flow. It has a unique flow pattern. Brain blood flow increased although the total flow of the circulation did not change in the frequency of 25 to 30 Hz. The quantitative evaluation of the autonomic nerve function during the left heart assistance with an oscillated blood flow was carried out by spectral analysis. Some influences on an autonomic nerve were observed by the VFP left heart assistance. We will continue development research with the aim of clinical application.

Animals↗
PubMed2001

Intraglomerular metastasis from pancreatic cancer.

Few case reports have shown the presence of metastatic tumor cells in renal glomeruli. We report one case with intraglomerular metastasis proved at renal biopsy. A 60-year-old man suffered from weight loss and fever of unknown origin. Urinalysis revealed proteinuria with cellular and granular casts. Because vasculitis was suspected, renal biopsy was performed. Presence of tumor cells occupying the glomerular capillary lumina was shown by means of light microscopy and electron microscopy. Laboratory findings revealed elevated leukocyte count (28.9 x 10(3)/mm(3)), serum granulocyte colony-stimulating factor (G-CSF) (77 pg/mL), and serum CA 19-9 (21,885 U/mL). The patient soon developed disseminated intravascular coagulation and died. Autopsy findings revealed pancreatic cancer showing positive staining for G-CSF and CA 19-9. Tumor cells in the glomerular capillary lumina showed positive staining for CA 19-9 and proliferating cell nuclear antigen (PCNA). These results suggest that the pancreatic tumor cells producing G-CSF were entrapped in the glomerular capillary lumina where they proliferated. This may have been the first step in renal metastasis.

CA-19-9 Antigen↗
PubMed2001

Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoantigens.

Antimitochondrial antibodies (AMA) are the serologic hallmark of primary biliary cirrhosis (PBC). However, depending on the clinical laboratory, from 5% to 17% of PBC patients are consistently AMA-negative, using native mitochondrial antigens and a variety of conventional assays including immunofluorescence (IMF) and enzyme-linked immunosorbent assay (ELISA). The major immunoreactive mitochondrial autoantigens are the E2 members of the 2-oxo-acid dehydrogenase complex family, including pyruvate dehydrogenase complex-E2 (PDC-E2), branched chain 2-oxo acid dehydrogenase complex-E2 (BCOADC-E2), and oxo-glutarate dehydrogenase complex-E2 (OGDC-E2); cDNAs of these proteins have now been cloned, sequenced, and their B-cell epitopes defined. In the present study, we cloned cDNAs encoding these proteins from human, not bovine, sources, and expressed the recombinant proteins in a newly developed ELISA that employs a unique Escherichia coli buffer, and compared the data with previous assays using both AMA-positive and -negative patients. Using this new assay and our criteria for positive as an optical density (OD) greater than 10 SD above the mean of control sera, the AMA-positive rate of 191 PBC sera was 94% (179 of 191) compared with 84% (161 of 191) by IMF. None of the 316 control sera were reactive. Using our recombinant assays, we focused attention on the 30 IMF-AMA-negative patients. Twenty-two of 30 (73%) of these patients were positive using this new ELISA. The group of 30 IMF-AMA-negative/ELISA-positive patients did not differ significantly from a comparable population of IMF-AMA-positive patients with respect to age, sex distribution, liver function tests, elevation of serum IgM, or pathologic stage.

Autoantibodies↗
PubMed2001

Assessing systemic 11beta-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure.

11beta-hydroxysteroid dehydrogenase (11beta-HSD), an enzyme regulating mineralocorticoid like action of glucocorticoid, oxidizes active cortisol to inactive cortisone. Impaired activity of this enzyme is associated with apparent mineralocorticoid excess (AME) syndrome and is characterized by hypertension and hypokalemia. Recent investigations suggest the presence of hypertensive subjects with low activity of 11beta-HSD. The blood concentration ratio of cortisone/cortisol reflects the overall conversion of cortisol to cortisone and may be an index to assess the systemic activity of 11beta-HSD. We evaluated the peripheral blood concentration ratio of cortisone/cortisol as a possible marker to identify subjects with hypertension thought to represent impaired 11beta-HSD activity. We compared this ratio in healthy subjects and patients with diabetes mellitus (DM) or chronic renal failure (CRF). Peripheral blood samples were collected from 69 healthy subjects, 44 DM, and 36 CRF patients in the morning (9:00 to 11:00 AM). Twenty-six DM patients (59%) and 32 CRF patients (89%) met the criteria for having hypertension. Serum cortisol and cortisone concentrations were determined by high performance liquid chromatography (HPLC). All values for serum cortisone and cortisol levels were within the normal range. Serum cortisone/cortisol ratio in the healthy subjects was distributed with a range of 0.113 to 0.494 (median, 0.243). Compared with healthy subjects, DM and CRF patients had significantly low (P <.01) serum cortisone/cortisol levels (median, 0.188 [range, 0.092 to 0.313] in DM and 0.088 [range, 0.031 to 0.140] in CRF). Bimodal distribution of cortisone/cortisol, found in DM patients with hypertension, represented high- and low-ratio groups around the border of the ratio 0.2. Kidney function, DM duration, and complications varied between the high- and low-ratio groups. The low ratio group (<0.2), whose 11beta-HSD activity was considered low, had an increase in blood urea nitrogen (BUN) levels and experienced nephropathy, neuropathy, retinopathy, and prolonged DM duration when compared with the group with a ratio greater than 0.2. The data suggest that the serum cortisone/cortisol ratio reflects the change in 11beta-HSD activity and is dependent kidney function. This is a possible marker to evaluate glucocorticoid excess hypertension observed in DM and CRF patients.

11-beta-Hydroxysteroid Dehydrogenases↗