Biomedical subjects

K Ojika

Publications and source records attributed to K Ojika.

At least 37 records · Page 2Linked to original sources

PubMed1996

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↗

PubMed1996

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↗

PubMed1996

Demonstration and characterization of hippocampal cholinergic neurostimulating peptide (HCNP) processing enzyme activity in rat hippocampus.

Hippocampal cholinergic neurostimulating peptide (HCNP) stimulates cholinergic activity of cultured medial septal nuclei explants. It consists of eleven amino acids that are located at the N-terminal region of its precursor protein. This report concerns the demonstration and characterization of an HCNP processing enzyme that cleaves the bioactive undecapeptide from the precursor. The enzyme was purified from the hippocampus of young Wistar rats. A synthetic deacetylated peptide (peptide(1-26)) consisting of the N-terminal 26 amino acids of the HCNP precursor protein served as substrate. The product of the enzyme reaction was identified and quantitated by HPLC using deacetylated HCNP as standard. The amount of undecapeptide generated was directly proportional to the time of incubation of the enzyme reaction mixture. From molecular sieving chromatography it was estimated that the molecular mass of the enzyme is close to 68 kDa. The HCNP processing enzyme has a pH optimum of 6.0 and a K m of 0.50 mM for peptide(1-26). Preincubation at 56 degrees C causes rapid inactivation of the HCNP processing activity. Enzyme activity is enhanced by EDTA and 1,4-dithiothreitol, and inhibited by antipain, chymostatin and E-64. These findings suggest that the enzyme probably has a thiol group in its active site. This novel enzyme of the hippocampus may represent a valuable tool for further studies on the general protein metabolism in the central nervous system, as well as for elucidating the neurochemical aspects of neurodegenerative disorders.

Amino Acid Sequence↗

PubMed1996

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↗

PubMed1996

[Autopsy findings of pontine lesions in the elderly].

The characteristics of multiple spongy necrosis of the basis pontis (MSN), central pontine myelinolysis (CPM), and cerebrovascular disease (CVD) of the pons developing in the elderly have not been fully clarified. We therefore studied 305 patients (aged 60-107, mean: 83.9) autopsied in Nagoya City Kohseiin Geriatric Hospital. MSN was found in four patients (1.3%). The major histologic finding was multiple necrosis of the basis pontis, characterized by loss of myelin and axons, no reactive astrocytes or inflammatory cells were found. Small foci of spongy necrosis appeared to unite with each other to form larger lesions. The central basis pontis was weakly stained by Klüver-Barrera stain in 15 patients, which suggested the presence of CPM. However, the diagnosis was only confirmed in one patient, (by the myelinolysis, loss of oligodendroglia, infiltration of macrophages, and reactive astrocytosis). With regard to CVD, none of the 305 patients had macroscopic pontine hemorrhage, but histologically small and old hemorrhagic lesions were found in 15. These lesions were associated with hypertensive or arteriosclerotic changes in the pontine vessels. Pontine infarction was evident in 77 patients (25.2%). In most lesions (74%) the area of infarction was smaller than 1 mm2. In 27 of the 74 patients with lacunar or microscopic infarcts, the pontine infarcts were found in areas where the blood was supplied through the short circumferential branch.

Age Factors↗

PubMed1995

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↗

PubMed1995

Sequence homology of rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding protein and rat 23-kDa protein associated with the opioid-binding protein.

The hippocampal cholinergic neurostimulating peptide (HCNP) enhances acetylcholine synthesis in rat medial septal tissues. We have cloned the cDNAs of the precursor proteins of rat and human HCNP and deduced their respective amino acid sequences. The HCNP sequences aligned at the N-terminal regions of their precursors. The deduced amino acid sequences showed homology with those of the bovine brain phosphatidylethanolamine-binding protein and the rat protein associated with the opioid-binding protein. These observations suggest that the HCNP precursor proteins may have multiple functions.

Acetylcholine↗

PubMed1995

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↗

PubMed1995

[A 115-year-old woman: the oldest individual in Japan].

The purpose of this study was to assess the background to the longevity of a 115-year-old woman who was the oldest individual in Japan as of September, 1994. The secrets of her social and medical profile appeared to be hereditary factors, well-balanced meals, no smoking or drinking, sufficient sleep and adequate exercise. From the viewpoints of psychological aspects and comprehensive functional assessment of the elderly, she clearly has a tenacious personality. Furthermore, she has maintained independence in her activities of daily living, and did not suffer from senile dementia until 107 years of age. From the medical standpoint, she has suffered from transient hypertension, but her left ventricle function has remained within the normal echocardiography range and no greatly abnormal values have been observed in blood chemistry tests. She has suffered from pneumonia and urinary tract infection many times since the age of 109, and on these occasions she was promptly admitted to our hospital and received appropriate medical treatment. We consider that this also played an important role in her longevity.

Activities of Daily Living↗

PubMed1994

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↗

PubMed1994

[Paraplegia in flexion and dementia].

The purpose of this study was to assess possible correlations between paraplegia in flexion and dementia in elderly patients in our special nursing home and geriatric hospital. At the time of our study, 10.5% of all our patients were suffering from paraplegia in flexion, with the ratio increasing with advancing age. Disorders of the nervous system, and in particular disorders caused by cerebrovascular disease were found at a high rate of frequency among the paraplegia in flexion patients, in whom the incidence of dementia was 97.8%. In most cases, the degree of dementia was severe, the types and respective percentages being as follows: vascular type 37.8%, Alzheimer's type 24.4%, mixed type 22.2% and others 15.6%. Many of these patients demonstrated pseudobulbar palsy, frontal sign, Babinski's sign, and typical reflexes of spinal automatism. We think that paraplegia in flexion is probably caused by reflexes of spinal automatism and extensive cerebral lesions.

Aged↗

PubMed1994

[Role of institutions for the elderly in senile dementia].

The purpose of this study was to assess the role of institutions for the elderly, and special nursing homes in particular, with regard to senile dementia. The subjects consisted of 81 cases who were institutionalized in our special nursing home from early November, 1992 to late October, 1993. Of these, 37 cases (45.7%) showed clinical dementia at the time of institutionalization. The severity and respective percentages of dementia were as follows: slight degree 32.4%, moderate degree 27.0% and severe degree 40.6%. The severity of dementia demonstrated significant correlation with age. Hasegawa's Dementia Scale, activity of daily living and physical conditions. The admission rate (40.5%) of the demented group for physical diseases was significantly higher than that (22.7%) of the non-demented group. The majority of families of both groups first sought advice at institutions other than our special nursing home and the welfare office in the city, prior to being institutionalized. The referral rate from such institutions was far higher than that for direct entry from their homes. We consider that special nursing homes, in addition to carrying for daily living requirements, should pay great attention to physical diseases in patients suffering from senile dementia, and cooperate with medical institutes, particularly referring hospitals, and other welfare and health facilities, in this regard.

Activities of Daily Living↗

PubMed1993

[Comprehensive functional assessment of the elderly in institutions, particularly in terms of social life].

The purpose of this study was to clarify aspects of social life in a comprehensive functional assessment of 160 elderly subjects, over 60 years of age, in institutions for the elderly. Five items were assessed: economic conditions, marital status, family conditions, family relationships and group behavior. The institutions were of 4 types: a geriatric hospital, a special nursing home for the aged, a home for the elderly and a home with moderate fees. The assessment of social life demonstrated significant correlation between the revised version of Hasegawa's Dementia Scale, activity of daily living and physical conditions. Inter-institution comparisons revealed significant differences in terms of economic conditions for the home for the elderly, family conditions for the home with moderate fees, and family relationships and group behavior for the geriatric hospital. Total grades across the 5 items were significantly lower for the geriatric hospital cases. This assessment proved useful to illuminate aspects of social life of the elderly in institutions.

Activities of Daily Living↗

PubMed1993

[Clinical and pathological study of myelopathy accompanied with cervical spinal canal stenosis--with special reference to complication of mental retardation or cerebral palsy].

We studied 3 cases with myelopathy caused by cervical spinal canal stenosis (developmental), who had been suffering from walking difficulty followed by tetraplegia, clinically and pathologically. In all 3 cases, mental retardation and/or cerebral palsy was diagnosed. We hypothesized that the brain damage in the developmental stage might also cause developmental disturbance in the cervical spine. In all cases, pathological investigation showed decreased antero-posterior diameter and degeneration in the gray matter and in the lateral and posterior column in the involved cervical spinal cord. The findings, such as relative preservation of the anterior column and cyst formation in the gray matter, were thought to be in common with cervical spondylotic myelopathy or ossification of the occipital longitudinal ligament (OPLL) which had been reported before. In one case we found aberrant peripheral nerve bundles and peripheral type remyelination in the transverse spinal cord lesion. Compared to the pathological change in the OPLL, our cases showed more severe degenerative change in the spinal segments with a relatively preserved antero-posterior diameter of the spinal cord, which supports the theory that the dynamic factor plays a more important role than the static compression factor. We concluded that the aging process and/or dystonic neck movement added spondylotic change to the narrow canal, and excess movement of the neck and/or falls caused dynamic injury to the spinal cord and secondary circulatory disturbance further worsened spinal lesions. When elderly patients with cerebral palsy develop motor symptoms, we should consider cervical spinal stenosis as a possible cause.

Aged↗

PubMed1992

Purification and structural analysis of hippocampal cholinergic neurostimulating peptide.

Hippocampal soluble fraction stimulates acetylcholine (AcCho) synthesis of medial septal nuclei in explant culture system. This stimulating activity was purified from 10-12-day-old rat hippocampus. During purification, the activity was separated into two fractions and a previously unreported peptide was purified from one fraction. The structure of this novel peptide is acetyl-Ala-Ala-Asp-Ile-Ser-Gln-Trp-Ala-Gly-Pro-Leu and we designated it as hippocampal cholinergic neurostimulating peptide (HCNP). Synthesized HCNP and de-acetylated HCNP (free-HCNP) stimulated AcCho synthesis of medial septal nuclei culture, in a dose-dependent manner, but not cultures of corpus striatum or anterior spinal cord. Mean half-maximal concentrations of HCNP and free-HCNP in AcCho synthesis of medial septal nuclei culture were 1.0 +/- 0.3 x 10(-10) M and 1.0 +/- 0.6 x 10(-11) M, respectively. Affinity purified polyclonal antibody to the free-HCNP neutralized the activity of crude hippocampal extract, as well as synthetic HCNP and free-HCNP. These observations suggested that HCNP was present in the hippocampal extract and was involved in development of specific cholinergic neuron in central nervous system.

Amino Acid Sequence↗

PubMed1992

[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↗

PubMed1992

[Five year follow-up study on dementia in institutions for the elderly].

The purpose of this study was to clarify the prognosis of senile dementia based on a 5-year follow-up study in institutions for the elderly. The subjects consisted of 747 cases over 60 years of age. Of these 316 cases showed clinical dementia but 431 cases had no intellectual disturbance in July, 1987. The mortality rate (56.3%) of the demented group was significantly higher than that (31.8%) of the non-demented group. The mortality rate of patients increased with aging. However, the mortality rate of the demented group did not correlate with the severity of dementia. An autopsy study revealed that the direct causes of death in 51.1% of demented patients were pneumonia and cardiovascular diseases. Among the demented patients followed up for 5 years, 22.5% showed severe worsening of dementia, 25.8% showed slight or moderate degree of worsening and 51.7% showed no change. Factors causing exacerbation of dementia included cerebrovascular disease and bone fracture.

Aged↗

PubMed1992

[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↗