Biomedical subjects

T Kitamoto

Publications and source records attributed to T Kitamoto.

At least 91 records · Page 5Linked to original sources

PubMed1992

Creutzfeldt-Jakob disease with amyloid angiopathy: diagnosis by immunological analyses and transmission experiments.

It was difficult to make a definite pathological diagnosis in a 73-year-old man with Creutzfeldt-Jakob disease (CJD) due to extensive amyloid angiopathy which lacked any severe spongiform changes. Immunostaining using anti-prion protein (PrP) antibody revealed fine granular deposits in the gray matter, after hydrolytic autoclaving pretreatment on tissue sections. Western blotting also revealed an abnormal isoform of PrP, but PrP gene analysis did not show any abnormalities. The primary transmission experiments were repeated three times and induced spongiform encephalopathy in a few mice after a long incubation period.

Aged↗

PubMed1992

Colocalization of prion protein and beta protein in the same amyloid plaques in patients with Gerstmann-Sträussler syndrome.

We examined paraffin-embedded brain sections from three patients with Creutzfeldt-Jakob disease (CJD) and four patients with Gerstmann-Sträussler syndrome (GSS) who also had beta protein deposits in the brains. Immunostaining using anti-prion protein (PrP) and anti-beta protein coupled with formic acid pretreatment, revealed PrP deposits and beta protein deposits, respectively. In all four GSS patients examined, sequential double immunostaining and single immunostaining in serial sections or simultaneous double immunofluorescence revealed the colocalization of PrP and beta protein in the same amyloid plaques. The plaques labeled with both antibodies were designated as beta-PrP plaques. Small kuru plaques of less than 15 microns in diameter were rarely found to coexist with beta deposits. The percentages of beta-PrP plaques in larger kuru plaques were not constant among the four GSS patients. The colocalization patterns of both deposits were observed as being roughly of two types as follows: (1) diffuse beta protein deposits located around the PrP core; and (2) a beta protein core and PrP core simultaneously existing in one amyloid plaque. Under an electron microscope, we were able to confirm the presence of both beta protein and PrP in a single plaque in four GSS patients older than 60 years old. In contrast, no colocalization of either deposits was seen in the amyloid plaque core fractions of a young GSS patient who had no beta protein deposits, even at the electron microscopic level. Therefore, the colocalization of both proteins in a single plaque is believed to be age-related and incidental in GSS patients but suggests a similar morphogenesis of both amyloid deposits.

Adult↗

PubMed1992

Gerstmann-Sträussler-Scheinker disease in an Alsatian family: clinical and genetic studies.

The clinical progression of Gerstmann-Sträussler-Scheinker disease in a family of Alsatian origin is reported. The age of onset and the duration of evolution were variable. The clinical picture became more complex over the generations: in the first generations, isolated dementia and in later generations a triad of pyramidal, pseudobulbar syndromes and dementia associated with spinal cord and cerebellar features. Prion gene analysis showed that four surviving patients carry double missense changes at codons 117 and 129, identical to those found in one case at necropsy and 10 other healthy members of the family. The missense changes were not found in 100 controls. No member of the family had modification of condons 102, 178, or 200. The lod score suggests linkage between the missense change at codon 117 and Gerstmann-Sträussler-Scheinker disease in this family.

Adult↗

PubMed1992

Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt-Jakob disease.

A new method, which enabled the first immunohistochemical documentation of abnormal prion protein (PrP) in all patients with Creutzfeldt-Jakob disease (CJD), was established. This method designated as "hydrolytic autoclaving" revealed punctate PrPCJD stainings around the neuronal cell bodies and dendrites in CJD brains. These punctate stainings were almost identical with that of synaptophysin, suggesting PrPCJD accumulations in the synaptic structures. Subcellular fractionation revealed that prion protein in Creutzfeldt-Jakob disease (PrPCJD) was most concentrated in the synaptosomal fraction. In CJD patients with a long clinical course, synaptophysin immunoreactivity decreased, and synaptic PrPCJD accumulated with a wider distribution. These results suggest that synaptic PrPCJD accumulations might be responsible for the neuronal dysfunction and degeneration in CJD.

Creutzfeldt-Jakob Syndrome↗

PubMed1992

The primary structure of the prion protein influences the distribution of abnormal prion protein in the central nervous system.

We immunohistochemically examined tissue sections from patients with prion protein (PrP) polymorphism using hydrolytic autoclaving enhancement. Abnormal PrP accumulations could be classified into plaque formations (plaque-type) and the diffuse gray matter stainings including synaptic structures (synaptic-type). Insertional polymorphism, a point mutation in codon 102 or 117/129, and a polymorphism in codon 129 (Val129) result in plaque-type PrP accumulations. The patients with codon 102 mutation also have synaptic-type PrP accumulations. However, a point mutation in codon 200 did not show plaque-type accumulations, and only showed synaptic-type PrP accumulations. Likewise, sporadic Creutzfeldt-Jakob disease patients without any known mutations only have synaptic type accumulations. These results imply that the primary structures of PrP influence the phenotype of prion diseases, especially in abnormal PrP distributions of the central nervous system.

Base Sequence↗

PubMed1992

Massive accumulation of modified tau and severe depletion of normal tau characterize the cerebral cortex and white matter of Alzheimer's disease. Demonstration using the hydrated autoclaving method.

Using the hydrated autoclaving method, a new immunohistochemical procedure to enhance tau immunoreactivity in formalin-fixed brain tissue, the authors recently reported that tau protein is detected in neuronal cell bodies and proximal dendrites, gray matter neuropil, axons, and glial cells in normal human hippocampus and neocortex. In the this study, the authors performed a comparative study of the distribution of normal and modified forms of tau in Alzheimer's disease (AD) and control brains. In the cerebral cortex and white matter of AD brains, a massive accumulation of modified tau and/or severe depletion of normal tau were documented in all the tau compartments. In mild AD cases, gray matter neuropil, axons, and glial cells were less severely involved than neuronal perikarya. In the controls, neuronal perikarya were often involved by modified tau accumulation, but the other compartments showed normal distribution. These observations suggest that modifications of tau which lead to neurofibrillary lesions in AD may begin in neuronal perikarya and extend to the other tau compartments in advanced stages of the disease.

Adult↗

PubMed1992

Analysis of cis-regulatory elements in the 5' flanking region of the Drosophila melanogaster choline acetyltransferase gene.

We have analyzed the cis-regulatory elements in the 5' flanking region of the Drosophila choline acetyltransferase gene (ChAT, E.C.2.3.1.6). DNA fragments were fused to the Escherichia coli lacZ reporter gene and introduced into the Drosophila germ line by P-element-mediated transformation. A 7.4 kb 5' flanking sequence directed beta-galactosidase expression in the adult optic lobes and other well-defined CNS structures with a pattern very similar to the distribution of endogenous ChAT protein. In contrast, the proximal 3.3 kb and 1.2 kb of 5' flanking DNA directed lacZ expression in only selected subsets of the structures seen with the 7.4 kb lacZ construct. Our results indicate that both qualitative and quantitative regulatory elements are present in the 5' flanking DNA and that these elements distinguish various subsets of cholinergic neurons. We have also fused the same 5' flanking DNA sequences to wild-type ChAT cDNA and used these constructs to transform Chatsl mutant flies. Not only the 7.4 kb cDNA construct, but also the 3.3 and 1.2 kb constructs, rescued Chatsl from temperature-dependent paralysis and adult lethality, indicating that the regulatory information in any of these genomic fragments can drive sufficient wild-type ChAT expression to overcome these mutant phenotypes.

Animals↗

PubMed1992

The sequential development of abnormal prion protein accumulation in mice with Creutzfeldt-Jakob disease.

The distribution and sequential development of prion protein (PrP) accumulation in the central nervous system (CNS) and non-neuronal organs of mice infected with Creutzfeldt-Jakob disease (CJD) were investigated immunohistochemically using a new pretreatment method that greatly enhanced the immunoreactivity of PrP. Prion protein accumulation in the CNS was first detected at 30 days after inoculation and then developed near the inoculation site or periventricular area, and later spread to the whole cerebrum and then to the pons. Its staining took some characteristic forms. Among non-neuronal organs, PrP accumulated in the follicular dendritic cells (FDCs) in spleen, lymph node, Peyer's patch, and thymus. FDCs staining appeared in spleen, lymph node, and Peyer's patch at 21 or 30 days after inoculation, and in thymus at 90 days. Germinal centers developed in the thymus of some CJD-infected mice. No PrP staining was detected in any examined organs of age-matched control mice.

Animals↗

PubMed1992

[Gerstmann-Sträussler-Scheinker disease with heterozygous codon change at prion protein codon 129].

A 53-year-old male was admitted to our hospital for progressive dementia and gait disturbance which had started at the age of 48. Examination indicated dementia, dysarthria, dysphagia, bilateral pyramidal signs, apraxia of the limbs, and extrapyramidal signs such as fine finger tremors, and rigidity of limbs. There were no cerebellar signs or myoclonus. His mother and elder brother showed similar symptoms and died at the ages of 53 and 50, respectively. EEG was normal. CT and MRI showed mild brain atrophy, but no cerebellar atrophy. T2 weighted image indicated low intensity areas covering bilateral caudate nuclei and putamina. A heterozygous amino acid change from methionine to valine was noted at codon 129 of the prion protein of the patient as well as in one of his son. The most likely diagnosis was Gerstmann-Sträussler-Scheinker (GSS) disease without cerebellar atrophy. GSS may include a broad spectrum of brain pathology. Whether the codon change is associated with pathology without cerebellar atrophy is a problem that awaits further investigation.

Atrophy↗

PubMed1991

CJD discrepancy.

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Amino Acid Sequence↗

PubMed1991

N-terminal sequence of prion protein is also integrated into kuru plaques in patients with Gerstmann-Sträussler syndrome.

Kuru plaques are one of the pathological hallmarks in Gerstmann-Sträussler syndrome, and are composed of prion protein (PrP). To elucidate whether N-terminal sequence of PrP is related to amyloid formation in vivo, we prepared antibody against synthetic N-terminal peptide (anti-PrP-N). Anti-PrP-N immunolabeled kuru plaques positively. Positive reactions were observed in the periphery of large kuru plaque cores, but not in the center. It is therefore postulated that one of the modifications of PrP is N-terminal truncation.

Amino Acid Sequence↗

PubMed1991

Diffuse deposition of immunohistochemically labeled prion protein in the granular layer of the cerebellum in a patient with Creutzfeldt-Jakob disease.

Amyloid plaques in Creutzfeldt-Jakob disease, kuru, and Gerstmann-Sträussler-Scheinker syndrome are known to contain an abnormal isoform of a cellular protein, the prion protein (PrP). The prion protein in its normal cellular isoform is a membrane-bound glycoprotein of unknown function. The mechanisms causing a modification of PrP and accumulation in amyloid plaques are unknown. Here we present a case of Creutzfeldt-Jakob disease with widespread deposition of immunohistochemically labeled PrP in the internal granular layer of the cerebellum. Immunohistochemically labeled PrP was deposited in delicate granules, which often were associated with cellular processes or the cytoplams of undefined cells, or diffusely deposited in the neuropil.

Cerebellum↗

PubMed1991

Increased senile plaques without microglia in Alzheimer's disease.

To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controls were investigated immunohistochemically by a double-labeling method using anti-beta-protein antiserum and anti-ferritin antibody, which is a recently reported microglia marker. In addition, a quantitative analysis was performed. The senile plaques which appeared initially in the nondemented aged controls consisted of a diffuse type without any amyloid cores and these were found in the group aged 50-59 years. The great majority of them were found to contain no ferritin-positive microglia. The number and proportion (percentage) of microglia-containing diffuse plaques increased with age. Classical and compact plaques began to appear in the brains of the group aged 70 years and over, and practically all of them contained microglia. These results suggest that microglia are not associated with initial plaque formation, but correlate with amyloid core formation. In AD, the most prominent feature was that the diffuse plaques, which contained either no or only a few ferritin-positive microglia, increased markedly.

Adult↗

PubMed1991

Immunoreactivity of cerebral amyloidosis is enhanced by protein denaturation treatments.

We investigated paraffin-embedded brain sections from three patients with Gerstmann-Sträussler syndrome and three patients with Alzheimer's disease or senile dementia of Alzheimer type using anti-human prion protein antisera and anti-beta/A4 protein antisera after protein denaturation treatments. After incubation with guanidine-thiocyanate, trichloroacetate, and phenol, the immunoreactivity of kuru plaques and senile plaques was enhanced to the same level as the formic acid treatment. These treatments revealed small compact amyloid deposits, amyloid deposits surrounding the plaque cores, and diffuse plaques. Most of these chemicals changed the congophilia of both amyloids. It is possible that these treatments denature amyloid fibril proteins and break down the structure of amyloid fibrils, thus revealing buried epitopes.

Adolescent↗

PubMed1991

Modified tau is present in younger nondemented persons: a study of subcortical nuclei in Alzheimer's disease and progressive supranuclear palsy.

Tau-positive neurons relating to neurofibrillary tangles and diffuse cytoplasmic stainings were quantitatively examined in the brains of 61 nondemented persons including 24 age-matched controls, 10 patients with Alzheimer's disease (AD) and 5 with progressive supranuclear palsy (PSP). In nondemented persons, the locus ceruleus (LC) was found to contain tau-positive neurons initially in persons in their 30s, whereas the hippocampus contained such neurons initially in persons in their 40s. The LC had a higher incidence and density than the hippocampus in almost all age classes. As neuronal tau accumulation is considered a histological change occurring with normal aging, the LC might be involved in the earliest aging in the normal brain. In AD there was conspicuous tau accumulation in the same sites which were vulnerable to tau accumulation in the age-matched controls. In PSP tau accumulated heavily in a set of sites different from the age-matched controls and AD. Thus, subcortical tau accumulation in AD is increased far more than that under normal aging process, while that in PSP is not simply in an increased state of the normal aging process.

Adult↗

PubMed1991

Practical methods for chemical inactivation of Creutzfeldt-Jakob disease pathogen.

Chemical inactivation of pathogen of Creutzfeldt-Jakob disease (CJD) was examined using the mouse-adapted CJD strain. A high concentration of formic acid, guanidine compounds, trichloroacetate and phenol prevented CJD transmission. NaOH between 0.25 and 2 N lengthened the incubation periods. Sodium dodecyl sulfate (SDS) in a concentration between 1 and 3% did not alter incubation at room temperature but did completely block the transmission after boiling for 3 min in 3% SDS. This method is recommended for practical disinfection.

Acids↗

PubMed1991

Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease.

We established that follicular dendritic cells (FDCs) are the site of abnormal prion protein (PrPCJD) accumulations in lymphoid tissues from mice infected with Creutzfeldt-Jakob disease. Evidence of positive FDC staining was observed in Creutzfeldt-Jakob disease-infected mice irrespective of the inoculation route, while no such staining was seen in the control mice. We also found that the severe combined immunodeficiency mouse trait is transmittable via the intracranial route but not via the intraperitoneal route. Mice with severe combined immunodeficiency did not have PrPCJD accumulation in FDCs.

Animals↗

PubMed1991

Immunohistochemical quantification of substance P in spinal dorsal horns of patients with multiple system atrophy.

Using a computer-assisted image analyser, an immunohistochemical quantification method of substance P-like immunoreactivity (SPLI) in laminae I + II of spinal dorsal horn was established and applied to 13 patients with multiple system atrophy (MSA) with no disturbance of pain sensation, including olivo-ponto-cerebellar atrophy and striatonigral degeneration, and 13 neurologically normal controls. To investigate whether alteration of SPLI is related to an autonomic disorder, myelinated fibre counts of the fourth thoracic ventral roots were performed. Eleven of 13 MSA patients showed a significant decrease in small and large myelinated fibres, and were diagnosed with definite Shy-Drager syndrome (SDS), with the exception of two who had no apparent history of autonomic dysfunction. SPLIs in laminae I + II in 10 of these 11 patients, when adjusted for age, were significantly decreased at both levels of the fourth thoracic and third lumbar spinal segments. The results suggest the disorder of SP-containing synapses of primary afferent neurons and/or those of interneurons in SDS.

Adult↗