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Biomedical subjects

I Tanaka

Publications and source records attributed to I Tanaka.

At least 127 records · Page 7Linked to original sources
PubMed1999

An immunohistochemical study of the mesenchymal and epithelial components of pulmonary chondromatous hamartomas.

Twenty-five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S-100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i. e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component.

Adult↗
PubMed1999

Roles of prostaglandin E receptors in mesangial cells under high-glucose conditions.

BACKGROUND: High glucose reportedly stimulates prostaglandin (PG) E2 production and DNA synthesis in mesangial cells (MCs). However, the pathophysiological significance of PGE2 in MCs has remained unclear. METHODS: The effects of prostanoids on [3H]-thymidine uptake and cAMP production in rat MCs cultured with 5.6 mM glucose, 25 mM glucose, or 5.6 mM glucose supplemented with 19.4 mM mannitol were examined. The gene expression of PGE2 receptor (EP) subtypes in MCs was analyzed with Northern blotting techniques. RESULTS: Northern blotting indicated EP1 and EP4 gene expression in MCs. EP1 agonists and PGE2 stimulated [3H]-thymidine uptake in MCs. EP1 antagonists dose dependently attenuated high-glucose-induced [3H]-thymidine uptake, which suggests EP1 involvement, by an increase in intracellular Ca2+, in DNA synthesis of MCs. On the other hand, forskolin, db-cAMP, and 11-deoxy-PGE1, an EP4/EP3/EP2 agonist, significantly decreased DNA synthesis in MCs. These inhibitory effects are thought to be mediated via EP4 as a result of an increase in cAMP synthesis. The effects via EP4 seem to be particularly important because PGE2-induced cAMP synthesis was significantly attenuated in the high-glucose group compared with the mannitol group, in which [3H]-thymidine uptake did not increase in spite of augmented PGE2 production. CONCLUSION: The increase in DNA synthesis in MCs under high-glucose conditions can be explained, at least in part, by the high-glucose-induced inhibition of cAMP production via EP4, which augments EP1 function in conjunction with the overproduction of PGE2.

1-Methyl-3-isobutylxanthine↗
PubMed1999

A method for detecting breakthrough of organic solvent vapors in a charcoal tube using semiconductor gas sensors.

This study developed a method for detecting organic vapors that break through charcoal tubes, using semiconductor gas sensors as a breakthrough detector of vapors. A glass column equipped with two sensors was inserted in Teflon tubing, and air containing organic vapor was introduced at a constant flow rate. After the output signal of the sensors became stable, a charcoal tube was inserted into the tubing at the upstream of the sensors. The resistance of the sensors was collected temporally in an integrated circuit (IC) card. The vapor concentration of the air near the sensors was measured with a gas chromatograph (GC) equipped with a flame ionization detector (FID) at intervals of 5 minutes to obtain the breakthrough curve. When the relative humidity was zero, the output signals of the sensors began to change before the breakthrough point (1% breakthrough time). This tendency was almost the same for methyl acetate, ethyl acetate, isopropyl alcohol (IPA), toluene, and chloroform. For dichloromethane and 1,1,1-trichloroethane, the time when the sensor output signals began to rise was almost the same as the breakthrough point. When the relative humidity was 80 percent, the sensors could also detect many vapors before the breakthrough point, but they could not perceive dichloromethane and chloroform vapors. A personal sampling system with a breakthrough detector was developed and its availability is discussed.

Air Pollution, Indoor↗
PubMed1999

Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles.

Diesel exhaust particles (DEP), an environmental pollutant, are known to induce lung cancer in experimental animals. To clarify whether reactive oxygen species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enzyme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response to ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP. The 8-OH-Gua repair activities in the DEP-treated groups decreased during the period from 2 h to 2 days following DEP exposure and then recovered to the level of the control group at 5 days after exposure. OGG1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after administration. In conclusion, the 8-OH-Gua level in rat lung DNA increases markedly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis.

Animals↗
PubMed1999

The high-resolution structure of DNA-binding protein HU from Bacillus stearothermophilus.

Protein HU is a ubiquitous prokaryotic protein which controls the architecture of genomic DNA. It binds DNA non-specifically and promotes the bending and supercoiling of the double helical structure. HU is involved in many DNA-associated cellular processes, including replication, transcription and the packaging of DNA into chromosome-like structures. Originally determined at medium resolution, the crystal structure of HU has now been refined at 2.0 A resolution. The high-resolution structure shows that the dimeric molecule is essentially a compact platform for two flexible and basic arms which wrap around the DNA molecule. To maximize the protein's stability, non-secondary structural regions are reduced to a minimum, there is an extensive aromatic hydrophobic core and several salt bridges and hydrogen-bonded water molecules knit together crucial regions. Based on the original medium-resolution structure of HU, several proposals were made concerning the structural basis of HU's ability to bind, bend and supercoil DNA. Each of these proposals is fully supported by the high-resolution structure. Most notably, the surfaces of the molecule which appear to mediate protein-DNA and protein-protein interactions have the ideal shapes and physicochemical properties to perform these functions.

Bacterial Proteins↗
PubMed1999

Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos.

Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.

Animals↗
PubMed1999

Characterization of Prophet of Pit-1 gene expression in normal pituitary and pituitary adenomas in humans.

Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and regulating its expression. According to a previous report, Prop-1 messenger RNA (mRNA) is expressed in the developing pituitary gland before Pit-1 mRNA expression and maximum expression are observed at e 12.0. After e 14.5, Prop-1 mRNA expression rapidly decreases, and only trace amounts of mRNA are detectable in adult mouse pituitary. Human Pit-1 is expressed considerably, not only in normal adult pituitary but also in pituitary adenomas, so we studied human Prop-1 gene expression in adult pituitary and pituitary adenomas. We also cloned human Prop-1 complementary DNA (cDNA) and sequenced the Prop-1 cDNAs in pituitary adenomas. The amino acid sequence of human Prop-1 cDNA that we cloned was identical to that of the previously reported sequence, except Thr substituted at codon 142 instead of Ala. This amino acid substitution is considered to be a polymorphism because it did not alter transcriptional activity, and 7 of 28 alleles were Ala. Human Prop-1 transcript was detected in normal adult pituitary, by Northern blot analysis, and in all pituitary adenomas examined by RT-PCR analysis. The expression of human Prop-1 in pituitary adenomas was confirmed by in situ hybridization in one of the somatotroph adenomas. The sequence analysis of human Prop-1 cDNAs in these pituitary adenomas revealed that there were no mutations, except 5 silent nucleic acid substitutions, suggesting that mutations of Prop-1 gene do not represent a frequent mechanism of human pituitary tumorigenesis.

Adenoma↗
PubMed1999

[Effects of allopurinol for oxidative injury of cisplatin-induced nephrotoxicity in mice].

The effects of allopurinol (Allop) on the lipid peroxidation in the nephrotoxicity of an antitumor drug, cisplatin (CDDP) were studied in mice. CDDP was administered intraperitoneally to two groups (CDDP + Allop group and CDDP + CMC-Na group) at single doses of 10 mg/kg, and mice were sacrificed 3 days after CDDP administration. The body weights of the CDDP-administered group gradually decreased to approximately 78% of the values of the control group (saline + Allop group and saline + CMC-Na group) within 3 days. Plasma urea nitrogen and creatinine, especially in the CDDP + Allop group, increased after 3 days. Lipid peroxides in the blood and kidney were monitored by measuring the production of malondialdehyde (MDA), which increased in the CDDP + CMC-Na group. On the other hand, MDA levels in the CDDP + Allop group increased in the kidney but remained unchanged in the blood. Changes were observed in tissue glutathione (reduced form, GSH; oxidized form, GSSG) levels in the CDDP + Allop group but not in the CDDP + CMC-Na group. Histomorphological examination demonstrated the degeneration of the proximal tubuli in the CDDP-administered groups. Especially in the CDDP + Allop group, the increase of mesangium cells in the glomeruli was observed. From these results, it was suggested that Allop was not able to inhibit CDDP-induced lipid peroxidation in the kidney, and the kidney function became more severely impaired by the administration of Allop.

Allopurinol↗
PubMed1999

Arginine-55 in the beta-arm is essential for the activity of DNA-binding protein HU from Bacillus stearothermophilus.

DNA-binding protein HU (BstHU) from Bacillus stearothermophilus is a homodimeric protein which binds to DNA in a sequence-nonspecific manner. In order to identify the Arg residues essential for DNA binding, four Arg residues (Arg-53, Arg-55, Arg-58, and Arg-61) within the beta-arm structure were replaced either by Gln, Lys, or Glu residues, and the resulting mutants were characterized with respect to their DNA-binding activity by a filter-binding analysis and surface plasmon resonance analysis. The results indicate that three Arg residues (Arg-55, Arg-58, and Arg-61) play a crucial role in DNA binding as positively charged recognition groups in the order of Arg-55 > Arg-58 > Arg-61 and that these are required to decrease the dissociation rate constant for BstHU-DNA interaction. In contrast, the Arg-53 residue was found to make no contribution to the binding activity of BstHU.

Arginine↗
PubMed1999

Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA.

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.

Animals↗
PubMed1999

A clearance model of inhaled man-made fibers in rat lungs.

A clearance model of inhaled man-made fibers (MMFs) was developed, and the calculated fiber numbers and dimensions were compared with the experimental ones using a glass fiber (GF), ceramic fiber (RF1) and two potassium octatitanate whiskers (PT1, TW). If the translocation rate by macrophages is constant and the effect of dissolution and disintegration can be ignored, the fiber number is expected to decrease exponentially with time. In the experimental study, however, the fiber number did not always decrease exponentially. In the case of RF1, the fiber number decreased almost exponentially and the diameter decreased linearly with the time. The clearance rate constant of GF during 3 to 6 months after the end of one-month exposure was greater than that during 1 to 3 months. On the contrary, the clearance rate constants of PT1 and TW during 1 to 6 months were greater than next six months. The diameter and the length of GF did not change significantly. The fiber length of PT1 tends to become longer with time although the diameter did not change significantly. Our theoretical model gives a satisfactory fit to these experimental results.

Administration, Inhalation↗
PubMed1999

A new digestion method for recovery of MMMFs from lungs.

A new tissue digestion method is proposed to recover man-made mineral fibers (MMMFs) from lungs, which is an improved Kjeldahl method using microwaves. Tissue digestion is carried out under five different conditions in this experiment, and the most suitable condition is found as follows; dried rat lung (0.5 g of wet weight) is put into a flask with 0.1 ml of H2SO4 and 2.0 ml of HNO3, and treated by microwaves for 5 min. After the treatment, 1.0 ml of H2O2 is added immediately and the sample is treated again under the same condition. Pure samples of glass fibers and refractory ceramic fibers are treated by this proposed method. Numbers and sizes of the fibers are measured before and after the treatment on enlarged photos taking by a scanning electron microscope. As no significant changes are observed in fiber dimensions and numbers, the proposed method is shown to be applicable to recover these MMMFs from lungs.

Acids↗
PubMed1999

Effects of mineral fibers on the gene expression of proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages.

To determine which parameters are useful for the risk assessment of man-made mineral fibers (MMMFs), we examined the gene expression of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and inducible nitric-oxide synthase (iNOS) in mineral fiber-exposed alveolar macrophages (AMs). Male Wistar rats were intratracheally exposed to saline or mineral fibers suspended in saline (2 mg of crocidolite, chrysotile, alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (TW)). Bronchoalveolar lavage was performed 4 weeks after the fiber-instillation, and the recovered AMs were stimulated by lipopolysaccharide for 2 or 6 hours. Expression of IL-1 alpha, TNF alpha, IL-6 and iNOS from AMs was observed using reverse transcription-polymerase chain reaction (RT-PCR). The levels of IL-1 alpha and IL-6 mRNA induced by mineral fiber exposure were greatest in AMs exposed to TW, crocidolite, chrysotile and RF1 in that order. However, both gene expression of iNOS and TNF alpha were not elevated in both crocidolite and TW exposure, despite their high pathological potential. These data suggested that IL-1 alpha and IL-6 may be useful indicators for the risk assessment of MMMFs.

Administration, Inhalation↗
PubMed1999

Non-suture end-to-end anastomoses between polytetrafluoroethylene graft and vessels for blood access.

BACKGROUND: Non-suture end-to-end anastomoses between polytetrafluoroethylene grafts and blood vessels were achieved using absorbable cuff material in experimental and clinical studies. The cuff was made of a synthetic biodegradable material, a lactic-glycolic acid copolymer, similar in composition to conventional absorbable surgical sutures. METHODS: In the experimental study, vascular anastomoses for prosthetic interposition of the infrarenal aorta in rabbits were created using the cuff method. Six months after surgery, the cuff anastomoses sites were examined angiographically and microscopically and found to be patent and smooth without neointimal hyperplasia. RESULTS: The cuff layer had been completely absorbed. The clinical application used a similar technique and involved the creation of forearm bridge graft fistula in twelve patients for hemodialysis. In eight patients, Doppler fistula flow rate ranged from 167 ml/min to 392 ml/min. Ten of the twelve patients continued dialysis uneventfully. The one-year patency rate was 78% (7/9). The longest patency period was 920 days and the graft access continued to maintain sufficient blood flow for hemodialysis. CONCLUSIONS: This absorbable cuff material is therefore well suited for the construction of prosthetic vascular end-to-end anastomoses.

Aged↗
PubMed1999

[Autopsy case of intravascular lymphomatosis with pancreatic carcinoma].

We report an autopsy case of intravascular lymphomatosis (IVL) that arose after radiation therapy and chemotherapy for an inoperable pancreatic carcinoma. A 66-year-old man who suffered from diabetes mellitus and pancreatic carcinoma presented with aggressive progression of consciousness disturbance and high fever. The laboratory findings disclosed marked thrombocytopenia, hypercalcemia, and elevated serum PTH-related peptide. The patient soon died of ventricular fibrillation due to uncontrollable hypercalcemia. Postmortem examination with immunohistochemical analysis revealed a well-differentiated tubular adenocarcinoma in the pancreatic body as well as an accumulation of neoplastic B-lymphocytes in small vessels throughout the body without systemic lymphadenopathy. To our knowledge, double neoplasms including IVL are extremely rare.

Adenocarcinoma↗
PubMed1998

Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel.

Recent genetic and molecular biological analyses have revealed many forms of inherited channelopathies. Homozygous ataxic mice, tottering (tg) and leaner (tgla) mice, have mutations in the P/Q-type Ca2+ channel alpha1A subunit gene. Although their clinical phenotypes, histological changes, and locations of gene mutations are known, it remains unclear what phenotypes the mutant Ca2+ channels manifest, or whether the altered channel properties are the primary consequence of the mutations. To address these questions, we have characterized the electrophysiological properties of Ca2+ channels in cerebellar Purkinje cells, where the P-type is the dominant Ca2+ channel, dissociated from the normal, tg, and tgla mice, and compared them with the properties of the wild-type and mutant alpha1A channels recombinantly expressed with the alpha2 and beta subunits in baby hamster kidney cells. The most striking feature of Ca2+ channel currents of mutant Purkinje cells was a marked reduction in current density, being reduced to approximately 60 and approximately 40% of control in tg and tgla mice, respectively, without changes of cell size. The Ca2+ channel currents in the tg Purkinje cells showed a relative increase in non-inactivating component in voltage-dependent inactivation. Besides the same change, those of the tgla mice showed a more distinct change in voltage dependence of activation and inactivation, being shifted in the depolarizing direction by approximately 10 mV, with a broader voltage dependence of inactivation. In the recombinant expression system, the tg channel with a missense mutation (P601L) and one form of the two possible tgla aberrant splicing products, tgla (short) channel, showed a significant reduction in current density, while the other form of the tgla channels, tgla (long), had a current density comparable to the normal control. On the other hand, the shift in voltage dependence of activation and inactivation was observed only for the tgla (long) channel. Comparison of properties of the native and recombinant mutant channels suggests that single tottering mutations are directly responsible for the neuropathic phenotypes of reduction in current density and deviations in gating behavior, which lead to neuronal death and cerebellar atrophy.

Animals↗
PubMed1998

Inspiratory inhibition of pulmonary rapidly adapting receptor relay neurons in the rat.

Second-order relay neurons (referred to as rapidly adapting pulmonary stretch receptors (RARs)-cells) activated by vagal afferents originating from RARs were identified electrophysiologically in Nembutal-anesthetized, paralyzed and artificially ventilated rats. Their location in the commissural subnucleus of the nucleus tractus solitarii (NTS) and firing properties in response to lung inflations and deflations were studied in detail for the first time in the rat. Importantly, in all the RAR-cells examined, their firing was suppressed to various extent during a period from inspiration to early expiration. This means that the information from the RARs to the central nervous system is gated by the central respiratory system at the level of RAR-cells in the NTS.

Action Potentials↗