The sensitivities of six silver-staining methods and immunohistology for beta and tau protein wer... more The sensitivities of six silver-staining methods and immunohistology for beta and tau protein were compared for their ability to demonstrate neurofibrillary tangles (NFT) and senile plaques (SP) in paraffin sections. Serial sections of the hippocampal area of 35 brains showing these neuropathological findings were cut and stained by the methods of Cross, Campbell, Bielschowsky, Gallyas,Yamaguchi, our variant (method of Reusche) and immunohistology. In the detection of NFT, the techniques of Gallyas, Bielschowsky, our method and tau protein immunostaining were the most sensitive methods. The procedure of Campbell and again our method were proven to be superior to the other stainings in demonstrating SP as well as diffuse and subpial amyloid. Moreover, our method reliably stained vascular and perivascular amyloid which can be identified in brains with congophilic angiopathy. Due to a lack of control in certain steps of the procedures most of the silver-staining methods are complicated and to not present reliable results. Our variant is easy to perform and, thus, may be used as a sensitive, simple and reliable alternative for the impregnation of the main lesions (NFTand SP) occurring in senile dementia of Alzheimer type and brains with normal aging for screening, retrospective and quantitative studies and for routine purposes.
Clinicopathological data of a woman with a 3-year course of concurrent amyotrophic lateral sclero... more Clinicopathological data of a woman with a 3-year course of concurrent amyotrophic lateral sclerosis and dementia are presented. Dementia had occurred at time of onset of motor disturbances and presented as typical frontal lobe dementia. Pathology confirmed motor neuron disease of amyotrophic lateral sclerosis and frontal lobe atrophy. Multiple senile plaques were distributed cortically and in the hippocampus, where diffuse spread of neurofibrillary tangles was seen. Hence, this Alzheimer's dementia in a patient with sporadic amyotrophic lateral raises the question of a possible association between the two conditions.
The sensitivities of six silver-staining methods and immunohistology for beta and tau protein wer... more The sensitivities of six silver-staining methods and immunohistology for beta and tau protein were compared for their ability to demonstrate neurofibrillary tangles (NFT) and senile plaques (SP) in paraffin sections. Serial sections of the hippocampal area of 35 brains showing these neuropathological findings were cut and stained by the methods of Cross, Campbell, Bielschowsky, Gallyas,Yamaguchi, our variant (method of Reusche) and immunohistology. In the detection of NFT, the techniques of Gallyas, Bielschowsky, our method and tau protein immunostaining were the most sensitive methods. The procedure of Campbell and again our method were proven to be superior to the other stainings in demonstrating SP as well as diffuse and subpial amyloid. Moreover, our method reliably stained vascular and perivascular amyloid which can be identified in brains with congophilic angiopathy. Due to a lack of control in certain steps of the procedures most of the silver-staining methods are complicated and to not present reliable results. Our variant is easy to perform and, thus, may be used as a sensitive, simple and reliable alternative for the impregnation of the main lesions (NFTand SP) occurring in senile dementia of Alzheimer type and brains with normal aging for screening, retrospective and quantitative studies and for routine purposes.
To identify the tau component in senile or kuru plaques, the authors examined brain sections from... more To identify the tau component in senile or kuru plaques, the authors examined brain sections from 12 patients with Alzheimer's disease (AD), 6 with Creutzfeldt-Jakob disease (CJD), and 20 nondemented aged controls using anti-beta protein, anti-buman prion protein, and affinity-purified tau-specific antibody. The tau component was identified both in senile and kuru plaques. In AD, tau-positive senile plaques were found in all cerebral cortices of almost all cases, and the tau-positivity of plaques in cerebral cortices was 5.1 to 27.5%. In CJD, tau-positive senile and kuru plaques were restricted to the hippocampus, and the tau-positivity was 4.3 and 1.2%, respectively. In nondemented aged controls, tau-positive senile plaques also were restricted mostly to the hippocampus, and the tau-positivity was 1.3%. Significant differences in the tau-positivity of senile plaques were found between AD and CJD and nondemented aged controls, and no significant differences were found between CJ...
To search for relationships between aging and cerebral amyloid, the brains of 66 clinically nonde... more To search for relationships between aging and cerebral amyloid, the brains of 66 clinically nondemented individuals were investigated, using the following three approaches for verification of the amyloid: Congo red staining as a histochemical method; immunostaining using anti-beta protein antiserum as an immunohistochemical identification; and biochemical extraction of amyloid from nonfixed brain tissues. That the incidence of cerebral amyloid increased with aging was determined using all three approaches. Immunostaining using anti-beta protein antiserum was more sensitive than Congo red staining. The biochemical extraction was most sensitive for detection of amyloid, and revealed that amyloid was extracted initially from more than half (67%) of the brains of 9 persons in their 50s and from almost all (97%) brains of 35 persons over 60 years of age. Amyloid was extracted even from brains in which amyloid deposits were not detected by histochemical or immunohistochemical methods. This result shows early appearance of the age-related cerebral amyloid.
To clarify the distribution, morphology, and density of amyloid deposits in patients with Alzheim... more To clarify the distribution, morphology, and density of amyloid deposits in patients with Alzheimer's disease (AD), tissue sections from various areas of the central nervous system of 14 patients with AD and from 20 nondemented aged controls were investigated immunohistochemically using anti-beta protein antiserum. beta-protein amyloid deposits were present not only in the cores of the senile plaques and in the vascular wall (amyloid angiopathy), but also in various sized plaque-shaped fibrillary, perivascular, subpial, and subependymal deposits. Amyloid deposits were found mainly in the cerebral cortex in nondemented controls, while in AD they were distributed widely in the regions that were not affected in nondemented controls. The positivity of amyloid deposits in AD was 100% in the cerebral cortex, hippocampus, amygdala, thalamus, caudate nucleus, claustrum, hypothalamus, nucleus basalis of Meynert, and cerebellar cortex. Putamen and brain-stem nuclei were affected frequentl...
Pronounced weight gain is a known side effect of the atypical antipsychotic agent olanzapine. In ... more Pronounced weight gain is a known side effect of the atypical antipsychotic agent olanzapine. In contrast, certain H 2 -blockers are reported to have an inhibitory effect on weight gain. However, there are yet to be any studies that confirm whether or not ranitidine can inhibit the weight gain induced by olanzapine. In an experiment to ascertain whether or not H 2 -blocker ranitidine has an inhibitory effect on weight gain induced by olanzapine, we explored differences in the weight changes between two groups of patients taking olanzapine, one group given ranitidine, and the other not. We also investigated difference in the effect of ranitidine on baseline BMI. First, we instituted an 8-week observation period for schizophrenia patients taking olanzapine. Patients in the ranitidine group were assigned to take ranitidine 300 mg/day. Patients with BMI ≥ 25.0 were designated the obese group and those with a BMI <25.0 the non-obese group. We obtained informed consent from 66 patients...
Despite a range of research on gender identity disorder (GID), at present there is no scientific ... more Despite a range of research on gender identity disorder (GID), at present there is no scientific consensus on whether the etiology of GID is mental or physical. In particular recent advances in the technology of neuroimaging research have led to an increased understanding of the biological basis of various mental disorders. GID also should be evaluated from this perspective. The aim of the present study was therefore to do the first trial to examine the regional cerebral blood flow (rCBF) in GID. Methods: Persons considered biologically male fulfilling the GID criteria are termed male to female (MTF) and, conversely, persons considered biological female are termed female to male (FTM). We compared 11 FTM subjects and nine age-and handedness-matched female control subjects. None of the subjects was regularly taking medication and none had any kind of physical or psychiatric comorbidity. To evaluate rCBF in GID subjects and control subjects, statistical parametric mapping analysis of 99m Tc-ethyl-cysteinate dimer singlephoton emission computed tomography was used. Results: GID subjects had a significant decrease in rCBF in the left anterior cingulate cortex (ACC) and a significant increase in the right insula compared to control subjects. The ACC and insula are regions that have been noted as being related to human sexual behavior and consciousness. From these findings, useful insights into the biological basis of GID were suggested.
sis often results from severe and sudden injury. It leads to rapid cell lysis and a consecutive i... more sis often results from severe and sudden injury. It leads to rapid cell lysis and a consecutive inflammatory response. In contrast, apoptosis proceeds in an orderly manner following a cellular suicide program involving active gene expression in response to physiological signals or types of stress. In general, a key feature of apoptosis is the cleavage of nuclear DNA into oligonucleosome length fragments by endonucleases. Morphologically, the apoptotic cell is characterized by condensation and fragmentation of the nuclear chromatin, and the segmentation of the cell into apoptotic bodies that are rapidly ingested by neighboring phagocytic cells. In addition, it is not usually accompanied by an inflammatory response. The development of a histochemical technique for in situ end-labeling of fragmented DNA, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), has greatly helped the recognition of apoptotic cells in tissue. Several TUNEL studies have suggested that neuronal death in scrapie-infected mice occurs by apoptosis. 9,10 These findings have been recently supported, in humans, by three TUNEL studies in fatal familial insomnia and CJD. However, our previous study demonstrated that TUNEL-positive cells did not increase in the cerebral cortex with CJD and GSS in comparison to normal controls. Ferrer 12 reported that none of TUNEL-positive cells had the typical morphology of apoptosis in the brains with sporadic CJD. In addition, it has been reported that TUNEL positivities were not absolutely specific for apoptosis. Therefore, no convincing in situ data are yet available on the morphology of apoptosis in human TSE, especially concerning apoptotic bodies, based on these previous reports. In the present study, we investigated apoptosis in post-mortem CJD brains, based on definite morphological evidence.
To determine whether the diffusion abnormalities in brains with Alzheimer&amp;amp;amp;amp;amp... more To determine whether the diffusion abnormalities in brains with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) correlate with disease severity, we studied 34 AD patients using diffusion tensor MRI. Mean diffusivity and fractional anisotropy (FA) as well as three eigenvalues (lambda1, lambda2, and lambda3) of the diffusion tensor of the posterior cingulate white matter correlated with the Mini-Mental State Examination (MMSE) score. The mean diffusivity and the three eigenvalues showed significant correlation with the MMSE score. On the other hand, no significant correlation was seen between the FA and MMSE score. Our results suggested that mean diffusivity and the eigen-values, but not FA, reflect progression of AD-related histopathlogical changes in the posterior cingulate white matter and may be useful biological indices to monitor AD.
Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistr... more Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistry are a characteristic finding of amyotrophic lateral sclerosis (ALS). Here we report ubiquitinated SLIs in the putamen and caudate nucleus from a case of ALS with dementia. A 48-year-old Japanese man developed apathy and amimia. Mental and neurological examinations revealed severe character change, muscle atrophy and fasciculation of the distal upper extremities and the tongue, and an exaggeration of the deep tendon reflex. He subsequently showed dysphagia and dysarthria. He died at the age of 51 years, after a total clinical course of about 2.5 years. By immunohistochemistry, ubiquitin-immunoreactive intraneuronal inclusions were observed in the spinal anterior horn cells, the frontal, temporal and entorhinal cortices, dentate fascia of the hippocampus and the amygdala. In addition, ubiquitinated inclusions were also seen in the putamen and caudate nucleus, which appeared as aggregates of thread-like structures similar to SLIs in the spinal anterior horn neurons. They were not seen on hematoxylin-eosin staining, and they also did not show any argentophilia nor did they react with other antibodies, including antibody against tau protein. To our knowledge, this is the first report of the presence of SLIs in non-motor neurons. Our results thus support the notion that ALS is a multisystem disease, and not simply a disease of the motor neurons.
We investigated the distribution of prion protein (PrP) in 14 German patients with sporadic Creut... more 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.
To clarify the association of microglia with senile plaques, the brains from 13 patients with Alz... more To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controis were investigated immunohistochemically by a double-labeling method using anti-fi-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.
Object: To clarify the emotional and instrumental support influencing male caregivers for people ... more Object: To clarify the emotional and instrumental support influencing male caregivers for people with dementia living at home. Patients/Materials and Methods: The subjects were 298 male caregivers. Nursing care burden was assessed using the Zarit Caregiver Burden Scale. Ability to cope with care problems was assessed using the Nursing Care Problems Coping Scale for Male Caregivers for People with Dementia Living at Home (NCSM). Emotional support was assessed using the Emotional Support Network Scale. Instrumental support was assessed using the question "Do you have someone to help when you have a problem with nursing care?". Results: There was a significant correlation (P < 0.04) between the point (index) of NCSM and Zarit Caregiver Burden Scale. A positive significant correlation was found in three coping styles. A negative significant correlation was found in one coping style, and no significant correlation in one coping style. The 'Solve the problem' coping style was linked to support from both within and beyond the family. Both 'Emotional avoidance' and 'Cognitive transformation' coping styles were linked to support from within the family, and "Request assistance" style only to external support. There were no correlations between the source of support and the "Careful supervision and waiting" coping style. Conclusion: Emotional and instrumental support for male caregivers was more than three times more likely to be obtained from within the family than outside it. With families becoming smaller, it is becoming more important for communities and society in general to provide emotional and instrumental support for male caregivers. Male caregivers need support from someone with whom they feel comfortable. It is particularly necessary to consider how to support male caregivers who use the "Emotional avoidance" coping style.
International Journal of Nursing & Clinical Practices, 2015
Background: The number of people with dementia and male caregivers has increased in Japan. We dev... more Background: The number of people with dementia and male caregivers has increased in Japan. We developed a coping scale about nursing care problems encountered by male caregivers of people with dementia living at home. This study tests its validity and reliability. Methods: A self-administered written questionnaire was completed by male caregivers recruited from across Japan. Reliability of factors was tested using Cronbach's alpha. Validity was assessed using concurrent validity and criterion-related validity (with three self-administered scales, the Japanese version of the Zarit Caregiver Burden Scale, the Depressive Symptoms and Self-Esteem Emotional Scale, and the Rosenberg Self-Esteem Scale). Values were compared between groups adopting aggressive or passive methods of coping, using principal component analysis (the major factor method and Promax rotation). Results: The statistical analysis produced a scale of 15 items and five factors. The cumulative contribution ratio was 57.18%. The five factors were labeled "Solve the problem type", "Avoidance and emotional type", "Transformation cognitive type", "Careful supervision and waiting type", and "Assistance request type". The reliability coefficient for the coping scale, measured using Cronbach's alpha, was 0.76, and 0.65 or more for each individual factor. There were significant correlations (P < 0.04) between the new coping scale and total scores on the Japanese version of the Zarit Caregiver Burden Scale, Depressive Symptoms and Self-Esteem Emotional Scale, and Rosenberg Self-Esteem Scale. The comparison between the two groups (aggressive and passive coping methods) showed that they had significantly different levels of depressive symptoms and self-esteem. Conclusion: The Nursing Care Problems Coping Scale for Male Caregivers for People with Dementia Living at Home was found be reliable and valid for measuring whether male caregivers are able to cope with the demands of a person with dementia living at home.
The purpose of this study was to design a method by which immunoperoxidase staining can be applie... more The purpose of this study was to design a method by which immunoperoxidase staining can be applied to formalin-fixed, paraffin-embedded tissue sections to demonstrate amyloid deposits in cerebral and systemic amyloidotic tissues. We used anti-prion protein, anti-beta-protein, anti-amyloid A, and anti-prealbumin antisera. The tissue sections were first treated with 100% formic acid for 5, 20, or 60 minutes and the unlabeled immunoperoxidase method (biotin-streptavidin system reagents) was used. This formic acid pretreatment enhanced immunoreactivity of the amyloid deposits which reacted positively with specific antiserum. The specificity of the immunostainings was well preserved. This method can also be used to demonstrate interspecies cross-reactivity, by using anti-human amyloid A and anti-scrapie hamster prion protein antisera, which stained negatively or faintly with amyloid deposits of heterogenous species. The technique is expected to reveal the buried epitopes of amyloid depos...
The sensitivities of six silver-staining methods and immunohistology for beta and tau protein wer... more The sensitivities of six silver-staining methods and immunohistology for beta and tau protein were compared for their ability to demonstrate neurofibrillary tangles (NFT) and senile plaques (SP) in paraffin sections. Serial sections of the hippocampal area of 35 brains showing these neuropathological findings were cut and stained by the methods of Cross, Campbell, Bielschowsky, Gallyas,Yamaguchi, our variant (method of Reusche) and immunohistology. In the detection of NFT, the techniques of Gallyas, Bielschowsky, our method and tau protein immunostaining were the most sensitive methods. The procedure of Campbell and again our method were proven to be superior to the other stainings in demonstrating SP as well as diffuse and subpial amyloid. Moreover, our method reliably stained vascular and perivascular amyloid which can be identified in brains with congophilic angiopathy. Due to a lack of control in certain steps of the procedures most of the silver-staining methods are complicated and to not present reliable results. Our variant is easy to perform and, thus, may be used as a sensitive, simple and reliable alternative for the impregnation of the main lesions (NFTand SP) occurring in senile dementia of Alzheimer type and brains with normal aging for screening, retrospective and quantitative studies and for routine purposes.
Clinicopathological data of a woman with a 3-year course of concurrent amyotrophic lateral sclero... more Clinicopathological data of a woman with a 3-year course of concurrent amyotrophic lateral sclerosis and dementia are presented. Dementia had occurred at time of onset of motor disturbances and presented as typical frontal lobe dementia. Pathology confirmed motor neuron disease of amyotrophic lateral sclerosis and frontal lobe atrophy. Multiple senile plaques were distributed cortically and in the hippocampus, where diffuse spread of neurofibrillary tangles was seen. Hence, this Alzheimer&#39;s dementia in a patient with sporadic amyotrophic lateral raises the question of a possible association between the two conditions.
The sensitivities of six silver-staining methods and immunohistology for beta and tau protein wer... more The sensitivities of six silver-staining methods and immunohistology for beta and tau protein were compared for their ability to demonstrate neurofibrillary tangles (NFT) and senile plaques (SP) in paraffin sections. Serial sections of the hippocampal area of 35 brains showing these neuropathological findings were cut and stained by the methods of Cross, Campbell, Bielschowsky, Gallyas,Yamaguchi, our variant (method of Reusche) and immunohistology. In the detection of NFT, the techniques of Gallyas, Bielschowsky, our method and tau protein immunostaining were the most sensitive methods. The procedure of Campbell and again our method were proven to be superior to the other stainings in demonstrating SP as well as diffuse and subpial amyloid. Moreover, our method reliably stained vascular and perivascular amyloid which can be identified in brains with congophilic angiopathy. Due to a lack of control in certain steps of the procedures most of the silver-staining methods are complicated and to not present reliable results. Our variant is easy to perform and, thus, may be used as a sensitive, simple and reliable alternative for the impregnation of the main lesions (NFTand SP) occurring in senile dementia of Alzheimer type and brains with normal aging for screening, retrospective and quantitative studies and for routine purposes.
To identify the tau component in senile or kuru plaques, the authors examined brain sections from... more To identify the tau component in senile or kuru plaques, the authors examined brain sections from 12 patients with Alzheimer's disease (AD), 6 with Creutzfeldt-Jakob disease (CJD), and 20 nondemented aged controls using anti-beta protein, anti-buman prion protein, and affinity-purified tau-specific antibody. The tau component was identified both in senile and kuru plaques. In AD, tau-positive senile plaques were found in all cerebral cortices of almost all cases, and the tau-positivity of plaques in cerebral cortices was 5.1 to 27.5%. In CJD, tau-positive senile and kuru plaques were restricted to the hippocampus, and the tau-positivity was 4.3 and 1.2%, respectively. In nondemented aged controls, tau-positive senile plaques also were restricted mostly to the hippocampus, and the tau-positivity was 1.3%. Significant differences in the tau-positivity of senile plaques were found between AD and CJD and nondemented aged controls, and no significant differences were found between CJ...
To search for relationships between aging and cerebral amyloid, the brains of 66 clinically nonde... more To search for relationships between aging and cerebral amyloid, the brains of 66 clinically nondemented individuals were investigated, using the following three approaches for verification of the amyloid: Congo red staining as a histochemical method; immunostaining using anti-beta protein antiserum as an immunohistochemical identification; and biochemical extraction of amyloid from nonfixed brain tissues. That the incidence of cerebral amyloid increased with aging was determined using all three approaches. Immunostaining using anti-beta protein antiserum was more sensitive than Congo red staining. The biochemical extraction was most sensitive for detection of amyloid, and revealed that amyloid was extracted initially from more than half (67%) of the brains of 9 persons in their 50s and from almost all (97%) brains of 35 persons over 60 years of age. Amyloid was extracted even from brains in which amyloid deposits were not detected by histochemical or immunohistochemical methods. This result shows early appearance of the age-related cerebral amyloid.
To clarify the distribution, morphology, and density of amyloid deposits in patients with Alzheim... more To clarify the distribution, morphology, and density of amyloid deposits in patients with Alzheimer's disease (AD), tissue sections from various areas of the central nervous system of 14 patients with AD and from 20 nondemented aged controls were investigated immunohistochemically using anti-beta protein antiserum. beta-protein amyloid deposits were present not only in the cores of the senile plaques and in the vascular wall (amyloid angiopathy), but also in various sized plaque-shaped fibrillary, perivascular, subpial, and subependymal deposits. Amyloid deposits were found mainly in the cerebral cortex in nondemented controls, while in AD they were distributed widely in the regions that were not affected in nondemented controls. The positivity of amyloid deposits in AD was 100% in the cerebral cortex, hippocampus, amygdala, thalamus, caudate nucleus, claustrum, hypothalamus, nucleus basalis of Meynert, and cerebellar cortex. Putamen and brain-stem nuclei were affected frequentl...
Pronounced weight gain is a known side effect of the atypical antipsychotic agent olanzapine. In ... more Pronounced weight gain is a known side effect of the atypical antipsychotic agent olanzapine. In contrast, certain H 2 -blockers are reported to have an inhibitory effect on weight gain. However, there are yet to be any studies that confirm whether or not ranitidine can inhibit the weight gain induced by olanzapine. In an experiment to ascertain whether or not H 2 -blocker ranitidine has an inhibitory effect on weight gain induced by olanzapine, we explored differences in the weight changes between two groups of patients taking olanzapine, one group given ranitidine, and the other not. We also investigated difference in the effect of ranitidine on baseline BMI. First, we instituted an 8-week observation period for schizophrenia patients taking olanzapine. Patients in the ranitidine group were assigned to take ranitidine 300 mg/day. Patients with BMI ≥ 25.0 were designated the obese group and those with a BMI <25.0 the non-obese group. We obtained informed consent from 66 patients...
Despite a range of research on gender identity disorder (GID), at present there is no scientific ... more Despite a range of research on gender identity disorder (GID), at present there is no scientific consensus on whether the etiology of GID is mental or physical. In particular recent advances in the technology of neuroimaging research have led to an increased understanding of the biological basis of various mental disorders. GID also should be evaluated from this perspective. The aim of the present study was therefore to do the first trial to examine the regional cerebral blood flow (rCBF) in GID. Methods: Persons considered biologically male fulfilling the GID criteria are termed male to female (MTF) and, conversely, persons considered biological female are termed female to male (FTM). We compared 11 FTM subjects and nine age-and handedness-matched female control subjects. None of the subjects was regularly taking medication and none had any kind of physical or psychiatric comorbidity. To evaluate rCBF in GID subjects and control subjects, statistical parametric mapping analysis of 99m Tc-ethyl-cysteinate dimer singlephoton emission computed tomography was used. Results: GID subjects had a significant decrease in rCBF in the left anterior cingulate cortex (ACC) and a significant increase in the right insula compared to control subjects. The ACC and insula are regions that have been noted as being related to human sexual behavior and consciousness. From these findings, useful insights into the biological basis of GID were suggested.
sis often results from severe and sudden injury. It leads to rapid cell lysis and a consecutive i... more sis often results from severe and sudden injury. It leads to rapid cell lysis and a consecutive inflammatory response. In contrast, apoptosis proceeds in an orderly manner following a cellular suicide program involving active gene expression in response to physiological signals or types of stress. In general, a key feature of apoptosis is the cleavage of nuclear DNA into oligonucleosome length fragments by endonucleases. Morphologically, the apoptotic cell is characterized by condensation and fragmentation of the nuclear chromatin, and the segmentation of the cell into apoptotic bodies that are rapidly ingested by neighboring phagocytic cells. In addition, it is not usually accompanied by an inflammatory response. The development of a histochemical technique for in situ end-labeling of fragmented DNA, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), has greatly helped the recognition of apoptotic cells in tissue. Several TUNEL studies have suggested that neuronal death in scrapie-infected mice occurs by apoptosis. 9,10 These findings have been recently supported, in humans, by three TUNEL studies in fatal familial insomnia and CJD. However, our previous study demonstrated that TUNEL-positive cells did not increase in the cerebral cortex with CJD and GSS in comparison to normal controls. Ferrer 12 reported that none of TUNEL-positive cells had the typical morphology of apoptosis in the brains with sporadic CJD. In addition, it has been reported that TUNEL positivities were not absolutely specific for apoptosis. Therefore, no convincing in situ data are yet available on the morphology of apoptosis in human TSE, especially concerning apoptotic bodies, based on these previous reports. In the present study, we investigated apoptosis in post-mortem CJD brains, based on definite morphological evidence.
To determine whether the diffusion abnormalities in brains with Alzheimer&amp;amp;amp;amp;amp... more To determine whether the diffusion abnormalities in brains with Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (AD) correlate with disease severity, we studied 34 AD patients using diffusion tensor MRI. Mean diffusivity and fractional anisotropy (FA) as well as three eigenvalues (lambda1, lambda2, and lambda3) of the diffusion tensor of the posterior cingulate white matter correlated with the Mini-Mental State Examination (MMSE) score. The mean diffusivity and the three eigenvalues showed significant correlation with the MMSE score. On the other hand, no significant correlation was seen between the FA and MMSE score. Our results suggested that mean diffusivity and the eigen-values, but not FA, reflect progression of AD-related histopathlogical changes in the posterior cingulate white matter and may be useful biological indices to monitor AD.
Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistr... more Skeins or skein-like inclusions (SLIs) in motor neurons detected by ubiquitin immunohistochemistry are a characteristic finding of amyotrophic lateral sclerosis (ALS). Here we report ubiquitinated SLIs in the putamen and caudate nucleus from a case of ALS with dementia. A 48-year-old Japanese man developed apathy and amimia. Mental and neurological examinations revealed severe character change, muscle atrophy and fasciculation of the distal upper extremities and the tongue, and an exaggeration of the deep tendon reflex. He subsequently showed dysphagia and dysarthria. He died at the age of 51 years, after a total clinical course of about 2.5 years. By immunohistochemistry, ubiquitin-immunoreactive intraneuronal inclusions were observed in the spinal anterior horn cells, the frontal, temporal and entorhinal cortices, dentate fascia of the hippocampus and the amygdala. In addition, ubiquitinated inclusions were also seen in the putamen and caudate nucleus, which appeared as aggregates of thread-like structures similar to SLIs in the spinal anterior horn neurons. They were not seen on hematoxylin-eosin staining, and they also did not show any argentophilia nor did they react with other antibodies, including antibody against tau protein. To our knowledge, this is the first report of the presence of SLIs in non-motor neurons. Our results thus support the notion that ALS is a multisystem disease, and not simply a disease of the motor neurons.
We investigated the distribution of prion protein (PrP) in 14 German patients with sporadic Creut... more 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.
To clarify the association of microglia with senile plaques, the brains from 13 patients with Alz... more To clarify the association of microglia with senile plaques, the brains from 13 patients with Alzheimer's disease (AD) and 23 nondemented aged controis were investigated immunohistochemically by a double-labeling method using anti-fi-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.
Object: To clarify the emotional and instrumental support influencing male caregivers for people ... more Object: To clarify the emotional and instrumental support influencing male caregivers for people with dementia living at home. Patients/Materials and Methods: The subjects were 298 male caregivers. Nursing care burden was assessed using the Zarit Caregiver Burden Scale. Ability to cope with care problems was assessed using the Nursing Care Problems Coping Scale for Male Caregivers for People with Dementia Living at Home (NCSM). Emotional support was assessed using the Emotional Support Network Scale. Instrumental support was assessed using the question "Do you have someone to help when you have a problem with nursing care?". Results: There was a significant correlation (P < 0.04) between the point (index) of NCSM and Zarit Caregiver Burden Scale. A positive significant correlation was found in three coping styles. A negative significant correlation was found in one coping style, and no significant correlation in one coping style. The 'Solve the problem' coping style was linked to support from both within and beyond the family. Both 'Emotional avoidance' and 'Cognitive transformation' coping styles were linked to support from within the family, and "Request assistance" style only to external support. There were no correlations between the source of support and the "Careful supervision and waiting" coping style. Conclusion: Emotional and instrumental support for male caregivers was more than three times more likely to be obtained from within the family than outside it. With families becoming smaller, it is becoming more important for communities and society in general to provide emotional and instrumental support for male caregivers. Male caregivers need support from someone with whom they feel comfortable. It is particularly necessary to consider how to support male caregivers who use the "Emotional avoidance" coping style.
International Journal of Nursing & Clinical Practices, 2015
Background: The number of people with dementia and male caregivers has increased in Japan. We dev... more Background: The number of people with dementia and male caregivers has increased in Japan. We developed a coping scale about nursing care problems encountered by male caregivers of people with dementia living at home. This study tests its validity and reliability. Methods: A self-administered written questionnaire was completed by male caregivers recruited from across Japan. Reliability of factors was tested using Cronbach's alpha. Validity was assessed using concurrent validity and criterion-related validity (with three self-administered scales, the Japanese version of the Zarit Caregiver Burden Scale, the Depressive Symptoms and Self-Esteem Emotional Scale, and the Rosenberg Self-Esteem Scale). Values were compared between groups adopting aggressive or passive methods of coping, using principal component analysis (the major factor method and Promax rotation). Results: The statistical analysis produced a scale of 15 items and five factors. The cumulative contribution ratio was 57.18%. The five factors were labeled "Solve the problem type", "Avoidance and emotional type", "Transformation cognitive type", "Careful supervision and waiting type", and "Assistance request type". The reliability coefficient for the coping scale, measured using Cronbach's alpha, was 0.76, and 0.65 or more for each individual factor. There were significant correlations (P < 0.04) between the new coping scale and total scores on the Japanese version of the Zarit Caregiver Burden Scale, Depressive Symptoms and Self-Esteem Emotional Scale, and Rosenberg Self-Esteem Scale. The comparison between the two groups (aggressive and passive coping methods) showed that they had significantly different levels of depressive symptoms and self-esteem. Conclusion: The Nursing Care Problems Coping Scale for Male Caregivers for People with Dementia Living at Home was found be reliable and valid for measuring whether male caregivers are able to cope with the demands of a person with dementia living at home.
The purpose of this study was to design a method by which immunoperoxidase staining can be applie... more The purpose of this study was to design a method by which immunoperoxidase staining can be applied to formalin-fixed, paraffin-embedded tissue sections to demonstrate amyloid deposits in cerebral and systemic amyloidotic tissues. We used anti-prion protein, anti-beta-protein, anti-amyloid A, and anti-prealbumin antisera. The tissue sections were first treated with 100% formic acid for 5, 20, or 60 minutes and the unlabeled immunoperoxidase method (biotin-streptavidin system reagents) was used. This formic acid pretreatment enhanced immunoreactivity of the amyloid deposits which reacted positively with specific antiserum. The specificity of the immunostainings was well preserved. This method can also be used to demonstrate interspecies cross-reactivity, by using anti-human amyloid A and anti-scrapie hamster prion protein antisera, which stained negatively or faintly with amyloid deposits of heterogenous species. The technique is expected to reveal the buried epitopes of amyloid depos...
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Papers by Koji Ogomori