Biomedical subjects

K Nishimura

Publications and source records attributed to K Nishimura.

At least 55 records · Page 3Linked to original sources

PubMed2002

Beta-adrenergic receptor-mediated growth of human airway epithelial cell lines.

Abnormal growth of airway epithelium and the resultant thickening of airway walls may produce narrowing of airway calibre, thereby contributing to deterioration of bronchoconstriction in chronic obstructive pulmonary disease (COPD). Beta2-adrenergic agonists have been widely used for the treatment of COPD, but their effects on the growth of airway epithelial cells is unknown. Growth of three human airway epithelial cell lines was studied in vitro. Exposure to salbutamol in serum-free medium increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide reduction and intracellular deoxyribonucleic acid (DNA) contents in 16-human bronchial epithelium (16-HBE) cells and NCI-H292 cells, but not in A549 cells. The growth-promoting effect of salbutamol in 16-HBE cells was equipotent to 10% foetal bovine serum and was inhibited by propranolol and a cyclic adenosine monophosphate (cAMP) antagonist, Rp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt (Rp-cAMPS). Likewise, forskolin and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) caused cell growth and DNA synthesis. Western blot analysis showed that salbutamol, forskolin, and 8-Br-cAMP each induced expression of the phosphorylated form of mitogen-activated protein (MAP) kinase, and that the salbutamol-induced phosphorylation was inhibited by propranolol, Rp-cAMPS, and the MAP kinase-kinase inhibitor PD98059. These results suggest that in certain airway epithelial cell lines stimulation of beta2-adrenergic receptors and the consequent production of cyclic adenosine monophosphate may upregulate cell growth, probably through activation of the mitogen-activated protein kinase cascade.

Adrenergic beta-Agonists↗

PubMed2002

Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation.

It is possible that enkephalins are involved in the pain-modulating mechanism in the spinal cord. Enkephalins, however, are short-lived, being rapidly degraded by various endogenous enzymes. Many substances that inhibit enkephalin-degradation have been investigated and it has been reported that some inhibitors (e.g. kelatorphan and RB101) alone showed anti-nociceptive activity. We found an endogenous factor that modulated enkephalin-degrading activity and purified it from bovine spinal cord based on its inhibitory activity toward enkephalin-degrading enzymes. Structural analysis revealed the factor to be Leu-Val-Val-Tyr-Pro-Trp-Thr and it was named spinorphin. It has been found that spinorphin inhibited the activity toward various enkephalin-degrading enzymes from monkey brain, especially dipeptidyl peptidase III (DPPIII, Ki=5.1 x 10(-7) M). Recently we reported that this inhibitor significantly inhibited bradykinin (BK)-induced nociceptive flexor responses. Importantly, the mode of inhibition to BK-responses by spinorphin was different from the case with morphine. The morphine-induced blockade of BK-response was attenuated by pertussis toxin treatment, whereas that of spinorphin was not. We also have reported roles for spinorphin in inflammation. Spinorphin significantly inhibited the functions of polymorphonuclear neutrophils (PMNs) by suppressing the binding of fMLF to its receptor on PMNs. Further, this inhibitor suppressed the carrageenan-induced accumulation of PMN in mouse air pouches after intravenous administration. These results indicate that spinorphin may be an endogenous anti-inflammatory regulator. The possible role of spinorphin and its analog as regulators in pain and inflammation will be discussed.

Aminopeptidases↗

PubMed2002

Concentrated platelets harvesting before cardiopulmonary bypass improved cardiac and pulmonary function.

BACKGROUND: Sequestration of concentrated platelets (P-con) during cardiopulmonary bypass (CPB) has been performed to preserve platelet function after cardiac surgery. Since P-con also harvests leukocytes simultaneously, there might be a possibility that the inflammatory effects or ischemia-reperfusion injuries associated with CPB, such as a cardiac or pulmonary dysfunction after cardiac surgery, are reduced with its use. METHODS: We retrospectively evaluated 53 patients who underwent cardiac surgery after the introduction of the P-con technique at our institute. There were 20 patients in the P-con group and 33 patients in the control group in whom concentrated platelet were not harvested. RESULTS: The patients characteristics and preoperative cardiac and pulmonary function did not differ between the two groups. The percentages of platelets and leukocytes sequestrated were 20.2+/-5.4% and 8.5+/-3.9% of the total estimated circulating cell counts, respectively. There were no significant differences in the postoperative dose of dopamine used, cardiac index, pulmonary capillary wedge pressure or intubation period between the two groups. However, the stroke volume index (p=0.005), left ventricular stroke work index (p=0.002), and ratio of the arterial oxygen tension to the inspired fraction of oxygen on extubation (p=0.02) were significantly greater in the P-con group as compared with those in the control. CONCLUSIONS: P-con improved cardiac and pulmonary function after CPB. Simultaneous sequestration of platelets and leukocytes by P-con during CPB may contribute to the improvement of cardiac and pulmonary function after cardiac surgery.

Aged↗

PubMed2002

Left renal artery aneurysm with left accessory renal arteries. A case report.

A 57-year-old man was suspected of having a left renal artery aneurysm on enhanced computed tomography (CT) findings. Aortic angiography showed 3 left renal arteries with an aneurysm of the distal main renal artery. A 3 mm upper pole renal artery which crossed near the aneurysm was preserved. Dissection of the aneurysm was followed by arterial reconstruction with end-to-end anastomosis.

Anastomosis, Surgical↗

PubMed2002

[Total arch replacement using prior selective cerebral perfusion].

Prior selective cerebral perfusion is the method whereby selective cerebral perfusion and systemic perfusion start almost simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization owing to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic canula. Twenty-seven consecutive patients underwent total arch replacement for degenerative aortic arch aneurysm using prior selective cerebral perfusion from 1992 to 2001. Surgical death (within 1 month after operation) was 2 cases (7.4%), in-hospital death was 5 cases (18.5%). Systemic circulatory arrest time is almost equal to the time which distal anastomosis takes. The time was 81.4 +/- 24.3 minutes. Selective cerebral perfusion time was 194.9 +/- 30.9 minutes. Extracorporeal circulation time was 280.6 +/- 55.3 minutes. The time for emergence from anesthesia was 6.0 +/- 2.7 hours. Permanent neurologic dysfunction which was thought to occurred within 48 hours after surgery was noted in 1 case (3.7%). Postoperative survival at 8 years was 73.3%. There was 1 arch aneurismal related accident. Prior selective cerebral perfusion may be useful for avoiding cerebral embolization.

Aged↗

PubMed2002

[Inferior vena cava cannulation using Forgaty catheter for partial cardiopulmonary bypass].

Partial cardiopulmonary bypass is adopted in operation for aneurysm of descending aorta or DeBakey IIIb dissection. Cannulation from left common femoral vein to inferior vena cava (IVC) is often difficult because of operative position and anatomical relation of iliac veins to IVC. In this paper, IVC cannulation using Forgaty catheter is reported to be easy and safe for prevention of IVC perforation.

Aortic Aneurysm↗

PubMed2001

Identification of species in Aspergillus section Flavi based on sequencing of the mitochondrial cytochrome b gene.

The partial sequences of the mitochondrial (mt) cytochrome b gene (402 bp) were determined for species of Aspergillus section Flavi. On the basis of identities of DNA sequences, 77 strains were divided into seven DNA types, from D-1 to D-7. The type strains of A. sojae, A. parasiticus, A. flavus and A. oryzae together, A. tamarii, and A. nomius were placed in DNA types D-1. D-2, D-4, D-5 and D-7, respectively. These species could be differentiated from each other. Furthermore, two other DNA types, D-3 and D-6 were found. DNA type D-3 was closely related to A. parasiticus (D-2) and included one strain that deposited as A. flatus var. flavus and produced aflatoxins B and G. DNA types D-6 included one strain named A. flavus and closely related to A. tamarii. The observations of conidial wall texture by SEM (Scanning Electron Microscopy) supported the relationships derived from the cytochrome b gene. The production of aflatoxins was also examined. Using the DNA sequence of cytochrome b gene, several strains were reidentified. The derived amino acids sequences were all the same in the studied strains. The mt cytochrome b gene is useful and reliable in distinguishing and identifying the species in Aspergillus section Flavi.

Amino Acid Sequence↗

PubMed2001

Total synthesis of (-)-neplanocin a by using lithium thiolate-initiated Michael-aldol tandem cyclization reaction.

(-)-Neplanocin A (1), S-adenosylhomocystein hydrolase inhibitor, was synthesized. The characteristic of this synthesis is a stereoselective construction of five-membered ring of neplanocin A by intramolecular aldol reaction of the lithium enolate that was generated by conjugate addition of lithium thiolate. TBS-protected chiral omega-oxo-alpha,beta-unsaturated ester 16, which was prepared from D-mannitol, was treated with 1.2 equiv of lithium benzylthiolate in THF at -20 degrees C to give three separable cyclization products in good yields and stereoselectivity. After conversions of protective groups, the benzylsulfanyl part of 21 was removed by oxidation to sulfoxide and subsequent thermal elimination to give the requisite double bond. Through the functional group transformations of 30, total synthesis of (-)-neplanocin A (1) was accomplished.

Adenosine↗

PubMed2001

Potential mechanism for the effects of dexamethasone on growth of androgen-independent prostate cancer.

BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has clinical benefit in patients with hormone-refractory prostate cancer (HRPC), but the mechanisms responsible for its effects are unknown. The nuclear factor-kappaB (NF-kappaB)-dependent cytokine interleukin (IL) 6 (IL-6) is thought to stimulate growth of HRPC. Because dexamethasone interferes with NF-kappaB activation, we determined whether dexamethasone inhibits prostate cancer growth by working through the glucocorticoid receptor (GR) to interfere with NF-kappaB-IL-6 pathway. METHODS: Three human prostate cancer cell lines (DU145, PC-3, and LNCaP) were assessed for GR expression and responsiveness to dexamethasone. Levels of GR, NF-kappaB, and the cytoplasmic NF-kappB inhibitor IkappaBalpha were determined by western blotting and of IL-6 by enzyme immunoassay. The subcellular localization of NF-kappaB was analyzed by immunofluorescence. The effects of dexamethasone (thrice weekly injections of 1 microg/mouse) on DU145 xenografts in nude and severe combined immunodeficient (SCID) mice were evaluated. GR expression in human prostate cancers was assessed by immunohistochemistry. All statistical tests were two-sided. RESULTS: Dexamethasone dose dependently decreased GR levels and inhibited the growth of DU145 and PC-3 but not LNCaP cells (DU145 cells, P< .001; PC-3 cells, P = .009). Dexamethasone increased IkappaBalpha protein levels and the cytosolic accumulation of NF-kappaB in DU145 cells and decreased secreted IL-6 levels to 37 pg/mL (95% confidence interval [CI] = 33 pg/mL to 41 pg/mL), compared with 164 pg/mL (95% CI = 162 pg/mL to 166 pg/mL) secreted by ethanol-treated control cells. Dexamethasone inhibited the growth of DU145 xenografts in nude (P = .006) and SCID (P = .026) mice without affecting GR levels. Eight of 16 human prostate cancers expressed GR at high levels (>or=30% GR-positive cells). CONCLUSION: Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.

Androgens↗

PubMed2001

Evaluation of the mechanical destructive force in the stomach of dog.

Orally administered dosage forms receive a destructive force in the gastrointestinal (GI) tract due to peristalsis. In this study, the destructive force was measured with a 'destructive force-dependent release system' (DDRS). DDRS is a press-coated tablet with an extremely brittle outer layer composed of highly hydrophobic Teflon(R) powder, which is molded with a weak compression force. Teflon(R) powder forms a porous but water-impermeable layer around the core tablet. A marker drug contained in the core tablet is released only when the tablet receives a force larger than its pre-determined crushing strength. A comparison of the physiological conditions in the GI tract of dogs with those of humans, including the destructive force against tablets in the stomach, helps us to understand their difference in bioavailability of oral dosage forms. With DDRS, it is possible to evaluate the destructive force of both human and dog stomach using the same method. Therefore, the destructive force data from human and dog can be directly compared. The destructive force in the dog stomach was evaluated to be 3.2 N, which was considerably stronger than that of humans.

Animals↗

PubMed2001

Initial effects of the left ventricular repair by plication may not last long in a rat ischemic cardiomyopathy model.

BACKGROUND: Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood. METHODS AND RESULTS: Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E(max)) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E(max) gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively. CONCLUSIONS: Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.

Animals↗

PubMed2001

Gelatin sheet incorporating basic fibroblast growth factor enhances healing of devascularized sternum in diabetic rats.

BACKGROUND: Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic patients. We have reported that a gelatin sheet that incorporates basic fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in normal rats. This study evaluated the effects of the above method for sternal healing in diabetic animals. METHODS AND RESULTS: Diabetic Wistar rats with blood glucose levels >400 mg/dL and body-weight loss >20 g were established by a single intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated bFGF (100 microg/sheet) on the posterior table of the sternum (FGF group, n=9) or no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the preoperative level (106+/-10% versus 82+/-9%, P<0.01), and marked angiogenesis was also observed around the sternum in the FGF group (30.5+/-3.2 versus 15.8+/-2.7 vessels/unit area, P<0.01). Deep sternal wound complications developed in 5 control rats but only in 1 rat in the FGF group (P<0.05). In the FGF group, histological examination showed improved sternal healing (excellent in 6 rats and slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray absorptometry was greater in the FGF group (75.9+/-18.1 versus 48.9+/-10.7 mg, P<0.05). Bone mineral density of the sternum was similar between the 2 groups. CONCLUSIONS: A gelatin sheet that incorporates bFGF may offset sternal ischemia and accelerate sternal bone regeneration and healing, even in diabetic patients.

Administration, Topical↗

PubMed2001

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Journal Article↗

PubMed2001

Dopamine-dependent synaptic plasticity in the striatal cholinergic interneurons.

The striatum, the input stage of the basal ganglia, is a critical brain structure for the learning of stimulus-response habits as well as motor, perceptual, and cognitive skills. Roles of dopamine (DA) and acetylcholine (ACh) in this form of implicit memory have long been considered essential, but the underlying cellular mechanism is still unclear. By means of patch-clamp recordings from corticostriatal slices of the mouse, we studied whether the identified striatal cholinergic interneurons undergo long-term synaptic changes after tetanic stimulation of cortico- and thalamostriatal fibers. Electrical stimulation of the fibers revealed a depolarizing and hyperpolarizing postsynaptic potential in the striatal cholinergic interneurons. The early depolarizing phase was considered to be a cortico/thalamostriatal glutamatergic EPSP, and the hyperpolarizing component was considered to be an intrastriatally evoked GABAergic IPSP. Tetanic stimulation of cortico/thalamostriatal fibers was found to induce simultaneously occurring long-term potentiation (LTP) of the EPSPs as well as the disynaptically mediated IPSPs. The induction of LTP of EPSP required a rise in intracellular Ca(2+) concentration and dopamine D(5), but not D(2) receptor activation. Ca(2+)-permeable AMPA receptors might also play a part in the LTP induction. Blockade of NMDA receptors, metabotropic glutamate receptors, or serotonin receptors had no significant effects. The long-term enhancement of the disynaptic IPSPs was caused by a long-term increase in the occurrence rate but not the amplitude of disynaptically mediated IPSP in the striatal cholinergic interneurons. This dual mechanism of synaptic plasticity may be responsible for the long-term modulation of the cortico/thalamostriatal synaptic transmission.

Acetylcholine↗

PubMed2001

Identification, classification and phylogeny of the Aspergillus section Nigri inferred from mitochondrial cytochrome b gene.

The partial mitochondrial cytochrome b gene from 32 strains of 12 species belonging to Aspergillus section Nigri was amplified by the polymerase chain reaction and sequenced directly. Using 402 nucleotide characters, nucleotide-based and amino acid-based phylogenetic trees were inferred and the genetic divergence among the species was evaluated. Based on analyses of the 402-bp nucleotide and 133-amino acid sequences, strains were divided into 11 DNA types and five amino acid types. Aspergillus niger and Aspergillus awamori showed different amino acid sequences. A. niger clade included A. niger var. niger and Aspergillus ficuum. A. awamori clade included A. awamori, Aspergillus phoenicis, Aspergillus pulverulentus, Aspergillus tubingensis, Aspergillus foetidus, and two varieties of A. niger, var. nanus and var. intermedius. Two varieties of A. niger will be reclassified. One strain of A. phoenicis and one strain of Aspergillus carbonarius were reidentified.

Aspergillus↗

PubMed2001

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗

PubMed2001

Crystallization and preliminary X-ray diffraction analysis of NADP-dependent glyceraldehyde-3-phosphate dehydrogenase of Synechococcus PCC 7942.

The NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Synechococcus PCC 7942 was crystallized in two different forms by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant. Form I crystals were hexagonal, space group P6(5) or P6(1), with unit-cell parameters a = b = 91.1, c = 428.6 A, gamma = 120 degrees. Form II crystals were monoclinic, space group C2, with unit-cell parameters a = 152.3, b = 80.9, c = 213.6 A, beta = 103.1 degrees. Native data were collected from a frozen crystal of form I to a resolution of 2.8 A using synchrotron radiation at SPring-8, whereas form II crystals were easily damaged by radiation at room temperature and increased mosaicity in cryoprotectant solutions. A molecular-replacement solution of the form I crystal was obtained in space group P6(5) using the program AMoRe and the structure of the NAD-dependent GAPDH from Bacillus stearothermophilus.

Crystallization↗

PubMed2001

Characterization of monoclonal antibodies against ascorbate peroxidase isoenzymes: purification and epitope-mapping using immunoaffinity column chromatography.

We have developed three monoclonal antibodies against spinach chloroplastic (chl-mAb3 and chl-mAb6) and cytosolic (cyt-mAb1) ascorbate peroxidase (APX) isoenzymes to analyze the cross-reactivity and the structure of the epitopes for each monoclonal antibody. All three antibodies reacted specifically with their respective isoenzymes, but none cross-reacted with the others. Immunoreactive fragments in proteolytic recombinant APX isoenzymes were detected by means of the absorption on the corresponding immunoaffinity column. The cyt-mAb1 reacted with a peptide fragment containing the distal His region obtained by the lysyl endopeptidase digestion. The chl-mAb6 was capable of binding to the fragment, D-I-K-E-K-R, which is consistent with an inherent region of chloroplastic isoenzymes. No fragments reacting to the chl-mAb3 could be found in this study, suggesting that the chl-mAb3 recognizes a conformationally constituted epitope of the chloroplastic APX molecule, which may be destroyed by the enzymatic cleavage. We concluded that the peptides identified as epitopes are characteristic evidence of monoclonal antibodies.

Amino Acid Sequence↗