Coagulation factor V Leiden mutation may have a racial background.
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Asian People↗
Biomedical subjects
H Fujimura
Publications and source records attributed to H Fujimura.
Involvement of the central nervous system in myotonic dystrophy.
To investigate the etiological factors responsible for intellectual impairment and mood changes in patients with myotonic dystrophy (DM), we evaluated 14 patients with DM by means of neuropsychological evaluation and magnetic resonance images (MRI). There were significant differences between patients and controls in regard to the Barthel index, Zung's depression scale, attention, verbal fluency and digit span. All patients had ventricular enlargement and white matter abnormalities on MRI. However, the severity was variable and there was no difference in neuropsychological testing between patients with mild ventricular dilatation and those with severe dilatation. On the other hand, significant differences were present between patients with mild white matter lesions and those with severe white matter abnormalities in regard to verbal fluency and attention. Neuropathologic examination of an autopsied brain showed an increase in the interfascicular space of the white matter which produced pallor on myelin staining. The present findings suggested that the white matter abnormalities were the cause of cognitive impairment among patients with DM.
Activities of Daily Living↗
Cloning and expression of myelin-associated oligodendrocytic basic protein. A novel basic protein constituting the central nervous system myelin.
We have screened genes predominantly expressed in the rat spinal cord, and we report here cloning of the most abundant unknown gene. It is a novel member of the central nervous system (CNS) myelin-constituting proteins, myelin-associated oligodendrocytic basic protein (MOBP). MOBP is abundantly expressed specifically in oligodendrocytes at the mRNA level only next to myelin basic protein (MBP) and proteolipid protein. Two isoforms have been confirmed. One of them has proline-rich tandem repeats and has 84% homology with human counterpart in terms of predicted amino acid sequences. The cDNA-derived primary structure predicts a small, soluble, basic protein. The immunoelectron microscopy has shown that MOBP is expressed throughout compact myelin. All these characteristics are similar to MBP. One definite difference between MBP and MOBP is that MOBP is expressed exclusively in the CNS myelin. These findings suggest that MOBP shares some important functions with MBP in the CNS myelin such as myelin compaction.
Amino Acid Sequence↗
Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A.
The human peripheral myelin protein 22 (PMP-22) gene has been mapped to chromosome 17p11.2 in the duplicated region associated with Charcot-Marie-Tooth disease type 1A. Southern blot analysis using PMP-22 as a probe indicated that the PMP-22 gene was duplicated in 5 patients from unrelated Japanese families with Charcot-Marie-Tooth disease type 1. In order to investigate whether or not an extra copy of PMP-22 has an effect on its gene expression, we analyzed relative expression of messenger RNA for PMP-22 and protein 0 (P0) against beta-actin by Northern blotting in biopsied nerves of the patients with type 1A disease, and compared the results with those of patients having other demyelinating neuropathies and the autopsied nerves of patients without neuropathies. The relative expression of PMP-22 messenger RNA in 5 patients with Charcot-Marie-Tooth disease type 1A was significantly higher than that in 5 patients with other demyelinating neuropathies (p < 0.05). There was no statistically significant difference in P0 expression between them. This study provided direct evidence for elevated expression of PMP-22 in peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A as the result of a gene dosage effect. However, the relation between elevated expression of PMP-22 and the mechanism causing demyelination remains undetermined.
Adult↗
A study of electrical promontory stimulation in tinnitus patients.
Electrical promontory stimulation relieved tinnitus in 74 (57.4%) of 129 ears (112 patients). There was no significant difference in etiology of tinnitus, age, average audiogram, or tinnitus frequency between patients who responded to electrical stimulation and those who did not. Most patients who did not respond to the initial stimulation trial did not respond to the subsequent trials, suggesting that the initial response to treatment predicts the subsequent response. Patients who did not respond to repetitive treatment were supposed to be under severe stress.
Adolescent↗
Survival of genetically-engineered and wild-type strains of the yeast Saccharomyces cerevisiae under simulated environmental conditions: a contribution on risk assessment.
A genetically-engineered strain of Saccharomyces cerevisiae employed for the industrial production of the human coagulation Factor XIIIa (rhFXIIIa) was used for a survival study under simulated environmental conditions. The homologous strain devoid of the recombinant plasmid and the homologous strain bearing the 2 microns-based vector plasmid without the rhFXIIIa-encoding DNA insert were compared. The strains were introduced into natural soil/water suspension, into soil/medium suspension and into waste water. After intervals, samples of cell suspensions were taken and viable cell numbers were determined by plating on antibiotic-containing medium. In addition, a non-radioactive technique involving enhanced chemiluminescence was employed to detect plasmid-bearing yeast cells. The rhFXIIIa expression plasmid showed a high stability during the simulated environmental condition. No differences in survival rates, however, could be detected for the plasmid-bearing and plasmid-less strains under the three conditions tested, suggesting that the presence of plasmid does not confer selective advantages on the survival of the yeast cells. It is concluded that, even after accidental release of the engineered yeast cells into the environment, elimination rates would be comparable to those for non-recombinant yeast strains.
Environmental Microbiology↗
[Transfer of multiple sclerosis into SCID mice].
Successful transfer of multiple sclerosis (MS) into severe combined immunodeficient (SCID) mice by intracisternal injection of cerebrospinal fluid (CSF) cells from six of 15 patients at exacerbation has been reported. The relative expression of mRNA for cytokines in demyelinated lesions from SCID-hu-MS by a semiquantitative reverse transcriptase-polymerase chain reaction analysis revealed marked increase in expression of mRNAs for TNF-alpha and IL-6. This result raised the possibility that these cytokines played an important role in the demyelinating process in SCID-hu-MS. To test whether or not an antibody (Ab) to murine TNF-alpha has a preventive effect on transfer of MS into SCID mice, intracisternal injection of CSF cells from two patients at exacerbation together with anti-murine TNF-alpha Ab was performed, and we observed effective prevention of transfer. In addition, we also found an Ab to human CD3 (OKT3) to have a preventive effect. The former result suggests that control of TNF-alpha may be effective in treatment of MS and the latter suggests that MS is a T cell-mediated disease.
Adolescent↗
Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) which is expressed predominantly in mouse central nervous system.
A novel cDNA clone encoding a putative G protein-coupled receptor (named GPCR21) was isolated from a mouse brain cDNA library along with its homologue, GPCR01 (the mouse counterpart of previously reported rat receptor R334 [(1991) FEBS Lett. 292, 243-248]) by the polymerase chain reaction using degenerate oligonucleotide primers. Northern blotting and reverse transcription-polymerase chain reaction analyses showed predominant expression of these two receptors in the central nervous system. In situ hybridization analysis revealed their prominent expression in the limbic system and further demonstrated the differential distribution of their mRNAs in mouse brain. Although the ligands for these receptors are yet to be identified, the significant sequence homology between these receptors suggests that they constitute a new receptor subfamily and they possibly represent different receptor subtypes for an unknown neurotransmitter.
Amino Acid Sequence↗
Case of ring chromosome 7: the first report of neuropathological findings.
We report on a boy with ring chromosome 7 who had severe mental retardation, growth failure, microcephaly, cleft lip and palate, café-au-lait spots, nevus flammeus, and genital abnormalities, and died of pneumonia at age 20 months. On autopsy he had fusion of the anterior cerebral hemispheres, accompanied by agenesis of olfactory bulbs and tracts, closely resembling those found in semilobar holoprosencephaly. In addition, heterotopic Purkinje cell clusters in the cerebellar white matter, absence of pigmentation within the brainstem pigmented neurons, and severe hypomyelination in the whole brain were noted. The patient may represent the most severe manifestation of ring chromosome 7, and this is the first detailed neuropathological report on this subject.
Abnormalities, Multiple↗
The outgrowth of lens epithelial cells onto the anterior capsule after intraocular lens implantation.
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Aged↗
Nephrosialidosis: ultrastructural and lectin histochemical study.
The neuropathological findings in a Japanese male with nephrosialidosis are reported. Clinically, coarse face, psychomotor retardation, macular cherry-red spot and proteinuria were noted at 1 year and 7 months. He was diagnosed to have nephrosialidosis on the basis of a deficiency of alpha-neuraminidase activity in both lymphocytes and cultured skin fibroblasts, and of severe glomerular and tubular involvement on renal biopsy. He died of multiple organ failure at 8 years and 6 months. There were numerous vacuoles and storage materials in visceral organs, particularly in the glomerular and tubular epithelial cells of the kidney and Kupffer cells as well as hepatocytes in the liver. Neuropathological examination revealed severe neuronal storage in the selected part of the central nervous system: lower motor neurons of the brain stem and spinal anterior horn cells, as well as neurons in the basal nucleus of Meynert. In the peripheral nervous system, sympathetic ganglia were severely affected. There was little or no neuronal storage in the basal ganglia, cerebral cortex or cerebellum, and demyelination was not found. Electron microscopic examination showed fine wavy multilamellar structures in the spinal anterior horn cells or Zebra body-like structures in the neurons of the Meynert's basal nucleus. Lectin histochemistry was positive for wheat germ agglutinin, Ricinus communis agglutinin-1 and peanut agglutinin within distended neurons. We conclude that the neuropathological feature in nephrosialidosis is not specific except for the selectiveness of the anatomical sites of involvement. It shares some aspects found in other types of sialidosis or galactosialidosis.
Brain↗
A kindred of hereditary adult-onset leukodystrophy with sparing of the optic radiations.
We describe a family with hereditary adult-onset leukodystrophy with sparing of the optic radiations, shown clinically, neuroradiologically and electrophysiologically. All five affected members developed their leukodystrophy in their fourth decade and clinical features steadily progressed. The sparing of the optic radiations is not typical of other leukodystrophies. We suggest that this is a new clinical entity.
Adult↗
Single-photon emission computed tomographic investigation of patients with motor neuron disease.
To investigate the correlation between involvement of the CNS in motor neuron disease (MND) and neuroimaging abnormalities, we studied 18 patients with MND by single-photon emission computed tomography (SPECT) and MRI. Patients were divided into four groups according to the results of SPECT. Group 1 consisted of four patients with reduced isotope uptake in the frontal lobe, including the motor area, and in the anterior part of the temporal lobe; group 2 consisted of two patients with reduced isotope uptake in the motor area spreading to the adjacent frontal lobe; group 3 consisted of eight patients with reduced isotope uptake confined to the motor area; and group 4 consisted of four patients without reduced isotope uptake. We found dementia in group 1, borderline dementia in group 2, and no cognitive deficit in group 3 or four. MRI demonstrated enhanced T2-weighted signals along the pyramidal tract in eight patients, but this finding also existed in some control subjects. SPECT appears useful in identifying the location of cortical neuronal degeneration in patients with MND.
Aged↗
Simplified isolation of chromosomal and plasmid DNA from yeasts.
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Biotechnology↗
Mitochondrial tRNA(Ile) mutation in fatal cardiomyopathy.
A patient with mitochondrial encephalomyopathy who died from progressive intractable cardiac failure at the age of 18 is reported. At the age of 4, he presented with short stature, but multiorgan disorders including deafness, focal glomerulosclerosis, epilepsy and dilated cardiomyopathy appeared later in his clinical course. Laboratory tests showed hyperlactatemia and hyperpyruvatemia. Histopathological findings demonstrated mitochondrial myopathy with ragged red fibers and focal cytochrome C oxidase-deficient fibers in skeletal and cardiac muscles. The activity of cytochrome C oxidase was 30% less than the control level in skeletal muscle. Sequencing of the entire mitochondrial tRNA genome revealed a novel point mutation in the tRNA(Ile) region (nt 4269). This A-to-G substitution was found in none of the 30 controls by screening using mispairing PCR and Ssp I digestion methods, suggesting that this new mutation was pathogenic in our case.
Adolescent↗
Molecular monitoring of the transcriptional activation of the yeast Saccharomyces kluyveri mating pheromone signal transduction by using FUS1-lacZ fusion gene.
To analyse the molecular mechanism by which a mating pheromone signal is transmitted in Saccharomyces kluyveri, the S. cerevisiae FUS1-lacZ fusion gene was introduced into S. kluyveri cells and its transcriptional activation was investigated. The expression of FUS1-lacZ fusion product was cell-type-specifically induced by pheromone treatment in S. kluyveri. The result suggests that S. kluyveri pheromone signal may be transduced by a mechanism similar to that in S. cerevisiae. This system may provide a model for analysing the molecular mechanism of the mating reaction in Saccharomyces kluyveri.
Conjugation, Genetic↗
Transfer of multiple sclerosis into severe combined immunodeficiency mice by mononuclear cells from cerebrospinal fluid of the patients.
To investigate the mode of the pathogenesis of multiple sclerosis (MS), we transferred cerebrospinal fluid (CSF) cells, predominantly mononuclear cells, from MS patients at both exacerbation and remission stages of the disease into severe combined immunodeficiency mice by intracisternal injection. As controls, (i) CSF cells from patients with cervical spondylosis and (ii) peripheral blood mononuclear cells from normal individuals were transferred. Four to 6 weeks after transfer, most mice transferred with CSF cells from MS patients at the exacerbation stage of the disease developed paralysis and ataxia. The histopathological examination on the sacrificed mice revealed multiple scattered, discrete lesions localized in the white matter of the brainstems and spinal cords. These lesions were characterized by various degrees of tissue necrosis, involving inflammatory-cell infiltration. Most infiltrating cells were macrophages, although a smaller number of granulocytes appeared in several foci. Reactive astrocytic gliosis was also seen around the necrotic foci. Furthermore, these lesions exhibited demyelination. These histopathological changes are similar to those seen in MS. In contrast, none of the severe combined immunodeficiency mice transferred with CSF cells from MS patients at the remission stage of the disease, or with CSF cells from the patients with cervical spondylosis, or with peripheral blood mononuclear cells from normal individuals showed any such histopathological changes. These observations provide convincing direct evidence of encephalitogenicity of mononuclear cells in CSF from MS patients at the exacerbation stage of the disease.
Animals↗
Familial amyloid polyneuropathy related to transthyretin Gly42 in a Japanese family.
A Japanese family is described in which 6 persons showed familial amyloid polyneuropathy (FAP). Mean ages of onset were 38 for 4 males and 54 for 2 females. Three of the 6 became emaciated and died after 4 to 10 years. In 5, muscular weakness and autonomic dysfunction were the initial symptoms followed by sensory disturbances. Amyloidotic cardiomyopathy was present in 3 of the subjects. Amyloid deposits showed an immunohistological relation to transthyretin (TTR). Analysis of 1 patient's TTR gene revealed a single base change (A----G) that led to amino acid substitution (Glu42----Gly). This base change produced a new restriction site for endonuclease Cfr13 I in exon 2. Polymorphic analysis of the length of the Cfr13 I-restriction fragment confirmed the base change, and made it possible to detect the mutant TTR Gly42 gene in the FAP subjects. Amino acid sequencing analysis showed a variant of TTR Gly42 in 1 patient's serum.
Adult↗