Biomedical subjects

M Nishida

Publications and source records attributed to M Nishida.

At least 163 records · Page 9Linked to original sources

PubMed1999

Serum hepatocyte growth factor levels in patients with renal diseases.

The serum levels of hepatocyte growth factor (HGF) were determined in patients with various renal diseases. In patients with acute-phase acute renal failure (ARF) and chronic tubulointerstitial nephritis (chronic TIN), the serum HGF levels were 0.55 +/- 0.24 and 0.44 +/- 0.37 ng/ml (mean +/- SD), respectively, and were significantly higher than that in the control group (0.12 +/- 0.12 ng/ml). The serum HGF level tended to be high also in patients with active-phase steroid-sensitive nephrotic syndrome (SSNS). The serum levels of HGF were not elevated in patients with IgA nephropathy (IgAN), Henoch-Schönlein purpura nephritis (HSPN), membranoproliferative glomerulonephritis (MPGN), poststreptococcal acute glomerulonephritis (PSAGN), unilateral renal atrophy, unilateral nephrectomy, or proximal tubular dysfunction. These observations suggest that glomerular disorders cause no apparent elevation of the serum HGF level, and that elevation of the serum HGF level may be associated with tubulointerstitial damage in renal diseases.

Adolescent↗

PubMed1999

CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta.

CD36 has been reported to be a receptor for oxidized LDL (Ox-LDL). In our previous study, the uptake of Ox-LDL in CD36-deficient macrophages was reduced by approximately 50% compared with that in control macrophages, suggesting an important role of CD36 as a receptor for Ox-LDL in humans. In the current study, we examined the immunohistochemical localization of CD36 in human aorta in comparison with that of scavenger receptor class A type I and type II (SRA). Cryostat sections were made from aortic tissues. For immunohistochemical staining, the following antibodies were used: (1) FA6-152, anti-CD36 antibody, and (2) SRI-2, which recognizes both type I and type II SRAs. Immunohistochemical staining for CD36 and SRA was performed using labeled streptavidin method. In macrophages scattered in aortic walls without atherosclerotic lesions, the expression of CD36 was hardly observed, whereas that of SRA was detected weakly but consistently. In contrast, in atherosclerotic lesions, macrophages around the core region showed a weak immunoreactivity to CD36 and a strong immunoreactivity to SRA. Furthermore, lipid-laden macrophages, which mainly existed in the core region, had a strongly positive immunoreactivity to CD36, but a low or moderate level of immunoreactivity to SRA. The distributions of CD36 and SRA were different from each other, and especially foamed, large-sized macrophages in atherosclerotic plaques tended to more abundantly express CD36 protein. These data demonstrate, for the first time, that the expression of both CD36 and SRA might be differentially regulated in aortic walls, and might play different roles in the formation of foam cells in atherosclerotic lesions.

Adult↗

PubMed1999

Serum hepatocyte growth factor as a possible indicator of vascular lesions.

To investigate the role of human hepatocyte growth factor (hHGF) in vascular lesions associated with endothelial injury, we measured serum hHGF concentrations in subjects with retinal arteriosclerosis, coronary atherosclerosis, or arteriolitis due to Henoch-Schönlein purpura. Individuals with more advanced grades of retinal arteriosclerosis showed higher serum hHGF concentrations [grade 0, 0.053+/-0.005 ng/mL (n = 68); grade 1, 0.144+/-0.022 ng/mL (n = 21; P<0.01 vs. grade 0); grade 2, 0.338+/-0.036 ng/mL (n = 20; P<0.01 vs. grade 0 or 1); grade 3, 0.526+/-0.051 ng/mL (n = 9; P<0.01 vs. grade 0, 1, or 2)]. Patients with active arteriolitis due to Henoch-Schönlein purpura showed higher (P<0.01) serum hHGF concentrations (0.347+/-0.038 ng/mL; n = 14) than those in the remission phase (0.097+/-0.017 ng/mL; n = 19). Mean serum hHGF concentrations were higher in subjects with coronary atherosclerosis than in those without, but a significant overlap in serum hHGF concentrations was found between subjects with and those without coronary atherosclerosis. Serum hHGF may be an indicator of the presence or development of arteriolar lesions.

Aged↗

PubMed1999

[beta gamma subunit of heterotrimeric G protein as a new target molecule for drug development].

Although ischemia-reperfusion produces reactive oxygen species and induces injury of the heart, the mechanism leading to injury is largely unknown. Hydrogen peroxide (H2O2) is widely used for a reagent to mimic the action of reactive oxygen species produced by ischemia-reperfusion. Treatment of the rat neonatal myocytes with H2O2 resulted in activation of mitogen-activated protein kinases (MAPKs) such as extracellular signal regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38. To study the involvement of beta gamma subunit of heterotrimeric G protein in H2O2-induced activation of MAPKs, we expressed the carboxyl terminus of G protein-coupled receptor kinase 2 (GRK2-ct) which can bind beta gamma subunit and inhibit the interaction with various effector proteins. Expression of GRK2-ct inhibited the H2O2-induced activation of ERK by 70% and also inhibited the activation of Akt by 30%. In contrast with H2O2-induced activation of ERK, the activation of ERK induced by phorbol ester PMA and the activation of JNK and p38 induced by H2O2 were not affected by expression of GRK2-ct, indicating that the activation of ERK but not JNK and p38 is dependent on beta gamma subunit. Among several inhibitors for analyzing intracellular signaling pathways, wortmannin inhibited the activation of ERK by H2O2 treatment. These data suggest that treatment of the rat neonatal myocytes with H2O2 releases beta gamma subunit from heterotrimeric G protein, and leads to activation of ERK in part by phosphatidylinositol-3 kinase dependent pathway. Thus beta gamma subunit may be a novel target molecule to selectively modulate the intracellular signaling cascade.

Animals↗

PubMed1999

Treatment with l-cis diltiazem before reperfusion reduces infarct size in the ischemic rabbit heart in vivo.

l-cis Diltiazem, an optical isomer of diltiazem, protects against myocardial dysfunction in vitro, whereas its Ca2+ channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidence that l-cis diltiazem actually protects against ischemia/reperfusion injury in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 min. Treatment with diltiazem before and during ischemia (bolus 200 microg/kg and 15 microg/kg per minute for 25 min, i.v.; 575 microg/kg total) showed slightly depressed hemodynamic parameters, while l-cis diltiazem (1150 microg/kg) had no effect. Treatment with l-cis diltiazem produced a high recovery of the thickening fraction and limited the infarct size in a dose-dependent manner. Furthermore, the treatment with l-cis diltiazem (1150 microg/kg) or diltiazem (575 microg/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that l-cis diltiazem affects some events in the onset of reperfusion, independently of Ca2+-channel-blocking action. Our observations are the first to show that l-cis diltiazem demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.

Anesthesia↗

PubMed1999

Differential diagnosis of gynaecological "stained glass" tumours on MRI.

Although multilocular cystic gynaecological masses in which the loculi show variable signal intensity on both T1 and T2 weighted images have been considered to be mucinous cystadenoma or adenocarcinoma, other gynaecological tumours can demonstrate this "stained glass" appearance. These include mature cystic teratoma, fibrothecoma, endometrioma, Brenner's tumour of the ovary and degenerated leiomyoma of the uterus, all of which may mimic mucinous tumours of the ovaries.

Diagnosis, Differential↗

PubMed1999

Platelet-derived endothelial cell growth factor/thymidine phosphorylase concentrations differ in small cell and non-small cell lung cancer.

OBJECTIVE: Platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase (TP) has been implicated in cancer angiogenesis, which is critical for tumor growth and metastasis. We investigated the relationship between the tissue concentration of PD-ECGF/TP and the clinicopathologic status in human lung cancer. METHODS: The concentrations of PD-ECGF/TP in the tumor extracts of 139 primary human lung carcinomas were measured by using a highly specific and sensitive enzyme-linked immunosorbent assay. RESULTS: PD-ECGF/TP was detected in the extracts from 137 of 139 specimens at concentrations that ranged from 2.0 to 169.5 U/mg protein. PD-ECGF/TP concentrations in patients with adenocarcinoma (n = 73) and squamous cell carcinoma (n = 49) were (mean +/- SD) 30.7+/-22.9 U/mg protein (range, 7.6 to 169.5 U/mg protein) and 32.0+/-19.8 U/mg protein (range, 8.0 to 84.4 U/mg protein), respectively. No significant difference was found in the PD-ECGF/TP concentration between these two types of non-small cell lung cancer (NSCLC). However, a > 8-fold lower mean concentration of PD-ECGF/TP was found in tissue extracts from small cell lung cancer (SCLC) (n = 17; 3.65+/-2.01 U/mg protein, ranging from undetectable to 6.1 U/mg protein) than in those from adenocarcinomas (p = 0.00005) or squamous cell carcinomas (p < 0.00001). CONCLUSIONS: The striking difference in PD-ECGF/TP concentrations between SCLC and NSCLC suggests that these two types of lung cancer use alternative pathways for angiogenesis. The present study suggests that inhibitors of PD-ECGF/TP, which have been recently developed and are under laboratory investigation to test their effectiveness as treatments for various types of cancer, may not be effective against SCLC.

Aged↗

PubMed1999

Persistent primitive hypoglossal artery associated with cerebral aneurysm and cervical internal carotid artery stenosis--case report.

A 71-year-old female had vertigo attacks once or twice a day secondary to vertebrobasilar insufficiency. Left carotid angiography revealed persistent primitive hypoglossal artery (PPHA) associated with a large internal carotid artery (ICA) aneurysm and severe stenosis of the ICA. The bilateral vertebral arteries were hypoplastic. The basilar artery was opacified via the PPHA but not via vertebral arteries. Clipping of the aneurysm was performed first because the risk of rupture of the aneurysm was not negligible. One month after clipping, carotid endarterectomy using a T-shaped shunt system was successfully performed. The postoperative course was uneventful and the vertebrobasilar ischemic attacks did not recur. Left carotid angiography demonstrated complete obliteration of the aneurysm and disappearance of the carotid artery stenosis. Low ICA flow (70 ml/min) and low stump pressure of the PPHA (25 mmHg) strongly suggested low perfusion of the posterior circulation. Carotid endarterectomy may be essential for augmentation of the posterior circulation in patients with PPHA associated with ICA stenosis.

Aged↗

PubMed1999

Neuroimaging findings of the development and resolution of solitary brainstem abscess: characteristics of neuroimagings in the early stage of brainstem abscess and importance of surgical management for brainstem abscess--case report.

A 64-year-old female presented with a solitary brainstem abscess. Magnetic resonance imaging and computed tomography demonstrated the development and resolution of the brainstem abscess with an unusual and fluctuating clinical course over several months. Serial neuroimaging examinations are required to detect a brainstem abscess in the early stage to establish the optimum treatment.

Brain Abscess↗

PubMed1999

[The future guaranteeing the advanced accuracy].

To guarantee the supply of accurate clinical information, the laboratory system uses external quality control, internal quality control, and data checking method. The correlation among these laboratory items and the continuity of the inter-subject variation are applied to self-acting assessment of data. In this text, we introduce other insights, not yet generalized to date, to guarantee the accuracy. First, we emphasize the importance of accurate data communication and redundancy of composition in the information equipment to improve the reliability of information transaction. Secondly, we applied the data checking system which synchronizes with pathophysiological changes in the patients to the diagnosis support system using the hypothesis deduction method. Thirdly, we present the mobility presumption method in the seat of protein electrophoresis crimp as a suitable example to obtain more accurate information processing of the original data.

Clinical Laboratory Information Systems↗

PubMed1999

[A case of multiple liver metastases from breast cancer successfully treated with intra-arterial administration of docetaxel].

Docetaxel is an excellent agent with a high antitumor effect for the treatment of advanced/recurrent breast cancer. A 55-year-old female with metastatic liver tumors from breast cancer showed a remarkable response to intra-arterial administration of docetaxel (20 mg/week, or 40 mg/2 weeks). Since CT and MRI imaging revealed multiple metastases in the liver, intra-arterial chemotherapy was selected. No critical side effect was found during this chemotherapy. A CT scan 3 months after chemotherapy showed a partial response. We conclude that this intra-arterial chemotherapy using docetaxel will be safe and useful for liver metastases from breast cancer.

Adenocarcinoma, Scirrhous↗

PubMed1999

[Phase I study of a combination chemotherapy of nedaplatin and cisplatin].

A new platinum complex, nedaplatin, has been reported to be effective for both ovarian and cervical cancers. We designated a phase I dose-escalation study of a combination chemotherapy of nedaplatin and cisplatin to investigate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Six patients, including two with advanced cervical cancer, three with ovarian clear cell adenocarcinoma and one with endometrial clear cell adenocarcinoma, were enrolled in this study. The doses of the two agents were escalated alternatively, i.e., a tandem method, from 40 to 80 mg/m2 by 20 mg/m2. Nedaplatin and cisplatin were administrated by intravenous drip infusion and repeated after an interval of at least 4 weeks, as a rule. The major toxicity observed was hematotoxicity. One of the 6 patients dropped out of this study because of severe hematotoxicity after 80 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin were administered. With a dose of 80 mg/m2 nedaplatin and 80 mg/m2 cisplatin, severe neutropenia was found in all 6 patients, and thrombocytopenia and anemia were found in 1 patient, respectively. A slight hearing loss was detected by audiometry in 5 patients, but no one was inconvenienced in daily life. Mild nausea and vomiting were also observed in all 6 patients. In conclusion, the DLT of this combination therapy was hematotoxicity and the MTD was 80 mg/m2 for nedaplatin and 60 mg/m2 for cisplatin, respectively. Thus, 60 mg/m2 of nedaplatin and 60 mg/m2 of cisplatin may be recommended for combined administration.

Adenocarcinoma, Clear Cell↗

PubMed1998

Involvement of NF-Y in transcriptional regulation of the phospholamban gene.

To understand the transcriptional regulation of the phospholamban gene, we analyzed a 5'-upstream region of the gene. Using a series of deletion constructs, we demonstrated that the region from -96 bp to -78 bp, containing the CCAAT sequence, is essential for transcription of this gene. This region specifically bound to nuclear proteins extracted from rat hearts, and gel-shift assays using competitive oligonucleotides, antibodies and recombinant proteins showed that this region binds to the NF-YA and NF-YB, members of the CCAAT-binding nuclear protein family. This region-dependent transcription in cardiac myocytes transfected with antisense cDNAs encoding NF-YA and NF-YB was decreased to approximately 50% of that seen in cells transfected with the same sense cDNAs. We, therefore, conclude that the region from -96 bp to -78 bp plays a critical role in expression of the phospholamban gene, which is regulated by binding of the nuclear protein NF-Y.

Animals↗

PubMed1998

Three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate: catalytic roles of Cys10 and His106.

Cytosolic glutathione S-transferase is a family of multi-functional enzymes involved in the detoxification of a large variety of xenobiotic and endobiotic compounds through glutathione conjugation. The three-dimensional structure of Escherichia coli glutathione S-transferase complexed with glutathione sulfonate, N-(N-L-gamma-glutamyl-3-sulfo-L-alanyl)-glycine, has been determined by the multiple isomorphous replacement method and refined to a crystallographic R factor of 0.183 at 2.1 A resolution. The E. coli enzyme is a globular homodimer with dimensions of 58 Ax56 Ax52 A. Each subunit, consisting of a polypeptide of 201 amino acid residues, is divided into a smaller N-terminal domain (residues 1 to 80) and a larger C-terminal one (residues 89 to 201). The core of the N-terminal domain is constructed by a four-stranded beta-sheet and two alpha-helices, and that of the C-terminal one is constructed by a right-handed bundle of four alpha-helices. Glutathione sulfonate, a competitive inhibitor against glutathione, is bound in a cleft between the N and C-terminal domains. Therefore, the E. coli enzyme conserves overall constructions common to the eukaryotic enzymes, in its polypeptide fold, dimeric assembly, and glutathione-binding site. In the case of the eukaryotic enzymes, tyrosine and serine residues near the N terminus are located in the proximity of the sulfur atom of the bound glutathione, and are proposed to be catalytically essential. In the E. coli enzyme, Tyr5 and Ser11 corresponding to these residues are not involved in the interaction with the inhibitor, although they are located in the vicinity of catalytic site. Instead, Cys10 N and His106 Nepsilon2 atoms are hydrogen-bonded to the sulfonate group of the inhibitor. On the basis of this structural study, Cys10 and His106 are ascribed to the catalytic residues that are distinctive from the family of the eukaryotic enzymes. We propose that glutathione S-transferases have diverged from a common origin and acquired different catalytic apparatuses in the process of evolution.

Amino Acid Sequence↗

PubMed1998

Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases.

A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1), beta-homonojirimycin (2), alpha-homomannojirimycin (3), beta-homomannojirimycin (4), alpha-3,4-di-epi-homonojirimycin (5), beta-4,5-di-epi-homonojirimycin (6), N-methyl-alpha-homonojirimycin (7), and N-butyl-alpha-homonojirimycin (8). Compound 1 was a potent inhibitor of a range of alpha-glucosidases with IC50 values of 1 to 0.01 microM. Compounds 2, 3, and 4 were surprisingly inactive as inhibitors of beta-glucosidase and alpha- and beta-mannosidases but were moderately good as inhibitors of rice and some mammalian alpha-glucosidases. Compound 4 was active in the micromolar range toward all alpha-glucosidases tested. Furthermore, compound 4, which superimposes well on beta-l-fucose, was a 10-fold more effective inhibitor of alpha-l-fucosidase than 1-deoxymannojirimycin (12) and 3, with a Ki value of 0.45 microM. Only compounds 5 and 6 showed inhibitory activity toward alpha- and beta-galactosidases (6with an IC50 value of 6.4 microM against alpha-galactosidase). The high-resolution structure of 1 has been determined by X-ray diffraction and showed a chair conformation with the C1 OH (corresponding to the C6 OH in 1-deoxynojirimycin) predominantly equatorial to the piperidine ring in the crystal structure. This preferred (C1 OH equatorial) conformation was also corroborated by 1H NMR coupling constants. The coupling constants for 7 suggest the axial orientation of the C1 OH, while in 8 the C1 OH axial conformation was not observed. The C1 OH axial conformation appears to be responsible for more potent inhibition toward processing alpha-glucosidase I than alpha-glucosidase II. It has been assumed that the anti-HIV activity of alkaloidal glycosidase inhibitors results from the inhibition of processing alpha-glucosidase I, but 1, 7, and 8 were inactive against HIV-1 replication at 500 microg/mL as measured by inhibition of virus-induced cytopathogenicity in MT-4 cells. In contrast, the EC50 value for N-butyl-1-deoxynojirimycin (11), which also inhibits processing alpha-glucosidase I, was 37 microg/mL. Compound 7 has been shown to be a better inhibitor of alpha-glucosidase I than 1 and 8 both in vitro and in the cell culture system. These data imply that inhibition of HIV by glycosidase inhibitors can be due to factors other than simply inhibition of processing alpha-glucosidase I.

1-Deoxynojirimycin↗

PubMed1998

Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts.

Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel fluoropyrimidine carbamate that is converted to 5-fluorouracil (5-FUra) by three enzymes located in the liver and tumors; the final step is the conversion of 5'-deoxy-5-fluorouridine (5'-dFUrd) to 5-FUra by thymidine phosphorylase in tumors. The present study compared the efficacy of capecitabine and 5-FUra at their maximum tolerated doses in CXF280, HCT116, COLO205, and WiDr human colon cancer xenograft models, and measured subsequent 5-FUra and 5'-dFUrd levels in tumors and in the plasma and muscle. Capecitabine was effective in the first three models, whereas 5-FUra was effective only in CXF280, which is a cell line highly susceptible to fluoropyrimidines. In the three susceptible models, 5-FUra AUCs in tumors after capecitabine administration were 210 to 303 nmol x hr/g, whereas those after 5-FUra administration were 8.54 to 13.1 nmol x hr/g. In addition, capecitabine gave higher levels of 5-FUra AUC in tumors than in plasma (114- to 209-fold higher) and muscle (21.6-fold higher), whereas 5-FUra was not selectively distributed to tumors. In the refractory model, WiDr, 5-FUra AUC in tumors after capecitabine administration was only 62.8 nmol x hr/g, although the level of the intermediate metabolite 5'-dFUrd was high (AUC: 695 nmol x hr/g). The ratio of 5-FUra/5'-dFUrd levels in the WiDr tumors was 0.09, which was 23.8-fold lower than that in the HCT116 tumors. The mechanism of resistance would be the inefficient conversion of 5'-dFUrd to 5-FUra by thymidine phosphorylase in tumors. Thus, capecitabine might show its high efficacy as a result of delivering high levels of 5-FUra selectively to the tumors.

Animals↗

PubMed1998

Effect of age on brown adipose tissue activity in the obese (ob/ob) mouse.

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity.

Adipose Tissue, Brown↗

PubMed1998

Molecular phylogeny and evolution of the deep-sea fish genus Sternoptyx.

A portion of mitochondrially encoded 12S and 16S ribosomal RNA genes were sequenced from all four valid species of the midwater deep-sea fish genus Sternoptyx (Teleostei: Sternoptychidae) and four sternoptychid outgroup taxa. Secondary structure-based alignment resulted in a character matrix consisting of 865 bp of unambiguously aligned, combined sequences of the two genes, which were subjected to phylogenetic analyses using the maximum parsimony and maximum likelihood methods. The resultant tree topologies from the two methods were congruent and supported by various tree statistics. Although the single most parsimonious tree was not statistically different from the two second parsimonious trees, independent morphological evidence from the anal fin pterygiophore configuration and associated structures strongly supported the former as the preferred hypothesis. Mapping of the contemporary geographic distribution patterns of the four species onto the tree suggested that there was a common ancestor of Sternoptyx with a circumglobal distribution, which had been subdivided into southern and northern ancestral populations along 30 degrees S, possibly through some large-scale oceanographic event. There has been no discernible speciation event in the southern population, though the northern population has subsequently speciated into three contemporary species with largely allopatric/microallopatric distributions.

Animals↗