[Hemocoagulation disorders in cerebral ischemia].
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Blood Coagulation↗
Biomedical subjects
T Miyazaki
Publications and source records attributed to T Miyazaki.
[Clinically diagnosed corticobasal degeneration (CBD)].
We reported a 67-year-old male, who suffered from apraxia and amnesia for 2 years and for muscle rigidity of right extremities for a year. Neurological examination revealed dysarthria, dysphagia, marked dystonia of right arm, hyperreflexia of all limbs and ataxic gait. He also had dementia and many other higher cortical dysfunction mostly due to left hemisphere damage. No impairment of eye movement was disclosed. Brain MRI as well as CT showed the significant brain atrophy in the left parieto-occipital region. A degenerative atrophy was suspected by 123I-IMP-SPECT and 18F-FDG-PET. By FDG-PET, the decrease of cerebral blood flow and glucose metabolism was detected not only affected unilateral cerebral cortex including primary motor area but ipsilateral basal ganglia and thalamus. Although, it is difficult to distinguish clinically CBD from atypical case of Alzheimer's disease, we speculated that in early stage of dementia, significant unilateral hypoperfusion and hypometabolism of basal ganglia and thalamus is characteristic of CBD.
Aged↗
[An autopsy case with recent memory disturbance, characterized by localized atrophy of parahippocampal gyrus, subiculum and amygdala].
We reported an autopsy case with recent memory disturbance, characterized by localized atrophy of parahippocampal gyrus, subiculum and amygdala. This patient initially exhibited recent memory disturbance at the age of 73. She was disoriented to time and place and immediately forgot having had a meal. At the age of 75, she was hospitalized because of progressive forgetfulness and congestive heart failure. One year later, she was admitted to our medical center. On admission, she was alert, but showed severe recent memory disturbance and disorientation to time and place. By contrast, she had neither aphasia nor apraxia. No other neurological symptoms were found. Brain CT showed localized atrophy of the medial part of bilateral temporal lobes and brain SPECT (123I-IMP) revealed a decrease of cerebral blood flow in the same regions. We considered her as early stage of Alzheimer type dementia (ATD) clinically. She died of pneumonia and DIC at the age of 78. Her illness lasted about 5 years. General autopsy showed prolapse of mitral valves, bronchopneumonia and DIC. The brain weighed 1,150 gm. Coronal sections of the brain revealed locarized atrophy of bilateral mediobasal part of the temporal lobes including the rostral parahippocampal gyrus, subiculum and amygdala. There were severe neuronal loss with astrogliosis and a few neurofibrillary tangles (NFT) in the rostral para-hippocampus, CA1 of the hippocampal formation, prosubiculum and amygdala. There were neither senile plaques (SP) nor NFT in the cerebral neocortex. This case lacked neocortical SP and NFT and showed bilateral localized atrophy of rostral parahippocampal gyrus, CA1, subiculum and related structure of the ventromedial temporal lobe with severe neuronal loss and astrogliosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
[Human embryo freezing with dimethylsulfoxide (DMSO) and sucrose as cryoprotectants].
176 supernumerary human embryos following treatment by IVF were cryopreserved with dimethylsulfoxide (1.5M) and sucrose (0.1M) as cryoprotectants. The embryos were frozen at the early cleavage stage (48-96 hours after insemination) in the programmable freezer, by means of the protocol providing for slow cooling until -40 degrees C and slow thawing. The survival rate (50% or more blastomeres were intact) after thawing was higher for the embryos at the 8 cell stage to the morulla stage (60-96 hours after insemination) than for the embryos at the 4 to 6 cell stage (48-60 hours after insemination) (87% and 66%, p < 0.001), and the overall survival rate was 80% (140/176). Out of 62 transfer cycles, 11 pregnancies (17.7%) and 6 deliveries (9.7%) were achieved. No fetal malformation or chromosomal aberration was observed.
Cryopreservation↗
[A case of a traumatic diaphragmatic true hernia manifesting itself 12 years after the accident].
A case of surgical treatment of a traumatic diaphragmatic true hernia was presented, which manifested itself as symptoms of left chest oppression 12 years after the accident. The patient was a 66-year-old woman, who met traffic accident in 1976. She was first pointed out abnormal shadow on the chest X-ray in 1981 and began to feel chest oppression in 1988. Barium examination of the upper gastrointestinal tract and chest CT scan revealed a part of corpus ventriculi and colon herniated into the left hemithorax. Diaphragmatic hernia was diagnosed and the operation was performed through the thoracic approach in June 1991. The diaphragm was found to have a hernia sac and a defect at the central tendon. The hernia sac containing the stomach and colon was opened to reduce it's contents into the abdominal cavity. The defect was closed by mattress suture with pledgets and continuous over and over suture. The patient ran a favorable post operative course. A true type among traumatic diaphragmatic hernia is a very rare case in the literature.
Aged↗
[Basic studies of BALL ELSA CA125-II KIT for detection of serum cancer antigen 125].
We made basic studies of BALL ELSA CA125-II KIT which is a solid phase two site immunoradiometric assay. The first monoclonal antibody (M11) is coated on the BALL ELSA solid phase, and the second one (OC125), radiolabeled with 125I, is used as a tracer. Since serum CA125 values varied by incubation time, incubation temperature and agitation speed, the conditions of the assay had to be kept strictly. Intra- and interassay reproducibility, recovery test and dilution test were well satisfied. Prozone phenomenon was observed over 5,000 U/ml. The minimum detectable concentration was 7.5 U/ml. Serum CA125 values measured using BALL ELSA CA125-II KIT was correlated with those measured using conventional CENTOCOR CA125 RIA KIT (y = 1.058x-0.106 r = 0.973), although in the serum of a patient with chronic pancreatitis the discrepancy between serum CA125 values measured using these kits was observed.
Adolescent↗
Intranasal immunization against herpes simplex virus infection by using a recombinant glycoprotein D fused with immunomodulating proteins, the B subunit of Escherichia coli heat-labile enterotoxin and interleukin-2.
To establish a novel strategy of mucosal immunization against herpes simplex virus type 1 (HSV-1) infection, we studied the immune responses elicited by intranasal immunization with several forms of a recombinant glycoprotein D (gD) of HSV-1. A truncated gD (t-gD) co-administered with heat-labile enterotoxin B subunit (LTB) from Escherichia coli induced both a mucosal immune response involving secretion of anti-gD IgA and serum IgG production. The levels of these responses are comparable to those in mice which have recovered from intranasal HSV-1 infections. The fusion protein (t-gD-LTB), consisting of t-gD and LTB, induced the responses more efficiently than did co-administration of t-gD and LTB, although GM1 ganglioside binding activity was significantly reduced in t-gD-LTB. We found that another fusion protein, consisting of t-gD and human interleukin-2 (t-gD-IL-2), also elicited antibody responses comparable to those induced by t-gD-LTB. Immunity acquired by intranasal immunization with t-gD-IL-2 protected mice from intraperitoneal HSV-1 infections, whereas t-gD-LTB or t-gD alone failed to provide protection against infection. Even in a mouse strain that responded highly to subcutaneously administered gD, intranasally administered t-gD did not elicit antibody responses. The lack of response to gD was clearly abrogated by co-administration with IL-2, and administration of t-gD-IL-2 induced an excellent level of antibody responses in this strain. These results suggest that the IL-2 fusion strategy yields a new type of mucosal immunization, the mechanism of which differs from that speculated for the mucosal adjuvant activity of LTB.
Administration, Intranasal↗
[Phase II clinical study of recombinant human erythropoietin on the anemia associated with multiple myeloma].
Safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with multiple myeloma whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha (3,000IU/body) was given subcutaneously daily for two weeks and the dosage was increased to 6,000IU, 12,000IU and 24,000IU every two weeks when the increment of Hb was insufficient. Cases in which Hb concentration increased by more than 1g/dl or in which blood transfusion requirements decreased by more than 50% were judged to be effective. The overall rate of efficacy was 52.6% (10/19). Response to epoetin alpha treatment was better in patients whose blood erythropoietin level was relatively low. The majority of patients responded to the treatment with up to 6,000IU/body/day but a dosage of more than 12,000IU/body/day was required in some cases. No serious adverse effects or abnormal laboratory findings were observed. These results suggest that high-dose subcutaneous epoetin alpha treatment is effective for anemia associated with multiple myeloma in terms of increasing Hb concentration and reducing blood transfusion.
Aged↗
[Phase II clinical study of recombinant human erythropoietin on the anemia of myelodysplastic syndrome].
The safety and efficacy of recombinant human erythropoietin (epoetin alpha) were investigated in anemic patients with myelodysplastic syndrome (MDS) whose hemoglobin (Hb) concentration was less than 10g/dl. Epoetin alpha was given subcutaneously daily at a dose of 3,000IU/body for two weeks and the dosage was increased to 6,000IU, 12,000IU, and 24,000IU at two week interval when the increment of Hb was insufficient. Patients in whom the Hb concentration increased by more than 1g/dl or whose blood transfusion requirement reduced to below 50% were considered to be cases of effective treatment. The overall rate of effectiveness was 20.6% (7/34). Response to epoetin alpha treatment was better in patients with refractory anemia (RA) or RA with ringed sideroblasts (RARS). The high dose epoetin alpha (12,000-24,000IU/body/day) was required for the patients to respond. These results suggest that the high dose subcutaneous epoetin alpha treatment is effective for the anemia associated with MDS in terms of increasing Hb concentration and reducing blood transfusion.
Adolescent↗
Inhibition of mitochondrial respiration by furancarboxylic acid accumulated in uremic serum in its albumin-bound and non-dialyzable form.
3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) accumulates markedly in uremic serum in its albumin-bound form. To determine if CMPF can be removed by newly developed dialyzers with high-flux membranes which are permeable to low-molecular-weight proteins, such as beta 2-microglobulin (beta 2-MG), serum levels of CMPF were determined before and after hemodialysis using these high-flux membrane dialyzers. In addition, to determine the pathogenic role of CMPF in uremic patients, its cellular toxicity due to its effect on mitochondrial respiration was studied. The reduction rates of CMPF by hemodialysis using the dialyzers ranged from -17% to -24%, demonstrating the nondialyzability of CMPF due to its strong albumin-binding, while those of beta 2-MG ranged from 11% to 43%. CMPF inhibited ADP-stimulated oxidation of NADH-linked substrates in isolated mitochondria dose-dependently regardless of the presence of serum albumin. This inhibition was observed even at a concentration of 0.2 mM, which is comparable to the serum levels of CMPF in the hemodialysis patients. In conclusion CMPF which cannot be removed even by high-flux membrane dialyzers, is a strong inhibitor of mitochondrial respiration, and novel purification methods to remove CMPF from the blood of uremic patients should be developed.
Animals↗
Components and proteolytic processing sites of arylsulfatase B from human placenta.
Previous studies have shown that mature arylsulfatase B purified from human sources is composed of two non-identical chains with apparent molecular masses of 43 kDa and 8 kDa. Arylsulfatase B purified from human placenta in the present study, however, included another 7 kDa component that could be detected only by carbohydrate staining on reducing SDS-PAGE employing the Tris-Tricine system. The 43 kDa and 7 kDa components contained a carbohydrate moiety, but the 8 kDa one did not, as demonstrated by periodic acid-Schiff staining, Con-A lectin blotting, endo-glycosidase treatment and in vitro phosphorylation by UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine 1-phosphotransferase. The purified arylsulfatase B migrated as a single polypeptide of 58 kDa on non-reducing SDS-PAGE, indicating that the three chains are linked by disulfide bonds. In order to determine the origin of the components, N-terminal sequencing of the isolated polypeptides was performed. As a result, the 43, 7 and 8 kDa components were found to commence with Ala-41, Ala-424 and Asp-466, respectively. These results suggest that after removal of the signal peptide, human arylsulfatase B undergoes proteolytic processing on at least two sites during maturation.
Amino Acid Sequence↗
Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules.
Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. NOD mice were shown to express major histocompatibility complex class I Kd and Db antigens. To examine the possible involvement of major histocompatibility complex class I molecules in the development of autoimmune insulitis, we attempted to express a different type of class I molecule in NOD mice by crossing C57BL/6 mice transgenic for the class I Ld gene with NOD mice. The backcross progeny expressed the Ld antigen on the peripheral blood lymphocytes at a level comparable with that of the BALB/c mice. The cell surface expression of endogenous class I and class II antigens on the peripheral blood lymphocytes was not affected. Analysis of these mice revealed that the expression of the class I Ld antigen significantly reduced the incidence of insulitis at 20 weeks of age. In situ hybridization of a biotinylated probe on mouse chromosomes showed that the Ld transgene was located in the E area of chromosome 6 with which no genetic linkage to insulin-dependent diabetes mellitus was demonstrated. These results suggest that the NOD-type class I molecules are involved in the development of insulitis in NOD mice.
Animals↗
Myristoylation-dependent membrane targeting and release of the HTLV-I Gag precursor, Pr53gag, in yeast.
The unprocessed HTLV-I Gag precursor, Pr53gag, was synthesized in yeast, Saccharomyces cerevisiae. The synthesized Pr53gag was myristoylated, associated with the cellular membrane, and released into the culture medium. The released Pr53gag was pelleted by centrifugation at 100,000 x g for 2 h. Conversion of Gly2 to Ala allowed synthesis of a non-myristoylated soluble Pr53gag which was not released into the culture medium. These results suggest that the release of the HTLV-I Gag precursors Pr53gag, occurs in yeast in a myristoylation-dependent manner.
Amino Acid Sequence↗
Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein-associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth.
Herbimycin A, a benzoquinoid ansamycin antibiotic, was demonstrated to decrease intracellular phosphorylation by protein tyrosine kinase (PTK). In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis. However, the same dose of herbimycin A did not inhibit in vitro growth of a broad spectrum of Ph1-negative human leukemia cells, and several other protein kinase antagonists also displayed no preferential inhibition. Furthermore, we demonstrated that herbimycin A has an antagonizing effect on the growth of transformed cells by a transfection of retroviral amphotrophic vector expressing P210bcr/abl into a murine interleukin (IL)-3-dependent myeloid FDC-P2 cell line. This inhibition was abrogated by the addition of sulfhydryl compounds, similar to the reaction previously described for Rous sarcoma virus transformation. The inhibitory effect of herbimycin A on the growth of Ph1-positive cells was associated with decreased bcr/abl tyrosine kinase activity, but no decrease of bcr-abl mRNA and protein, suggesting that the inactivation of bcr-abl tyrosine kinase activity by herbimycin A may be induced by its binding to the bcr-abl protein portion that is rich with sulfhydryl groups. The present study indicates that herbimycin A is a beneficial agent for the investigation of the role of the bcr-abl gene in Ph1-positive leukemias and further suggests that the development of agents inhibiting the bcr-abl gene product may offer a new therapeutic potential for Ph1-positive leukemias.
Benzoquinones↗
Gene expressions and activities of protein phosphatases PP1 and PP2A in rat liver regeneration after partial hepatectomy.
We have examined the levels of gene expressions and activities of protein phosphatases, PP1 and PP2A, in rat regenerating livers. PP1 alpha mRNA started to increase from 6 h after partial hepatectomy (PH) and showed two peaks at 12 and 48 h. PP2A mRNA level showed two peaks at 6 and 10-12 h. Protein phosphatase activities were determined both in non-nuclear fraction and in nuclei. While spontaneous PP1 activity in non-nuclear fraction was nearly constant, potential PP1 activity revealed by Co(2+)-trypsin treatment showed a small peak between 7 and 12 h. In nuclei, both spontaneous and potential PP1 activity began to increase from 4-7 h after PH, reached a maximum (about 2.5-fold over control levels) at 12 h, the time which corresponds to the G1 to S transition in the cell cycle, and then declined back to control levels by 7 days. PP2A activity in non-nuclear fraction was nearly constant in both spontaneous and potential forms. PP2A activity in both forms in nuclei was very low throughout. These results suggest the possibility that PP1 in nuclei plays some role in the G1 to S transition in the cell cycle of hepatocyte proliferation.
Animals↗
Structure of a heteroglycan isolated from the fungus Omphalia lapidescens.
The major, water-soluble polysaccharide isolated from the sclerotia of Omphalia lapidescens, and purified by chromatography on DEAE-Sephadex A-50 and Toyopearl HW-65F, is a heteroglycan (OL-3), [alpha]D20 - 50 degrees (c 1, water), which is composed of D-glucose, 2-acetamido-2-deoxy-D-glucose, and D-glucuronic acid in the molar ratios 1.21:1.00:1.38. Methylation analysis, partial acid hydrolysis, and f.a.b.-m.s. of the hydrolysates indicated OL-3 to have a highly branched structure involving (1----3)-, (1----4)-, (1----6)-, and (1----3,6)-linked, and non-reducing terminal D-glucopyranosyl residues, and also to contain 2 acetamido-2-deoxy-beta-D-glucopyranosyl-(1----4)-beta-D- glucopyranosyluronic acid and beta-D-glucopyranosyl-(1----4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl -(1----4)-beta-D-glucopyranosyluronic acid segments.
Agaricales↗
Hepatitis B virus envelope L protein particles. Synthesis and assembly in Saccharomyces cerevisiae, purification and characterization.
The hepatitis B virus envelope gene encodes three transmembrane proteins in frame; S, the product of S gene; M, the product of M (pre-S2 + S) gene; and L, the product of L (pre-S1 + pre-S2 + S) gene. Unlike the S and M proteins, attempts to efficiently synthesize L proteins and assemble them into L protein particles in various eukaryotic cells have been unsuccessful, probably because of the presence of the pre-S1 peptide with an unknown function which appears to be inhibitory to the host secretory apparatus. To investigate the role of the pre-S1 peptide, we constructed an L gene fused with a synthetic gene for chicken-lysozyme signal peptide (C-SIG) at the 5'-terminal and placed the resultant gene under the control of the yeast glyceraldehyde-3-phosphate dehydrogenase gene promoter. After the fused-C-SIG peptide was correctly processed by the yeast secretory apparatus, a yeast transformant synthesized a protein with a molecular mass of approximately 52 kDa at a level of 42% of the total soluble protein. Electron micrographic observation showed that the gene products assembled into 23-nm spherical and filamentous particles. The pre-S peptide of the gene product was deposited into the endoplasmic reticulum (ER) lumen and well-glycosylated. It seemed that the gene products were accumulated as particles in certain specific membrane structures of the yeast secretory apparatus. Moreover, both the amount of mRNAs specific for the L gene and the in vivo stability of the synthesized L proteins did not change significantly by the addition of the C-SIG gene. These findings indicated that, if the pre-S1 peptide penetrates the ER membrane efficiently, the L proteins can be synthesized cotranslationally, translocate across the ER membrane with its S region, and then assemble by themselves into the particle form. Therefore, the pre-S1 peptide may involve weak or reduced signal peptide activity for recognition by the secretory apparatus and/or for the transport of the pre-S peptide into the ER lumen.
Amino Acid Sequence↗
Synergistic effects of cyclic AMP and Ca2+ ionophore A23187 on de novo synthesis of histidine decarboxylase in mastocytoma P-815 cells.
In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172-178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187.
Animals↗