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Biomedical subjects

S Mitake

Publications and source records attributed to S Mitake.

At least 37 records · Page 2Linked to original sources

Mixed connective tissue disease associated with acute polyradiculoneuropathy.

A rare case of mixed connective tissue disease (MCTD) with acute polyradiculoneuropathy is reported. A 23-year-old woman presented with high body temperature, arthralgia and a headache, and developed gait disturbance two weeks later. She had many clinical features common to patients with MCTD. Her neurological manifestations were diagnosed as acute polyradiculoneuropathy based on the clinical picture, combined with supportive ancillary data, including cerebrospinal fluid (CSF) analysis, electrophysiological evaluation, sural nerve biopsy, peroneus brevis muscle biopsy, and magnetic resonance imaging (MRI). Her neurologic deficits, as well as associated laboratory findings, were improved by corticosteroid therapy.

Acute Disease↗

Hirano bodies and Alzheimer's disease.

Hirano bodies are refractile eosinophilic rod-like structures, initially observed in Guamanian (Chamorro) patients with amyotrophic lateral sclerosis and parkinsonism-dementia complex. Subsequent investigations revealed that Hirano bodies have a distinct topographic distribution in the hippocampus, and that their number increases in the pyramidal layer of Sommer's sector but not in the stratum lacunosum with advancing age. Since patients with Alzheimer's disease (AD) have significantly more Hirano bodies than normal subjects in the same age range, the inclusions appear seem to be of relevance in this disease. Immunohistochemical and electron microscopic studies have demonstrated that the main components of Hirano bodies are abnormal micro-filaments, and that not only molecules associated with cell cytoskeleton, but also some stress-related proteins and growth factors such as beta-amyloid precursor protein, hippocampal cholinergic neurostimulating peptide (HCNP), transforming growth factor beta 3 are present in Hirano bodies. The accumulation of HCNP in Hirano bodies suggests that patients bearing these inclusions may have a disturbance of the septohippocampal cholinergic system, considered to be of importance for le arning and memory formation, and hence be related to the memory impairment of AD.

Alzheimer Disease↗

Demonstration of the biological activity of peptide fragments related to human and rat hippocampal cholinergic neurostimulating peptide (HCNP).

Human and rat hippocampal cholinergic neurostimulating peptides (HCNPs) are 54.5% homologous; both stimulate acetylcholine synthesis in rat medial septal nuclei cultures. This in vitro system was used to test the bioactivity of short peptides containing human or rat HCNP sequences. Peptides with sequences corresponding to the N-termini and middle regions of both, and to the shared three C-terminal residues were not active. Tetrapeptides and hexapeptides whose C-terminus is this common sequence enhanced acetylcholine production, indicating that the minimum consensus sequence for HCNP activity is X-Gly-Pro-Leu.

Acylation↗

Immunohistochemical study of intracytoplasmic inclusion bodies of the thalamus in myotonic dystrophy.

Intracytoplasmic inclusion bodies of the thalamus in eight patients with myotonic dystrophy (MyD) were studied immunohistochemically. The intracytoplasmic inclusion bodies of the thalamus (thalamic inclusions, TIs) were strongly immunostained with anti-ubiquitin antibody (Ab) and some of them were mildly stained with anti-microtubule associated protein 1 (MAP 1) and anti-MAP 2 antibodies. However, TIs did not react with any of the following: anti-neurofilament protein Ab, anti-tau Ab, anti-paired helical filament Ab, anti-tubulin Abs (alpha and beta), anti-neuron-specific enolase Ab, anti-glial fibrillary acidic protein Ab, anti-synaptophysin Ab, anti-myelin basic protein Ab, anti-actin Ab and anti-phosphorylated epitope of neurofilaments Ab. Thus, our study demonstrates the unique immunohistochemistry of TIs in MyD which differentiates them from other intracytoplasmic inclusions in various neurodegenerative disorders.

Aged↗

Distribution of hippocampal cholinergic neurostimulating peptide (HCNP) immunoreactivity in the central nervous system of the rat.

Hippocampal cholinergic neurostimulating peptide (HCNP), an undecapeptide isolated from the hippocampal tissue of young rats, enhances the cholinergic development in explant cultures of medial septal nuclei. This report concerns the distribution of HCNP immunoreactivity in the central nervous system (CNS) of 11- and 28-day-old Wistar rats; two affinity-purified anti HCNP antibodies were used. Immunoblot analyses of extracts of different regions of the brain revealed a single 23 kDa band that corresponded to the presumed HNCP precursor protein. Immunostaining of the various CNS structures of the 28-day-old rats was more intense than in those of 11-day-old animals. HCNP immunoreactivity was detected in neurons as well as in glia cells, particularly oligodendroglia. The perikarya of neurons in the cerebral cortex, hippocampus, limbic cortex, caudate, putamen, arcuate nucleus of hypothalamus, trigeminal subnuclei, rostroventrolateral reticular nucleus and dorsal horn of the spinal cord were positively stained. In addition, nerve fibers and terminals in the hypothalamic subnuclei, zona incerta, thalamic subnucleus, caudate, putamen, locus coeruleus, trigeminal subnuclei, dorsal motor nucleus of the vagus, dorsal horn of the spinal cord and intermediolateral column also displayed HCNP immunoreactivity. These observations would suggest that HCNP and its related molecules may have multifunctional roles in the CNS.

Animals↗

Distribution of hippocampal cholinergic neurostimulating peptide (HCNP)-like immunoreactivity in organs and tissues of young Wistar rats.

This report concerns the distribution of the hippocampal cholinergic neurostimulating peptide (HCNP) in tissues and organs of 11-day-old Wistar rats. HCNP, originally isolated and purified from the hippocampus of young rats, is an undecapeptide (acetyl-Ala-Ala-Asp-Ile-Ser-Gln-Trp-Ala-Gly-Pro-Leu). HCNP distribution was investigated by using immunohistochemical techniques, employing an affinity-purified rabbit antibody that specifically recognizes HCNP and its 21-kDa precursor protein. Positively stained cells were detected in a variety of tissues and organs, including salivary gland, small intestine, colon, pancreas, bronchiole, adrenal gland, testis, as well as several others. The nerve fibres around blood vessels of almost all organs expressed HCNP. Our results suggest that HCNP or its precursor, or both, may have a specific function not only in the central nervous system, but also in the peripheral nervous system, and possibly in certain specialized duct and gland cells as well.

Amino Acid Sequence↗

Possible implication of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano body formation.

We have previously demonstrated that hippocampal cholinergic neurostimulating peptide (HCNP)-related components accumulate in almost all Hirano bodies in Sommer's sector of the hippocampus of elderly individuals, and that the number of HCNP-positive Hirano bodies is greater in patients with Alzheimer's disease. Although Hirano bodies occur preferentially in the neuronal processes of the stratum pyramidale of the hippocampus, they can be seen occasionally as small inclusions, intermingled with neurofibrillary tangles and in association with senile plaques. Here we show that the small inclusions are also recognized by an anti-HCNP antibody, and by using immunoelectron microscopy demonstrate that these HCNP-positive inclusions, intermingled with tau protein-positive neurofibrillary tangles and beta-amyloid-positive senile plaques are indeed Hirano bodies. These findings strongly suggest that HCNP-related components may be involved in Hirano body formation.

Aged↗

Neuronal loss in the medullary reticular formation in myotonic dystrophy: a clinicopathological study.

Respiratory insufficiency occurs frequently in patients with myotonic dystrophy (MyD). We have performed a quantitative study of neurons linked to respiratory function in the dorsal central medullary nucleus (DCMN), the ventral central medullary nucleus (VCMN), and the subtrigeminal medullary nucleus (SMN) in seven patients with MyD and eight age-matched controls. Alveolar hypoventilation of the central type occurred in three of the MyD patients but not in the remaining MyD patients or controls. The densities of neurons of the DCMN, the VCMN, and the SMN in MyD patients with hypoventilation were significantly lower than in MyD without hypoventilation and controls. These data suggest the neuronal loss of the DCMN, VCMN, and SMN is associated with the presence of hypoventilation in MyD and may be an important feature of MyD.

Aged↗

Demonstration of deacetylated hippocampal cholinergic neurostimulating peptide and its precursor protein in rat tissues.

This report concerns the demonstration of hippocampal cholinergic neurostimulating peptide (HCNP), its deacetylated analogue (free HCNP) and HCNP precursor protein in rat tissues. To avoid possible enzymatic degradation during sample manipulation, tissue extracts were prepared under acidic conditions using trifluoroacetic acid. The tissue contents of free HCNP and of precursor protein were determined by radioimmuno-assay (RIA) using two antibodies with different specificities, and by a combination of HPLC and RIA. Free HCNP was detected in neuronal and renal tissues, but not in liver. All tissues examined had measurable amounts of HCNP precursor protein. The concentrations of free HCNP and precursor in neuronal tissues were inversely related to the age. These results suggest that the deacetylated analogue of HCNP and its precursor protein may have significant physiological functions, especially in the central nervous system of young animals.

Aging↗

Neuronal cell loss in the dorsal raphe nucleus and the superior central nucleus in myotonic dystrophy: a clinicopathological correlation.

A quantitative study of neurons in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) was performed in seven patients with myotonic dystrophy (MyD), five of whom showed hypersomnia, and in eight age-matched controls. The densities of neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and control subjects. There was an appreciable positive correlation in the density of neurons between the DRN and the SCN in all MyD patients. These data suggest that the neuronal loss of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

Aged↗

Accumulation of hippocampal cholinergic neurostimulating peptide (HCNP)-related components in Hirano bodies.

We have previously isolated from the hippocampus of young rats a novel peptide termed 'hippocampal cholinergic neurostimulating peptide' (HCNP) which specifically enhances the cholinergic activity of the septohippocampal system in vitro. Cloning and base sequence analysis of HCNP-specific cDNA from rat and human cDNA libraries revealed that the 1.1 kDa peptide aligns at the N-terminal region of its 21 kDa precursor protein. An affinity-purified rabbit antibody to rat HCNP prepared by us recognizes the C-terminal domain of the peptide, while an antibody against human HCNP binds to a large portion of the peptide. In this report we show that both antibodies react with HCNP-related components present in the soluble cytosol fraction of human brain tissue. Immunohistochemical examination of human nervous system tissues from elderly individuals revealed that Hirano bodies in Sommer's sector of the hippocampus were specifically stained by anti-HCNP antibodies. The number of HCNP-positive Hirano bodies was greater in patients with Alzheimer's disease than in normal, age-matched individuals. The immunohistochemical results were substantiated by immunoelectron microscopy. The present findings indicate that HCNP-related components accumulate in Hirano bodies, suggesting that patients who bear these inclusions may have a disturbance of the septo-hippocampal cholinergic system, considered to be of importance for learning and memory formation.

Aged↗

Two different molecules, NGF and free-HCNP, stimulate cholinergic activity in septal nuclei in vitro in a different manner.

Hippocampal cholinergic neurostimulating peptide (HCNP), a novel peptide purified from 10- to 12-day-old rat hippocampus, specifically enhances acetylcholine (AcCho) synthesis in medial septal nuclei in vitro, synthetic de-acetylated HCNP (free-HCNP) elicits more potent enhancement than HCNP. Nerve growth factor (NGF), a neurotrophic substance found in the hippocampus, enhances the cholinergic activity of medial septal nuclei both in vivo and in vitro. The effects of free-HCNP on the development of various cholinergic phenotypes and the interaction of NGF and free-HCNP on cholinergic neurons in vitro were studied. In medial septal nuclei, free-HCNP enhanced AcCho synthesis and choline acetyltransferase (ChoATase) activity and increased Vmax. It did not modulate culture morphology, choline (Cho) uptake, or acetylcholinesterase (AcChoEase) activity. NGF stimulated AcCho synthesis and both ChoATase and AcChoEase activity in the medial septal nuclei and also enhanced AcCho synthesis in a corpus striatum culture. Compared with the effect of either agent alone, the simultaneous application of 3.8 x 10(-11) M NGF and 3 x 10(-11) M free-HCNP (maximal stimulation) to medial septal nucleus culture resulted in a more than additive enhancement of AcCho synthesis, an additive increase in ChoATase activity, and a significant increase in Cho uptake. In corpus striatum and spinal cord cultures, there was no cooperative increase in AcCho synthesis with NGF and free-HCNP nor any enhancement of AcCho synthesis by free-HCNP. These findings suggest that NGF and free-HCNP play a cooperative role during the biochemical differentiation of cholinergic neurons in medial septal nuclei.

Acetylcholine↗

[Bedridden elderly and dementia].

The purpose of this study is to clarify possible correlations between dementia and long term bedridden elderly patients in our special nursing home and geriatric hospital. At the time of our study, 42.6% of all our patients were bedridden, and the ratio increased in those groups of advanced age. The percentage of bedridden female patients was higher than that of males. Most bedridden patients, suffered disorders of the nervous system particularly disorders caused by cerebrovascular disease. Among the bedridden patients, the incidence of dementia was 82.8%. In most these cases, the degree of dementia was severe. The types and respective percentages of dementia were as follows: Vascular type 45.1%, Alzheimer's type 23.2%, mixed type 19.5% and others 12.2%. We think that Alzheimer's type dementia may cause a patient to become bedridden. On the other hand, vascular type dementia may be promoted by a patient's being bedridden for a long time. Tube-fed patients comprised 20% of all bedridden patients and all of these patients showed dementia. We believe that a patient's getting out of bed and receiving rehabilitation as soon as possible is vital to the prevention of becoming permanently bedridden. In respect to the present study of bedridden dementia patients, we would like to further study tube feeding and terminal care.

Aged↗

[Intellectual ability and activity of daily living of centenarians in institutions for the elderly].

The purpose of this study was to assess the intellectual ability and activity of daily living (ADL) of 12 centenarians in institutions for the elderly and to compare them with individuals in the 62-99 age group. At the time of our study, 66.7% of the centenarians were severely demented, three quarters of them suffering from Alzheimer's type dementia and the other one quarter the mixed type. There were qualitative differences between non-demented centenarians and the demented elderly in general, particularly in regard to understanding of surrounding objects and the presence or absence of mental symptoms indicating intellectual deterioration. A total of 50% of the centenarians were bedridden, but 41.7% of them could eat without assistance. Intellectual ability and ADL directly decreased with aging. We think centenarians do not present a special case and our clinical observations suggest a continuous process of aging. Five of the centenarians recently died and were autopsied. The agreement rate between clinical diagnoses and pathological findings with respect to dementia was 80%.

Activities of Daily Living↗

[A case of an aged patient suspected of craniopharyngioma with a chief symptom of eunuchoidism accompanied with panhypopituitarism].

A 78-year-old man with developmental disturbance of the genital organs and eunuchoidism was reported. He also had a high pitched voice, thickness of the lower lip and kyphosis of the thorax. He seemed to be fretful, but his intelligence was normal. Neurological tests revealed bilateral hemianopsia and decreased tendon reflexes. A plain skull radiograph clearly showed an egg shaped calcified mass extending upward from the sella turcica which resembled a ballooning shape. Brain CTs showed a high density round mass which expanded the sella turcica and raised the floor of the third ventricle. The inner part of the tumor showed irregular high density. T1-weighted MR imaging revealed an iso signal intensity, and T2 showed low signal intensity in the mass. These findings strongly supported the diagnosis of calcificated craniopharyngioma. Endocrinological study showed panhypopituitarism caused by the tumor compressing the pituitary gland and the hypothalamus. The main reasons why there were no apparent symptoms of hypopituitarism were because the receptors were up-regulated and secondarily because the thyroid and the adrenal cortical functions decreased while struggling to maintain balance with each other. There was also a possibility that these symptoms might have been masked by normal aging. Benign monoclonal hypergammopathy was also indicated, although we could not find a clear correlation between this finding and others.

Adrenocorticotropic Hormone↗

[Clinical and pathological study of cerebrovascular disease in the 60-101 age group].

The purpose of this study is to clarify the clinical and pathological characteristics of cerebrovascular disease in nonagenarians and centenarians. In all autopsied cases from 1981 to 1986 (60-101 years old, 138 men and 157 women), cerebrovascular disease was observed in 32 cases (90-101 years old, 8 men and 24 women) and 174 cases (60-89 years old, 95 men and 79 women) in our hospital. The incidence of cerebrovascular disease was 58.3%, 68.8%, 75.1% and 64%, pathologically, in their sixties (60's), seventies (70's), eighties (80's) and over nineties (90's) respectively. In those who had cerebrovascular disease, cerebral infarctions were found in 79.9% of the cases of the under-90 group and 81.2% of cases of the over-90 group. In both groups, infarction was mainly found in over 2 regions, in the putamen, caudate, thalamus and in the white matter and cortex of the frontal lobe. In the over-90 group, the medium-sized infarctions decreased and small-sized infarctions increased. Cerebral hemorrhages were found in 16.1% of cases in the under-90 group and 12.6% of cases in the over-90 group. In the over-90 group, large-sized hemorrhages were found in 75%, and the incidence of hemorrhages was 50%, 50% in the lentiform nucleus and the subcortex respectively. The frequency of mental symptoms, frontal signs and oral dyskinesia in the over-90 group was significantly higher than in the under-90 group. The onset of cerebrovascular attacks was unknown in 43.8% cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[An autopsy case of progressive supranuclear palsy with central pontine myelinolysis].

An autopsy case of progressive supranuclear palsy (PSP) associated with central pontine myelinolysis (CPM) is reported. A 73-year-old male patient suffered from gait disturbance for about 5 years. The clinical features were characterized by gradual development of supranuclear ophthalmoplegia, tremor, bradykinesia, rigidity, neck dystonia, dementia and pseudobulbar palsy at the advanced stage of his illness. Treatment with levodopa did not improve his neurological signs and symptoms. PSP or multiple system atrophy was considered as a clinical diagnosis of the patient. He died of pneumonia, acute pancreatitis and liver dysfunction in November 1985. The main neuropathological findings were neuronal loss and gliosis with neurofibrillary tangles of globose type in the globus pallidus, subthalamic nucleus, substantia nigra and dentate nucleus, and at the base of the pons, bilateral and symmetrical demyelination was found. In addition, myelin staining revealed circumscribed pallor in the cerebral white matter. The histologic diagnosis was PSP associated with CPM. An association of PSP with CPM is rare in the elderly and possible etiologic factors of both diseases were discussed.

Aged↗

[Effect and prognosis of rehabilitation for cerebrovascular dementia in the elderly].

The effect of rehabilitation and prognosis for elderly cases of cerebrovascular dementia were evaluated by comparing the group of the patients receiving rehabilitation with those who did not receive rehabilitation. There were no significant differences in the age, neurological symptoms, psychotic symptoms, physical complications, ADL and Hasegawa's dementia rating scale between the two groups. The main reason for rehabilitation was recurrence of cerebrovascular attack (42.9%), disuse atrophy (42.9%) and bone fracture and others (14.3%). There was significant improvement of ADL in the patients showing a score of more than 10 on Hasegawa's dementia rating scale and in the patients given drugs to improve cerebral circulation and metabolism, but there was no significant improvement of Hasegawa's dementia rating scale. Concerning the prognosis of patients receiving the rehabilitation, there was no change of ADL and Hasegawa's dementia rating scale. In the group of patients which did not receive rehabilitation, significant decrease of ADL was noted, but there was no change of Hasegawa's dementia rating scale.

Activities of Daily Living↗