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Biomedical subjects

G Kato

Publications and source records attributed to G Kato.

At least 55 records · Page 3Linked to original sources

Membrane-bound N-acetyl-beta-glucosaminidase. Different binding specificity in control and I-cell disease livers.

Several lysosomal enzymes solubilized at pH 4 from saponin-treated membranes showed markedly variable affinities to the bovine liver phosphomannosyl receptor in both bovine and human livers. The enzymes from I-cell disease liver did not bind the receptor in spite of normal intracellular activities. N-Acetyl-beta-glucosaminidase was effectively released from the membrane preparation of a control liver by mannose 6-phosphate, and other sugars showed little effect in this experiment. However, in the I-cell disease liver, dissociation occurred not by mannose 6-phosphate but by other sugars, such as fucose, mannose and N-acetyl-D-glucosamine. These results indicate the presence of an alternate transport system other than the pathway mediated by the mannose 6-phosphate receptor, and the role of other sugar-binding proteins is discussed in intracellular processing and transport of newly synthesized enzymes.

Acetylglucosaminidase↗

Neurotransmitters and receptors: clinical implications.

With the advent of new techniques such as the radioreceptor binding assay, significant advances have been made in the field of psychopharmacology during the past seven years. In this paper we discuss some of these contributions regarding our understanding about the nature of different psychopathological conditions such as anxiety, depression and schizophrenia.

Anxiety↗

Studies on the activity of Obioactin with acetylspiramycin on mice infected with Toxoplasma gondii.

In acutely infected mice, acetylspiramycin (ASPM) administered in combination with Obioactin , or sulfamethoxypyrazine ( SMPZ ), prevented Toxoplasma organisms from encysting in the brain and heart tissues. When administered alone, ASPM prevented these organisms from encysting in the heart but not in the brain. All the regimens used failed to reduce the bulk of parasites in the brain and heart tissues of chronically infected mice. Treatment with an ASPM- Obioactin combination, however, brought about the most remarkable reduction, or 52.4%, of the cyst count in the brain of all the methods of treatment applied. Light and electron microscopy of the mice with chronic Toxoplasma infection revealed no changes in the brain or heart tissue of the ASPM- Obioactin treated mice and degenerative changes in the cyst wall and bradyzoites and a remarkable increase of microglias with cysts in the brain in some of these mice.

Animals↗

[Angiographic analysis of vascular anatomy in gastric cancer].

Celiac, left gastric, common hepatic and superior mesenteric angiography was performed in 296 gastric cancer patients. Relationship between anatomical variations and the mode of lymphatic metastasis was discussed. The emergence of right gastric artery was from hepatic artery proper in 46.9%, right, middle and left hepatic in 26.4%, common hepatic and gastroduodenal in 18.6%, and others in 5.4%. The rate of metastasis to suprapyloric nodes was the highest (20.0%) among the cases, in which the right gastric artery was given off distal to the hepatic artery proper. Left gastric artery emerged from the celiac in 94.9%, splenic in 2.7%, abdominal aorta in 2.1%, and common hepatic in 0.3%. Knowledge of the origin of the arteries is essential to thorough dissection of the perivascular lymph nodes. The accessory hepatic arteries emerged from left gastric artery in 17.9% of the cases, in which the rate of lymph node metastasis along left gastric artery was higher than others. Left gastric artery should be severed at its point of emergence for thorough dissection of lymph nodes along this artery in gastric cancer. However, the fact that 20.8% of accessory left hepatic arteries were perfusing more than 2 liver segments must be into consideration.

Angiography↗

[Histopathological evaluation of transarterial one shot infusion of adriamycin as a preoperative adjuvant chemotherapy for the breast cancer].

Thirty patients with resectable breast cancer were treated with transarterial one shot infusion of 20 mg of adriamycin as a preoperative adjuvant chemotherapy. After breast angiography by Seldinger's method, adriamycin at a dose of 20 mg was administered through the feeding artery with one shot injection. Anticancer effect of adriamycin was evaluated microscopically after radical mastectomy. In the primary tumor, the effective histological changes were found in 9 (30%) of 30 cases. In the metastatic lymph nodes, the effective changes were found in 5 (50%) of 10 cases. Mild side effects were seen in 70% of the cases, but not serious. It was suggested that transarterial one shot infusion of 20 mg adriamycin was a histopathologically effective procedure as preoperative chemotherapy for breast cancer.

Adult↗

Central nervous system receptors in neuropsychiatric disorders.

1. Introduction of radioligand binding techniques has opened new possibilities in the study of the biological basis of psychiatric disorders. 2. The possible role of CNS receptors in schizophrenia, depression, anxiety, Huntington's disease and Alzheimer's dementia is discussed. 3. Data are presented in a systematic manner starting with the identification of receptors which appear to be the primary locus of action of drugs currently used in the treatment of these disorders. 4. A review of the data on the changes in receptor levels and/or affinity that might be associated with the respective disease follows. 5. Changes in receptor number and/or affinity after chronic drug therapy are outlined and the possible utilization of radioligand binding techniques in drug plasma level determination is discussed.

Aging↗

Reduced number of alpha- and beta-adrenergic receptors in the myocardium of rats exposed to tobacco smoke.

The concentration of alpha- and beta-adrenergic receptors--as measured by specific [3H]WB-4101 and (-)-[3H]dihydroalprenolol binding--was diminished by 60% below control values in the hearts of rats exposed to tobacco smoke. These changes in receptor numbers took place almost immediately after tobacco smoke exposure and were rapidly reversible after termination of the exposure. The dissociation constant, KD, for [3H]WB-4101 was identical in exposed (KD = 0.34 +/- 0.09 nM) and control (KD = 0.35 +/- 0.07 nM) hearts but was significantly different in the case of (-)-[3H]dihydroalprenolol binding (exposed, KD = 2.83 +/- 0.30 mM vs. control KD = 5.22 +/- 0.61 nM). For beta-receptor binding there was no significant difference between exposed and control animals in the Ki values for (-)-epinephrine, (-)-norepinephrine, (-)-alprenolol, (+/-)-propranolol or timolol. (-)-Isoproterenol, however, was found to bind with lower affinity in exposed compared with control hearts. For alpha-receptor binding there was no significant difference between control and 'smoked' animals in the Ki values for (-)-epinephrine, (-0)-norepinephrine or phentolamine. The decrease in alpha- and beta-adrenergic receptor concentration may be related to the phenomenon of receptor desensitization resulting from a release of catecholamines in rats exposed to tobacco smoke.

Animals↗

[Acetylcholine receptors (author's transl)].

The actions of acetylcholine can be classified as nicotine-like or muscarine-like. Nicotinic actions of acetylcholine are seen at the skeletal neuromuscular junction and at autonomic ganglia whereas muscarinic transmission occurs at parasympathetic effector organs and in the brain. The sites on the membrane surface of a neuronal cell body or dendrite where acetylcholine acts is called a receptor site. There has been marked progress in the last few years in the identification and quantification of acetylcholine receptors by biochemical methods by means of specific radioactive ligands of very high activity and very high affinity for these receptors. Using these techniques it has been possible to: determine the regional distribution of nicotinic and muscarinic receptors in the brain, evaluate new drugs acting on these receptors, and determine the concentration of these receptors in neurologic disorders.

Acetylcholine↗

Fluidity of the lipids next to the acetylcholine receptor protein of torpedo membrane fragments. Use of amphiphilic reversible spin-labels.

Choline esters of spin-labeled fatty acids (long-chain acylcholines) were used to probe the hydrophobic environment of the acetylcholine receptor protein in membrane fragments from Torpedo marmorata. These spin-labels competitively inhibit the binding of [3H]acetylcholine to the receptor site. Their inhibition constants (KI) were close to 200 nM. At the high membrane concentration required for electron spin resonance (ESR) experiments, the apparent inhibition constants (KIapp) differed from KI determined by using dilute membrane concentration. This is due to the amphiphilic character of long-chain acylcholine. For most spin-labels used, only difference ESR spectroscopy provided reliable spectra corresponding to receptor-bound spin-labeled acylcholines. Acetylcholine receptor agonists and antagonists displaced the acylcholine from the receptor sites, whereas choline had only a weak effect. This produced a modification in the ESR spectra of the bound acylcholines and provided evidence that the acylcholines bound to the receptor sites in a specific manner. The interpretation of the spectra of receptor-bound spin-labels favored a strong barrier to the motion of the probe when attached to the middle of the acyl chain. However, when the probe was close to the methyl terminal of a stearoylcholine molecule a much greater fluidity was found. Short-range spin-spin interactions were created between spin-labels bound to the receptor site and spin-labels in a fluid phase. This indicates that lipids next to the receptor protein are not completely immobilized in spite of the semicrystalline organization of the proteins in the postsynaptic region.

Acetylcholine↗

Biochemical studies on muscarinic receptors.

Muscarinic receptors have been characterized in smooth muscle and brain by the binding of reversible (e.g. atropine, quinuclidinylbenzylate) or irreversible (benzilylcholine or propylbenzilylcholine mustards) ligands. There is a close correlation between affinity constants derived from binding experiments and the affinities of muscarinic ligands for these sites obtained in pharmacological experiments on smooth muscle. Whereas atropine shows a single high affinity binding component (in subcellular preparations) several other ligands (QNB, ACh, oxotremorine) show multiple affinity binding. This indicated the existence of several types of binding sides which show selectivity toward certain cholinergic effectors. Most detergents inhibit the binding of ligands to the receptor site and therefore cannot be used to solubilize the receptor protein from the membrane. Treatment of brain subcellular membrane preparations with high salt concentrations (2M NaI) solubilize proteins which possess the muscarinic ligand binding properties observed in the membrane preparation. The affinities for muscarinic antagonists however are decreased, which suggests that a conformational change occurs in the protein upon solubilization.

Acetylcholine↗