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T Kitamoto

Publications and source records attributed to T Kitamoto.

At least 91 records · Page 5Linked to original sources
PubMed1995

Inherited prion diseases and transmission to rodents.

Clinico-pathological phenotypes of patients with prion diseases were compared with their PrP genotypes and transmission rate to mice. Sporadic and iatrogenic CJD patients without mutation and familial CJD patients with E200K showed uniform clinico-pathological features, synaptic-type deposition of PrPCJD and high rate of transmission of the disease to mice. GSS patients with P102L showed long duration of ataxia, numerous plaques in cerebellar cortex and transmitted the disease to mice in only one third of inoculated cases. Other mutations such as P105L, A117V, Y145stop, V180I, M232R and various insertions have particular phenotypes, distinct distribution patterns of PrPCJD, and untransmitted or inconclusive transmission to mice. Polymorphism at codon 129 may modify the phenotypes and transmission rate to mice. Therefore, prion diseases have a wide range from infectious disease to non-infectious, hereditary metabolic disease.

Animals↗
PubMed1995

The original Gerstmann-Sträussler-Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype.

We present new data on the original Austrian kindred with Gerstmann-Sträussler-Scheinker disease (GSS) which encompasses currently 221 members in 9 generations. The mode of inheritance is autosomal dominant. Predominant clinical features are slowly progressive ataxia and late impairment of higher cerebral functions. In contrast, a recent case with proven P102L mutation of the PRNP gene had rapidly developing dementia and severe cortical damage indistinguishable from the clinicopathological phenotype of Creutzfeldt-Jakob disease (CJD). PRNP codon 129 was homozygous for methionine in both the historic and recent cases. Neuropathology confirms spongiosis of variable degree and numerous protease resistant/prion protein (PrP) amyloid plaques scattered throughout most of the brain as constant features in this family. Some amyloid deposits are surrounded by dystrophic neurites with accumulation of phosphorylated neurofilaments and abnormal organelles, reminiscent of Alzheimer-type plaques. Severe telencephalic damage and a synaptic-type fine granular immunoreactivity in laminar distribution in the cortex with anti-PrP after hydrated autoclaving of sections were seen only in the recent patient. In conclusion, factors in addition to the PRNP genotype at codons 102 and 129 must play a role in determining clinicopathological characteristics of this inherited brain amyloidosis.

Adult↗
PubMed1995

[An autopsy-verified case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180 point mutation].

An autopsied case of Creutzfeldt-Jakob disease is reported. A 79-year-old Japanese female showed extrapyramidal sign (resting tremor, and rigidity) and dementia. She developed myoclonus and became akinetic within one year from the onset, and then died of pneumonia at age of 81. None of the members of her family had neuromuscular disorders. CT and MRI studies revealed progressive brain atrophy. Consecutive study of EEG did not reveal periodic synchronous discharges (PSD). Codon 129 polymorphism (Met/Val) and codon 180 point mutation (Val/Ile) were detected. The autopsy revealed spongiform change of cerebral cortex and negative Kuru plaques, confirming the diagnosis of Creutzfeldt-Jakob disease. Immunohistochemical study revealed weak synaptic prion staining. Western blot analysis showed positive Proteinase K resistant prion protein. Gene analysis of autopsied brain showed the same prion DNA polymorphism and mutation. The combination of codon 129 polymorphism and 180 point mutation might associate with an atypical clinical form of CJD, which shows the extrapyramidal signs at the onset, and negative PSD in EEG.

Aged↗
PubMed1995

A POU homeo domain protein related to dPOU-19/pdm-1 binds to the regulatory DNA necessary for vital expression of the Drosophila choline acetyltransferase gene.

Expression of the choline acetyltransferase (ChAT) gene in Drosophila melanogaster is responsible for production of the neurotransmitter acetylcholine and is necessary for viability. In previous studies, we have shown that the regulatory region for normal ChAT expression is large and composed of multiple regulatory elements (Kitamoto et al., 1992; Kitamoto and Salvaterra, 1993). In this study, using various lengths of 5' flanking DNA fused to wild type ChAT cDNA, we have defined a 0.3 kilobase (kb) region of the cis-regulatory DNA, which is essential for restoring viability of Cha lethal mutants. DNase I footprinting analysis of this 0.3 kb DNA revealed a protected 22 bp sequence that contains an octamer-like motif (ATTCAAAT) with one base difference from the consensus octamer motif (ATGCAAAT). Electrophoretic mobility shift assays and Southwestern blot analysis confirmed the presence of specific binding factor(s) for the 22 bp sequence in embryo nuclear extracts, and competition studies established the importance of the octamer-like motif for high-affinity binding. Using the 22-mer as a probe, we have isolated a cDNA clone encoding the Drosophila POU homeo domain protein, dPOU-19/pdm-1, whose target genes and specific binding sequences have not been identified. We propose that vital expression of the Drosophila ChAT gene is regulated by a member of the dPOU-19/pdm-1 putative transcription factor family.

Animals↗
PubMed1994

MIB1 staining index and scoring of histologic features in meningioma. Indicators for the prediction of biologic potential and postoperative management.

BACKGROUND: The biology of brain tumors, including cell kinetics, has been studied. Recently, monoclonal antibody to Ki67 (MIB1), a nuclear protein related to cell proliferation, has been analyzed immunohistochemically using tissue prepared from paraffin embedded sections. METHODS: The authors assessed the prognostic usefulness of various histologic indicators of the biologic potential of meningiomas in patients who underwent total resection (Simpson's Grade I and II) by evaluating the time to recurrence as an end point. Forty-three patients with a total of 36 meningiomas and 7 hemangiopericytomas were investigated by immunohistochemical analysis using MIB1. RESULTS: MIB1 staining index (SI) and histologic score were well correlated with the recurrence-free interval (r = -0.6749, P = 0.002 and r = -0.4939, P = 0.027, respectively) and with each other (r = 0.7909, P < 0.001). The MIB1 SI and histologic score in the nonrecurrence group were significantly lower than those in the recurrence/metastasis group (P < 0.001 and P = 0.001, respectively). The values of these indicators showed that as the value increased, so did the recurrence rate. CONCLUSIONS: Evaluation using the MIB1 SI and total histologic score of meningioma is useful in assessing the prognosis as well as postoperative management of these patients.

Adolescent↗
PubMed1994

A variant of Gerstmann-Sträussler-Scheinker disease carrying codon 105 mutation with codon 129 polymorphism of the prion protein gene: a clinicopathological study.

A case was reported of variant Gerstmann-Sträussler-Scheinker disease (GSS) carrying codon 105 mutation (Pro to Leu) with codon 129 polymorphism (Met/Val) of the prion protein (PrP) gene. The male patient had developed clumsiness of the right hand at age 42, and subsequently exhibited slowly progressive spastic paraparesis, ataxia, dysarthria, memory disturbance and apraxia. Myoclonus or periodic synchronous discharge was not observed. He died at age 53. The cerebral cortex and white matter showed atrophy, which was prominent in the frontal regions. There were numerous amyloid plaques throughout the cerebral cortex, which were reactive with the antibody to PrP, but not to beta/A 4 peptide. PrP immunostaining also revealed many amorphous deposits in the deep cortical layers, where neuronal loss and glial proliferation was evident. The cerebellum was almost intact, except a few amyloid plaques in the white matter. This variant GSS with codon 105 mutation has been found in four pedigrees, only in Japan up to the present, and the clinicopathological phenotype is summarized as follows: (1) onset at age 38-48, with a duration of 7-11 years, (2) prominent spastic paraparesis, associated with dementia and ataxia, (3) numerous amyloid plaques in the cerebral cortex, (4) amorphous PrP deposits with neuronal loss in the deep cortical layers, and (5) minor change of cerebellum.

Adult↗
PubMed1994

Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis.

Identification of the localization of human T lymphotrophic virus type I (HTLV-I) proviral DNA in the central nervous system (CNS) is crucial to the understanding of the pathogenesis of HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) pathogenesis. We have developed a sensitive detection method, called two-step polymerase chain reaction (PCR) in situ hybridization, which enabled us to detect the HTLV-I proviral DNA in paraffin-embedded spinal cord tissue sections from HAM/TSP patients. HTLV-I proviral DNA was detected only in the nucleus of lymphocytes that had infiltrated into the spinal cord. However, no proviral DNA was amplified in any neuronal cells, including neurons and glial cells. This indicates that the demyelination of the spinal cord by HTLV-I as a result of viral infection of oligodendrocytes or neuronal cells is unlikely. The T cell receptor V beta gene sequence from lymphocytes in the spinal cord lesions taken from the same HAM/TSP autopsy cases revealed unique and restricted CDR3 motifs, CASSLXG(G) (one-letter amino acid. X is any amino acid), CASSPT(G), and CASSGRL which are similar to those described in T cells from brain lesions of multiple sclerosis (MS) and in a rat T cell clone derived from experimental allergic encephalomyelitis (EAE) lesions. The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients.

Adult↗
PubMed1994

TNF-beta produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts.

Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT-2 supernatants were found to be dose dependent and were reduced by heat treatment at 100 degrees C for 5 min, but not at 56 degrees C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-alpha and rTNF-beta also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30-kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-beta mAb, although they were not blocked by anti-TNF-alpha mAb. In a Western blot assay, the 25- and 27-kDa bands of TNF-beta were shown clearly in the HUT102 supernatant, although no TNF-alpha bands appeared. These findings suggest that TNF-beta is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts.

Cell Division↗
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↗