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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 613 records · Page 34Linked to original sources

Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome.

We found 3 novel missense variants in the open reading frame of the prion protein (PrP) gene. The codon 105 point mutation (proline to leucine) was found on a codon 129 (Valine) PrP allele in 4 patients from 3 different Japanese families with Gerstmann-Sträussler syndrome. The codon 180 variant PrP (valine to isoleucine) was found in Creutzfeldt-Jakob disease (CJD) patients with a similar clinical course to that of codon 178 mutation. The codon 232 variant PrP (methionine to arginine) was documented in the CJD patients with typical clinical and pathological findings. These variant PrP molecules were not detected in 200 normal Japanese PrP alleles. PrP has a large repertoire of variant forms, and each primary structure of PrP corresponds to the distinct phenotype of prion diseases.

Base Sequence↗

The structure and expression of the FGF receptor-1 mRNA isoforms in rat tissues.

In this paper, we describe the structure of rat FGF receptor-1 mRNA isoforms and their expression in a variety of rat tissues. The rat FGFR-1 has the characteristics of FGFR-1 as well as mouse, human and chicken homologs. FGFR-1 mRNA was detectable in all the tissues examined by Northern analysis or polymerase chain reaction, indicating that FGFR-1 mRNA is widely expressed in rat tissues. The rat FGFR-1 mRNA has isoforms in both the extracellular and intracellular regions. The extracellular isoforms which have two or three immunoglobulin-like domains, are expressed almost equally in the tissues except for brain. However, the large form is a major form in the brain. Furthermore, in the brain, half of FGFR-1 mRNAs have the six nucleotides, which encode a potential serine-threonine kinase phosphorylation site in the intracellular juxta-membrane region, deleted. In contrast to the brain, the deletion isoform is a minor form in the other tissues. The tissue-specific expression of the isoforms indicates that they have different physiological functions. Although other isoforms of FGFR-1 mRNA in tumor cell lines have been reported, the isoforms were undetectable in all rat tissues examined, indicating the isoforms are products of abnormal alternative splicing in tumor cell lines.

Amino Acid Sequence↗

Nucleotide sequence of the cDNA encoding nucleoside diphosphate kinase II from spinach leaves.

The primary structure of nucleoside diphosphate (NDP) kinase II, one of the two isozymes found in spinach leaves, has been deduced from its cDNA sequence. NDP kinase II comprises 233 amino acid residues and has a molecular mass of 26,107 Da, which is larger than that of the purified NDP kinase II subunits (18 kDa) by about 8 kDa, suggesting that NDP kinase II might be post-translationally processed. Homology was found between the sequence of spinach NDP kinase II, and the sequences of spinach NDP kinase I, rat NDP kinases alpha and beta, Dictyostelium discoideum NDP kinase, the human Nm23-H1 and Nm23-H2 proteins and the awd protein of Drosophila melanogaster.

Amino Acid Sequence↗

Treatment and prognosis of primary thymic carcinoma.

From 1972 to 1990, we treated eight cases of thymic carcinoma (6 squamous cell and 2 small cell carcinomas). According to the classification by Masaoka et al., they consisted of one stage I, four stage III, one stage IVa, and two stage IVb. A complete resection of the primary tumour could be done in only three patients; the others had diagnostic biopsy and then radiation treatment. Four of five patients had a prolonged regression of the primary tumors after irradiation at 40-61.2 Gy. Six patients suffered from extrathoracic metastases. All patients received systemic chemotherapy with different regimens to counter either metastatic or locally recurrent lesions. Only two patients (with a regimen including cyclophosphamide, doxorubicin, and vincristine) obtained a partial response. The median survival of the eight patients was 70 months after surgical operation. The identification of an effective drug combination may thus improve the long-term prognosis of thymic carcinoma since radiotherapy is able to control primary lesions, even in the case of unresectable advanced disease.

Adult↗

Treatment of invasive thymoma with pleural dissemination.

The outcome of eight patients with invasive thymoma accompanying pleural dissemination was investigated. Only two patients had mediastinal tumor resection and pleural disseminated tumor excision. Seven patients underwent radiotherapy to the mediastinum and/or disseminated tumors. A clinical response to radiotherapy was achieved in the six patients with evaluable lesions (complete response in five patients and partial response in one). The estimated 5-year survival rate was 87.5%. Four patients were alive more than 10 years. So far, the mediastinal tumors of seven patients have been controlled for periods ranging from 42 to 154 months. Recurrence in six patients appeared as pleural tumors. Four out of the six patients had five courses of radiotherapy to the recurrent pleural tumors, four of which achieved complete response. No distant metastases were observed at any time. These observations suggest that radiotherapy should be the primary mode of treatment in cases of invasive thymoma with pleural dissemination.

Adult↗

An intrathoracic vagus nerve schwannoma invading the trachea.

A patient with a schwannoma of the intrathoracic vagus nerve is presented. The tumor invaded the trachea and caused dyspnea. It was successfully excised by a segmental resection of the trachea with end-to-end anastomosis. This instance of an intrathoracic vagus tumor invading the trachea is, as far as we know, the first reported in the world.

Cranial Nerve Neoplasms↗

Intracranial adenoid cystic carcinoma mimicking meningioma: report of two cases.

Two cases of intracranial adenoid cystic carcinoma mimicking meningioma are reported. In one, MRI showed not only a homogeneously enhancing extra-axial tumour attached to the dura mater of the posterior cranial fossa, but also surrounding dural enhancement, the "dural tail sign". In the second, CT demonstrated a well-demarcated enhancing extra-axial tumour, indistinguishable from a sphenoid ridge meningioma extending into the orbit. The neuroradiological features of intracranial adenoid cystic carcinoma may thus closely resemble those of meningioma.

Aged↗

Structures of asparagine linked oligosaccharides of immunoglobulins (IgY) isolated from egg-yolk of Japanese quail.

Structures of the Asn linked oligosaccharides of quail egg-yolk immunoglobulin (IgY) were determined in this study. Asn linked oligosaccharides were cleaved from IgY by hydrazinolysis and labelled with p-aminobenzoic acid ethyl ester (ABEE) after N-acetylation. The ABEE labelled oligosaccharides were then fractionated by a combination of Concanavalin A-agarose column chromatography and anion exchange, normal phase and reversed phase HPLC before their structures were determined by sequential exoglycosidase digestion, methylation analysis, HPLC, and 500 MHz 1H-NMR spectroscopy. Quail IgY contained only neutral oligosaccharides of the following categories: the glucosylated oligomannose type (0.6% Glc alpha 1-3Glc alpha 1-3Man9GlcNAc2; 35.6%, Glc alpha 1-3Man7-9GlcNAc2). oligomannose type (15.0%, with the structure Man5-9GlcNAc2) and biantennary complex type with core structures of -Man alpha 1-3(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc (9.9%), -Man alpha 1-3 (GlcNAc beta 1-4)(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc (25.1%) and -Man alpha 1-3(GlcNAc beta 1-4)(-Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc (11.4%). Although never found in mammalian proteins, glucosylated oligosaccharides (Glc1Man7-9GlcNAc2) have been located previously in hen IgY.

Animals↗

Possible beta-mannosidosis chimera. Altered expression of metabolic perturbations.

An aberrant beta-mannosidosis phenotype in a 5-month-old triplet goat kid was characterized by a late postnatal onset of mild neurological symptoms. Necropsy examination revealed relatively normal myelination; however, the distribution of cytoplasmic vacuolation in the kidney and brain was similar to that observed in neonatal beta-mannosidosis. Variable engraftment of donor stem cells, resulting from transplacental transfusion of stem cells from a normal sibling during the immunotolerant period, may have modified the expected severe beta-mannosidosis phenotype. This investigation was designed to determine the effects of a possible chimeric state on organ-specific metabolic perturbations. Residual beta-mannosidase enzyme activity was found in plasma, kidney, liver and spleen but not in brain. Other lysosomal enzyme activities were comparable to normal values. Immunoreactive beta-mannosidase was estimated to be less than 10% of normal levels. Kidney, brain grey matter and brain white matter contained 33%, 12% and 4%, respectively, of the oligosaccharides expected in the organs of beta-mannosidosis animals. There were no detectable oligosaccharides or cytoplasmic vacuolation in the liver or spleen. Studies of this possible chimera provided preliminary evidence for the efficacy of prenatal treatment of early-onset neurodegenerative disorders.

Animals↗

DNA ploidy pattern of each carcinomatous component in adenosquamous lung carcinoma.

The relationship between adenocarcinomatous and squamous carcinomatous components in 12 surgically resected adenosquamous lung carcinomas was analyzed using DNA flow cytometry. Well-preserved parts of the tumor showing either adenocarcinoma or squamous cell carcinoma were identified on paraffin blocks. The cells obtained from each component were stained with propidium iodide for DNA flow cytometry. In the analysis of DNA flow cytometry, both components in the same tumor were defined as being related to each other when they showed diploidy or when at least one DNA index of abnormal clones between two aneuploid components was identical. According to these criteria, 8 (67%) of the 12 tumors showed a relationship between adenocarcinomatous and squamous carcinomatous components. This suggests that, despite the different phenotypes, both components of some adenosquamous lung carcinomas may share similar biological characteristics.

Adenocarcinoma↗

Conversion of a NADPH-dependent aldehyde reducing enzyme into aldose reductase.

1. Aldose reductase, aldehyde reductase and high-Km aldose reductase were purified from the inner medulla of dog kidney. 2. Compared with aldose reductase, high-Km aldose reductase had a lower isoelectric point, a lower activity for aldo-sugars and a lower sensitivity for aldose reductase inhibitors, and it was not activated by sulfate ions. Both reductases had the same molecular weight (38,500) and immunochemical properties. 3. High-Km aldose reductase was easily converted into an aldose reductase-like enzyme, namely a generated reductase upon incubation in neutral buffer solution. 4. The generated reductase was identical with aldose reductase with respect to the isoelectric point, substrate specificity, activation by sulfate ions and IC50 values for aldose reductase inhibitors. The generated reductase revealed immunochemical identity with aldose reductase as well as high-Km aldose reductase.

Aldehyde Reductase↗

Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence.

Seventy male Fischer 344 (F-344) rats were treated with s.c. injection of (-)deprenyl (0.5 mg/kg, n = 35) or physiological saline (n = 35) 3 times a week from the age of 18 months until the time of their natural death. The fifty percent survival time was 28 months in control animals and 30 months in the deprenyl treated group. The mean survival time after the start of treatment (18 months) and after 24 months were 378.3 +/- 97.4 days (mean +/- SD) and 196.3 +/- 97.4 days, respectively, in deprenyl treated rats and 328.7 +/- 108.8 days and 146.7 +/- 108.7 days in control rats. The increases in average life expectancies caused by deprenyl treatment (15% from 18 months and 34% from 24 months) were both statistically significant (P < 0.05, two-tailed t-test). The average body weights were comparable for both groups but the variation of body weight was greater in control groups, thus excluding the possibility that the life prolonging effect of deprenyl results from reduced dietary intake. The results confirm those of two previous studies (1,2) which reported a significant life prolonging effect of deprenyl in aged rats and lend added support to the results of a study on male F-344 rats where the effect was only marginally significant (16% increase after 24 months, P = 0.048 by one-tailed t test) (2).

Animals↗

The roles of GABA in the central regulation of AVP and ANP release and blood pressure in hypertonic saline infusion and hemorrhage.

In order to assess the central effects of gamma-aminobutyric acid (GABA) on arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) release and cardiovascular function, the following two experiments (Exp) were carried out in conscious rats (n = 24). Experiment I: GABA (10 micrograms/kg.min) was intracerebroventricularly (i.c.v.) administered into conscious rats receiving an intravenous (i.v.) infusion of 2.5 M NaCl, and the vehicle alone was i.c.v. administered under i.v. 2.5 M NaCl in the control group. Experiment II: GABA (12 micrograms/kg.min) was infused i.c.v. in conscious rats during hemorrhage (1.6% of BW) and the vehicle alone was i.c.v. administered during hemorrhage in the control study. In Experiment I, plasma AVP and ANP and mean arterial blood pressure (MABP) increased in response to 2.5 M NaCl, but heart rate (HR) slightly decreased. I.C.V. GABA attenuated the AVP and ANP responses, but did not affect MABP and HR. In Experiment II, plasma AVP increased due to decreases in MABP induced by hemorrhage, but plasma ANP and HR never changed. I.C.V. GABA did not affect plasma AVP and ANP, MABP and HR. These results show that i.c.v. GABA has an inhibitory effect on AVP and ANP release in response to hypertonic NaCl, but not to hemorrhage, but never affected hypertonic NaCl-induced increases in blood pressure.

Animals↗

Potential role of thymoma and other mediastinal tumors in the pathogenesis of myasthenia gravis.

Ten non-myasthenic thymoma patients and 12 patients with other mediastinal tumors were compared with 19 myasthenic thymoma patients with regard to an increase in circulating CD4+CD8+ cells and the presence of anti-acetylcholine receptor and anti-skeletal muscle antibodies. Although seven non-myasthenic thymoma patients showed positive results, the proportion of myasthenic thymoma patients who were positive for more than one parameter was significantly larger than that of non-myasthenic thymoma patients (89% vs. 40%). Moreover, one patient with a non-thymomatous mediastinal tumor showing a high CD4+CD8+ cell level had a recent history of seronegative myasthenia gravis. The results indicate that measurements of these parameters may predict the risk of the development of MG in patients with thymoma and other mediastinal tumors.

Adult↗

Expression of highly polysialylated neural cell adhesion molecule in calcitonin-producing cells.

Calcitonin-producing cells are endocrine derivatives of the neural crest and have several neuron-like properties. Expression of the neural cell adhesion molecule in calcitonin-producing cells was examined using two types of antibodies to neural cell adhesion molecule: monoclonal antibody 12E3 recognizes the polysialic acid portion of highly polysialylated neural cell adhesion molecule, and monoclonal antibody AF11 and polyclonal antiserum react with the polypeptide portion common to three major isoforms of neural cell adhesion molecule. An immunohistochemical study revealed that highly polysialylated neural cell adhesion molecule was expressed both in fetal rat thyroidal calcitonin-producing cells and in a calcitonin-producing cell line, rMTC 6-23, established from explantable neoplasm of rat calcitonin-producing cells. The neural cell adhesion molecule in the rMTC 6-23 cells was further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis. Two anti-neural cell adhesion molecule monoclonal antibodies, 12E3 and AF11, revealed a broad positive band around 200,000-250,000 mol. wt in solubilized proteins. When the polysialic acids were eliminated by neuraminidase treatment, the immunoreactivity to monoclonal antibody 12E3 was completely abolished, and core polypeptide corresponding to neural cell adhesion molecule with a molecular weight of 120,000 was detected by monoclonal antibody AF11. These results suggest that cells of the calcitonin-producing cell line express on their surfaces highly polysialylated 120,000 mol. wt form of neural cell adhesion molecule polypeptide.

Animals↗

Comparison of the lateral diffusion constant of hepatocyte membrane proteins in two wild mouse strains of considerably different longevity: FRAP studies on liver smears.

The liver cells of male and female wild mice (Peromyscus leucopus and Mus musculus) have been studied in young, adult, and old age groups. Because P. leucopus displays a life expectancy of 7-8 years, the age groups of this strain were from 5.5 to 68 months. M. musculus survives only to about 2.5 years; therefore, the age groups of this strain ranged from 6 to 27 months. Protein lateral diffusion in hepatocyte membranes was measured by means of fluorescence recovery after photobleaching (FRAP) in liver smears. The peroxide-induced autofluorescence was utilized as a fluorescent label, which in H2O2 treated liver smears is caused by the oxidation of riboflavin bound uniformly to all proteins of the cell membrane. This way the average lateral diffusion constant (D) and the fractional recovery of those proteins can be measured. In both males and females of both strains D displayed a negative linear age correlation. Intraspecies sex differences were small and statistically insignificant. However, interspecies comparisons of males or females resulted in a strongly significant difference: although the intercept points of the regression lines describing D were identical in both strains (3.1 x 10(-10) cm2/sec), the decay of D with aging was about 2.5 times faster in the short-living M. musculus than in the long-living P. leucopus. By the end of life expectancy, both strains reached practically identical values (about 1.9 x 10(-10) cm2/sec). The results lend further support to the membrane hypothesis of aging.

Aging↗

Polymorphism of crystals of Salmonella minnesota Re and Ra lipopolysaccharides.

Salmonella minnesota Re and Ra lipopolysaccharides (LPSs) formed three-dimensional crystals when they were precipitated by the addition of 2 volumes of 95% ethanol containing 375 mM MgCl2 and incubated in 70% ethanol containing 250 mM MgCl2 at 4 C. Besides typical shapes of crystals, hexagonal plates and solid columns, which were already reported (J. Bacteriol. 172: 1516-1528 (1990)), the LPSs thus treated formed crystals possessing various shapes such as square or rectangular plate, lozenge plate, discoid, and truncated hexangular pyramid forms. Electron diffraction patterns from all these crystals except square or rectangular plate crystals obtained by electron irradiation from the direction perpendicular to the basal plane were essentially the same as those from hexagonal plate crystals, indicating that they consist of hexagonal lattices with the lattice constant of 4.62 A. From these results as well as the results of electron microscopic observations of these crystals, it was concluded that all these crystals except square or rectangular plate crystals are composed of hexagonal plate sheets as the basic structural units. Square or rectangular crystals were assumed to correspond to the (1011) planes of solid hexagonal column crystals.

Crystallography↗