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Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 811 records · Page 45Linked to original sources

[Fundamental study on nuclear medicine imaging of cholinergic innervation in the brain: changes of neurotransmitter and receptor in animal model of Alzheimer's disease].

A fundamental study was performed on the nuclear medicine imaging of cholinergic innervation in the brain. In a cholinergic denervation model prepared by producing an unilateral basal forebrain lesion in the rat, which is reported to be one of animal models of Alzheimer's disease, quantitative determination of acetylcholine in parietal cortices revealed statistically significant 31% decrease on an average in the ipsilateral side relative to the contralateral side to the lesion. In vitro receptor autoradiography showed no significant differences in total, M1 and M2 muscarinic acetylcholine receptors between the ipsilateral and contralateral cortices to the lesion. Simultaneous mapping of presynaptic cholinergic innervation using 3H-2-(4-phenylpiperidino) cyclohexanol (AH5183) demonstrated significant 14% decrease of AH5183 binding on an average in the ipsilateral relative to the contralateral fronto-parieto-temporal cortices to the lesion. These results suggest that AH5183 is a promising ligand for mapping cholinergic innervation in nuclear medicine imaging.

Acetylcholine↗

Autoradiographic analysis of iodoamphetamine redistribution in experimental brain ischemia.

The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a "physical" phenomenon (only flow related) rather than a "biologic" one.

Amphetamines↗

[Brain perfusion SPECT imaging before and during the acetazolamide test using 99mTc-HMPAO].

A new method using brain perfusion 99mTc-HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide test with a short period. The first SPECT study was carried out for 13.5 min to obtain SPECT images at the resting state after 3 min postinjection of 555 MBq (15 mCi) of 99mTc-HMPAO. At the same time as the start of the first SPECT study, 1 g of acetazolamide was intravenously injected. Immediately after the stop of the 1st SPECT study, 925 MBq (25 mCi) of 99mTc-HMPAO from the same vial as in the first study was additionally injected. Three minutes later the second SPECT study was carried out for 10 min. After reconstruction the tomographic images in the first study were subtracted from the images in the second study to obtain those during the acetazolamide test after correction of the time differences in data acquisition between the two studies. This subtraction technique gives independent brain perfusion SPECT images before and during the acetazolamide test. Besides, the regional flow changes during the test were quantitatively analyzed. In conclusion this method seems to be practically useful for evaluating regional brain perfusion before and during drug treatments as a consecutive study with a short period of approximately 30 min.

Acetazolamide↗

Cell type-specific expression of the genes for the protein kinase C family: down regulation of mRNAs for PKC alpha and nPKC epsilon upon in vitro differentiation of a mouse neuroblastoma cell line neuro 2a.

By the use of cloned cDNAs for protein kinase C isozymes alpha, beta I, beta II, gamma, and those for novel protein kinase C, epsilon and zeta, the expression of the corresponding mRNA species was examined in various mouse tissues, human lymphoid cell lines, and mouse cell lines of neuronal origin. In adult brain, mRNAs for all the isozymes of PKC family are expressed. However, the expression of these mRNA species in brain is low at birth. A similar pattern of expression was also observed for beta I/beta II mRNAs in spleen. These expression patterns are in clear contrast to that for beta I/beta II mRNAs in thymus where the mRNAs are expressed at birth and the levels of expression decrease with age. Human lymphoid cell lines express large amounts of PKC beta mRNAs in addition to PKC alpha. Further, nPKC epsilon mRNA is expressed in some of these cell lines. On the other hand, all the mouse cell lines of neuronal origin tested express nPKC epsilon and zeta in addition to PKC alpha. In a mouse neuroblast cell line, Neuro 2a, down modulation of mRNAs for both PKC alpha and nPKC epsilon was observed in association with in vitro differentiation.

Animals↗

Molecular cloning of a full-length cDNA for human alpha-N-acetylgalactosaminidase (alpha-galactosidase B).

In the process of molecular cloning of cDNA for proteins associated with a purified human placental sialidase fraction, we discovered one of the proteins with apparent molecular weight of 46 kDa is in reality alpha-N-acetylgalactosaminidase. The full length cDNA, pcD-HS1204, codes for 358 amino acids with the first 17 residues representing a putative signal peptide. The predicted amino acid sequence shows striking homology with human alpha-galactosidase A and yeast alpha-galactosidase. The substrate specificities as well as the behavior of the 46 kDa protein on hydroxylapatite chromatography confirmed that the 46 kDa protein is in reality alpha-N-acetylgalactosaminidase.

Amino Acid Sequence↗

Induction of astroglial growth inhibition and differentiation by sialosyl cholesterol.

Normal rat astroblasts in culture were exposed to 11 sialosyl or cholesterol derivatives at concentrations lower than 20 microM. Synthesized sialosyl cholesterols (alpha- and beta-D-N-acetyl neuraminyl cholesterols) and cholesterol sulfate showed a marked growth inhibitory action. Sialosyl cholesterol uniquely evoked an astroglia-like stellation resembling that induced by glia maturation factor (GMF) as well as a suppression of GMF-induced mitogenesis of astroblasts. The minimal incubation period of sialosyl cholesterol for the initiation of growth inhibition was as short as one hour. The inhibitory effect retained an irreversibility even after removal of the drug. Cytosolic protein with 58 kDa Mr in size was specifically phosphorylated by sialosyl cholesterol through a certain protein kinase dependent on neither Ca2+ nor cyclic AMP. The competition experiment of sialosyl cholesterol action revealed that sialosyl and cholesterol moieties were indispensable for the phenomena. These results most likely imply that sialosyl cholesterol alters the membrane microenvironment to affect the affinity of growth factor receptor, protein kinase activity, and/or cytoskeletal anchorages.

Animals↗

Bioactive ganglioside-mediated carbohydrate recognition in coupling with ecto-protein phosphorylation.

Recent studies, including ours, on bioactive gangliosides revealed that certain gangliosides have an interesting ability to modulate a variety of cell functions. For instance, we demonstrated that a tetrasialoganglioside, GQ1b, promotes neurite outgrowth when added in nanomolar concentrations to cells from two human neuroblastoma cell lines. Also, phosphorylation of several cell surface proteins was observed on addition of ATP. Several lines of evidence indicated that this phosphorylation is probably catalysed by a novel cell surface membrane-bound protein kinase which is specifically activated by a particular ganglioside (Gg). Because of its location on the cell surface we proposed calling this type of kinase(s) ecto-Gg kinase. A procedure to inhibit the phosphorylation of the cell surface protein resulted in suppression of the GQ1b-dependent promotion of neuritogenesis, strongly suggesting that these two cellular events are intricately coupled. Other evidence also indicated that the GQ1b-dependent neuritogenesis is mediated through a receptor-coupled process of the cell surface membrane. Thus, it is likely that this represents a new type of biosignal transduction that is mediated through cell surface carbohydrate recognition (ecto biosignal transduction system).

Cell Line↗

Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man.

The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO2) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO2 level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO2 decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO2 which might be related to weakening of mucosal defensive factors.

Adult↗

Reexamination of 123I-IMP-SPECT at interictal stages in adult partial epilepsy.

123I-IMP-SPECT scans at the interictal stages in 13 epileptic patients with normal X-ray CT findings were reexamined at intervals of 1.9 +/- 0.8 years. Interictal scalp EEGs were recorded a few hours after each SPECT scan. All of the SPECT abnormalities indicated focal hypofixation images of 123I-IMP, i.e. zones of a decreased rCBF reflecting a functional inactivation. Among 11 patients with the SPECT abnormalities in the first SPECTs, eight cases had the complete or partial regional reproduction of the abnormalities in the second SPECTs. As changes in the SPECT findings, an alteration from the abnormal SPECT images to normal images (normalization), the reverse change, the enlargement and reduction of hypofixation sites were seen. Also the EEG foci had various changes (right and left regional changes, etc.). Because of these SPECT and EEG changes, the regional relationship between the SPECT abnormalities and EEG foci altered in 7 patients (a change from disagreement to agreement, etc.). The high reproduction rate of SPECT abnormalities appears to increase the reliability or utility of SPECT scans for a regional diagnosis of epileptic foci. The present SPECT changes, especially the normalization or the severse change, suggest that the interictal epileptic focus may have a functional fluctuation. In addition, the causes of regional disagreement between the SPECT abnormalities and EEG foci were discussed on the basis of the present SPECT and EEG changes.

Adult↗

Adrenoleukodystrophy presenting as spinocerebellar degeneration.

The clinical features of 3 patients from a kindred with adrenoleukodystrophy and the analysis of their plasma sphingomyelin are described. Onset of symptoms was between the ages of 33 and 54 years. Ataxic gait and spasticity were the only symptoms noted during the early stage of the disorder. Dementia and optic atrophy were present in two of the cases. Baseline plasma cortisol was normal, but adrenocorticotropic hormone was elevated. Analysis of plasma sphingomyelin demonstrated an increase in very-long-chain (C24-C26) fatty acid. This study demonstrates that adrenoleukodystrophy may present with spinocerebellar symptoms.

Adrenocorticotropic Hormone↗

Acetylcholine in neurons and paraneurons: a histochemical study.

Several years ago we proposed a method for the localization of acetylcholine in the cholinergic nerve terminals. The method is based on a rapid precipitation of quarternary ammonium cations (such as acetylcholine or choline) by molybdic or tungstic heteropolyanions (such as phosphomolybdic acid, phosphotungstic acid and silicotungstic acid). The insoluble salts formed can be directly visualized under the electron microscope. In the synaptic vesicles, acetylcholine was localized as point-like precipitates, while the membranes were well preserved. Since these fixations are based on a rapid ionic interaction, the term "ionic fixation" was proposed. The ionic fixation performed on motor end-plates in various physiological conditions, provided different forms of cytochemical precipitates of acetylcholine (point-like, spot-like, diffuse or laminar). In contrast with the numerous physiological and neurochemical investigations into the acetylcholine mechanism of neurons, very little is known about paraneurons. The historical evolution of paraneuron research, more or less bound to that of the sympathetic paraganglion and of the APUD cells may explain this lack of results. In certain physiological conditions, acetylcholine can be revealed in paraneurons and seems to reflect a plasticity of the cells, as already observed in sympathetic ganglion cells. This paper further overviews the cholinergic mechanisms of exocrine secretory cells. The presence of a high cholinesterase activity exist in most of these exocrine cells, as far as we could verify. In addition to cholinesterase activity, the presence of acetylcholine, probably related to exocrine cell metabolism, was investigated with our histochemical method.

Acetylcholine↗

Changes in the intracellular calcium ion concentration in the gastric mucosa in a rat ischemia-reperfusion model.

To investigate the role of the intracellular calcium ion in the development of acute gastric mucosal lesions, phosphorylase a activity was measured as an index of the intracellular calcium ion concentration ([Ca2+]i), using Lowry's method, in the rat ischemia-reperfusion model. [Ca2+]i increased significantly at the end of the ischemic state without acute mucosal lesions (AGML). After reinfusion, [Ca2+]i showed a slight increase and AGML developed. Continual intravenous infusion of the calcium channel blocker, diltiazem (1 mg/kg/hr), inhibited the increase in [Ca2+]i in the ischemic state and reduced the development of AGML after reinfusion. These results suggest that the increase in [Ca2+]i in the ischemic state plays an important role in the development of AGML.

Animals↗

Two apparent molecular forms of bovine lactoferrin.

Bovine lactoferrin was prepared by CM-Sephadex column chromatography from defatted colostrum. When partially purified lactoferrin was analyzed by SDS-PAGE apparently two polypeptides of different size appeared. The polypeptides were transferred to a nitrocellulose sheet and visualized using antirabbit serum raised against the small polypeptide. Two polypeptides appeared clearly when stained by an immunological method. The color intensity of the two polypeptides was similar when the polypeptides were stained with Coomassie Brilliant Blue R-250. A high similarity of cyanogen bromide cleavage patterns between the two polypeptides was also observed in those stained with dye and immunologically visualized. Therefore, it is suggested that these polypeptides are lactoferrins. Comparison of the peptide patterns of the two lactoferrin molecules being deglycosylated suggested that sugar moieties may be one, but not all, of the causes of the size heterogeneity in lactoferrin. These results suggest that bovine colostrum contains two lactoferrin molecules of different size, although the physiological significance of the heterogeneity is not yet known.

Animals↗

[Late-infantile form galactosialidosis with psychomotor retardation and spastic paraparesis].

We described a case of late-infantile form of galactosialidosis. This male patient was a product of normal pregnancy. His parents were first cousins. He first sat at eight months, walked and talked at two years of age. His gait gradually became unsteady and he was diagnosed as spastic paraparesis at the age of five years. Abnormally slow learning was first pointed out at seven years of age. At the age of nine years, we evaluated him in detail at our university hospital. Physical examination revealed a short stature for his age, slightly coarse face, short neck, funnel chest, genu, pes and hallucis valgus. Corneal clouding, hernia and angiokeratoma were not found. Neurological examination showed mental retardation, bilateral optic atrophy without cherry-red spots, and spastic and slightly ataxic gait. Slight muscular atrophy with weakness was also seen in the extremities, more remarkable in the lower limbs. Deep tendon reflexes were hyperactive with bilateral ankle clonus and no extensor planter response. Routine examination of blood, urine and cerebrospinal fluid were normal except for approximately 10% lymphocytes containing cytoplasmic vacuoles. X-ray films of the backbone exhibited vertebral plana with anterior breaking at the second lumbar vertebra level. The electroencephalography showed the multiple spike and slow wave complexes. Brain CT depicted the atrophy of cerebellum. The activities of sialidase and beta-galactosidase were markedly reduced in white blood cells and cultured skin fibroblasts in this patient. His urinary excretion of sialyloligosaccharides increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbohydrate Metabolism, Inborn Errors↗

[Ganglioside modulation of protein kinase activities: it's implication in cell growth and differentiation].

Recently, some groups including ours found that some ganglioside species could specifically modulate the certain protein kinase activities on the cell surface membrane. We show here two representative cases. One is the ganglioside-dependent modulation of autophosphorylation of EGF or PDGF receptors, by which altered the cell growth. Another is the ganglioside dependent ecto-type protein kinase activities on the cell surface of a human neuroblastoma cell line, GOTO. The latter activities may be closely correlated with the ganglioside GQ1b dependent neuritogenesis.

Animals↗