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T Kitamoto

Publications and source records attributed to T Kitamoto.

At least 55 records · Page 3Linked to original sources
PubMed1994

Human prion diseases with variant prion protein.

Recent molecular genetic studies revealed that the human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to a distinct type of prion diseases. We report herein that it is useful to classify prion diseases into plaque type or non-plaque type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 105, codon 129, codon 145 and insertional polymorphisms belong to the plaque type prion diseases, whereas the wild-type PrP and the variants including codon 180, codon 200, and codon 232 polymorphisms belong to the non-plaque type. The non-plaque type prion diseases showed a rapidly progressive dementia, myoclonus and periodic synchronous discharges in the electroencephalogram, and in the pathological findings diffuse grey matter PrP accumulations including the synaptic structures. The plaque type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposits in the central nervous system influences the clinical and pathological aspects of prion diseases. Thus, PrP accumulations may play a central role in the pathogenesis of prion diseases.

Adult↗
PubMed1994

Distribution of prion protein in German patients with Creutzfeldt-Jakob disease is different from that in Japanese patients.

We investigated the distribution of prion protein (PrP) in 14 German patients with sporadic Creutzfeldt-Jakob disease (CJD) and compared it with that observed in Japanese patients. Immunohistochemical study revealed diffuse gray matter stainings including synaptic structures in all cases. In addition, 4 patients showed plaque-type deposition which was very rarely observed among sporadic Japanese patients without known mutation of the PrP gene but with valine at codon 129. A higher incidence of PrP plaques in German sporadic CJD may be related to the racial difference in the PrP gene.

Adult↗
PubMed1994

An exon 8-spliced out transcript of neurofibromatosis 2 gene is constitutively expressed in various human tissues.

We succeeded in cloning the exon 8-spliced out transcript of neurofibromatosis 2 (NF2) gene in human glioma cell lines. We then investigated the expression of the spliced out form in various human tissues by PCR analysis followed by Southern blot hybridization and sequencing to evaluate whether it was generated by normal alternative splicing or by a splicing mutation. The analysis revealed the splicing out of exon 8 in the various tissues, and the transcript missing exon 8 should thus be considered as a product of normal alternative splicing. Our results further support the possibility that the NF2 gene expresses multiple alternatively-spliced transcripts variantly in different tissue types.

Base Sequence↗
PubMed1994

Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene.

We report the first Japanese case of familial Creutzfeldt-Jakob disease (CJD) with the heterozygous point mutation at codon 200 of the prion protein gene. This suggests that the mutation is not race-specific. The clinical and pathologic features of this case are not different from those of sporadic CJD without point mutations. Some healthy members of the family also carry the same mutation in the autosomal dominant inheritance expression.

Adolescent↗
PubMed1994

Creutzfeldt-Jakob disease transmitted by a cadaveric dura mater graft.

We report a case of Creutzfeldt-Jakob disease developing in a 31-year-old woman 56 months after she received a cadaveric dura mater graft after the removal of a giant pituitary adenoma. Creutzfeldt-Jakob disease was confirmed by a brain autopsy and the existence of an abnormal isoform of prion protein, verified by both immunohistochemical and Western blot analysis. Moreover, prion protein gene analysis was shown in this case to possess a wild-type genotype. The characteristics of Creutzfeldt-Jakob disease after a cadaveric dura mater graft are reviewed and discussed.

Adenoma↗
PubMed1994

[Molecular genetics in Creutzfeldt-Jakob disease].

Recent molecular genetic studies revealed that human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to the distinct type of prion diseases. We report herein that it is useful to classify prion diseases into Creutzfeldt-Jakob disease (CJD) type or Gerstmann-Sträussler syndrome (GSS) type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 105, codon 129, codon 145 and insertional mutations belong to the GSS type, while the wild type PrP and the variants including codon 180, codon 200, codon 210, and codon 232 mutations belong to the CJD type. The CJD type prion diseases showed a rapidly progressive dementia, myoclonus, and periodic synchronous discharges in the electroencephalogram, and showed diffuse gray matter PrP accumulations including the synaptic structures in the pathological findings. The GSS type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposit in the central nervous system influences the clinical and pathological aspects of prion diseases.

Creutzfeldt-Jakob Syndrome↗
PubMed1994

[Creutzfeldt-Jakob disease with a point mutation at codon 232 of prion protein--a case report].

We report a 50-year-old female with sporadic Creutzfeldt-Jakob disease who revealed a point mutation at codon 232 of prion protein (Met to Arg). The initial symptom was visual disturbance. The patient then developed progressive dementia, cerebellar ataxia and myoclous. About eight months after the onset, the patient went into the state of akinetic mutism. The electroencephalogram showed periodic synchronous discharges. From the prion protein's DNA sequencing of the patient's family members, the 84-year-old father without any neurological symptoms was also detected to have a point mutation at codon 232. These findings which, have not been reported before, are interesting when considering the relation between the pathogenesis of Creutzfeldt-Jakob disease and mutations of prion protein gene.

Aged↗
PubMed1993

Double mutations at codon 180 and codon 232 of the PRNP gene in an apparently sporadic case of Creutzfeldt-Jakob disease.

Several polymorphisms of the prion protein gene are associated with the occurrence of familial Creutzfeldt-Jakob disease. We described a 84-year-old Japanese man with neuropathologically verified Creutzfeldt-Jakob disease of apparently sporadic type. His clinical presentation was atypical in point of a very late age at onset and absence of periodic synchronous discharge on electroencephalography. The patient carried double hitherto undescribed mutations of the prion protein gene; at codon 180 on one allele and at codon 232 on another. The mutation at codon 180 abolishes the Tth111I cutting site, which may be misunderstood to represent codon 178 mutation on routine restriction fragment length polymorphism study.

Aged↗
PubMed1993

Immunohistochemical distribution of amyloid precursor protein during normal rat development.

This study focused on the immunohistochemical identification of the beta/A4 amyloid precursor protein (APP) in various developmental stages of both the rat central nervous system (CNS) and the peripheral nervous system (PNS). A comparative study with myelin basic protein (MBP) and synaptophysin (SYP) facilitated the understanding of neuronal maturation and synaptogenesis on both prenatal and postnatal development. Our immunohistochemical study revealed APP to be widely distributed through the nervous system while existing mainly in the cytoplasm, dendrites and axons of the neurons. However, immunoreactivity was also observed in either the ependymal cells or the choroid plexus epithelial cells. Our immunostaining was carried out by the hydrated autoclaving method and revealed the expression of APP at embryonic day 15 in the neuron of the mesencephalic nucleus of the trigeminal nerve and the anterior horn of the spinal cord, trigeminal and spinal ganglion, ependymal cells and the choroid plexus. We thus observed dramatic changes of APP expression in the cerebellum from the embryonic stage. The maturation of synaptogenesis in the cerebellar molecular layer was parallel to the extension of the dendrites of Purkinje cells, which revealed immunoreactivity for APP. These findings suggested that APP played an important role in neuronal maturation and synaptogenesis. Thus, APP is considered to be a useful marker for neuronal development.

Amyloid beta-Protein Precursor↗
PubMed1993

An amber mutation of prion protein in Gerstmann-Sträussler syndrome with mutant PrP plaques.

We found an amber mutation in the open reading frame of the prion protein (PrP) gene. The codon 145 mutation (tyrosine to stop) was recognized on a PrP allele of a patient with Alzheimer-type clinical course. Pathologic examination revealed many amyloid plaques and neurofibrillary changes. However, the amyloid plaques in this patient were not composed of beta/A4 protein, but of PrP. Both wild and mutant PrP alleles were detected in the cerebral mRNA; however, only C-terminal truncated PrP was detected in the kuru plaques. We herein present evidence that only mutant PrP aggregates to make kuru plaques in the central nervous system.

Adult↗
PubMed1993

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↗
PubMed1993

A new inherited prion disease (PrP-P105L mutation) showing spastic paraparesis.

We report the clinicopathological findings of 5 patients with an inherited prion disease with a codon 105 (Pro to Leu) mutation. All of the patients had a spastic gait disturbance and progressive dementia without either cerebellar signs, myoclonus, or periodic synchronous discharges. Autopsy of 3 patients revealed numerous amyloid plaques in the cerebral cortex, especially in the motor cortex and the frontal lobe where neuronal loss and severe gliosis were observed in the absence of spongiform changes. The cerebellum was preserved histologically except for only a few amyloid plaques. The pyramidal tracts in the brainstem and spinal cord showed vacuolated changes and a loss of myelin, but no prion protein accumulations. Thus, the prion protein codon 105 mutation is considered to correspond to a new variant of the Gerstmann-Sträussler syndrome with spastic paraparesis.

Adult↗
PubMed1993

Widespread distribution of tau in the astrocytic elements of glial tumors.

Recently tau immunoreactivity has been observed in astrocytes in Alzheimer's disease and other neurological diseases. We examined the immunohistochemical localization of tau in 110 human brain tumors. Tau was widely distributed in the glial neoplastic cells and the reactive astrocytes in tumor tissues. In human surgical specimens positive immunostaining for tau was frequently observed in astrocytic tumors, oligodendroglial tumors, and glioblastoma, as well as neuronal tumors. The astrocytic neoplastic cells in medulloblastoma and other poorly differentiated tumors were also stained. In contrast, no immunoreactivity was observed in meningiomas and schwannomas. The expression of tau in brain tumors was mainly restricted to those cells with astrocytic features rather than small immature cells. The expression of tau mRNA was also demonstrated in astrocytic tumors. In conjunction with the findings of tau-positive astrocytes in some degenerative disorders, astrocytes are considered to have a potential to express tau through neoplastic transformation and reactive processes.

Animals↗
PubMed1993

Alzheimer's amyloid precursor protein mRNA without exon 15 is ubiquitously expressed except in the rat central nervous system.

The expression of L-beta A4 amyloid precursor protein (L-APP) mRNA, which is a splicing product excluding exon 15 of the APP gene, was investigated in various tissues of adult rats by a polymerase chain reaction analysis of reverse-transcribed RNA (RT-PCR). L-APP mRNA was ubiquitously expressed in all the examined tissues including the liver, kidney, heart, skeletal muscle, spleen, thymus, adrenal, stomach, submandibular gland, testis and ovary, except for the central nervous system (CNS) tissues such as the brain and spinal cord. The DNA sequence analysis of the RT-PCR products from adult rat liver showed an L-APP cDNA form, in which exon 14 was spliced from exon 14 to exon 16, and exon 15 of the APP gene was excluded. In addition, regarding as the brain and liver, L-APP mRNA expression was examined during the development of the embryonic stage. In the brain, no L-APP mRNA expression was detected even in the embryonic stage, whereas L-APP mRNA expression of the liver was still found in the embryonic stage. These results suggest that the splicing event excluding exon 15, which is exactly adjacent to exon 16 and exon 17 encoding the beta A4 protein, would probably occur very rarely in the CNS and that the splicing of L-APP might already be regulated in the embryonic stage.

Amyloid beta-Protein Precursor↗
PubMed1993

Developments in diagnosis for prion diseases.

The protease resistant isoform of prion protein (PrP) is a diagnostic marker of spongiform encephalopathies in humans and animals. Immunoblotting is a sensitive method but requires either fresh or frozen, unfixed materials. Immunohistochemistry using formalin-fixed, paraffin-embedded materials is now also considered to be sensitive and comparable to immunoblotting after various treatments, especially using the hydrolytic autoclaving method on tissue sections before staining. The advantage of this method is that it can be applied to routine pathology materials or long preserved materials. The kuru plaque-type deposition of PrP suggests abnormalities of the PrP gene, while synaptic-type deposition suggests either sporadic CJD or particular familial CJD. PrP gene abnormalities are thus related to PrP deposition and modify clinical symptoms and their progression. A PrP gene analysis can be done using either preclinical, clinical or post-mortem materials.

Genes, Viral↗
PubMed1993

The rat central nervous system expresses Alzheimer's amyloid precursor protein APP695, but not APP677 (L-APP form).

A novel splicing form of beta A4 amyloid precursor protein (APP) lacking exon 15, corresponding to 18 residues, was first reported in leukocytes and then in ubiquitous organs. To determine which APP molecules (APP695, APP751, or APP770) either with (N-APP) or without (L-APP; leukocyte-derived APP) exon 15 were expressed in various organs, we investigated the alternative splicing at exon 15 in the rat brain, kidney, heart, and testis by a PCR analysis of reverse-transcribed RNA and Southern blot analysis. Regarding APP695 without exons 7 and 8, L-APP was either seldom or never expressed in the brain, whereas both N- and L-APP were expressed in other organs. On the other hand, regarding APP751/770 containing exon 7, which codes for the Kunitz-type serine protease inhibitor domain, both N- and L-APP were expressed in all the organs examined, including the brain. These results suggest that a particular alternative regulation system related to exon 15 might be present in only APP695 of the brain and influence the proteolytic processing of APP.

Alzheimer Disease↗