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Biomedical subjects

M Izawa

Publications and source records attributed to M Izawa.

At least 109 records · Page 6Linked to original sources

[An adult case of moyamoya disease associated with marked advance of occlusive lesion in the bilateral carotid system].

We reported an adult case with moyamoya disease in which unilateral obstructive process proceeded to the bilateral lesion during a period of 45 months. A 30-year-old female was admitted to our institute due to frequent ischemic episodes since she was 25 years old. At the time of admission, she was asymptomatic with slightly disturbed psychogenic reactions. At the time of the initial cerebral angiography when she was 25 years old, the right cerebral angiography demonstrated stenosis of the right ICA terminal portion with moyamoya vessels in the basal area and leptomeningeal anastomosis at the right parietal area. The left cerebral angiography revealed normal ICA system with a lightly narrowing Al portion, without Moyamoya vessels. The second cerebral angiography, taken 45 months after the initial angiography, demonstrated progression stenosis of the right ICA terminal portion, with decreasing moyamoya vessels at the basal area, obstruction of the left ICA terminal portion, stenosis at the Al portion with newly developed moyamoya vessels in the left basal area. We concluded at this time that this case was a definite case of moyamoya disease. The third cerebral angiography after right SDP (synangio-dural plasty), 49 months after the initial angiography, revealed, in the right angiography, newly formed anastomotic vessels perfusing the middle cerebral artery region via the extracerebral arteries and in the left cerebral angiography, and an increased obstruction of the ICA terminal portion, transdural anastomosis via the extracerebral arterial system, and a decrease of moyamoya vessels in the basal area. This rare case provided us a good picture of the pathogenic mechanism of moyamoya disease.

Adult↗

Ischemic stroke in infancy, childhood, and adolescence.

The authors studied 34 patients with juvenile ischemic cerebrovascular disease over a 15-year period. Of the 34 patients, 23 had intracranial occlusions attributed to cerebral thrombosis or embolism and 11 had occlusions resulting from moyamoya disease. Clinicopathological features were evaluated in the 23 cases with ischemic stroke, but not those with moyamoya disease. The cause of the arterial occlusion remained undetermined in 11 patients and was found to be an embolism based on congenital heart disease in 8, on trauma in 3, and on infection in 1. Cerebral angiography was performed in 21 patients. Of these, 17 had stenoses or occlusions corresponding to their symptoms. CT scans were performed in 10 patients; the lesion in question showed no stenosis or occlusion with cerebral angiography. With regard to prognosis, patients with unknown etiology had good outcomes compared with those with congenital heart disease. With respect to "acute infantile hemiplegia", 10 patients had convulsive seizures and 4 had a history of an earlier infection. Angiography and CT scans in patients with congenital heart disease demonstrated arterial occlusive sites in the middle cerebral artery region. Three patients had abscesses after their ischemic lesions.

Adolescent↗

Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs.

Restriction length fragment polymorphism of the L-MYC gene was examined in DNAs from lung cancer tissues and normal tissues of 51 Japanese patients with lung cancer. In individual patients, no difference was seen between the restriction length fragments of the two alleles of L-MYC [6-kilobase (kb) and 10-kb fragments in EcoRI digests] in lung cancer tissues and normal tissues. But a striking correlation was found between the restriction length fragment polymorphism pattern of L-MYC and the extent of metastasis, particularly to the lymph nodes at the time of surgery: Patients with only the L band (10 kb) had few lymph node metastatic lesions, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastatic lesion. A similar correlation was found between the presence of the S band and metastases to other organs. This correlation was particularly marked in cases of adenocarcinoma. These results indicate a clear genetic influence on metastases and a consequent poor prognosis for certain patients of lung cancer; L-MYC restriction length fragment polymorphism is thus shown to be a useful marker for predicting the metastatic potential of human lung cancer.

Adult↗

Secretion of an active nonglycosylated form of the repressible acid phosphatase of Saccharomyces cerevisiae in the presence of tunicamycin at low temperatures.

The role of mannan chains in the formation and secretion of active acid phosphatase of yeast (Saccharomyces cerevisiae), a repressible cell surface mannoprotein, was studied in yeast protoplast systems by using tunicamycin at various temperatures. At 30 degrees C, tunicamycin-treated protoplasts did not produce active acid phosphatase; however, at 25 or 20 degrees C they formed and secreted active enzyme. This form of acid phosphatase gave 59-, 57-, and 55-kDa bands on SDS-PAGE which neither bound to concanavalin A Sepharose, nor changed in molecular weight upon treatment with endoglycosidase H, indicating that the peptides are nonglycosylated. The nonglycosylated form, like its glycosylated counterpart, is a dimer on the basis of gel permeation chromatography. The Km for para-nitrophenyl-phosphate and Ki for inorganic phosphate of both glycosylated and nonglycosylated acid phosphatases were almost the same. These results suggested that 1) the conformation of the nonglycosylated acid phosphatase secreted at low temperatures is probably identical with that of the glycosylated one, and 2) the conformation of acid phosphatase is very important for its secretion. The rate of intracellular transport of nonglycosylated acid phosphatase is about one-fourth that of the glycosylated enzyme, indicating that glycosylation facilitates the transport of acid phosphatase proteins.

Acid Phosphatase↗

Electron microscopical observation of RNA on the surface of Ehrlich ascites tumor cells.

The structure of RNA on the surface of Ehrlich ascites tumor cells was studied under an electron microscope using both plasma polymerization replica films and ultrathin sections of the cells. Necklace-like structures were found on the cell surface where anti-RNA antibody was bound in replica film, and particles which resemble cytoplasmic ribosomes in size and density were found distributed sparsely on the cell surface in ultrathin sections. These particles were found to gather at one pole of the cell surface after the cell was incubated at 4 degrees C with anti-RNA antibody and then incubated at 37 degrees C for 10 min in antibody-free medium. On the other hand, L1210 cells which do not bind with anti-RNA antibody showed hardly any such structures on the cell surface. These results suggest that RNA on the surface of Ehrlich ascites tumor cells is present in the form of particles.

Animals↗

Cloning of glucocorticoid-responsive mRNA in the rat thymus.

To elucidate the molecular mechanism of rat thymus involution induced by administration of glucocorticoid, we screened a cDNA library for polysomal poly(A)+RNA from adrenalectomized rat thymi by a differential colony hybridization method. Labeled cDNAs for mRNAs isolated from thymi of adrenalectomized rats and rats receiving dexamethasone (Dex) treatment were used as probes. Eight cDNA clones for mRNAs which had a diminished response to administration of Dex were isolated. The relative concentration of cloned mRNAs in the thymic polysomal RNA was significantly decreased 3 h after hormone administration, while changes in the nuclear RNA were not significant after Dex administration. One of the selected cDNA clones designated pRTGR-8 corresponded to mRNA of about 3,000 nucleotides, and a nuclear run-off transcription assay indicated that the rate of transcription of pRTGR-8 RNA was repressed by Dex administration. The cloned cDNAs obtained in this experiment may provide useful probes for studying the negative regulation mechanism of gene expression by glucocorticoids.

Animals↗

Comparison among lipid constituents in native LDL, ultra-water-soluble LDL, and vessel wall, and their significance in arteriosclerosis.

The lipid constituents in native low-density lipoproteins (LDL), ultra-water-soluble LDL (UWS-LDL), and aortic intimal tissues were compared. These lipoproteins were obtained from healthy persons and patients with atherosclerotic diseases. Also, aortic intimas were separated from arterial walls obtained within 5 hr after the donor's death. (1) From the native LDL, cholesterol esters (CE), triglycerides (TG), small amounts of free fatty cid (FFA), free cholesterol (CF), and phospholipids (PL) were demonstrable by iodine vapor on TLC, but from UWS-LDL the above lipids plus a new lipid (spot X) were observed between TG and FFA on TLC. And also, an unknown spot with the same Rf value as spot X was recognized on TLC of lipid extract from the atherosclerotic lesion, but not from the normal intima. (2) The production of spot X in UWS-LDL is probably related to the oxidation of lipids in native LDL. Also, the spot X in UWS-LDL and the spot X in the atherosclerotic lesions are probably related to the oxidation of CE in these lipids. (3) The existence of UWS-LDL is important to the initiation and probably the progression of atherosclerosis.

Aorta↗

Hemorrhagic stroke in infancy, childhood, and adolescence.

The authors report on factors influencing the outcome after hemorrhagic strokes in infants, children, and adolescents over a period of 14 years. Their series comprised primary hemorrhage in 24 cases (46.2%), including 5 cases of vitamin K deficiency; arteriovenous malformation in 20 cases (38.5%); intracranial aneurysm and moya-moya disease in 3 cases (5.7%) each; and spinal angioma in 2 cases (3.9%). Ten of 52 patients with juvenile hemorrhagic strokes died despite surgical treatment. These fatal cases involved an intraparenchymal hematoma with ventricular casts, and unilateral hydrocephalus suggesting acute, uncontrollable intracranial hypertension. The "child's biologic plasticity" plays an important role in the favorable prognosis in infants, children, and adolescents with hemorrhagic strokes. On the contrary, cases with intraventricular hemorrhage due to any pathologic condition have an unfavorable prognosis.

Adolescent↗

Ribosomal RNA on the surfaces of nonleukemic mouse ascites tumor cells.

RNAs on the cell surfaces of two nonleukemic and two leukemic strains of mouse ascites tumor cells were studied by fractionating the RNAs released from the cell surface by gentle pronase treatment after sucrose density gradient centrifugation, by indirect membrane immunofluorescence that used anti-RNA antibody and by cell electrophoresis. RNA was extracted from the cell supernatants of Ehrlich ascites tumor and sarcoma 180 cells (nonleukemic) that had been treated or not treated with pronase (1 microgram/ml, 37 degrees C, 20 min) followed by sucrose density gradient centrifugation. It was clearly demonstrated that the amounts of ribosomal RNA (18S and 28S) released after pronase treatment were approximately 80% greater than that of nonpronase-treated cells. Ehrlich ascites tumor cells that had been treated with actinomycin D (100 micrograms/kg body weight of mouse, 16 h) in vivo released an amount of ribosomal RNA after pronase treatment only 20% greater than the value for untreated cells. Actinomycin D treatment greatly reduced both the cell surface negative charge and the cell surface immunofluorescence when rabbit anti-RNA antibody was used. Under the same experimental conditions with actinomycin D, only ribosomal RNA synthesis showed preferential inhibition, not the syntheses of poly A-containing messenger RNA, 4S or other small-size RNAs. In contrast, L1210 and C1498 cells (leukemic) showed no change in the amounts of ribosomal RNA released after pronase treatment. L1210 cells also showed no change in the surface negative charge after being treated with actinomycin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Receptor binding in the rat liver nuclear matrix.

3H-Dexamethasone (Dex)-receptor complexes prepared from the rat liver cytosol efficiently bound to the nuclear matrix from the same tissue. The binding was increased with the concentration of the 3H-Dex-receptor complex added and reached a maximum plateau. However, when the partially purified 3H-Dex-receptor complex was used, saturation of the binding sites in the nuclear matrix was not observed in the range of concentration of 3H-Dex-receptor complex used. Therefore, it was considered that the apparent saturability observed in the binding of the unpurified receptor complexes is caused by the translocation inhibitor(s) in the cytosol. When the binding capacity was expressed on the basis of unit weight of DNA, the nuclear matrix exhibited 20 times more of that of the unfractionated nuclei. However, no line of evidence of enrichment of the binding sites in the DNA isolated from the nuclear matrix was observed. These observations show that the role of the nuclear matrix in the action of glucocorticoid is quite uncertain.

Animals↗

Teratocarcinoma derived from mouse zygotes after the introduction of activated human c-Ha-ras DNA.

We attempted to produce transgenic mice harboring the normal or activated human c-Ha-ras gene in order to examine the function of activated oncogenes in tumorigenesis. During the process of development, it happened that not only normal looking fetuses were obtained but also malformants, developmentally arrested conceptuses and tumors. Six such abnormally developed embryos were found to have been integrated with the activated human c-Ha-ras gene. One of the two tumors thus obtained was formed after the injection of 6.3 kb DNA fragment containing the gene for p21 with valine at the twelfth position. This tumor was integrated with two copies of the introduced DNA at a particular site in a chromosome and arranged in tandem in a head to tail direction. Histological analysis revealed that this tumor was constructed from at least three types of cells: two originating from different germ layers (one endoderm and the other mesoderm) and the third from an extra-embryonic ectoderm. The other tumor revealed similar features. Thus, it was strongly suggested that these tumors were derived from the very early developmental stage of the embryo, and had features very similar to those of teratocarcinoma.

Animals↗

[Autoimmune antibody in moyamoya disease].

The association of autoimmune antibody and HLA antibody has been documented concerning the pathogenesis of moyamoya disease. In this paper, we study the autoimmune antibody in moyamoya disease and discuss its relationship with the pathogenesis. Autoimmune antibody was evaluated in 13 cases of moyamoya disease. The age distribution of the patients ranged from 13 to 55, with an average of 37 years. Eight were females, 5 males. Autoantibody was studied with native DNA (double strand DNA) and ANA (antinuclear antibody). Antibody was noted in 3 cases (23%) in native DNA study, and 2 cases (15%) in ANA study. Significantly high incidence was recognized compared with normal control (4%). In relation to the clinical features, such as initial symptoms, time of onset, neurological findings, no significant correlation was recognized. This study suggests that immunological factors might play a partial role in the pathogenesis of moyamoya disease.

Adolescent↗

[Pharmacological effects of CM6912 and its main metabolites].

Pharmacodynamic effects of ethyl 7-chloro-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4- benzodiazepine-3-carboxylate (CM6912), a new benzodiazepine derivative, and its main metabolites (CM6913 = M1, CM7116 = M2) on the peripheral systems were investigated in several species of animals. In pentobarbital-anesthetized rabbits, CM6912 and M2 (1 or 5 mg/kg, i.v.) had little effect on blood pressure, heart rate and ECG, but it slightly reduced the respiration rate. M1 decreased the heart rate without affecting respiration, blood pressure and ECG. In conscious rabbits, CM6912 and M2 (1 mg/kg, i.v.) did not affect respiration, blood pressure, heart rate and ECG, but M1 (1 mg/kg, i.v.) increased the heart rate. CM6912 (5 or 30 mg/kg), when administered orally, also increased heart rate. In pentobarbital-anesthetized dogs, CM6912 and its metabolites (5 mg/kg, i.v.) decreased respiration and heart rate without affecting blood pressure and ECG. CM 6912 (5 mg/kg, i.v.) did not affect cardiovascular responses to the carotid occlusion, vagus stimulation, and pre- and post-ganglionic stimulation of cardiac ganglion in anesthetized dogs. CM6912 and its metabolites affected neither the spontaneous contraction nor the heart rate of isolated rabbit atria. These compounds also had no action on isolated aortic strips from rabbits. CM6912 and its metabolites did not affect the muscle tone of isolated guinea pig intestine, and it had no effects on the contractile responses to acetylcholine, histamine, serotonin and barium chloride. In isolated rabbit intestine, CM6912 and M2 slightly reduced the amplitude of contraction, while M1 had no effect. CM6912 and its metabolites did not affect the spontaneous motility of isolated non-pregnant and pregnant rat uteri as well as in situ non-pregnant rat uterus and isolated guinea pig vas deferens, including the contractile response to adrenaline. CM6912 and M2 relaxed isolated guinea pig trachea strips only at high concentrations. CM6912 and its metabolites did not affect the contractile responses of isolated rat diaphragm to electrical stimulation of the phrenic nerve. CM6912 (2 or 10 mg/kg, p.o.) did not affect the rat renal and hepatic functions. CM6912 influenced neither blood coagulation in rabbits nor blood hemolysis in rats. CM6912 and its metabolites did not affect the pupil size and its light reflex, and they did not produce a local anesthesia and edema. The present results suggest that CM6912 and its main metabolites exert only slight effects on the peripheral systems in animals.

Animals↗

Properties of binding of partially purified glucocorticoid receptor from rat liver with glucocorticoids of different biopotencies.

To elucidate the relationship between binding parameters and biopotencies of glucocorticoids, we partially purified the receptor from the liver cytosol of rats in a dexamethasone-bound and unactivated form by precipitation with protamine sulfate, gel filtration and DEAE-cellulose chromatography (approximately 100-fold) and examined the interaction of the preparation with 3 glucocorticoids of different biopotencies (dexamethasone; Dex, corticosterone; Cort and prednisolone; Pred). The partially purified receptor (PPR) was stable at -20 degrees C for at least 2 months in the presence of bovine serum albumin, glycerol, molybdate and dithiothreitol. Treatment of the PPR with p-hydroxymercuribenzoate liberated the ligands and the treated PPR reassociated 3H-glucocorticoids efficiently following the addition of dithiothreitol. The reassociated PPR was bound to the DNA-cellulose after a brief heating. Metabolic activity on ligands and inactivation of the binding sites in the PPR were insignificant under the conditions used. Kd's were approximately 0.9, approximately 3 and approximately 6 nM for Dex, Cort and Pred, respectively (at 0 degree C). Relative binding affinity of ligands to the PPR which was estimated by competitions was higher in the order of triamcinolone acetonide greater than Dex greater than Cort greater than Pred greater than progesterone greater than cortexolone. Association of Dex and Cort was relatively rapid and significantly accelerated by raising the incubation temperature, while the association of Pred was slower and effects of the temperature was moderate. The rate of dissociations was also varied with ligands. The rate of dissociation of Dex was the lowest among the 3 ligands and was elevated by raising the temperature. Because the effect of temperature was more pronounced in the dissociation than in the association, apparent Ka's decreased at higher temperature. Thermodynamic examinations of glucocorticoid binding in the PPR revealed that the binding reaction proceeds at a higher rate in the order of Dex greater than Cort greater than Pred. Because the relative biopotencies of these 3 glucocorticoids in vivo is higher in the order of Dex greater than Pred greater than Cort, from the results obtained in the present study, it appears that biopotency of glucocorticoids in vivo does not correlate with the affinity of the binding to the receptor estimated in vitro.

Animals↗

Adsorption of anionic chloro complexes of 59Fe and 195Au on non-ionic resins of macro-reticular type.

Adsorption behavior of 59Fe and 195Au on the non-ionic macro-reticular resin, Amberlite XAD-7 is studied. Distribution coefficients (Kd) for both nuclides in hydrochloric acid or lithium chloride solutions above 6M are particularly high. In nitric acid solution below 2M, 195Au is highly adsorbed on the resin but 59Fe is negligible over any concentrations. This resin did not adsorb other important radionuclides such as 54Mn, 60Co, 65Zn, 90Sr, 106Ru, 137Cs and 144Ce at all. Based on such peculiar adsorption behavior, application to selective separation and determination of radio and stable iron in sea water was also studied.

Acrylic Resins↗

[The effect of large dose dexamethasone on local cerebral blood flow (L-CBF) in ischemic rat brain].

Changes of local cerebral blood flow (l-CBF) were estimated by autoradiographic techniques in middle cerebral artery occlusion rats given a large dose of (3 mg/kg) dexamethasone. The sensory-motor, parietal, auditory and olfactory cortices showed a significant reduction (greater than 25%) of l-CBF. In MCA occlusion with large dose dexamethasone group, ischemic cortices showed significant reduction from the only MCA occlusion group (highest 36%). There was no significant reduction of l-CBF in the deep structures. The effects of dexamethasone on drains with various pathologies have been studied both clinically and experimentally with many kinds of techniques. These effects are now being reevaluated. Still controversial however, is the mechanism that determines whether dexamethasone has beneficial, non-beneficial, or harmful effect. This study may help us to unravel the mechanism of steroid effects, as well as the relationship between corticosteroid and central nervous system.

Animals↗