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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 55 records · Page 3Linked to original sources
PubMed2001

Characterization of plant proliferating cell nuclear antigen (PCNA) and flap endonuclease-1 (FEN-1), and their distribution in mitotic and meiotic cell cycles.

The biochemical and cell cycle-dependent properties of proliferating cell nuclear antigen (OsPCNA) and flap endonuclease-1 (OsFEN-1) were characterized from rice (Oryza sativa). OsPCNA was physically associated with OsFEN-1 and increased the flap-endonuclease activity of OsFEN-1 by 2.5-fold. Northern and Western blotting analysis revealed that OsPCNA and OsFEN-1 were present in meristematic tissues such as cultured cells, shoot apical meristem and root apical meristem. No expression was detected in the mature leaves, although they were exposed to UV. Both of these proteins were localized in the nuclei of the interphase cells including G1, S and G2, and in the nuclear region at telophase. The distribution patterns of plant PCNA and FEN-1 in meiotic cell progression were investigated using microsporocytes of lily (Lilium longiflorum cv. Hinomoto). During the leptotene to pachytene stages, PCNA and FEN-1 were localized in the nuclear region. The florescence gradually disappeared from diplotene to metaphase I. Interestingly, signals for PCNA formed 10-20 intense spots at leptotene. The number of spots decreased to 1-5 at zygotene and finally to 1 at pachytene. The roles of OsPCNA and OsFEN-1 in mitotic and meiotic cell cycles are discussed.

Antibodies↗
PubMed2001

Role of connective tissue growth factor in profibrotic action of transforming growth factor-beta: a potential target for preventing renal fibrosis.

Tubulointerstitial fibrosis is a crucial process determining the progression and prognosis of various renal diseases. Connective tissue growth factor (CTGF), a novel fibrogenic protein induced by transforming growth factor-beta (TGF-beta), is upregulated in various clinical and experimental nephropathies, but the significance of CTGF in the profibrotic action of TGF-beta is still poorly defined. To explore the implication of CTGF in renal fibrosis, we investigated gene expression of CTGF, fibronectin, and alpha1(I) collagen in an obstructive nephropathy model in rats. Furthermore, to elucidate the role of CTGF in TGF-beta-stimulated extracellular matrix accumulation, we analyzed the effects of blockade of endogenous CTGF using antisense oligodeoxynucleotides (ODNs) in cultured rat renal fibroblasts. After unilateral ureteral obstruction, TGF-beta1 and CTGF messenger RNA (mRNA) expression in the obstructed kidney was coordinately upregulated from the early stage of interstitial fibrosis, followed by marked induction of fibronectin and alpha1(I) collagen mRNA expression. In cultured normal rat kidney fibroblast (NRK-49F) cells, CTGF antisense ODN transfection significantly attenuated TGF-beta1-induced fibronectin and alpha1(I) collagen mRNA expression compared with control reverse ODNs. These results indicate that CTGF has a crucial role in the profibrotic action of TGF-beta in renal fibroblasts, providing a potential therapeutic target against tubulointerstitial fibrosis.

Animals↗
PubMed2001

Comparison of gene expression of cytokines mRNA in lungs of rats induced by intratracheal instillation and inhalation of mineral fibers.

To investigate whether the results of intratracheal instillation studies on mineral fibers reflect the findings obtained by long-term inhalation data on mineral fibers, we have examined gene expression of cytokines and pathological features in lungs induced by intratracheal instillation and inhalation of mineral fibers. Male Wistar rats were given a single intratracheal instillation of 2 mg alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (PT1), and were sacrificed 4 wk after the fiber instillation. Long-term inhalation studies were also performed. In these, animals were exposed to fiber aerosol of RF1 or PT1 for 5 days/wk for 1 yr, and sacrificed after 1 yr of inhalation. Expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta1) from lungs was observed by reverse-transcription polymerase chain reaction (RT-PCR). The expression of TNF-alpha, IL-6, and TGF-beta1 mRNA in PT1-exposed lung was significantly higher than for those exposed to RF1 in both intratracheal instillation and inhalation studies. Pathological findings revealed that mild pulmonary fibrosis was seen in the lungs after intratracheal instillation and inhalation of PT1 but not RF1. Similarities were observed not only in gene expression of cytokines but in pathological features between both studies. These data suggested that the results of intratracheal instillation reflect the findings obtained from long-term inhalation data.

Aluminum Silicates↗
PubMed2001

Inhibition of creatine kinase activity in rat brain by methyl bromide gas.

Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/day, 3 times/wk for 4 to 8 wk. Creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum (hemisphere and vermis) and largest in the brainstem (hypothalamus, midbrain, and medulla oblongata). The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose (290 to 495 ppm) or on prolonging exposure period (4 to 8 wk). Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.

Administration, Inhalation↗
PubMed2001

Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos.

We examined 8-hydroxyguanine (8-OH-Gua) formation and 8-OH-Gua repair enzyme activity in pulmonary type-II-like epithelial cells to determine whether oxidative stress induced by asbestos plays a role in its carcinogenic mechanism. A549 cells were incubated with crocidolite asbestos at concentrations of 0, 10, 50 and 100 microg/ml over 27 h. We then evaluated 8-OH-Gua formation, 8-OH-Gua repair enzyme activity and gene expression of 8-oxoguanine-DNA glycosylase 1 (hOGG1) and human MUtT homologue (hMTH1). This was done using a high-performance liquid chromatography system equipped with an electrochemical detector, endonuclease nicking assay and reverse transcription polymerase chain reaction, respectively. Crocidolite induced the formation of 8-OH-Gua in DNA at concentrations of 50 and 100 microg/ml. 8-OH-Gua levels increased at 9 h and had declined to near baseline at 27 h, whereas 8-OH-Gua repair enzyme activity peaked at 18 h post-crocidolite exposure. hOGG1 and hMTH1 mRNA levels were also increased by crocidolite exposure. These data suggest that crocidolite asbestos is associated with epithelial cell injury in the process of carcinogenesis through oxidative stress.

Actins↗
PubMed2001

The OmpR-family of proteins: insight into the tertiary structure and functions of two-component regulator proteins.

The Escherichia coli DNA-binding protein OmpR is the best characterized of those regulator proteins making up "two-component system," the simplest known form of bacterial signal transduction systems. Previous inspections of the E. coli genome DNA sequences have revealed that there are 15 proteins whose amino acid sequences show extensive similarities to that of OmpR (the OmpR-family of proteins). The three-dimensional structures of several OmpR-family proteins have been determined. In this review, we investigated the structures and amino acid sequences of this family of proteins. The results reveal several notable conservative varieties in their tertiary structures and functions.

Amino Acid Sequence↗
PubMed2001

The structure of the archaebacterial ribosomal protein S7 and its possible interaction with 16S rRNA.

Ribosomal protein S7 is one of the ubiquitous components of the small subunit of the ribosome. It is a 16S rRNA-binding protein positioned close to the exit of the tRNA, and it plays a role in initiating assembly of the head of the 30S subunit. Previous structural analyses of eubacterial S7 have shown that it has a stable alpha-helix core and a flexible beta-arm. Unlike these eubacterial proteins, archaebacterial or eukaryotic S7 has an N-terminal extension of approximately 60 residues. The crystal structure of S7 from archaebacterium Pyrococcus horikoshii (PhoS7) has been determined at 2.1 A resolution. The final model of PhoS7 consists of six major alpha-helices, a short 3(10)-helix and two beta-stands. The major part (residues 18-45) of the N-terminal extension of PhoS7 reinforces the alpha-helical core by well-extended hydrophobic interactions, while the other part (residues 46-63) is not visible in the crystal and is possibly fixed only by interacting with 16S rRNA. These differences in the N-terminal extension as well as in the insertion (between alpha1 and alpha2) of the archaebacterial S7 structure from eubacterial S7 are such that they do not necessitate a major change in the structure of the currently available eubacterial 16S rRNA. Some of the inserted chains might pass through gaps formed by helices of the 16S rRNA.

Amino Acid Sequence↗
PubMed2001

Monoclonal antibody against brain natriuretic peptide and characterization of brain natriuretic peptide-transgenic mice.

OBJECTIVE: Brain natriuretic peptide (BNP) is a ventricular hormone with natriuretic, diuretic and vasodilatory actions. Acute infusion of BNP reduces cardiac pre- and after-load in healthy and diseased subjects, but its long-term therapeutic usefulness remains unclear. DESIGN: We prepared a monoclonal antibody specific to mouse BNP, and characterized transgenic mice overexpressing BNP in the liver (BNP-Tg mice) as a model of its chronic overproduction. METHODS: Radioimmunoassay and neutralization experiments using the monoclonal antibody, KY-mBNP-I, were performed in BNP-Tg mice in conjunction with examinations of blood pressure (BP) and other markers for body fluid homeostasis. RESULTS: We developed highly sensitive radioimmunoassay to mouse BNP. In BNP-Tg mice, the plasma BNP concentration increased more than 100-fold, while ventricular BNP concentration did not alter, suggesting that ventricular BNP production was not down-regulated in BNP-Tg mice. The BNP concentration in the kidneys was 10-fold higher than nontransgenic (nonTg) littermates, accompanied with marked reduction in the atrial natriuretic peptide (ANP) concentration, that may be due to binding of circulating BNP to the natriuretic peptide receptors. BNP-Tg mice showed significantly low arterial BP, and a bolus intraperitoneal administration of KYmBNP-I completely abolished enhanced cGMP excretion in the urine and significantly increased the systolic BP. CONCLUSION: These results suggested that biological actions of BNP last and reduce cardiac overload in its longterm overproduction in the transgenic mouse model.

Animals↗
PubMed2001

Altered growth response to prostaglandin E2 and its receptor signaling in mesangial cells from stroke-prone spontaneously hypertensive rats.

OBJECTIVE: Prostaglandin (PG) E2, a major arachidonic acid metabolite in the kidney, acts on four receptor subtypes (EP1, EP2, EP3 and EP4). One of major causes of end-stage renal failure is hypertensive renal disease, in which enhanced renal PGE2 production has been shown. In this study, to explore the pathophysiological significance of EP subtypes in the kidney, we examined the role of EP subtypes on proliferation of mesangial cells (MCs) from stroke-prone spontaneously hypertensive rats (SHRSPs), which show faster growth than those from normotensive Wistar-Kyoto rats (WKYs). DESIGN AND METHODS: Using MCs from SHRSPs and WKYs, we investigated DNA synthesis and its upstream event, the phosphorylation of extracellular signal-regulated kinase (ERK), together with the gene expression of EP subtypes. RESULTS: Sulprostone, an EP1 agonist, dose-dependently increased DNA synthesis and the phosphorylation of ERK in MCs from both strains. The EP4 agonist, 11-deoxy-PGE1, inhibited sulprostone-induced phosphorylation of ERK in WKY-MCs. In contrast, 11-deoxy-PGE1 failed to inhibit the ERK activity in SHRSP-MCs. Interestingly, cAMP production mediated by EP4 was markedly attenuated in SHRSP-MCs as compared with that in WKY-MCs, despite the overproduction of endogenous PGE2 in SHRSP-MCs. Similar gene expressions of EP1 and EP4 and only faint expression of EP3 were detected in MCs from both strains. CONCLUSIONS: These results indicate that the PGE2/EP4 system counteracts the PGE2/EP1 system at the level of the intracellular signaling pathway. The altered EP4 signaling may play a critical role in the exaggerated mesangial growth in SHRSPs.

Animals↗
PubMed2001

Possible role of telomerase activation in the multistep tumor progression of periampullary lesions in patients with familial adenomatous polyposis.

OBJECTIVES: The role of telomerase in periampullary tumor progression in patients with familial adenomatous polyposis (FAP) was investigated. METHODS: Relative telomerase activity was measured using a telomerease amplification protocol in periampullary biopsy specimens of normal mucosa and adenoma obtained from patients with FAP, and was compared with that of periampullary normal mucosa and cancer specimens from patients without FAP. RESULTS: None of normal mucosa from the non-FAP patients showed a telomerase ladder. Telomerase was positively detected in three of seven normal mucosa (42.9%) and in five of seven adenoma from FAP patients (62.5%). In papillary cancer from the non-FAP patients, seven of nine tissue specimens (77.8%) showed positive activity. When semiquantitatively analyzed, the relative telomerase activity increased in accordance with the progression of the diseases. CONCLUSIONS: Telomerase is activated even in normal mucosa of FAP patients, and the intensities of telomerase may reflect the malignant potential of periampullary neoplasms.

Adenomatous Polyposis Coli↗
PubMed2001

Increased expression of matrix metalloproteinase in Clara cell-ablated mice inhaling crystalline silica.

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by examining pulmonary matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels in mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg) in a corn oil vehicle. The mice were then exposed to crystalline silica (Min-U-Sil-5 silica, 97.1 +/- 9.5 mg/m(2), 6 hr/day, 5 days/week) for up to 2 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by reverse transcription-polymerase chain reaction. Gene expression of both MMP-2 and MMP-9 was significantly more marked in the Clara cell-ablated group than in the group with Clara cells, indicating that Clara cells inhibit MMP expression. Our findings suggest that Clara cells inhibit pulmonary inflammation induced by crystalline silica via MMPs in vivo.

Animals↗
PubMed2001

Acute severe alcohol-induced bronchial asthma.

We report the case of a severe bronchial asthma attack 15 minutes after the ingestion of food containing small amounts of alcohol. Although an ethanol inhalation test was negative, an acetaldehyde inhalation test was positive. Furthermore, it was discovered that the patient was homozygous for a mutation of the aldehyde dehydrogenase-2 (ALDH-2) gene. We subsequently diagnosed his attack as acute severe alcohol-induced asthma. Since bronchial asthma patients who are homozygous for mutant ALDH-2 genes are susceptible to acute severe alcohol-induced asthma attacks, strict clinical attention is thought a necessity.

Acetaldehyde↗
PubMed2001

In vivo studies of man-made mineral fibers--fibrosis-related factors.

Pneumoconiosis that pursues a chronic course may result from repeated injury and repair caused by dust particles that remain in the lungs, leading to fibrosis. We will introduce in vivo studies concerning these processes using animals exposed to man-made mineral fibers and asbestos. We will report on whether there are developmental changes with the mineral fiber and animal model in proinflammatory cytokine, chemokine, free radicals, proteinase and other genes that lead to injury, as well as in genes that effect repair such as growth factor, and we will also report on the effects of surfactant protein and clara cell secretory protein on fibrosis.

Animals↗
PubMed2001

Biopersistence of man-made fibers by animal inhalation experiments in recent reports.

Biopersistence of man-made fibers by animal inhalation experiments was mainly reviewed. This report showed that the biopersistence and maximum tolerated dose are significantly important factors for hazard assessment for man-made fibers as well as fiber size (diameter/length), chemical compositions and surface properties.

Administration, Inhalation↗
PubMed2001

Short term effect of silicon carbide whisker to the rat lung.

We studied the short-term effect of silicon carbide whisker (SiCW) in vivo by instillation and inhalation to the rat lung. SiCW was instilled low dose (2 mg/0.5 ml saline) or high dose (10 mg/ 0.5 ml) intratracheally into the lungs of 25 rats. SiCW was also inhaled to another 25 rats at the average concentration of 10.4 mg/m3 for 1 month. In instillation study, the lung had focal alveolitis with the destruction of alveolar wall especially at 3 days after the instillation, and the lesion remained as an aggregated foci of SiCW at 6 months. The 'inflammation-score' of the instilled group by point counting method of the specimen correspondingly decreased gradually. In inhalation group, a minimum inflammatory change was observed. Collagen deposition in the aggregated foci of SiCW with accumulated alveolar macrophages and neutrophils was not progressive during the observed period. These findings suggest that SiCW may cause a minor effect to the rat lung in 6 months after exposure.

Administration, Inhalation↗
PubMed2001

[A case of retroperitoneal malignant fibrous histiocytoma with marked response to cisplatin, ifosfamide and doxorubicin].

A 61-year-old man was admitted to our hospital in December 1994 for a suspected retroperitoneal tumor. Systemic imaging investigations demonstrated retroperitoneal solid tumor, which was diagnosed as malignant fibrous histiocytoma (MFH) by immunohistochemistry for alpha 1-antitrypsin. In March 1995, he was treated with 3 courses of systemic chemotherapy with cisplatin, ifosfamide and doxorubicin followed by the same therapy in March 1996, without serious side effects. MFH is known to be resistant to ordinary chemotherapy. However, the CT showed a marked decrease in the size of the tumor, and the tumor disappeared within 2 months after the first treatment. The patient also recovered rapidly from abdominal pain, for which complete remission has been achieved for more than 5 years. The present chemotherapy may be an effective treatment for retroperitoneal MFH.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Sampling and detection of Legionella pneumophila aerosols generated from an industrial cooling tower.

Cooling tower water has frequently been cited as a source of infection in outbreaks of Legionnaires' disease. However, there have been few reports on the presence of legionellae in aerosols from cooling towers. This paper describes our use of an impinger or a six-stage microbial impactor for detecting legionellae in air around a cooling tower contaminated with L. pneumophila (1.2+/-0.3x10(5) CFU/100 ml). Phosphate-buffered saline, Page's saline, 2% yeast extract solution and buffered yeast extract (BYE) broth were tested to evaluate their collection efficiency. These solutions were compared in laboratory experiments using an aerosol of L. pneumophila serogroup (SG) 1. Because BYE broth was the most efficient and storable collecting fluid among them, it was used for outdoor air sampling. In the outdoor air sampling, aerosolized L. pneumophila SG 6 was detected in the air around the cooling tower by the impinger (0.09 CFU/l. air). No legionellae were detected by the impactor with Legionella-selective agar plates (WYOalpha) because the plates were overgrown with fungi. Repetitive element PCR (rep-PCR) and arbitrarily primed PCR (AP-PCR) were employed to assess the epidemiological relationship among Legionella isolates from the air sample and the cooling tower water samples. L. pneumophila SG 6 isolated from the aerosols produced rep-PCR and AP-PCR fingerprints identical to those of L. pneumophila SG 6 strains from the cooling tower water, suggesting that the bacterium was aerosolized from the cooling tower.

Aerosols↗