Biomedical subjects
T Dohi
Publications and source records attributed to T Dohi.
[The effect of LDL-apheresis on the long-term prognosis of hypercholesterolemic patients with coronary artery bypass grafts: a multicenter study].
Hypercholesterolemia is well known as a risk factor which had been shown to affect the long-term prognosis after coronary artery bypass grafting (CABG). The data were collected from multi-institutions documenting the long-term results of CABG in 61 hypercholesterolemic patients who received LDL-apheresis. Mean post-CABG period was 50 +/- 34 (+/- SD) months. Mean period of therapy by LDL-apheresis using Liposorber system after CABG was 25 +/- 17 months with a frequency of once per 2.6 +/- 1.3 weeks. Before initiating LDL-apheresis mean serum cholesterol (TC) and LDL-cholesterol (LDL-C) were 327 mg/dl and 261 mg/dl, respectively. With combined LDL-apheresis and lipid-lowering drug therapy mean TC and LDL-C were reduced to 247 mg/dl and 177 mg/dl immediately pre-apheresis and 106 mg/dl and 60 mg/dl immediately post-apheresis, respectively. Two of 61 patients had PTCA post CABG. Percent free from cardiac event during the long-term period post CABG as calculated by the life-table method was 97% at 3 years and 94% at 4 years and thereafter. While number of the patients is still small, the aggressive cholesterol-lowering therapy by LDL-apheresis is suggested to improve the prognosis of hypercholesterolemic patients with bypass grafts.
Substrate specificity and distribution of UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase in the human stomach.
The detailed substrate specificity of the UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase to form the Sd(a+) blood group active carbohydrate determinant GalNAc beta 1-4(NeuAc alpha 2-3)Gal was studied using a membrane fraction prepared from human gastric fundic mucosa. Various sialosylated oligosaccharides and gangliosides were examined as acceptor substrates. Oligosaccharide substrates were fluorescence-labelled with 2-aminopyridine, and the transferase activity was quantified by h.p.l.c. using a reversed-phase column. The structures of the products were determined by glycosidase degradation and proton n.m.r. 3'-Sialyl-lactose (II3NeuAcLac), 3'-sialyl-lactotetraose (IV3NeuAcLc4), and 3'-sialyl-lactoneotetraose (IV3NeuAcnLc4) were good substrates for the beta 1-4GalNAc transferase in gastric fundic mucosa, but 6'-sialyl-lactoneotetraose (IV6NeuAcnLc4) or 6'-sialyl-lactose (II6NeuAcLac) were not. Gangliosides with a terminal NeuAc alpha 2-3Gal residue such as GM3, sialylparagloboside, GM1b and GD1a were also studied. The activity of beta 1-4GalNAc transfer to sialylparagloboside was much higher than that to GM2, GM1b or GD1a in spite of them having the same terminal residue. Measurement of the activity of the beta 1-4GalNAc transferase in biopsy specimens demonstrated that the activity was localized in gastric fundic mucosa and was absent in pyloric mucosa, intestinal metaplasia and gastric cancer tissue. Thus the beta 1-4GalNAc transferase present specifically in fundic mucosa required a NeuAc alpha 2-3Gal residue connected to either type-1-chain or type-2-chain oligosaccharides. In glycolipids, the acceptor specificity was restricted to NeuAc alpha 2-3Gal beta 1-4GlcNAc because the NeuAc alpha 2-3Gal beta 1-3GalNAc structure in ganglio-series glycolipids was not a good acceptor substrate.
Involvement of Ca2+ entry and inositol trisphosphate-induced internal Ca2+ mobilization in muscarinic receptor-mediated catecholamine release in dog adrenal chromaffin cells.
Catecholamine (CA) release from adrenal medulla evoked by muscarinic receptor stimulation has been studied using isolated perfused adrenal gland and cultured chromaffin cells from dogs. Muscarine and oxotremorine (1-100 microM), and bethanechol (0.1-1 mM) dose-dependently stimulated CA release. Muscarine-evoked CA release was antagonized with M1-antagonist, pirenzepine and, to a lesser extent, with atropine; and was reduced either by removal of extracellular Ca2+ or treatment with Ca2+ channel blockers. Muscarine caused an increase of 45Ca uptake and 22Na uptake. Tetrodotoxin (TTX) did not affect muscarine-evoked increase of 22Na uptake and CA release. Under the absence of extracellular Ca2+, muscarine stimulated a 45Ca efflux. Muscarine-induced CA release was attenuated by treating the cells with 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate-HCl (TMB-8) which blocks Ca2+ release from the intracellular store. A phospholipase C inhibitor, neomycin, markedly reduced muscarine-induced CA release but not nicotine- and high K(+)-evoked release. Cinnarizine, a Ca2+ channel blocker, attenuated muscarine-evoked but not caffeine-induced CA release and 45Ca efflux in the absence of extracellular Ca2+. Muscarine caused an increase in intracellular free Ca2+ concentration ([Ca2+]i) in the presence of extracellular Ca2+. It caused a similar increase, but to a lesser extent, in the absence of extracellular Ca2+. The increase of [Ca2+]i induced by muscarine without extracellular Ca2+ was reduced by neomycin and cinnarizine. Polymixin B and retinal, which reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced CA release, had little effect on muscarine-induced CA release. Muscarine increased cellular Ins(1,4,5)P3 production, and atropine inhibited this increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Ganglioside composition and its relation to clinical data in brain tumors.
The ganglioside composition of 15 cases of meningioma, 15 cases of astrocytoma, 5 cases of neurinoma, 4 cases of ependymoma, 3 cases of metastatic brain tumor and 1 case each of mixed glioma, oligodendroglioma, medulloblastoma, embryonal carcinoma, and cultured glioma cell line were analyzed by thin-layer chromatography. The GM2, GD3, and GD2 content of the tumors was determined using specific monoclonal antibodies (MAb). Cases were grouped according to the difference in ganglioside pattern and various clinical features. In meningiomas and astrocytomas, GM3 and GD3 were the major gangliosides. The tumor content of the rather simple gangliosides (GM3, GM2, GD3, GD2) increased or was almost equal to that of normal tissue (leptomeninges tissue in the case of meningiomas, and brain tissue in the case of astrocytomas), while the tumor content of complex gangliosides (GM1, GD1a, GT1a, GT1b) decreased as compared with normal tissue. The GM3 content of meningiomas increased in middle-aged patients, who comprised the majority of the patients with these tumors. The GD2 content decreased in middle-aged patients with initial symptoms of meningioma within a year. The GM3 content of astrocytomas decreased in patients who underwent radiotherapy. The amount of GM3 and GD3 increased in small tumors. GM3 may be related to the early proliferative stage. The ganglioside patterns of brain tumors are shown in this study to differ according to clinical features and also to be changeable in their clinical courses.
Mechanical circulatory support with a centrifugal pump after open heart surgery.
Since December 1988, a centrifugal ventricular assist device (VAD) was used to support the circulation in 5 patients who could not be weaned from cardiopulmonary bypass (CPB) or developed cardiogenic shock after removal from CPB. Three patients required a left VAD, one needed a right VAD. One patient had biventricular support using a centrifugal left VAD and a diaphragm type right VAD. The duration of the centrifugal VAD support ranged from 6 to 136 (mean 72)h. All patients were weaned from the VAD, but only 2 patients were discharged from the hospital. Two patients died of multiple organ failure, and one died of cardiogenic shock caused by intractable arrhythmia. Infection occurred in all non-survivors, and 2 of them developed renal failure. We conclude that the centrifugal VAD is effective to recover a failing ventricle. The factors related to the unsuccessful recovery were delayed start of the VAD support and major complications such as infection as infection and renal failure.
Machine perfusion of isolated kidney at 37 degrees C using pyridoxalated hemoglobin-polyoxyethylene (PHP) solution, UW solution and its combination.
To preserve isolated kidney normothermically, PHP containing UW components were evaluated as perfusates. Kidneys were flushed out by Lactate Ringer solution immediately after isolation from mongrel dogs, and then connected to the perfusion circuit which consists of a preservation box, a reservoir of perfusate, a membrane oxygenator and a drive unit. PHP containing 140 mEq/l of Na+ and 4 mEq/l of K+ (PHP(E)), UW solution (UW) and UW components added PHP(E) were prepared and adjusted at pH 7.4 prior to use. Temperature and perfusion pressure were controlled at 37 degrees C and 100 mmHg, respectively. During 12 hour perfusion, remarkable changes in pH were seen in UW group and PHP group while higher oxygen consumption was noted in PHP(E)+UW group than that in PHP(E) group. The histological findings showed moderate damages of tubular epithelial cells and maintaining normal glomerular structure in PHP(E)+UW while severe damage of both tubulus in UW group were seen. There was no edematous degeneration in both UW and PHP(E)+UW groups, however, it was seen in PHP(E) alone. It was suggested that components of UW solution have positive effect on normothermic machine perfusion with PHP(E) solution.
[Glycolipid in gastric cancer].
Explore the source record for details and available documents.
Localization of UDP-GalNAc:NeuAc alpha 2,3Gal-R beta 1,4(GalNAc to Gal)N-acetylgalactosaminyltransferase in human stomach. Enzymatic synthesis of a fundic gland-specific ganglioside and GM2.
A glycolipid detected in human gastric mucosa with anti-GM2 monoclonal antibody was characterized to be GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4GlcNAc beta 1-3Gal 1-4Glc-Cer (NGM-1), which was lost in gastric cancer tissue with complementary increase of GM2 sharing the same terminal carbohydrate structure as NGM-1 (Dohi, T., Ohta, S., Hanai, N., Yamaguchi, K., and Oshima, M. (1990) J. Biol. Chem. 265, 7880-7885). The study on differential expression of NGM-1 in gastric fundic mucosa, pyloric mucosa, gastric cancer, and various other tissues indicated that NGM-1 existed specifically in fundic mucosa. The content of GM3 and sialylparagloboside (SPG), which are the substrates for the synthesis of GM2 and NGM-1, respectively, were not significantly different in these tissues. Therefore, the presence of two kinds of beta 1,4GalNAc transferases having different substrate specificity was considered to be critical for the expression of NGM-1 and GM2. The activity of beta 1,4GalNAc transferase which synthesizes GM2 or NGM-1 was determined by detecting the products with specific monoclonal antibodies. The activity of beta 1,4GalNAc transfer to SPG was high in fundic mucosa, while it was absent in pyloric mucosa or cancer. On the other hand, the increased activity of beta 1,4GalNAc transfer to GM3 was observed in cancer tissues and cancer cell lines which were rich in GM2. Our conclusion is that the limited expression of NGM-1 in fundic mucosa and the increase of GM2 in cancer are attributed to two types of beta 1,4GalNAc transferases localized in each region with different substrate specificity; the one in fundic mucosa transfers GalNAc to SPG but not to GM3, and the other one enhanced in cancer transfers GalNAc to GM3 but not to SPG.
Calcium-dependent biosynthesis of platelet-activating factor by submandibular gland cells.
Isolated dog submandibular gland cells synthesize platelet-activating factor (PAF) when stimulated with acetylcholine (ACh). This production of PAF was concentration- and time-dependent, and was inhibited by pretreatment with anticholinergic agents. PAF that had accumulated in cells through prior stimulation with ACh vanished rapidly on addition of atropine. Phenylmethanesulphonyl fluoride produced an accumulation of PAF in non-stimulated cells and greatly potentiated further ACh-induced accumulation. PAF production and [14C] arachidonic acid (AA) liberation induced by ACh were increased by higher concentrations of extracellular Ca2+, and ACh failed to stimulate PAF formation in the absence of Ca2+, although ACh still stimulated the liberation of [14C]AA without Ca2+. Both the Ca2+ ionophore ionomycin in intact cells and Ca2+ (at concentrations greater than or equal to 300 nM) in digitonin-permeabilized cells facilitated PAF formation. 1-O-Alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase activity rapidly increased in cells incubated with ACh or ionomycin. These results suggest, at least, that the stimulation of a remodelling pathway is involved in the increased PAF synthesis induced by ACh. Dithiothreitol-insensitive cholinephosphotransferase activity was also activated by ACh. However, the activation of both enzymes by ACh was transient, in spite of the fact that ACh-stimulated PAF formation was continuous. This may suggest that additional mechanism(s) other than the activation of these enzymes play an important role in controlling PAF synthesis. The present study provides further evidence that the exocrine submandibular gland cells of dogs have the capacity to increase PAF turnover upon stimulation in a Ca(2+)-dependent manner and retain PAF within the cells partly associated with the membrane and partly released into the cytosol.
Stimulation by carrageenan of arachidonate 12-lipoxygenase activity in dog gingival tissue.
At 4 h after injection of carrageenan into the gingiva, the 12-lipoxygenase activity of the gingival homogenate was markedly increased. Activity in the cytosol and microsomal fractions was markedly increased when assessed as the specific activity based on nmol/min/mg of protein, and in the cytosol fraction as the percentage distribution of total activity. The 12-lipoxygenase activity in the homogenate from carrageenan-treated gingiva was not affected by either EDTA or calcium ion, or a combination of the two. 12-lipoxygenase activity in both carrageenan-treated and untreated gingiva was inhibited dose-dependently by AA861, a striking difference from its effect on platelet 12-lipoxygenase. There was a marked increase of 12-lipoxygenase activity in experimentally inflamed gingiva compared to the non-inflamed gingiva.
Calcium dependency of adrenergic and muscarinic cholinergic stimulation of mucin release from dog submandibular gland cells.
Stimulation of muscarinic cholinergic, alpha-adrenergic and beta-adrenergic receptors elicited mucin release from dispersed dog submandibular cells. The secretory response to acetylcholine was much more pronounced than to adrenergic agonists, and largely dependent on the presence of extracellular Ca2+, but the dependency on extracellular Na+ was slight. Ionomycin also stimulated mucin release. In rat submandibular cells, neither muscarinic cholinergic agonists nor ionomycin were as effective mucosecretagogues as beta-adrenergic agonists. alpha-Adrenoceptor-mediated release was decreased by chelating extracellular Ca2+ with EGTA. The beta-adrenoceptor-mediated response was diminished by extensive exposure of cells to EGTA, due at least in part to the requirement of Ca2+ for beta-adrenoceptor stimulation of cAMP formation. 8-br-cAMP stimulated 45Ca2+ release from cells preloaded with 45Ca2+. The 8-br-cAMP-induced mucin release was eliminated in ionomycin-pretreated cells, but not inhibited by chelating extracellular Ca2+ and by the treatment of the cells with TMB-8 or in the cells loaded with BAPTA. These results suggest that not only the adrenergic system but also the muscarinic cholinergic system may participate in the regulation of mucin release in dog submandibular gland, and also provide the possibility that, in addition to a cAMP-mediated mechanism, Ca(2+)-dependent mechanisms may be involved in mucosecretion in dog submandibular acini.
Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells.
1. gamma-Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and enhances the stimulation-evoked CA secretion via facilitation of Ca2+ entry in a Cl(-)-dependent manner. The present study was designed to investigate further the ionic mechanism of modulation by GABA of CA secretion from adrenal medulla, using a primary culture of bovine chromaffin cells. 2. Tetrodotoxin (TTX), a voltage-sensitive Na+ channel blocker, reduced GABA-evoked CA secretion. 3. Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA-evoked CA secretion in a TTX-sensitive manner. 4. Tetraethylammonium (TEA) and cesium, which are known to block some types of K+ channels, markedly enhanced GABA-evoked CA secretion in a concentration-related fashion. TEA-induced enhancement of the GABA-evoked CA secretion was attenuated by TTX or replacement of extracellular Na+ by choline. On the other hand, ouabain accelerated the effect of TEA. 5. TEA and ouabain also enhanced GABA-induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. 6. Veratridine increased accumulation of cytosolic Ca2+ in a TTX-sensitive manner. GABA facilitated the veratridine-induced elevation of cytosolic Ca2+ even when the GABA-induced rise of cytosolic Ca2+ levelled off. 7. These results suggest the involvement of repetitive action potentials in modulation of GABA by Ca2+ mobilization and, as a consequence, of the CA secretion in chromaffin cells.
Inhibition of lipoxygenase by phenolic compounds.
Eugenol dose-dependently inhibited 5-HETE (5-hydroxy-5,8,10, 14-eicosatetraenoic acid) and 15-HETE formation by human polymorphonuclear leucocytes. p-Chlorophenol, guaiacol and phenol also inhibited the lipoxygenases. Formation of HETEs by rat dental pulp was inhibited by eugenol and p-chlorophenol. The concentrations of the phenolics required to inhibit lipoxygenases were in the similar range with those used for inhibiting cyclooxygenase. These results showed that phenolic compounds inhibited lipoxygenases and thus suggest that these compounds may be dual inhibitors of lipoxygenase and cyclooxygenase.
Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions.
Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. alpha-Methyl-p-tyrosine (alpha-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The incidence of lidocaine-induced convulsions was decreased by treatments with alpha-MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihydroxyphenylalanine (L-DOPA), although the brain DA level was increased by L-DOPA. Methamphetamine and desipramine increased the incidences of lidocaine-induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ-seizure, act to facilitate lidocaine-induced convulsions.
[Computer aided system in blood purification].
Explore the source record for details and available documents.
[Wearable artificial kidney, portable artificial kidney and implantable artificial kidney].
Explore the source record for details and available documents.
Development of a computer-aided surgery system: three-dimensional graphic reconstruction for treatment of liver cancer.
Simulation of the needle puncture and volume estimation for the tumors in the liver were carried out with the three-dimensional image reconstruction system, which consists of a medical image acquisition system, a data processing system, and a graphic display. A set of sliced-image data from a computerized tomography and/or a magnetic resonance imaging was used to reconstruct the liver, the vessels, and the tumors of the patients with liver cancer. A good agreement of anatomic locations of both the intrahepatic vessels and the tumors between the reconstructed liver model and the echography done intraoperatively was observed. Surgical simulations with these graphic models clearly indicated safety areas for needle puncture in the laser coagulation therapy. In addition liver volumes were calculated within 3% of error in comparison to the measured values. These results indicate that the computer-aided surgery system is a highly promising method that avoids cumbersome stereoscopic recognition of the anatomical location of the diseased area and the vessels, before and after surgery.