PubMed Health⌕ Search

Biomedical subjects

T Kitamoto

Publications and source records attributed to T Kitamoto.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1993

Intestinal pseudo-obstruction in patients with amyloidosis: clinicopathologic differences between chemical types of amyloid protein.

A clinicopathologic study was made of 16 patients with amyloidosis and with clinical signs of intestinal pseudo-obstruction. amyloid deposits in the small intestine were proved in all cases by endoscopic or intra-operative biopsies, and immunohistochemical study identified the chemical types of amyloid protein: amyloid A protein (AA) in 13 cases, light chain protein (AL) in two, and beta 2-microglobulin (AH) in one. Clinically, an acute self limiting obstructive condition was evident in 13 cases with AA, and 12 of them returned to normal bowel function after receiving total parenteral nutrition. Two cases with AL and one with AH presented chronic, intermittent, obstructive symptoms, and medical treatment, including total parenteral nutrition, was ineffective with no recovery of intestinal propulsion. Pathological examination of the necropsy specimens in seven cases showed considerable differences in the preferential sites of gastrointestinal deposits between the chemical types of amyloid; extensive infiltration and replacement of the muscularis propria by amyloid deposits throughout the gastrointestinal tract, especially the small intestine, were found in the AL and the AH cases, while amyloid deposits in the myenteric plexus without appreciable muscle infiltration were shown in the AA cases. These results show that intestinal pseudo-obstruction in patients with amyloidosis is caused by either myopathy or neuropathy, and that chemical types of amyloid may determine which of the two factors has the dominant affect on the bowel function.

Adult↗
PubMed1993

Accumulation of abnormal prion protein in mice infected with Creutzfeldt-Jakob disease via intraperitoneal route: a sequential study.

We immunohistochemically studied the location of abnormal prion protein in the central nervous system and visceral organs at the clinical and preclinical stages of mice infected with Creutzfeldt-Jakob disease via intraperitoneal route. Abnormal prion protein was diffusely distributed in the central nervous system. The sequential study showed that its stainings were first detected 120 days after inoculation, were found in all mice after 180 days, and were the most intense and widespread after 270 days. There was no restricted involvement at the early stages nor rostrally dominant distribution of the stainings that had been found in mice infected via intracerebral route. Abnormal prion protein was also located in the follicular dendritic cells in the spleen, lymph nodes, intestinal Peyer's patch, and thymus. Its stainings were first detected in the spleen, lymph nodes, and Peyer's patch 14 or 30 days after inoculation. In the thymus, however, the stainings were first detected after 210 days in the germinal centers formed in the medulla.

Animals↗
PubMed1992

Successful transmission of Creutzfeldt-Jakob disease from human to mouse verified by prion protein accumulation in mouse brains.

The accumulation of prion protein (PrP) was revealed in the brains of mice inoculated with the brain homogenate from seven patients with Creutzfeldt-Jakob disease (CJD) by immunohistochemistry using hydrolytic autoclaving. It was not found in the brains of mice inoculated with material from either two patients with Gerstmann-Sträussler syndrome or two with other dementing illnesses. PrP accumulation took the forms of diffuse neuropil accumulation in the gray matter and plaque-like accumulation in the white matter and was observed in particular areas in the supratentorial structure. Its distribution was narrower than that in the brains of mice infected with a mouse-adapted CJD strain. PrP accumulation was found not only in all histopathologically positive mice, but also in some histopathologically negative mice. In all groups of mice inoculated with the material from each CJD patient, the percentage of mice with PrP accumulation was equal to or exceeded that of mice with the histopathological findings. PrP immunohistochemistry using formic acid pretreatment stained such plaque-like accumulation less intensely than that using hydrolytic autoclaving and did not stain diffuse neuropil accumulation. Therefore, PrP accumulation which can be revealed in the brains of first-passage CJD mice by this new immunohistochemical method may be the most sensitive hallmark of successful transmission.

Animals↗
PubMed1992

Cellular retinoic acid binding protein type II was preferentially localized in medium and posterior parts of the progress zone of the chick limb bud.

The expression and distribution of cellular retinoic acid binding protein II (CRABP II) was examined in chick limb buds. CRABP II was detected in the limb buds at Hamburger and Hamilton (1) stage 21 and the amount of CRABP II was gradually increased during stages 21-27 and thereafter decreased. CRABP II was mainly located in the progress zone, and the dorsal and ventral premuscular mass in the proximal region of the limb buds at stage 23. CRABP II was preferentially localized in the medium and posterior parts rather than the anterior part of the progress zone; The content of CRABP II in the medium and posterior parts was 8-9 times more than that in the anterior part.

Animals↗
PubMed1992

Alzheimer's amyloid precursor protein accumulates within axonal swellings in human brain lesions.

By using a monoclonal antibody and polyclonal antibodies to human beta amyloid precursor protein (APP), we immunohistochemically examined axonal swellings (spheroids). The immunoreactivity of APP was observed in numerous spheroids, which were found around the areas of old cerebral infarctions, in the globus pallidus with Hallervorden-Spatz disease as well as in or around brain abscesses. The axonal swellings were not immunolabeled with beta protein. These results implied that APP accumulated in spheroids regardless of beta protein depositions.

Aged↗
PubMed1992

Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative study of patients with codon 102 point mutation or without mutations.

We examined 7 patients with Creutzfeldt-Jakob disease (CJD) with a methionine-to-valine change at prion protein (PrP) codon 129 (CJD129 patients). These CJD129 patients did not have either a codon 117 or 198 point mutation. For comparison, we also examined 7 patients with Gerstmann-Sträussler syndrome (GSS) with a proline-to-leucine change at PrP codon 102 (GSS102 patients) and 13 patients without any known mutations at codons 102, 117, 129, 178, or 200 (CJDwild patients). CJD129 patients had a long clinical duration and ataxia at onset, but rarely had any periodic synchronous discharge in their electroencephalogram. Unlike CJDwild patients, all CJD129 patients have typical congophilic PrP plaques in their brain. These clinicopathological findings were similar to those of GSS102. However, the distribution and morphology of PrP deposits revealed by immunohistochemistry were different between CJD129 and GSS102. In GSS102 more numerous and various types of PrP plaques are seen throughout the brain, while in CJD129 patients a unicentric core was the major feature of PrP plaques. The change in codon 129 influences the clinical course and pathological findings in CJD.

Adult↗
PubMed1992

The coexistence of Alzheimer's disease and Creutzfeldt-Jakob disease in a patient with dementia of long duration.

We report here a 75-year-old-male with a slowly progressive dementia of 5-year duration along with a rapid exacerbation of symptoms in the terminal 3 months. Neuropathological examinations revealed findings consistent with conspicuous Alzheimer's disease and mild Creutzfeldt-Jakob disease (CJD). The plaque amyloid was exclusively composed of beta-protein. The immunohistochemistry of prion protein using hydrolytic autoclaving pretreatment showed diffuse gray matter stainings in the sections of both the cerebral and cerebellar cortices. This method was thus considered useful in confirming the diagnosis of CJD for this case.

Aged↗
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↗