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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 325 records · Page 18Linked to original sources
PubMed1998

Antiatherogenic effects of the antioxidant BO-653 in three different animal models.

Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2, 2-dipentyl-4,6-di-tert-butylbenzofuran), designed to exhibit antioxidative potency comparable to that of alpha-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo. In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.

Animals↗
PubMed1998

Pitx2 determines left-right asymmetry of internal organs in vertebrates.

The handedness of visceral organs is conserved among vertebrates and is regulated by asymmetric signals relayed by molecules such as Shh, Nodal and activin. The gene Pitx2 is expressed in the left lateral plate mesoderm and, subsequently, in the left heart and gut of mouse, chick and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 expression, whereas inhibition of activin signalling blocks it. Misexpression of Pitx2 alters the relative position of organs and the direction of body rotation in chick and Xenopus embryos. Changes in Pitx2 expression are evident in mouse mutants with laterality defects. Thus, Pitx2 seems to serve as a critical downstream transcription target that mediates left-right asymmetry in vertebrates.

Activin Receptors, Type II↗
PubMed1998

Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM-CSF) during follicular growth and luteinization in gonadotropin-primed immature rodents.

To obtain clues as to whether granulocyte-macrophage colony-stimulating factor (GM-CSF) is related to ovarian physiology, the sites, the gene expression and the production of GM-CSF in the ovary during follicular development and luteinization were studied in equine CG (eCG)-primed immature mice and rats. During follicular development, the expression of GM-CSF mRNA was localized in theca-interstitial tissues, oocytes and granulosa cells of small developing follicles in mice. In the mouse ovary after ovulation, luteal tissues as well as the above components had intense signals for GM-CSF mRNA. Mast cells, which were present mainly in the ovarian medulla, also expressed mRNA for GM-CSF in rats. Immunohistochemical analyses with two different antibodies against murine GM-CSF revealed that GM-CSF-like immunoreactivity was detectable mainly in theca-interstitial, luteal tissues, oocytes and mast cells. Intense GM-CSF positive cells in theca-interstitial and luteal tissues were stained with anti-CD11b antibody in mice. Messenger RNAs for GM-CSF receptor subunits were expressed in mast cells of the medulla and in luteal tissues in rat ovary. The levels of GM-CSF released into the culture media by rat ovarian dispersed cells 1-2 days after eCG treatment were higher than those before the treatment, although no significant change in the levels of ovarian GM-CSF mRNA was detected by reverse transcription-polymerase chain reaction analysis. The secretion of GM-CSF was also increased by treatment of the cells with immune stimulators such as phorbol ester, interleukin-1 and lipopolysaccharide. These data indicate that ovarian macrophages and mast cells in addition to theca-interstitial cells, synthesize and release GM-CSF during ovarian cycles, and that ovarian GM-CSF secreting capacity is enhanced during early stages of follicular development in rodents.

Animals↗
PubMed1998

Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q.

Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor suppressor gene. Previous analysis of DNA from 79 patients identified a commonly deleted segment of 5 centimorgans. Complementation analysis was used to further localize a putative tumor suppressor gene. Three yeast artificial chromosome (YAC) clones spanning the minimal loss of heterozygosity region were modified, and spheroplast fusion was used to transfer them into human A549 NSCLC or murine Lewis lung carcinoma (LLC) cell lines. The resulting yeast x human hybrid cell lines containing an intact copy of a 1.6-Mb YAC, 939b12, showed reduced growth in vitro. Injection of parental A549 cells into athymic (nu/nu) mice resulted in tumor formation at 27 of 28 injection sites. In contrast, two independent 939b12-containing cell lines formed tumors at only 3 of 20 injection sites. 939b12 also suppressed tumor formation by LLC NSCLC cells in nude mice, but YACs 785e12 and 911f2, which flank 939b12, had no suppressor activity. Further localization of tumor suppression activity on 939b12 was accomplished by introduction of defined fragmentation derivatives into A549 cells and by analysis of YACs that were broken on transfer into LLC cells. This complementation approach localized tumor suppression activity to the central 700 kb of 939b12 and provides a functional assay for positional cloning of this tumor suppressor gene.

Animals↗
PubMed1998

Identification of the hydrophobic amino acid residues required for heme assembly in the rhizobial oxygen sensor protein FixL.

Rhizobial FixL is a novel heme protein, which senses environmental oxygen tension and directs signal transduction via protein phosphotransfer. To identify the essential residues for heme assembly in Rhizobium meliloti FixL, we individually replaced the 18 invariant hydrophobic amino acid residues (F, I, L, and V) in the heme-containing domain with alanine and histidine. Spectroscopic measurements of the soluble fractions from fixL recombinant Escherichia coli revealed that V152, F162, F170, I172, L185, F226, L230, and F243 as well as the proximal ligand H194 were indispensable for heme assembly. Autoxidation rates of purified I209H, I210A, and I210H were 65-fold, 15-fold, and 15-fold, respectively, faster than that of the wild type, although they retained heme in the protein. The absorption peak in the Soret region of the ferric I209H or I210H was red-shifted, suggesting that the ferric heme is a hexa-coordinate form in these mutants.

Amino Acid Sequence↗
PubMed1998

Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen.

In order to evaluate the targeting potential of mouse monoclonal antibody ONS-M21 recognizing a human astrocytoma- and medulloblastoma-associated antigen, the internalization ability of this antibody and the selective cytotoxicity in the toxin-conjugated form were examined. Internalization assay with 125I-labeled ONS-M21 showed that about 20% of the total radioactivities was detected in the cellular fraction of human medulloblastoma cell line ONS-76 cells and that the reaction reached a plateau level in 30 min. To examine the selective delivery capacity of a high molecular substance in place of 125I, an immunotoxin was prepared with ricin A chain and ONS-M21 via disulfide bonds. A cytotoxic effect against ONS-76 cells was found with [3H]thymidine incorporation assay using the immunotoxin, but not against antigen-negative HuH-7 and SW480 cells. These results suggest that ONS-M21 could effectively deliver toxins, chemotherapeutic agents or radionuclei to malignant glioma specifically.

Animals↗
PubMed1998

Fabrication and characterization of multilayer supermirrors for hard X-ray optics.

Multilayer supermirrors stacked with three sets of Pt/C combinations have been fabricated on a flat float-glass and conical replica foil mirror using a magnetron DC sputtering system, and applied to X-ray optical systems in the hard X-ray region. The design of the supermirror is optimized to obtain the highest integrated reflectivity in the energy band and at the grazing angle concerned. X-ray reflectivities of 30% in the 25-35 keV band at an incidence angle of 0.3 degrees were obtained.

Journal Article↗
PubMed1998

Characterization of substrates for use in X-ray multilayer optics.

The optical performance of platinum-carbon multilayers deposited onto different substrates has been examined. Specular reflectivity and non-specular diffuse scattering were measured to study the replication of substrate roughness into the multilayer structure. Surface topography was measured before and after deposition using a scanning probe microscope and a mechanical profiler.

Journal Article↗
PubMed1998

gp130 is involved in stretch-induced MAP kinase activation in cardiac myocytes.

We have recently reported that mitogen activated protein kinase (MAP kinase) is activated by the stretch of the cultured cardiac myocytes in the angiotensin II deficient state in the angiotensinogen-deficient mice (Atg-/-), suggesting that factors other than the cardiac renin-angiotensin system are involved in the stretch-induced MAP kinase activation. We examined the contribution of cytokines using RX435, an anti-gp130 antibody. Leukemia inhibitory factor, which is one of the cytokines and has the common receptor subunit gp130, activated MAP kinase and the response was completely blocked by pretreatment of the Atg-/- cardiac myocytes with RX435. RX435 pretreatment greatly reduced stretch-induced activation of MAP kinase in Atg-/- cardiac myocytes. Interestingly, the same results were obtained in the cardiac myocytes of control mice. These results suggest that cytokine-gp130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardiac myocytes.

Angiotensinogen↗
PubMed1998

A Case of Multiple Juvenile Papillomatosis of the Breast and Its Immunohistochemical Pathology.

Juvenile papillomatosis(JP)is a benign proliferative disease of the breast affecting young women. Some patients with JP develop breast carcinoma. We recentlytreated and followed a case of JP in a 16-year-old female, and studied its immunohistochemical characteristics. The patient noticed a small tumor, 5 mm in diameter, in the periareolar region on the medial side of the right breast. She underwent an excisional biopsy and pathology demonstrated JP. However, 6 months later, two new lesions were discovered by routine echogram examination, and were later excised. Immunohistochemistry demonstrated that the JP tumors were negative for estrogen receptor, but positive for progesterone receptor, epidermal growth factor receptor and erbB-2. In addition, tests for p53 were negative and Rb protein was normally expressed. Immunohistochemical analysis suggested that an abnormality in estrogen receptor is important in the pathogenesis of JP, and that the patient had a relatively high risk of developing breast carcinoma, since her JP is multicentric and recurrent. The present study also suggests that immunohistochemical pathology may be beneficial in assessing the malignant potential of JP.

Journal Article↗
PubMed1998

Multiple digit formation in Xenopus limb bud recombinants.

We prepared recombinant limb buds of Xenopus tadpoles by grafting a mesenchyme mass of the hindlimb bud. The Xenopus recombinant limb buds with dissociated and reaggregated mesenchyme developed more than 30 digits with cartilage segmentation, while those with undissociated mesenchyme developed a limb with normal cartilage pattern. Before the formation of multiple digits, a patchy expression pattern of fgf-8, an AER marker, was observed in the distal region of recombinant limb buds. shh, a ZPA (zone of polarizing activity) marker, was expressed broadly in the distal region of recombinants. Recombinant limb buds with the reaggregated mesenchyme of anterior halves formed anterior digits with claws, and those with the mesenchyme of posterior halves formed posterior digits without claws. The temporal and spatial changes in the potency of multiple digit formation are discussed with reference to the regenerative capacity of Xenopus limb buds.

Animals↗
PubMed1998

CP-060S interacts with three principal binding sites on the L-type Ca2+ channel.

CP-060S, (-)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxypheny1]-3-[3-[N-met hyl-N-[2-(3,4-methylenedioxyphenoxy)ethyl]amino]propyl]-1,3-thi azolidin-4-one hydrogen fumarate is a novel cardioprotective drug, which is able to prevent Na+-, Ca2+-overload and also has Ca2+ channel blocking activity. The latter action of CP-060S was characterized by radioligand binding experiments with rat cardiac membranes in terms of the interaction with the three principal binding sites on the L-type Ca2+ channel, which bind such drugs as the 1,4-dihydropyridines, phenylalkylamines and benzothiazepines. CP-060S exhibited complete and concentration-dependent inhibition of [3H](+)-PN200-110, [3H](-)-desmethoxyverapamil and [3H]cis-(+)-diltiazem binding to their specific binding sites. Saturation studies showed that CP-060S increased the Kd of [3H](+)-PN200-110 and [3H](-)-desmethoxyverapamil without causing a significant change in the maximum binding density. The dissociation kinetics of the three radioligands were accelerated by CP-060S. These results suggest that CP-060S interacts with a novel binding site on the L-type Ca2+ channel and has a negative allosteric interaction with the three principal binding sites for the 1,4-dihydropyridines, phenylalkylamines and benzothiazepines.

Animals↗
PubMed1998

Inhibitory regulation of inhibin gene expression by thyroid hormone during ovarian development in immature rats.

To explore the role of the thyroid gland in ovarian development during the initiation process of puberty, we examined the effects of hypothyroidism on the secretion of ovarian hormones during equine chorionic gonadotropin (eCG)-induced follicle development in immature female rats. Immature rats at 22 days of age were thyroidectomized (Tx) to cause hypothyroidism and then given a single s.c. injection of 5 IU eCG at 26 days of age to induce normal first ovulation. The blood samples were collected at 0, 24, and 48 h after eCG treatment to measure inhibin and estradiol by radioimmunoassay. Serum inhibin and estradiol levels in eCG-primed Tx animals were significantly higher at 24 and 48 h after eCG treatment than those in controls (eCG treated non-Tx rats). The number of healthy follicles larger than 400 microns in diameter and ovarian weight were significantly increased in Tx rats at 48 h after eCG treatment, compared to those in controls. The number of oocytes which are ovulated by an injection of human chorionic gonadotropin (10 IU) was significantly increased on the day after eCG treatment, compared to that of eCG treated non-Tx rats. The increments in both hormones levels, the number of large antral follicles, and ovarian weight in eCG-primed Tx animals were suppressed up to control levels with daily administrations of 5.0 micrograms thyroxine (T4) for 6 days during 22 to 27 days of age. The expression of mRNAs for inhibin alpha and beta A subunits increased in eCG-primed Tx rats at 48 hr after eCG treatment, and the increase in inhibin mRNAs was suppressed by T4 treatment up to control levels. These results clearly demonstrate that thyroid hormone takes part in an inhibitory regulation of ovarian hormonal secretion and folliculogenesis in eCG-primed immature female rats.

Animals↗
PubMed1998

Primary bronchopulmonary fibrosarcoma: report of a case.

We herein report a case of primary bronchopulmonary fibrosarcoma in a 70-year-old man. The patient was referred to our hospital for investigation of hemosputum and an abnormal shadow. On admission, chest radiograph and computed tomography scan showed a mass lesion in right S3 and an infiltrative shadow in the right upper lobe. Transbronchial biopsy specimens showed findings of malignancy, and adenocarcinoma was suspected. A right pneumonectomy was performed, and pathologic examination confirmed a diagnosis of fibrosarcoma. The patient had an uneventful recovery and no sign of recurrence has been found in the year since his operation, although strict follow-up is essential.

Aged↗
PubMed1998

Primary sclerosing pancreatitis and cholangitis.

CONCLUSION: The clinical course of our patient suggests the association between chronic pancreatitis and primary sclerosing cholangitis (PSC), as well as the usefulness of prednisolone for the treatment of this condition. BACKGROUND: Although alterations in the pancreatic duct have been reported, the association between chronic pancreatitis and PSC remains uncertain. METHODS AND RESULTS: A long-term follow-up case of chronic pancreatitis accompanied by PSC is presented. A 58-yr-old man complaining of epigastric distress was admitted to our hospital in July 1990. Endoscopic retrograde cholangio-pancreatography (ERCP) showed a stricture of the distal common bile duct and a narrowing of the main pancreatic duct (MPD) with mild ectasia of its branches in the head of the pancreas. ERCP taken in June 1992 revealed localized narrowings in both the right and the left main hepatic ducts, and irregularity of the MPD through the entire pancreas. An ERCP taken in June 1996 showed a progression of the narrowings of the bile ducts. The patient was diagnosed as having chronic pancreatitis accompanied by PSC. ERCP revealed a remarkable improvement of the bile ducts after 4 wk of treatment with prednisolone.

Anti-Inflammatory Agents↗