PubMed Health⌕ Search

Biomedical subjects

M Nishimura

Publications and source records attributed to M Nishimura.

At least 325 records · Page 18Linked to original sources
PubMed1999

Multifocal polyradiculoneuropathy and carcinoma of the thymus.

We studied a patient with polyradiculoneuropathy with anaplastic carcinoma of the thymus. Motor manifestations dominated. Postmortem examinations indicated that the primary changes were in the spinal nerve roots, peripheral nerves and, possibly, the spinal anterior horn cells. The posterior funiculi and posterior root ganglia were also affected, implying multifocal and multiphasic degeneration. This unusual polyradiculoneuropathy is a form of carcinomatous neuropathy.

Aged↗
PubMed1999

PKA-mediated phosphorylation of the human K(ATP) channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation.

ATP-sensitive potassium (K(ATP)) channels play important roles in many cellular functions such as hormone secretion and excitability of muscles and neurons. Classical ATP-sensitive potassium (K(ATP)) channels are heteromultimeric membrane proteins comprising the pore-forming Kir6.2 subunits and the sulfonylurea receptor subunits (SUR1 or SUR2). The molecular mechanism by which hormones and neurotransmitters modulate K(ATP) channels via protein kinase A (PKA) is poorly understood. We mutated the PKA consensus sequences of the human SUR1 and Kir6.2 subunits and tested their phosphorylation capacities in Xenopus oocyte homogenates and in intact cells. We identified the sites responsible for PKA phosphorylation in the C-terminus of Kir6.2 (S372) and SUR1 (S1571). Kir6.2 can be phosphorylated at its PKA phosphorylation site in intact cells after G-protein (Gs)-coupled receptor or direct PKA stimulation. While the phosphorylation of Kir6.2 increases channel activity, the phosphorylation of SUR1 contributes to the basal channel properties by decreasing burst duration, interburst interval and open probability, and also increasing the number of functional channels at the cell surface. Moreover, the effect of PKA could be mimicked by introducing negative charges in the PKA phosphorylation sites. These data demonstrate direct phosphorylation by PKA of the K(ATP) channel, and may explain the mechanism by which Gs-coupled receptors stimulate channel activity. Importantly, they also describe a model of heteromultimeric ion channels in which there are functionally distinct roles of the phosphorylation of the different subunits.

ATP-Binding Cassette Transporters↗
PubMed1999

Pattern of expression of beta-defensins in oral squamous cell carcinoma.

Human beta-defensin (hBD)-1 and hBD-2 are antimicrobial peptides that have been detected in certain types of epithelia, including the skin and oral epithelia. It has been suggested that bacterial infection is an important factor in the process of carcinogenesis. The expression of hBDs in oral squamous cell carcinoma (SCC) may be down-regulated. We studied the pattern of expression of hBD-1 and hBD-2 mRNA in oral (SCC) cell lines and in tumor samples obtained from four patients with oral SCC who underwent surgical resection, by reverse transcription-polymerase chain reaction (RT-PCR). Human gingival epithelial (HGE) cells were used as the control. The effect of various inflammatory cytokines on hBD-1 and hBD-2 expression in the HGE cells and SCC cell lines, was also studied. hBD-1 mRNA was detected in the Ca-9, SCC-9 and HSC-4 cell lines, but not in the SAS and KB cell lines. hBD-2 mRNA was detected in all five cell lines. All four tumor samples expressed both hBD-1 and hBD-2 mRNA, although the mRNA level of each protein varied. These results indicate that SCCs in which hBD expression is downregulated, may be susceptible to bacterial infection.

Aged↗
PubMed1999

Expression level of Bcl-2 determines anti- or proapoptotic function.

Bcl-2 is an oncogene with antiapoptotic function. However, Bcl-2 is converted to a Bax-like death effector by caspases, suggesting that the expression of Bcl-2 may not favor the growth of cancers. We introduced the Bcl-2 gene to gliomas via adenovirus (Adv; Adv-Bcl-2) with the Adv for Fas (Adv-Fas) and the Adv for Fas ligand (Adv-FL) to evaluate the antiapoptotic function of Bcl-2. In U251 glioblastoma cells, Bcl-2 at a low level of expression repressed apoptosis induced by Adv-Fas and Adv-FL, whereas Bcl-2 at a high level of expression did not. On the other hand, Bcl-X(L) showed antiapoptotic function against Fas-mediated apoptosis, irrespective of its expression level. In glioblastoma cells, induction of Bcl-2 alone at a high level induced apoptosis, whereas induction of Bcl-X(L) alone did not. As the multiplicity of infection of Adv-Bcl-2 was increased, the quantity of a cleaved product of Bcl-2 increased. Induction of caspase-inhibitory genes (CrmA and p35) inhibited apoptosis induced by Adv-Bcl-2. Induction of Bcl-2 led to alteration of the membrane potential and structure of the mitochondria. In summary, although Bcl-2 at a low level of expression was antiapoptotic, Bcl-2 at a high level of expression was proapoptotic to Fas-mediated apoptosis. Overexpression of Bcl-X(L) was consistently antiapoptotic to Fas-mediated apoptosis.

Apoptosis↗
PubMed1999

A novel acyl-CoA oxidase that can oxidize short-chain acyl-CoA in plant peroxisomes.

Short-chain acyl-CoA oxidases are beta-oxidation enzymes that are active on short-chain acyl-CoAs and that appear to be present in higher plant peroxisomes and absent in mammalian peroxisomes. Therefore, plant peroxisomes are capable of performing complete beta-oxidation of acyl-CoA chains, whereas mammalian peroxisomes can perform beta-oxidation of only those acyl-CoA chains that are larger than octanoyl-CoA (C8). In this report, we have shown that a novel acyl-CoA oxidase can oxidize short-chain acyl-CoA in plant peroxisomes. A peroxisomal short-chain acyl-CoA oxidase from Arabidopsis was purified following the expression of the Arabidopsis cDNA in a baculovirus expression system. The purified enzyme was active on butyryl-CoA (C4), hexanoyl-CoA (C6), and octanoyl-CoA (C8). Cell fractionation and immunocytochemical analysis revealed that the short-chain acyl-CoA oxidase is localized in peroxisomes. The expression pattern of the short-chain acyl-CoA oxidase was similar to that of peroxisomal 3-ketoacyl-CoA thiolase, a marker enzyme of fatty acid beta-oxidation, during post-germinative growth. Although the molecular structure and amino acid sequence of the enzyme are similar to those of mammalian mitochondrial acyl-CoA dehydrogenase, the purified enzyme has no activity as acyl-CoA dehydrogenase. These results indicate that the short-chain acyl-CoA oxidases function in fatty acid beta-oxidation in plant peroxisomes, and that by the cooperative action of long- and short-chain acyl-CoA oxidases, plant peroxisomes are capable of performing the complete beta-oxidation of acyl-CoA.

Acyl-CoA Dehydrogenase↗
PubMed1999

Angiopoietin-3, a novel member of the angiopoietin family.

A cDNA clone encoding angiopoietin-3 protein (Ang3), a novel member of the angiopoietin family, was identified. Ang3 cDNA was cloned from a human aorta cDNA library. Ang3 is a 503 amino acid protein having 45.1% and 44.7% identity with human angiopoietin-1 and human angiopoietin-2, respectively. Ang3 mRNA is expressed in lung and cultured human umbilical vein endothelial cells (HUVECs). Ang3 mRNA expression in HUVECs was slightly decreased by vascular endothelial cell growth factor treatment, suggesting that the regulation of Ang3 mRNA expression is different from that of Ang2.

Amino Acid Sequence↗
PubMed1999

Expression of norepinephrine and serotonin transporter mRNAs in the rat superior cervical ganglion.

We investigated the gene expression of three monoamine transporters (norepinephrine transporter, NET; serotonin transporter, SERT; and dopamine transporter, DAT) in the rat superior cervical ganglion (SCG). Most of principal ganglion neurons abundantly expressed NET mRNA. In addition, about 30% of principal ganglion neurons also expressed SERT mRNA. However, DAT mRNA expression was not observed there. These results suggest that serotonin as well as norepinephrine works as a neurotransmitter in a subset of principal ganglion neurons.

Animals↗
PubMed1999

Vacuolar processing enzyme is self-catalytically activated by sequential removal of the C-terminal and N-terminal propeptides.

A vacuolar processing enzyme (VPE) responsible for maturation of various vacuolar proteins is synthesized as an inactive precursor. To clarify how to convert the VPE precursor into the active enzyme, we expressed point mutated VPE precursors of castor bean in the pep4 strain of Saccharomyces cerevisiae. A VPE with a substitution of the active site Cys with Gly showed no ability to convert itself into the mature form, although a wild VPE had the ability. The mutated VPE was converted by the action of the VPE that had been purified from castor bean. Substitution of the conserved Asp-Asp at the putative cleavage site of the C-terminal propeptide with Gly-Gly abolished both the conversion into the mature form and the activation of the mutated VPE. In vitro assay with synthetic peptides demonstrated that a VPE exhibited activity towards Asp residues and that a VPE cleaved an Asp-Gln bond to remove the N-terminal propeptide. Taken together, the results indicate that the VPE is self-catalytically maturated to be converted into the active enzyme by removal of the C-terminal propeptide and subsequent removal of the N-terminal one.

Amino Acid Sequence↗
PubMed1999

Multiple functional proteins are produced by cleaving Asn-Gln bonds of a single precursor by vacuolar processing enzyme.

Precursor-accumulating vesicles mediate transport of the precursors of seed proteins to protein storage vacuoles in maturing pumpkin seeds. We isolated the precursor-accumulating vesicles and characterized a 100-kDa component (PV100) of the vesicles. Isolated cDNA for PV100 encoded a 97,310-Da protein that was composed of a hydrophobic signal peptide and the following three domains: an 11-kDa Cys-rich domain with four CXXXC motifs, a 34-kDa Arg/Glu-rich domain composed of six homologous repeats, and a 50-kDa vicilin-like domain. Both immunocytochemistry and immunoblots with anti-PV100 antibodies showed that <10-kDa proteins and the 50-kDa vicilin-like protein were accumulated in the vacuoles. To identify the mature proteins derived from PV100, soluble proteins of the vacuoles were separated, and their molecular structures were determined. Mass spectrometry and peptide sequencing showed that two Cys-rich peptides, three Arg/Glu-rich peptides, and the vicilin-like protein were produced by cleaving Asn-Gln bonds of PV100 and that all of these proteins had a pyroglutamate at their NH2 termini. To clarify the cleavage mechanism, in vitro processing of PV100 was performed with purified vacuolar processing enzyme (VPE). Taken together, these results suggested that VPE was responsible for cleaving Asn-Gln bonds of a single precursor, PV100, to produce multiple seed proteins. It is likely that the Asn-Gln stretches not only provide cleavage sites for VPE but also produce aminopeptidase-resistant proteins. We also found that the Cys-rich peptide functions as a trypsin inhibitor. Our findings suggested that PV100 is converted into different functional proteins, such as a proteinase inhibitor and a storage protein, in the vacuoles of seed cells.

Amino Acid Sequence↗
PubMed1999

Effects of antithrombin on Binswanger's disease with antiphospholipid antibody syndrome.

The authors present a family with Binswanger's disease (BD) and antiphospholipid antibody syndrome (APAS). In one patient from this family, lupus anticoagulant and high levels of hemostatic markers were detected. The presence of BD and the clinicobiological improvements observed after antithrombin treatment in this patient are peculiar to this familial case of APAS.

Antiphospholipid Syndrome↗
PubMed1999

Potential use of serum CD44 as an indicator of tumour progression in acute leukemia.

CD44 is a widely expressed cell surface glycoprotein with various functions. This molecule is shed from the cell surface and released as a soluble molecule. High serum levels of CD44 have been demonstrated in some solid tumours. In this study we measured serum CD44 in 25 patients with acute leukemia, in 12 with bacterial infections, and in 13 normal controls. The levels of serum CD44 of patients with bacterial infections were significantly higher (mean 531.3+/-60.1 ng/ml, p<0.001) than those of normal controls (299. 0+/-115.4 ng/ml). Acute leukemia patients before treatment had almost four-fold higher levels of serum CD44 than normal controls (mean 1301.9+/-1384.6 ng/ml, p<0.01). Serum CD44 levels were correlated with clinical status. After treatment the serum CD44 levels significantly decreased, but they were still higher than in normal controls. Patients in complete remission all relapsed if serum CD44 levels were higher than 500 ng/ml (normal+2 SD) after chemotherapy. The serum CD44 levels were correlated with the absolute numbers of leukemic cells in peripheral blood. The results demonstrated that serum CD44 levels correlate well with the clinical status of acute leukemia, and such evaluation may provide a reliable tumour marker of acute leukemia.

Acute Disease↗
PubMed1999

Computed tomography-fluoroscopy guided injection of cyanoacrylate to mark a pulmonary nodule for thoracoscopic resection.

BACKGROUND: There have been several reports regarding aids to localize small and/or deeply situated peripheral pulmonary lesions thoracoscopically. However, we have found that they were not always reliable and have attempted to use a cyanoacrylate adhesive as an alternative. METHOD: We injected 0.1-0.2 ml of Histoacryl (n-butyl-2-cyanoacrylate) blue through a 22 gauge long needle to the lung parenchyma immediately beneath the pleural surface that was nearest to the target nodule. Following local anesthesia of the thoracic wall, we inserted the needle tip to the desired position under CT-fluoroscopic guidance. After retracting the syringe piston to confirm that no blood was aspirated, we injected the adhesive and immediately removed the needle. RESULTS: The adhesive polymerized immediately after its injection into the lung parenchyma to form a hard nodule. There was no complication except mild pneumothorax and slight pain at the puncture site. The adhesive nodule measured 1.0-1.5 cm in diameter and was hard enough to be easily located thoracoscopically in all the 8 patients/9 nodules studied. The nodule was also recognizable by its blue color visible under the pleura. CONCLUSION: CT-fluoroscopy guided injection of Histoacryl blue provided a reliable marker for the localization of pulmonary nodules, especially in those patients with severe anthracosis in the pulmonary parenchyma.

Adult↗
PubMed1999

First brain dead donor heart transplantation under new legislation in Japan.

The first heart transplantation was carried out in Japan successfully, after the brain death and organ transplantation law was settled in 1997. The recipient patient was a 47-year-old man with the dilated phase of hypertrophic cardiomyopathy who had been on a Novacor implantable left ventricular assist system for the previous 4 months. Since the donor hospital was about 200 km from the recipient hospital which took approximately 2 hours for transportation, the total ischemic time was 3 hours and 24 minutes. The post-transplant course was smooth, and the patient was discharged on postoperative day 75.

Brain Death↗
PubMed1999

Clinical role of blood heparin level monitoring during open heart surgery.

Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 +/- 0.14, 2.31 +/- 0.17 and 0.13 +/- 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 +/- 224 vs. 1559 +/- 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 +/- 22 vs. 286 +/- 18 dyne.s.cm-5.m2, p = 0.0137) and the IL-8 levels (just after protamine: 26.9 +/- 5.1 vs. 43.5 +/- 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 +/- 12.1 vs. 86.8 +/- 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.

Anticoagulants↗
PubMed1999

Analysis of the elephant trunk method in patients with extensive thoracic aortic aneurysm.

We assessed the appropriate length of an elephant trunk prosthesis based on our experience with 9 patients experiencing extensive thoracic aneurysms. There were 3 patients with a true aneurysm, 5 patients with a dissecting aortic aneurysm, and 1 patient with a true plus dissecting aortic aneurysm. The subjects were 4 men and 5 women and, at the time of operation, were from 38 to 74 years old. The second-stage operations were performed on 6 patients from 9 days to 6 months after the first-stage operation. In the first-stage operation, one patient died of pneumonia during the hospital stay and another died of multi-organ infarction after 15 months. In the second-stage operation, two patients died of brain hemorrhage in the chronic stage after the operation. The length of the elephant trunk prosthesis was 3 cm in the three early patients, and in one of them the elephant trunk could not be utilized due to its insufficient length. In the next three patients, the length was extended to 5 cm, but one of patient experienced an expansion of the aneurysm in the descending aorta due to a graft of insufficient length which could not decompress the aneurysmal wall. Therefore, in the last three patients, the length was further extended to 10 cm, and the second-stage operation was performed uneventfully on the 64th, 9th and 45th day, respectively after the first-stage operation within a continuous hospital stay. Neither expansion of the aneurysm nor thromboembolism was found during the waiting period for any of the second-stage operations. Accordingly, we recommend using a 10 cm elephant trunk prosthesis.

Adult↗
PubMed1999

Dynamic measurement of intrinsic PEEP does not represent the lowest intrinsic PEEP.

OBJECTIVE: Dynamic intrinsic PEEP (PEEPi-dyn) is the airway pressure required to overcome expiratory flow and is considered to represent the lowest regional PEEPi. However, there are few data to validate this assumption. We investigated if PEEPi-dyn represents the lowest PEEPi. SETTING: The animal laboratory at the Osaka University Medical School. MEASUREMENTS AND RESULTS: We compared static PEEPi (PEEPi-stat) and PEEPi-dyn in healthy animals. Five adult white rabbits (2.77+/-0.05 kg) were anesthetized, tracheostomized, and intubated with several different sizes of endotracheal tubes (ETT) (2.0, 2.5, 3.0, 3.5, or 4.0 mm i.d.). The animals were paralyzed and ventilated (Siemens Servo 900C). Baseline ventilator settings were at a rate of 50/min, inspiratory:expiratory (I:E) ratio of 2:1 or 4:1, and minute ventilation was manipulated to create 3 or 5 cm H2O PEEPi-stat. PEEPi-stat was measured using the expiratory hold button of the ventilator. PEEPi-dyn showed large variations. In all ventilator settings, PEEPi-dyn was higher than PEEPi-stat (p<0.001). The larger the ETT, the higher the PEEPi-dyn at an I:E ratio of 2:1 (p<0.05). The higher the minute ventilation, the greater the difference between PEEPi-stat and PEEPi-dyn. The tidal volume and the difference showed a significant correlation (r2 = 0.514, p<0.001). CONCLUSIONS: The value of PEEPi-dyn was dependent on ventilatory settings, and PEEPi-dyn does not necessarily represent the lowest regional PEEPi within the lungs.

Animals↗
PubMed1999

Application of the RLGS image analysis tool (RAT) to the construction of a genetic linkage map of recombinant inbred strain SMXA.

The construction of a genetic linkage map is the first, fundamental step to analyze the genetic properties of any organism. For this purpose, the restriction landmark genome scanning method (RLGS) can be used and has been shown to have high productivity in various genetic analyses. However, construction of a genetic linkage map by the RLGS method is laborious, because hundreds of spots must be scored, usually by visual observation. In order to reduce human involvement in the data processing, we developed an image analysis software, RAT (RLGS Analysis Tool). We evaluated its accuracy and feasibility by comparing the parental distribution patterns of RLGS spots obtained by RAT and by human observation, using Syrian hamster strain backcross progeny. We then used RAT to construct a genetic linkage map of the recombinant inbred strain SMXA. We were able to obtain 121 progenitor strain-specific spots that were assigned to a specific chromosome.

Animals↗