[Portable blood glucose meters using the enzyme electrode].
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Biosensing Techniques↗
Biomedical subjects
Y Nishikawa
Publications and source records attributed to Y Nishikawa.
Differential effects of systemic morphine on responses elicited by tooth pulp stimulation of nociceptive neurons in lateral and medial thalamic nuclei.
The effects of intravenous morphine on responses of feline thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were investigated. Morphine suppressed responses to TP stimulation in both tooth pulp specific (TPS) and wide dynamic range (WDR) neurons with TP input recorded from the nucleus ventralis posteromedialis (VPM). However, there was scant morphine effect on responses to stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. Furthermore, in nociceptive neurons with TP input recorded from nucleus centralis lateralis (CL) and parafascicularis (Pf) of the intralaminar nuclei, intravenous morphine suppressed responses both to stimulation of the mesencephalic reticular formation (MRF) as well as TP stimulation. The suppressive action of morphine on responses elicited by TP stimulation of VPM, CL and Pf neurons was antagonized by intravenous naloxone (1 mg/kg). Results suggest that intravenous morphine suppresses synaptic transmission of nociceptive impulses in the intralaminar nuclei as well as in the lower brain stem but not in the VPM.
Analgesics, Opioid↗
Contribution of nitric oxide to metabolic coronary vasodilation in the human heart.
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Coronary Circulation↗
Purification and characterization of rabbit small intestinal cytochromes P450 belonging to CYP2J and CYP4A subfamilies.
A new form of P450 designated P450ib2 was purified from rabbit small intestine microsomes. This P450 had properties very similar, to P450ib (CYP2J1), and showed 88% identity with CYP2J1 in its first 20 NH2-terminal amino acid sequence, excluding 3 undetermined residues. Both P450ib and P450ib2 were immunohistochemically detected in the mucosal epitherial cells of the duodenum, jejunum, and ileum in the small intestine, whereas no immunoreactivity was observed in other tissues including liver, kidney, lung, colon, and stomach. The results support that the two closely related P450s are specifically localized in the rabbit small intestine. Another small intestinal P450, P450ia, was found to hydroxylate a wide variety of fatty acids including straight-chain, branched-chain, unsaturated, or hydroxy fatty acids, and prostaglandin A at the omega and (omega-1) positions. P450ia was identical with a rabbit kidney fatty acid omega-hydroxylase, CYP4A7, in its 25 NH2-terminal amino acid sequence, excluding 2 undetermined residues. The results identify P450ia as CYP4A7.
Amino Acid Sequence↗
Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors.
We have isolated a cDNA clone encoding a novel murine cell-surface glycoprotein. This polypeptide is predicted to be composed of a signal peptide of 23 amino acids, an extracellular region of 620 amino acids that contains six immunoglobulin-like domains with five potential N-glycosylation sites, a transmembrane sequence of 20 amino acids, and a cytoplasmic tail of 178 amino acids with four sets of sequences similar to the immunoreceptor tyrosine-based inhibition motif. The relative molecular mass of the mature polypeptide is calculated to be 90,520 Da. The polypeptide, designated as p91, shows striking homologies to human killer cell inhibitory receptors, a murine gp49B1 protein, a bovine Fcgamma2 receptor, and a human Fcalpha receptor. The mRNA of p91 was especially abundant in murine macrophages. Western blot analysis using p91-specific anti-peptide sera detected a 130-kDa polypeptide in macrophages. Surface biotinylation and immunoprecipitation analysis verified the surface expression of the translation products on COS-1 cells transfected with the p91 cDNA, but the cells failed to show any Fc binding activity.
Amino Acid Sequence↗
Nicotinamide derivatives as a new class of gastric H+/K(+)-ATPase inhibitors. 1. Synthesis and structure-activity relationships of N-substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides.
A new series of N-Substituted 2-(benzhydryl- and benzylsulfinyl)nicotinamides 7 and 8 were synthesized. Upon acid activation in the acidic environment of the parietal cell, these compounds are converted into their active forms, 2,3-dihydro-3-oxoisothiazolo[5,4-b]pyridines 5, which inhibit gastric H+/K(+)-ATPase. Inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cAMP in isolated rabbit parietal cells in vitro and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration in vivo were evaluated, and the structure-activity relationships were examined. Among the compounds synthesized, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridyl)nicotinamide (8b) showed potent inhibitory activities in vitro and in vivo equivalent to those of omeprazole, a typical H+/K(+)-ATPase inhibitor. Moreover, 8b was much more stable at neutral and weakly acidic pH than omeprazole, lansoprazole, and pantoprazole. Compound 8b is considered to be a promising agent for treating acid-related gastrointestinal disorders.
Aminopyrine↗
Inhibition of spermidine synthase gene expression by transforming growth factor-beta 1 in hepatoma cells.
We screened genes responsive to transforming growth factor-beta (TGF-beta 1) protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential display technique, in order to investigate the mechanisms involved in TGF-beta-induced growth suppression. We found a gene that was down-regulated by TGF-beta 1 to be completely identical in an approx. 620 bp segment to the gene for the enzyme spermidine synthase, which mediates the conversion of putrescine into spermidine. Both spermidine synthase mRNA expression and its enzyme activity were decreased after TGF-beta 1 treatment of Hep3B cells. The inhibition of spermidine synthase gene expression by TGF-beta 1 protein was also observed in other hepatoma cell lines. The expression of genes for other biosynthetic enzymes in polyamine metabolism (ornithine decarboxylase and S-adenosylmethionine decarboxylase) was also inhibited to the same extent as for spermidine synthase, while the gene expression of spermidine/spermine N1-acetyltransferase, a catabolic enzyme, was relatively resistant to TGF-beta 1. Spermine levels in Hep3B cells were decreased by TGF-beta 1 treatment, although the levels of spermidine and putrescine were unchanged, probably due to compensation by remaining spermidine/spermine N1-acetyltransferase activity. Exogenously added spermidine or spermine, but not putrescine, partially antagonized the growth-inhibitor effects of TGF-beta 1 on Hep3B cells. Our data suggest that down-regulation of gene expression of the enzymes involved in polyamine metabolism, including spermidine synthase, may be associated with the mechanism of TGF-beta-induced growth suppression.
Carcinoma, Hepatocellular↗
Role of nitric oxide in coronary vasomotion during handgrip exercise.
BACKGROUND: Endothelium-dependent modulation of coronary vasomotion during increased sympathetic tone remains unclear in normal and atherosclerotic human coronory arteries. METHODS AND RESULTS: We evaluated the role of endothelium-derived nitric oxide in vasomotion during isometric exercise in normal subjects (n = 7) and in patients with coronary artery disease (CAD) (n = 10). Coronary blood flow and epicardial coronary artery diameter to the handgrip test were measured before and after intracoronary administration of 100 micromol/min of N(G)-monomethyl L-arginine (L-NMMA). Heart rate and aortic blood pressure increased during handgrip test. Handgrip test caused a significant dilation in the diameter of the epicardial coronary artery in normal subjects (9.9% +/- 3.9%, mean +/- SD) and in the diameter of smooth segments of patients with CAD (5% +/- 3.7%, p < 0.05 vs normal subjects). In contrast, the diameter of irregular segments in patients with CAD decreased during handgrip test (-9.8 +/- 3.9%). After L-NMMA, the epicardial coronary artery significantly increased during handgrip test compared with before L-NMMA in normal subjects. L-NMMA did not have any effect on handgrip test induced vasodilation in the smooth segments and vasoconstriction in the irregular segments in the patients with CAD. Handgrip test-induced increases in coronary blood flow did not change after L-NMMA in both groups. CONCLUSIONS: Nitric oxide does not play a major role in HNG-induced vasodilation in epicardial and microcirculatory vessels in normal human coronary circulation. Although the decreased release in nitric oxide may modulate the abnormal response of the epicardial coronary artery to handgrip test, this does not explain the paradoxic constrictive response from the depressed but still dilatory response in the patients with CAD.
Coronary Angiography↗
Importance of nitric oxide in the coronary artery at rest and during pacing in humans.
OBJECTIVES: The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states. BACKGROUND: Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation. METHODS: NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects--9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire. RESULTS: Infusion of 25 mumol/min of L-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 +/- 2% (mean +/- SE) and 11 +/- 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 +/- 13% during L-NMMA infusion. L-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of L-NMMA. During pacing, infusion of L-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF. CONCLUSIONS: Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.
Blood Flow Velocity↗
Small cell carcinoma of the esophagus: a case report.
This article reports a case of primary undifferentiated small cell carcinoma of the esophagus with lymph node metastasis which invaded the stomach wall. The patient was treated with chemotherapy alone, consisting of CDDP and VP-16. The patient had a complete response to chemotherapy, with no evidence of disease for nine months, after six courses of the regimen. Small cell carcinoma of the esophagus is an aggressive tumor with an extremely poor prognosis. Because its characteristics are similar to small cell carcinoma of the lung, small cell carcinoma of the esophagus should be treated by multi-drug chemotherapy including CDDP, with or without radiation as the first line treatment. This chemotherapy regimen may achieve a long disease-free survival time.
Antineoplastic Combined Chemotherapy Protocols↗
Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.
The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.
Basement Membrane↗
Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors II. Synthesis and structure-activity relationships of 2[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides.
Members of a new series of 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamides were synthesized and evaluated for their gastric antisecretory activity and the ability to inhibit cytochrome P450-dependent O-dealkylation of 7-ethoxycoumarin (7-EC) in rat liver microsomes. Several of the compounds synthesized exhibited potent inhibitory activities against both [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats when administered intraduodenally; their inhibitory activities were equivalent to or superior to those of the parent compound [2- [(2,4-dimethoxybenzyl)sulfinyl]-N-(4-pyridinyl)pyridine-3-carboxamide] and omeprazole. Among the compounds having potent antisecretory activity in vitro and in vivo, 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,5-dimethyl-4-pyridinyl) pyridine-3-carboxamide and 2-[(2,4-dimethoxybenzyl)sulfinyl]-N-(2,6-dimethyl-4-pyridinyl)pyridine-3 - carboxamide in particular showed lower inhibitory activity against the 7-EC deethylase than omeprazole. It seems probable that, unlike omeprazole, these compounds do not interact with a metabolism of other drugs in vivo. These compounds, therefore, are considered to be more promising candidate agents for treating acid-related gastrointestinal disorders than the parent compound reported previously.
7-Alkoxycoumarin O-Dealkylase↗
Nicotinamide derivatives as a new class of gastric (H+/K+)-ATPase inhibitors. III. Synthesis and gastric antisecretory activity of 2-[(2- and 4-aminobenzyl, and alpha-methylbenzyl)sulfinyl]-N-(4-pyridinyl) -3-pyridinecarboxamides.
A new series of 2-[(2-aminobenzyl, 4-aminobenzyl, and alpha-methylbenzyl) sulfinyl]-N-(4-pyridinyl)-3-pyridinecarboxamides. was synthesized and evaluated for gastric antisecretory activities. Several of the compounds synthesized exhibited potent inhibitory activities against [14C]aminopyrine accumulation stimulated by dibutyryl cyclic AMP in isolated rabbit parietal cells and histamine-induced gastric acid secretion in pylorus-ligated rats by intraduodenal administration. In particular, the more polar diastereoisomer of 2-[(4-methoxy-alpha-methylbenzyl)sulfinyl] -N-(4-pyridinyl)-3-pyridinecarboxamide (13b) showed in vivo inhibitory activity equivalent or superior to that of omeprazole and was a more selective (H+/K+)-ATPase inhibitor than omeprazole.
Animals↗
Total necrosis of hepatocellular carcinoma with a combination therapy of arterial infusion of chemotherapeutic lipiodol and transcatheter arterial embolization: report of 14 cases.
Combination therapy consisting of Lipiodol (Laboratoire Guerbet, Villepinte, France) containing styrene maleic acid neocarzinostatin and transcatheter arterial embolization (L-TAE) has been an important conservative therapy for hepatocellular carcinoma (HCC). We examined the clinical and pathologic characteristics of 14 HCC cases that achieved total tumor necrosis in response to L-TAE. The HCCs of all cases were resected 45 +/- 17 days after L-TAE and were confirmed to be totally necrotic. Ultrasonography showed a mean tumor size of 2.5 +/- 1.0 cm, often with a halo formation around the tumor. Angiographically, neovascularity and clear tumor stains were observed in all cases. Computed tomography portography showed nodular perfusion defects in all the cases examined. There were portal invasions in two cases. On Lipiodol-computed tomography, Lipiodol was densely and homogeneously retained within the whole tumor. The number of tumors was single in all diagnostic images. Macroscopic view of HCCs were single nodular type in nine cases and single nodular type with extra growth in four cases. Clear capsular formation was seen in each HCC nodule. Soft x-rays were taken to observe the exact distribution of Lipiodol in the operative specimens. Microscopic intrahepatic metastases were found histologically in four cases. Histologic examination showed the trabecular pattern with broad blood spaces in which Lipiodol was positive with Sudan III staining. Necrosis was seen not only in the main tumor, but also in the capsular invasions and microscopic metastases with Lipiodol deposition. The characteristics of the cases with total tumor necrosis were as follows. Deposition of Lipiodol throughout the tumor was essential, and clinically the cases showed a single HCC tumor with a diameter of more than 5 cm and arterial hypervascularity. The pathologic findings included expansive growth with capsular formation and trabecular-type HCC with abundant blood spaces. These findings are important for evaluating the radical efficacy of L-TAE.
Aged↗
[Histopathological effect of neoadjuvant chemohormonal therapy for prostatic cancer].
To improve the therapeutic results in prostatic cancer, radical prostatectomy or total cystoprostatectomy were performed with chemohormonal therapy before operation. Radical prostatectomies were conducted in eight patients with localized prostatic cancer and total cystoprostatectomies in ten patients with severe cystic infiltration. The administration schedule of chemohormonal therapy was as follows: prior to operation, 30-60 mg/sqm/day of etoposide was administered for 7 days every 3 weeks, 250-500 mg/day of diethylbestrol diphosphate for 30 days, and 3.6 mg of LH-RH agonist was also administered. Sixteen of the subjects survived, and were socially rehabilitated (14 cases of NED, 1 case of NC and 1 case of PD) and 2 of the subjects died of cancer. Histopathological findings showed 9 cases of poorly differentiated adenocarcinoma, 4 cases of well differentiated adenocarcinoma and 5 cases of moderately differentiated adenocarcinoma. Histopathological effect of neoadjuvant chemohormonal therapy in surgical specimen showed that 2 of the subjects had grade 0a effect, grade 0b in 7 cases, grade 1 in 5 cases and grade 2 in 4 cases.
Adenocarcinoma↗
Tooth pulp neurons in the caudal medulla oblongata of the cat.
The medulla oblongata caudal to the obex was explored for neurons responsive to tooth pulp (TP) stimulation in cats. Four different subclasses of TP neurons were found. The latter included TP specific (TPS) neurons, trigeminal wide dynamic range (trigeminal WDR) neurons with TP input, trigeminal subnucleus reticularis ventralis (trigeminal SRV) neurons with TP input and convergent reticular formation (convergent RF) neurons with TP input. TPS neurons were located in the dorsal marginal rim of the trigeminal subnucleus caudalis, i.e., in the marginal layer or the outer zone of substantia gelatinosa. WDR neurons with TP input were found in the neck region of medullary dorsal horn which corresponds to the lateral part of subnucleus reticularis dorsalis (SRD). Trigeminal SRV neurons with TP input were located in the lateral part of SRV. Convergent RF neurons with TP input were found in the middle third of the caudal bulbar RF consisting of SRD and SRV. Both TPS neurons and WDR neurons with TP input included trigeminothalamic neurons as evidenced by the antidromic activation from the nucleus ventralis posteromedialis of the contralateral thalamus. A significant proportion of both trigeminal SRV and convergent RF neurons with TP input were antidromically activated by stimulation of the nucleus centralis lateralis of the contralateral thalamus. The former two subclasses may subserve the sensory-discriminative aspect of toothache, while the latter two subclasses, the emotional-motivational aspect.
Animals↗
Methylcobalamin induces a long-lasting enhancement of the field potential in rat suprachiasmatic nucleus slices.
Optic nerve stimulation has been reported to evoke a field potential (FP) in rat suprachiasmatic nucleus (SCN) slices. Methylcobalamin,delta-(5,6-dymethylbenzimidazolyl)-Co-methyl-cobam ide (Me-B12) enhanced this FP and the enhancement lasted more than 1 h after washing out. Maximal enhancement (143.6 +/- 9.8%) was achieved at a concentration of 10 microM. By contrast, cyanocobalamin containing CN- instead of CH3- showed no enhancement of the amplitude in the FP. Me-B12 induced enhancement of FP was strongly blocked by an N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV). These results indicate that CH3- in the Me-B12 is required to modulate the FP amplitude and the NMDA receptor is involved in the long-lasting FP enhancement induced by Me-B12. The present results suggest that Me-B12 modifies the photic entrainment of the circadian clock in the suprachiasmatic nucleus via an activation of NMDA receptors.
2-Amino-5-phosphonovalerate↗
Bafilomycin A1 induces apoptosis in PC12 cells independently of intracellular pH.
PC12 cells growth-arrested with bafilomycin A1 died showing apoptotic chromatin condensation in the nuclei. The bafilomycin A1-induced chromatin condensation was preceded by neurite outgrowth (NOG), required higher concentrations of bafilomycin A1 than NOG, and was suppressed by cycloheximide and aurintricarboxylic acid. NH4Cl (10 mM), another acidotropic pH perturbing agent, neither induced apoptotic chromatin condensation by itself nor suppressed that induced by bafilomycin A1, suggesting that bafilomycin A1-induced apoptosis occurs independently of intracellular pH in PC12 cells.
Ammonium Chloride↗