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Biomedical subjects

H Kato

Publications and source records attributed to H Kato.

At least 271 records · Page 15Linked to original sources

[Drug consultation for a terminal cancer patient at home care-management of dyspnea and pain by morphine].

We studied on the points of that a management of dyspnea and pain by morphine for a terminal cancer patient at Home care. It was suggested that a necessary on management of symptoms for a terminal cancer patient before home drug therapy, a education to patient and his family by drug consultation before and after home drug therapy, a confirmation of dyspnea and pain for a terminal cancer patient from one drug to the next, and a importance of communication between medical staffs.

Dyspnea↗

Production of tissue factor pathway inhibitor in cardiomyocytes and its upregulation by interleukin-1.

Tissue factor pathway inhibitor (TFPI) is a protease inhibitor that regulates tissue factor (TF)--initiated coagulation. We report here that cardiomyocytes express TFPI and the expression could be increased by Interleukin-1(IL-1beta). The TFPI expression in cardiomyocytes was confirmed by Northern blotting with rat cardiomyocytes and also by immunostaining with anti-TFPI antibody on human heart specimens from patients either with sarcoidosis, myocarditis or myocardial infarction. The regulation of TFPI expression in cardiomyocytes differs from that in endothelial cells because TFPI expression is not induced in human endothelial cells by IL-1beta.

Animals↗

[Guidelines for antibiotic agents in the field of respiratory tract surgery].

This paper provides information on the use of antibiotic agents during the postoperative period from three aspects. 1) It is important to evaluate the risk factors of postoperative infection based on the patient's preoperative condition. Diseases treated with respiratory tract surgery are frequently caused by heavy smoking. Therefore it must be remembered that the patients may have low respiratory function. 2) In the prevention of postoperative infection, the special circumstances after respiratory surgery (e.g., the disintegration of the clearance system in the airway caused by the dissection of lymph nodes, the suppression of respiration, and cough caused by thoracotomy accompanied by resection of the ribs) must be considered. Therefore we usually administer antibiotic agents for 3 to 4 days. In general, we select second-generation cephalosporins, be cause gram-negative rod infection frequently occurs. 3) Postoperative infection is diagnosed based on fluctuations in fever, laboratory data (number of white blood cells and C-reactive protein), chest X-ray findings, and properties of drainage fluid. When bacteria are not identified, we must consider MRSA as a gram-positive bacterium and Pseudomonas aeruginosa as a gram-negative bacterium. After the identification of bacteria causing the infection, the antibiotic agents may be changed based on the results of sensitivity tests. The appropriate usage of antibiotic agents in the field of respiratory tract surgery is discussed based on actual clinical experience in our department.

Anti-Bacterial Agents↗

New molecular tumor markers for endometrial cancer.

Although the International Federation of Gynecology and Obstetrics officially changed the classification system of endometrial cancer from a clinically staged to a surgically staged disease in 1988, optimal management of patients with endometrial cancer is still controversial. Gynecologists happen to experience that patients with tumors that are identical in grade and stage often have significantly different clinical outcomes or responses to therapy. In order to identify an objective biological factor correlating with tumor aggressiveness, many tumor markers have been investigated. So far, CA125 is one of the most reliable tumor marker for adenocarcinoma of the uterus and frequently used in a clinical setting. Recently, with the advent of molecular biological techniques, many genes and regions of the genome related to endometrial cancer have been identified. We undertook a genome-wide screening to detect genetic changes by comparative genomic hybridization (CGH) in primary endometrioid cancers, since CGH analysis provides comprehensive information concerning relative chromosomal losses and gains in tumors by a single hybridization. In this paper, the usefulness of serum tumor markers and the new promising molecular tumor markers for endometrial cancer are discussed.

Biomarkers, Tumor↗

Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation.

This study analyzes the effects and mechanisms of heme oxygenase-1 (HO-1)-mediated cytoprotection in rat livers exposed to cold preservation. In the first series, rats were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4 degrees C for 24 h, and then perfused ex vivo for 2 h. Livers pretreated with CoPP had significantly higher portal venous blood flow and increased total bile production, as compared with the ZnPP group. This correlated with histologic (Banff) criteria of hepatocyte injury/liver function. In the second series, rat livers were stored at 4 degrees C for 24 h or 40 h, and then transplanted into syngeneic recipients. After 24 h of preservation, 80% of rats bearing CoPP-pretreated liver grafts survived 21 days (vs. 50% in controls). After 40h of cold preservation, liver transplant survival at day 1, 7 and 21 for the CoPP group was: 100%, 71% and 57%, respectively (vs. 50%, 50% and 33% in controls). This correlated with improved hepatic function/histologic (Suzuki) criteria of hepatocyte injury after HO-1 overexpression (immunohistology/Western blots) by infiltrating macrophages. This study documents the potential utility of HO-1-inducing agents in preventing ischemia/reperfusion injury resulting from prolonged storage of liver transplants.

Animals↗

Element-selective single atom imaging.

Electron energy-loss spectroscopy (EELS) is widely used to identify elemental compositions of materials studied by microscopy. We demonstrate that the sensitivity and spatial resolution of EELS can be extended to the single-atom limit. A chemical map for gadolinium (Gd) clearly reveals the distribution of Gd atoms inside a single chain of metallofullerene molecules (Gd@C82) generated within a single-wall carbon nanotube. This characterization technique thus provides the "eyes" to see and identify individual atoms in nanostructures. It is likely to find broad application in nanoscale science and technology research.

Journal Article↗

One-dimensional metallofullerene crystal generated inside single-walled carbon nanotubes.

Electron microscope imaging for gadolinium metallofullerenes encapsulating in single-wall carbon nanotubes [(Gd@C82)n@SWNTs] identifies the single Gd atom encaged in each. The intermolecular distance between Gd@C82 is extremely regular, regarding the chains of Gd@C82 as novel one-dimensional crystals. Chemical state analysis of Gd atoms suggests evidence for charge transfer from Gd to either a fullerene cage or a nanotube. The slopes of the temperature dependence of electric resistance for the mat-like films of (Gd@C82)n@SWNTs and (C60)n@SWNTs are much steeper than that for empty SWNTs, suggesting the electron scattering due to the electrostatic potential from inside fullerenes playing an important role.

Journal Article↗

Identification of the phospholipid-binding site of human beta(2)-glycoprotein I domain V by heteronuclear magnetic resonance.

To understand the mechanism of the interaction between human beta(2)-glycoprotein I (beta(2)-GPI) and negatively charged phospholipids, we determined the three-dimensional solution structure of the fifth domain of beta(2)-GPI by heteronuclear multidimensional NMR. The results showed that the molecule is composed of well-defined four anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. Backbone dynamic analysis demonstrated significant mobility of the flexible loop on a subnanosecond time scale. Structural modeling of the nicked fifth domain, in which the Lys317-Thr318 peptide bond was specifically cleaved, revealed the importance of this long C-terminal loop for the interaction between beta(2)-GPI and negatively charged phospholipids. A titration experiment with the anionic surfactant SDS showed that this highly mobile loop, as well as the short beta-hairpin between betaC and betaD strands, which is rich in positively charged residues, specifically interact with the surfactant. The mobile loop, together with the surrounding positively charged residues, probably construct the binding site for negatively charged phospholipids such as cardiolipin.

Amino Acid Sequence↗

Postischemic changes in the immunophilin FKBP12 in the rat brain.

An immunosuppressant tacrolimus (FK506) protects against neuronal damage following cerebral ischemia. On the other hand, the major physiological role of the immunophilin FK506-binding protein-12 (FKBP12) is a modulation of intracellular calcium flux. Since an increase in intracellular calcium concentration is a major mediator of ischemic neuronal death, we investigated the changes in FKBP12 following cerebral ischemia in the rat. We induced focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery for 1 h, and global cerebral ischemia for 10 min by bilateral carotid artery occlusion combined with hypotension. The animals were killed at 4 h to 7 days after reperfusion. Immunohistochemistry was performed on paraffin sections using a monoclonal antibody raised against recombinant FKBP12. Immunoreactivity to FKBP12 in control brains was most pronounced in the CA1 subfield of the hippocampus and the striatum, the localization being primarily neuronal. Following focal ischemia, FKBP12 immunoreactivity decreased rapidly in the ischemic core by 4 h, but increased in surviving neurons in penumbra areas (4 h-7 days). Within an area of infarction, invading leukocytes and macrophages exhibited immunoreactivity to FKBP12 (3-7 days). Following global ischemia, FKBP12 immunoreactivity in CA1 neurons decreased after 1 day, and then it was lost between 2 and 7 days, although many CA1 neurons showed a transient increase in FKBP12 at 2 days. No FKBP12 immunoreactivity was observed in reactive glial cells. Thus, FKBP12 declined in dying neurons, whereas FKBP12 was upregulated in less severely injured neurons. The findings suggest that (1) FKBP12 plays an important role in the process of neuronal survival and death following cerebral ischemia, and (2) FKBP12 is involved in inflammatory reactions that occur within an area of infarction.

Animals↗

Identification of ERSE-II, a new cis-acting element responsible for the ATF6-dependent mammalian unfolded protein response.

Herp is a 54-kDa membrane protein in the endoplasmic reticulum (ER). The mRNA expression level of Herp is increased by the accumulation of unfolded proteins in the ER. Transcriptional changes designed to deal with this type of ER stress is called the unfolded protein response (UPR). Most mammalian UPR-target genes encode ER-resident molecular chaperones: GRP78, GRP94, and calreticulin. The promoter regions of these genes contain a cis-acting ER stress response element, ERSE, with the consensus sequence of CCAAT-N(9)-CCACG. Under conditions of ER stress, p50ATF6 (the active form of the transcription factor, ATF6) binds to CCACG when CCAAT is bound by the general transcription factor, NF-Y/CBF. Here, we report the genomic structure of human Herp and the presence of a new ER stress response element, ERSE-II, in its promoter region. The gene for Herp consists of eight exons, localized to chromosome 16q12.2-13. The promoter region contains a single ERSE-like sequence. In reporter gene assays, disruption of this cis-element resulted in a partial reduction of the transcriptional response to ER stress, suggesting that the element is functional for the UPR. These results also suggest the involvement of additional elements in the UPR. Further analysis, using an optimized plasmid containing an mRNA-destabilizing sequence, revealed ERSE-II (ATTGG-N-CCACG) as the second ER stress response element. Interestingly, ERSE-II was also dependent on p50ATF6, in a manner similar to that of ERSE, despite the disparate structure. The strong induction of Herp mRNA by ER stress would be achieved by the cooperation of ERSE and ERSE-II.

Activating Transcription Factor 6↗

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy.

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Antibiotics, Antineoplastic↗

Possible association of thioredoxin and p53 in breast cancer.

Expression of thioredoxin (TRX), a dithiol-reducing enzyme, and mutations of p53 have been detected in various cancer tissues. We recently reported that TRX-dependent redox regulation plays a crucial role in DNA binding activity of p53. In this study, we investigated the possibility of functional association between TRX and p53 in breast cancer. First, we examined the expression of TRX and mutated p53 in 100 primary breast cancer tissues by immunohistochemistry. Expression of TRX was detected in cases of 84/100 (84%) and expression of p53, which means existence of mutated p53, in cases of 63/100 (63%). TRX positive cases was 89% (56/63) in mutant p53 positive cases. Next, we examined the expression of TRX and p53 in breast cancer cell line MCF-7 cells after CDDP treatment or irradiation. CDDP treatment or irradiation augmented expression of TRX and p53 in MCF-7 cells by western blotting. Immunofluorescence cell analysis by confocal microscopy showed that CDDP treatment induced translocation of TRX into nuclei. These results suggest the possible association of TRX with p53-dependent function including DNA repair in breast cancer.

Adult↗

Phosphorylation of protein phosphatase-1 inhibitors, inhibitor-1 and DARPP-32, in renal medulla.

Inhibitor-1 and DARPP-32 (dopamine and cAMP-regulated phosphoprotein, Mr 32 kDa) are each phosphorylated by cAMP-dependent protein kinase, resulting in their conversion to potent inhibitors of protein phosphatase-1. Protein phosphatase-1 is involved in the regulation of Na(+) reabsorption from renal tubule by modulating the activity of Na(+),K(+)-ATPase. In this study, we have investigated the regulation of inhibitor-1 and DARPP-32 phosphorylation in slices of renal medulla. Activation of cAMP-dependent protein kinase by forskolin and 8-bromo-cAMP increased the level of phosphorylated inhibitor-1. Okadaic acid (1 microM), used to inhibit protein phosphatase-2A, increased the level of phosphorylated inhibitor-1, but cyclosporin A had no effect. DARPP-32, like inhibitor-1, was phosphorylated by cAMP-dependent protein kinase and dephosphorylated only by protein phosphatase-2A. These data demonstrate that the phosphorylation of inhibitor-1 and DARPP-32 is regulated by the balance of phosphorylation by cAMP-dependent protein kinase and dephosphorylation by protein phosphatase-2A in renal medulla. Furthermore, the phosphorylation step is regulated by pharmacological stimuli such as activation of beta(1)-adrenoceptors and dopamine D1 receptors.

8-Bromo Cyclic Adenosine Monophosphate↗

Molecular evolutionary analysis of the complete nucleotide sequence of hepatitis B virus (HBV) in a case of HBV infection acquired through a needlestick accident.

To elucidate needlestick transmission of hepatitis B virus (HBV), strains isolated from 1 physician who acquired HBV infection through a needlestick accident and 3 patients with chronic hepatitis B (donor patients A, B, and C) were tested using molecular evolutionary analysis based on full-length HBV genomic sequences. Nucleotide sequences of these isolates were aligned with 55 previously reported full-length genomic sequences. Genetic distances were estimated using the 6-parameter method, and phylogenetic trees were constructed using the neighbor-joining method. Strains isolated from patient A and the recipient pair were clustered within a closer range of evolutionary distances than were strains recovered from the recipient pair and patients B and C. Furthermore, strains from patient A and the recipient were also clustered on the S gene sequences of HBV. These results demonstrated that patient A alone was the source of direct transmission to the recipient. This approach can be used to investigate the transmission route of HBV.

Adult↗

Expression of microglial response factor-1 in microglia and macrophages following cerebral ischemia in the rat.

Microglial response factor-1 is a newly isolated microglial gene, which encodes a Ca(2+) binding protein MRF-1 expressed in microglia and macrophages. We induced 1 h of focal cerebral ischemia or 10 min of global cerebral ischemia in the rat, and investigated the expression of MRF-1 immunoreactivity following ischemia. MRF-1 was present in resting microglia and was upregulated in response to microglial activation. MRF-1 was localized to all the cells of the mononuclear phagocyte system (microglia, monocytes, and perivascular cells) that appeared in the ischemic brain.

Animals↗

Immunological aspects of rat models of HTLV type 1-infected T lymphoproliferative disease.

The level of host immune responses against human T cell leukemia virus type 1 (HTLV-1) varies among HTLV-1-infected individuals. In the present study, we investigate the role of host immunity on HTLV-1 leukemogenesis in vivo by using animal models. At first, we examined the effect of the routes of HTLV-1 transmission on the host anti-HTLV-1 immune responses. When immune competent adult rats were inoculated with HTLV-1-infected cells, the orally infected rats were persistently infected with HTLV-1 without humoral and cellular immune responses against HTLV-1, whereas all intravenously or intraperitoneally inoculated rats showed significant levels of immune responses. Next, we examined in vivo tumorigenicity of HTLV-1-immortalized cells in the absence of T cell immunity, by using athymic F344/N Jcl-rnu/rnu (nu/nu) rats. When inoculated into nu/nu rats, not all but some HTLV-1-immortalized rat cell lines including syngeneic FPM1-V1AX could grow and form T cell lymphoma in vivo. This syngeneic lymphoma formation was inhibited by adoptively transferred immune T cells. Furthermore, immunocompetent rats allowed in vivo growth of HTLV-1-infected lymphoma, when treated with antibodies that block costimulatory signals for T cell activation. These observations indicated that (1) host anti-HTLV-1 immunity can be affected by the conditions of the primary infection, (2) under the low pressure of anti-HTLV-1 immunity, some HTLV-1-infected cell clones grow in vivo, and (3) T cell immunity is required for in vivo surveillance against these HTLV-1-infected cell clones.

Animals↗

Evidence for early aging in the mucosal immune system.

Despite recent advances in the cellular and molecular analysis of induction and regulation of mucosal immune responses, little is yet known about differences which occur in aging. To address this important issue, we have compared the mucosal and systemic immune responses of aged (12- to 14-mo- or 2-year-old) and young adult (6- to 8-wk-old) C57BL/6 mice. Both aged and young mice were immunized weekly with three oral doses of 1 mg of OVA and 10 microg of cholera toxin (CT) as mucosal adjuvant. Both groups of mice over 1 or 2 years of age showed reduced levels of Ag-specific mucosal or systemic immune responses at day 21. An Ag-specific B cell enzyme-linked immunospot assay confirmed these results at the cellular level. When the Ag-induced cytokine responses were examined at both protein and mRNA levels, CD4(+) T cells from spleen and Peyer's patches of young adult mice revealed elevated levels of IL-4 production; however, these cytokine responses were significantly diminished in aged mice. In contrast to mucosal immunization, mice s. c. immunized with OVA plus CT resulted in impaired OVA-specific but intact CT B subunit-specific immune responses in 12- to 14-mo-old mice although the responses to both Ags were depressed in 2-year-old mice. These results provide the first evidence that the development of age-associated alterations possibly occurs earlier in the mucosal immune system than in the systemic immune compartment.

Adjuvants, Immunologic↗