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Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 1,783 records · Page 99Linked to original sources

The appearance of "exhausted" platelets at the time of stroke in stroke-prone spontaneously hypertensive rats.

Stroke was induced in stroke-prone spontaneously hypertensive rats (SHRSP) by NaCl loading. They were killed at 3 weeks and cerebral lesion was confirmed by autopsy. About 2/3 of them had strokes. Platelet count and thrombin-induced aggregation were reduced to 36% and 66%, respectively, compared with the level of those in the healthy SHRSP group which did not have stroke with the same treatment. ADP and serotonin content in platelets diminished by 45% and by 65%, respectively, due to stroke while plasma thiobarbituric acid reacting substances (TBARS, lipid peroxides) in the stroke group was two-fold that in the healthy group. Blood TBARS levels were significantly higher in rats with lower platelet serotonin content than in rats with normal serotonin content. These results suggest that marked activation of platelets has occurred due to vascular injuries at the time of stroke with a consequent decrease in platelet serotonin content and increase in plasma TBARS.

Adenosine Diphosphate↗

Metabolism of 2-oxoaldehydes in yeasts. Purification and characterization of lactaldehyde dehydrogenase from Saccharomyces cerevisiae.

NAD-dependent lactaldehyde dehydrogenase, catalyzing an oxidation of lactaldehyde to lactate, was purified approximately 70-fold from cell extracts of Saccharomyces cerevisiae with a 28% yield of activity. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The relative molecular mass of the enzyme was estimated to be 40 000 on Sephadex G-150 column chromatography and on sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The enzyme was most active at pH 6.5, 60 degrees C and specifically oxidized L-lactaldehyde to L-lactate in the presence of NAD. The Km values for L-lactaldehyde and NAD were 10 mM and 2.9 mM, respectively. The purest enzyme was extremely unstable and almost completely inactivated during storage at -20 degrees C, pH 7.5. For the reactivation of the enzyme, halide ions such as Cl-, I- and Br- were required.

Aldehyde Oxidoreductases↗

Benzoylalanine: detection and identification of an alanine conjugate with benzoic acid in hyperammonemic patients treated with sodium benzoate.

Urine of four hyperammonemic patients who were treated with large amounts of sodium benzoate were analyzed. Gas chromatographic and gas chromatograph-mass spectrometric analysis showed the presence of large amounts of benzoylalanine in addition to much hippuric acid. Benzoylalanine was identified by comparison with an authentic standard by means of its mass spectrum and the gas chromatographic retention time of its trimethylsilyl derivative. This abnormal metabolite is thought to be derived from the conjugation of benzoyl CoA with alanine. It is suggested that the excretion of benzoylalanine results from a reduction in the liver free glycine level caused by hippuric acid synthesis.

Alanine↗

Evidence for unique homologous peptide sequences around the glycosylated seryl and threonyl residues in polysialoglycoproteins isolated from the unfertilized eggs of the Pacific salmon Oncorhynchus keta.

Structures of glycopeptides obtained by exhaustive Pronase digestion of high molecular weight (1.7 X 10(5)) salmon egg polysialoglycoprotein have been elucidated. Six principal glycopeptides isolated by gel chromatography and DEAE-Sephadex A-25 chromatography in the absence or presence of borate ion were analyzed for their carbohydrate and amino acid composition, as well as amino acid sequence, and found to be of two distinct types: glycotripeptides, Thr*-Ser*-Glu, and glycotetrapeptides, Thr*-Gly-Pro-Ser, where an asterisk indicates the amino acid residues to which either the Gal beta 1----3GalNAc or Fuc alpha 1----3GalNAc beta 1----3Gal beta 1----4Gal beta 1----3GalNAc chain is attached. Their final yield corresponds to 64% of the original desialylated glycoprotein. In view of the simple amino acid composition of salmon egg polysialoglycoprotein (molar ratio Asp2Thr2Ser3Glu1Pro1Gly1Ala3) and the result of alkaline beta-elimination indicating three carbohydrate units linked to two of two threonine and one of three serine residues, a unique primary structure comprising repetitive sequences of the above two types of glycopeptides, which are interspersed by short nonglycosylated peptides consisting of alanine and aspartic acid, has been proposed for the core protein. The molecular secondary ion mass spectra of underivatized glycopeptides were used to obtain their structural information. The anomeric configuration of the proximal sugar-peptide linkages was proven to be alpha by proton nuclear magnetic resonance spectroscopy. This is the first systematic reported study of O-glycosidically linked glycopeptides by these instrumental methods.

Amino Acid Sequence↗

Frontal affinity chromatography of ovalbumin glycoasparagines on a concanavalin A-sepharose column. A quantitative study of the binding specificity of the lectin.

The interactions of Sepharose 4B-immobilized concanavalin A (ConA) with 10 glycoasparagines derived from ovalbumin were investigated quantitatively by frontal affinity chromatography. In this method, a carbohydrate solution is applied continuously to a ConA-Sepharose column and the retardation of the elution front is measured as a parameter of the strength of the interaction. The dissociation constant (Kd) for each saccharide with ConA can be determined. An analysis of the binding of p-nitrophenyl-alpha,D-mannoside has shown that the binding properties of ConA do not change essentially after immobilization on Sepharose 4B. Each of the ovalbumin glycoasparagines was labeled with tritium by the reductive methylation method for analysis. A comparison of the Kd values obtained showed that the binding of ConA varies considerably with very slight structural differences of the glycosyl chain. The results suggest that ConA recognizes a specific glycosyl chain structure, Man alpha 1-6(Man alpha 1-3)Man, in which at least one hydroxyl group at the C-3 position of C-6-linked mannose should be free. The glycoasparagines containing this structure bound strongly to ConA-Sepharose with dissociation constants below 3.4 X 10(-7) M.

Chemical Phenomena↗

The clinical value of tissue polypeptide antigen in patients with gynecologic tumors.

Tissue polypeptide antigen (TPA) was measured by radioimmunoassay in sera from patients with various gynecologic tumors: 64 uterine myomas, 129 cervical cancers, 31 endometrial cancers, and 173 ovarian tumors (89 benign, 18 low-grade malignant (LGM) and 66 malignant tumors). Among the cervical cancer patients, the incidence of elevated TPA levels increased with stage of disease from 12% in the preinvasive stage to 67% in the advanced stage. Similarly, the TPA values were elevated in 35% of the endometrial cancer patients. Among the patients with ovarian malignancies, serum TPA was elevated in the following order: LGM cases (33%), Stage I (44%), and advanced (88%). Serum TPA values varied directly with the stage and malignancy of disease, and also correlated with the effect of treatment. However, serum TPA was elevated in 22% of the patients with uterine myoma and in 12% of those with ovarian benign tumors. The current observations demonstrate that the lack of tumor specificity of TPA limits its diagnostic value in gynecologic malignancies, but that serial measurements of this antigen appear to be useful for the evaluation of therapy and monitoring of patients.

Female↗

Distribution and morphology of callosal commissural neurons within the motor cortex of normal and reeler mice.

Retrograde transport of horseradish peroxidase was used to examine the cells of origin of the callosal commissural fibers (CC neurons) in the primary motor cortex of normal and reeler mice. Quantitative analysis of the intracortical, laminar distribution, and dendritic orientation of CC neurons was performed in conjunction with qualitative observation of their morphology. For comparison, similar quantitative data were obtained for the cells of origin of the corticospinal tract (CST) of normal and reeler mice from materials described previously by Terashima et al. ('83). In the normal mouse, CC neurons are distributed in a bilaminar pattern such that the largest number of cells are located in supragranular layers II and III and in infragranular layer V. The majority of CC neurons are normal (upright) pyramids, although a few in the upper zone of layer VI are inverted pyramidal cells. In the reeler mutant, CC neurons are found in all cortical layers, but two-thirds are situated in the lower half of the cortex. On the basis of the celL shape and orientation of the apical dendrite, CC neurons of the reeler were classified into six morphological types: (1) typical pyramidal, (2) inverted pyramidal, (3) tumbled, (4) hook-shaped, (5) polymorphic, and (6) simple. The apical dendrites of the CC neurons in all layers of the cortex of the reeler mouse are randomly oriented; no direct relationship between the intracortical position of the soma and orientation of the apical dendrite was found. In contrast, CST neurons in the reeler mutant are concentrated in the outer third of the cortex, and there is a relationship between the laminar distribution of these cells and the alignment of their dendrites with respect to the pial surface: the apical dendrites of CST neurons lie in superficial layers tend to be oriented obliquely, whereas those of CST neurons in the deeper of cortex most often are oriented vertically, i.e, toward the pial surface. Quantitative analysis revealed that the relative intracortical positions of CC and CST neurons are reversed in the reeler mutant although both populations exhibited greater laminar disposition, and as a consequence, there is more intermingling of the two cell groups in the reeler than in the normal mouse. Thus, the present study suggests that the normal cytoarchitectonics of the primary motor cortex are inverted in the reeler mutant mouse.

Animals↗

Altered metabolic profiles of valproic acid in a patient with Reye's syndrome.

Urinary valproate metabolite and endogenous organic acid profiles in a 6-yr-old girl with Reye's syndrome were investigated by means of gas chromatography-mass spectrometry. 2-n-Propyl-3-oxovaleric acid, normally the major metabolite of valproate in man, was undetectable, while 2-n-propylglutaric acid, the end product via omega-oxidation was markedly increased. Polyunsaturated valproate was not found. Valproate-glucuronide was still found as the major metabolite. The clinical findings coupled with a greatly increased excretion of lactate and adipate was compatible with Reye's syndrome. Ketone bodies were not detectable. This case study shows that Reye's syndrome causes altered valproate metabolism, consistent with the defective mitochondrial beta-oxidation of medium chain fatty acids, and suggests that valproic acid should not be used in the treatment of seizures in patients with this syndrome.

Biotransformation↗

Effects of short-term treatment with calcium on the parathyroid gland of the rat, under particular consideration of the alteration of storage granules.

Short-term effects of CaCl2-treatment on parathyroid cells of the rat, especially on their storage granules, were studied at the ultrastructural level. After an injection of 4% CaCl2, serum calcium levels (SCL) rapidly increased from 9.1 mg/dl (controls) to a maximum of 14.9 mg/dl at 20 min. At 5 min after the injection, the number of type-I storage granules (large core) [NSG-I] and that of type-II storage granules (small core) [NSG-II] remained unchanged, in spite of elevated SCL (12.4 mg/dl). As soon as SCL rose to 13.2 mg/dl at 7.5 min, NSG-I gradually decreased to a minimum at 30 min; in contrast, NSG-II gradually increased to a maximum at 30 min. Vacuolar bodies also increased together with the augmentation of type-II storage granules. The average diameter of the core of the storage granules decreased significantly after the injection. Protein A-gold method for immunocytochemistry showed that the cores of these granules contain parathormone. Acid-phosphatase activity was occasionally found in storage granules of both types, especially in those of type II. It is concluded that type-I storage granules may be transformed into vacuolar bodies via type-II granules as a result of hydrolysis, and that these processes may be accelerated during hypercalcemia.

Acid Phosphatase↗

Transpetrosal-transtentorial approach and its application in the therapy of retrochiasmatic craniopharyngiomas.

Our experience with the transpetrosal-transtentorial approach to retrochiasmatic craniopharyngiomas is herein reviewed and an operative technique is described. Excellent exposure of the retrochiasmatic and suprasellar regions is gained with a minimal retraction of the temporal lobe and cerebellum. Eight cases of retrochiasmatic craniopharyngiomas that extended into the posterior hypothalamus were operated on utilizing this approach. The operative results were excellent in five patients, good in one, and poor in one. There was one death later. The principal advantage of this technique is that it allows the hypothalamus, even in cases in which the structure is remarkably displaced upwards, the third ventricular walls in cases of the intraventricular extension of the tumor, and the inferior surface of the optic chiasma and nerves to be visualized directly and thus safely preserved.

Adolescent↗

Observations on Golgi epithelial cells and granule cells in the cerebellum of the reeler mutant mouse.

Cerebella of reeler mutant mice at two months of age were studied by the Golgi impregnation method to elucidate the detailed configurations of the Golgi epithelial cells and granule cells. On the basis of configuration of their Bergmann fibers, the Golgi epithelial cells of the reeler were relatively normal, or assumed inverted, swan neck, stellate, bipolar, small, or fan shapes, although their morphological changes were continuous rather than abrupt. Radially ascending Bergmann fibers, as well as disoriented ones, arose from the soma of these varieties of Golgi epithelial cells. In many areas, the granule cells were normally aggregated under the molecular layer and constituted the granular layer, although several granule cells were regionally arrested in migration within the molecular layer in some small areas. The axon of the granule cells ascended sinuously or obliquely, extended horizontally, looped around, or descended. In some cases, the granule cells had no T-like bifurcation of the axon, and assumed a bipolar form.

Animals↗

Synthesis and antitumor activity of tropolone derivatives. 2.

Structural requirement for antitumor activity of tropolone derivatives 2-4 was explored. Isochroman derivatives (6-17, 20, and 23) and alpha, alpha-disubstituted compounds 26-30 were synthesized and their antitumor activities were tested. These nontroponoid derivatives were all inactive, implying that a tropolone ring is essential for the activity. Several compounds related to the monotropolone analogue 3 were synthesized. Among them, 31-33 showed significant activity, but their potencies were considerably weaker than those of binary tropolone analogues 4.

Animals↗

[Embolization of the hepatic artery in primary hepatocellular carcinoma].

Between April 1981 and October 1984, 189 embolisations of the hepatic artery were carried out in 82 patients with primary hepato-cellular carcinomas. Two types of embolisation were performed: 1) embolisation using only gel foam and 2) a combination of peripheral and proximal embolisation using Lipiodol and gel foam. Embolisation of the hepatic artery is indicated for inoperable carcinoma, provided less than 75% of the liver is involved or for localised carcinomas in patients whose general condition makes surgery impossible, often because of severe cirrhosis of the liver. Complications following embolisation include pain, fever and transient changes in liver function. Deaths, abscesses or rupture of the tumour did not occur.

Adult↗

[Indications for the intra-arterial infusion of urokinase in the treatment of acute intestinal ischemia in patients with heart disease].

The poor prognosis of acute mesenteric artery occlusion can be improved by reaching a rapid angiographic diagnosis and by instituting treatment at an early stage. In addition to operative embolectomy, success may be expected from the use of urokinase infused super-selectively into the superior mesenteric artery. This treatment is only likely to be successful if it is carried out within ten hours of the onset of clinical signs and symptoms. In patients with heart disease, angiography is recommended as soon as there is any suspicion of mesenteric occlusion, in order to confirm the diagnosis, localise the embolus and decide on the form of treatment. Urokinase treatment can be successful for embolic occlusion of the main branches or peripheral branches of the superior mesenteric artery. However, complete occlusion of the main superior mesenteric artery should be treated operatively. A contra-indication to urokinase therapy is occlusion due to infected emboli from an endocarditis.

Acute Disease↗