Search PubMed⌕ Search

Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 55 records · Page 3Linked to original sources
PubMed2000

Health risks among Japanese men with moderate body mass index.

BACKGROUND: Despite the westernized lifestyle, most Japanese are not prominently obese. As their obesity may be obscured, we want to further explore central fat distribution and health risks among this population. METHODS: 2668 men (body mass index (BMI) 20- < 26.4 kg/m2) were identified from 3343 men (BMI 14.0-37.7, median of waist-to-height ratio (W/Ht) 0.50) who underwent routine health examinations. They were divided into four groups: (1) BMI 20- < 24, W/Ht < 0.50; (2) BMI 20- < 24, W/Ht > or = 0.50; (3) BMI 24- < 26.4, W/Ht < 0.50; and (4) BMI 24- < 26.4, W/Ht > or = 0.50. The metabolic risks and physical activities were compared. RESULTS: W/Ht > or = 0.50 comprised 35% of the subjects of BMI 20- < 24, 91% of BMI 24- < 26.4, only 1% of BMI < 20 and up to 99% of BMI > or = 26.4. After adjusting for age and smoking and with group 1 as the reference group, odds ratios (ORs) were significantly higher in both groups 2 and 4 for the risk of hypertension (1.42, 1.98), hyperglycaemia (1.49, 1.78), hypertriglyceridaemia (1.95, 2.56), low HDL cholesterol (1.87, 2.20), hyperuricaemia (2.00, 2.51) and fatty liver (2.57, 5.64) and additionally in group 4 for hypercholesterolaemia (1.35). ORs in group 3 were only significantly higher for risk of hypertension (1.86) and fatty liver (1.89). Significantly lower frequencies of regular physical activity were noted in the higher W/Ht groups (0.75, 0.47, 1.10, 0.52 days per week, from groups 1-4, respectively). CONCLUSIONS: Measurement of waist circumference may be a preliminary method for the survey of people at higher risk of lifestyle-related disorders in Japanese men, especially among those with moderate BMI.

Abdomen↗
PubMed2000

Clinicopathological studies on diffuse Lewy body disease.

With reports of dementia cases with numerous cortical Lewy bodies and our proposal that this be named 'diffuse Lewy body disease' (DLBD), this condition has received a great deal of attention, first in Japan and subsequently in Europe and North America. In the early 1990s, similar types of nomenclature were considered, and at the First International Workshop in 1995, it was proposed that 'dementia with Lewy bodies' be used as a generic term for Lewy body dementia, including the DLBD form. We review our previous clinicopathological findings and describe our recent immunohistochemical studies on DLBD.

Brain↗
PubMed2000

Diffuse Lewy body disease.

Diffuse Lewy body disease (DLBD) has been studied from various viewpoints and, although clinical diagnostic criteria for DLBD have been proposed, diagnosis remains difficult. DLBD has been reported to be the second most common form of dementia in the aged, following Alzheimer-type dementia. It has, however, been clinically under-diagnosed. Therefore, the search for diagnostic markers for DLBD must continue. Very recently, 'dementia with Lewy bodies' (DLB) was proposed as a generic term for various forms of dementia with Lewy bodies, including DLBD and similar disorders. Cortical Lewy bodies are the most important pathologic marker for diagnosis of DLBD. At present, however, the mechanism responsible for cortical Lewy body formation has yet to be disclosed.

Brain↗
PubMed2000

An autopsy case of Alzheimer's disease presenting with primary progressive aphasia: a clinicopathological and immunohistochemical study.

This report describes an autopsied Alzheimer's disease (AD) patient with primary progressive aphasia (PPA) as an early symptom. The patient developed a progressive speech disturbance at the age of 70 years, and difficulty in comprehension became apparent 2 years later. Magnetic resonance imaging scan disclosed asymmetrical brain atrophy, predominantly on the left temporal lobe. At the age of 74 years, the patient's dementia rapidly progressed with parkinsonism and he died after a disease duration of 6 years. At autopsy, the brain showed a marked temporo-frontal lobe atrophy, predominantly on the left side. There was severe neuronal loss with gliosis and tissue rarefaction in the atrophied cerebral cortex and amygdala. Many neurofibrillary tangles with neuropil threads were found in the cerebral cortex. Numerous amyloid deposits were distributed throughout the cerebral cortex, accompanied by amyloid angiopathies. This patient was clinically diagnosed with temporal lobe-dominant Pick's disease, although the possibility of corticobasal degeneration was made. The neuropathological diagnosis was AD with asymmetrical brain atrophy and widespread amyloid angiopathies.

Aged↗
PubMed2000

Lack of association in Japanese patients between neuroleptic malignant syndrome and a debrisoquine 4-hydroxylase genotype with low enzyme activity.

Decreased activity of debrisoquine 4-hydroxylase (CYP2D6), which participates in hepatic metabolism of several frequently used neuroleptics and antidepressants, is inherited as an autosomal recessive trait through polymorphic CYP2D6 gene alleles. In eastern Orientals, a C --> T substitution at nucleotide 188 (Pro34Ser) is primarily responsible for decreased ability to metabolize CYP2D6 substrates. We therefore studied a possible association between neuroleptic malignant syndrome (NMS) and the C188T mutation. We examined the frequency of the C188T mutation by polymerase chain reaction and restriction fragment length polymorphism analysis in 36 Japanese patients previously diagnosed with NMS and 107 neuroleptic-treated schizophrenic patients with no NMS history. The C188T allele frequency was 0.417 in NMS patients and 0.463 in patients without NMS. No significant allele or genotype associations were observed. We cannot conclude that low CYP2D6 activity genotype causes susceptibility to NMS in Japanese patients.

Adult↗
PubMed2000

Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy.

OBJECTIVES: NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synuclein in sporadic Parkinson's disease and other related disorders including diffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/alpha-synuclein antibodies. METHODS: A total of 58 necropsied brains, from seven patients with Parkinson's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three with ALS and dementia, one with Huntington's disease, two with progressive supranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrophy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. RESULTS: In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brainstem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neurons in MSA. These widespread accumulations were not seen in other types of dementia or spinocerebellar ataxia. CONCLUSION: Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major step in the pathological cascade of both diseases and provides novel strategies for the development of therapies.

Aged↗
PubMed2000

[Diabetology].

Explore the source record for details and available documents.

Animals↗
PubMed2000

[Reconstruction of chest wall using myocutaneous flap].

Reconstruction of chest wall using myocutaneous flap has been performed in 2 cases. A 72-year-old female referred to our hospital for locally recurrent left breast cancer without any distant metastases. The other patient was a 77-year-old female, having locally recurrent liposarcoma of the left lateral chest wall. Chest wall was resected with wide margin of normal tissue, and myocutaneous flaps of latissimus dorsi were used for reconstruction of skin defect (13 x 8 cm and 14 x 10 cm) in both cases. Although additional split-thickness skin graft was required for one of them, myocutaneous flaps were useful for the reconstruction of widely defected chest wall. By using this technique, wider margin can be obtained, which could decrease the risk for local recurrence of malignant tumor.

Aged↗
PubMed1999

Membrane topology of Alzheimer's disease-related presenilin 1. Evidence for the existence of a molecular species with a seven membrane-spanning and one membrane-embedded structure.

A significant member of early-onset familial type of Alzheimer's disease cases has been shown to be caused by dominant mutations in either of the two genes encoding presenilin 1 (PS1) and presenilin 2 (PS2). These two proteins are highly homologous to each other and have been reported to be mainly localized to the membranes of intracellular compartments such as the endoplasmic reticulum. Information about the membrane topological structures of these proteins is indispensable for understanding their physiological and pathological roles. Although several models have been proposed previously, their precise membrane topologies remain unknown. In this study, we examined this issue in detail by expressing a series of C-terminally deleted PS1 mutants fused to the hydrophilic portion of Escherichia coli leader peptidase in vitro using a reticulocyte lysate in the presence of microsomal membranes. Our results predict that PS1 exists mainly in a seven membrane-spanning structure with its C-terminal end exposed to the luminal space. This was also confirmed by expressing these fusion proteins in cultured cells. We further showed that a ninth hydrophobic segment is tightly bound to the membrane without spanning it. Based on the above observations, we propose a novel "seven membrane-spanning and one membrane-embedded" topological model for presenilins.

Alzheimer Disease↗
PubMed1999

Frequent coexistence of Lewy bodies and neurofibrillary tangles in the same neurons of patients with diffuse Lewy body disease.

We examined the frequency of neurons with coexistent Lewy bodies (LB) and neurofibrillary tangles (NFT) in diffuse Lewy body disease brains, by a double-immunostaining method using MDV2 and Human tau. Double-positive neurons were frequently observed in the limbic areas. These neurons mostly revealed the feature of intermingled MDV2- and Human tau-positive substances. Immunoelectron microscopically, the MDV2-positive components were not in continuity with the MDV2-negative paired helical filaments (PHF). The MDV2-positive LB were surrounded by the small PHF bundles, frequently accompanied by the randomly oriented PHF within LB. In the intermingled neurons, MDV2-positive non-filamentous components without LB were found among the large PHF bundles. These non-filamentous components may represent the early stage of LB formation.

Aged↗
PubMed1999

Distinctive neuronal organization of the olfactory bulb of the laboratory shrew.

The organization of the main olfactory bulb of an insectivore, the laboratory shrew (Suncus murinus), was studied morphologically. We found particular small spherical regions, nidi, at the border between the glomerular and external plexiform layer (EPL), which were intensely GAD positive, 30-60 microm in diameter, and where no olfactory nerves were seen. Around the nidus small calbindin D28k-positive GABAergic neurons, perinidal cells, were clustered. Furthermore, a distinctive type of newly discovered neurons, which we named tasseled cells, located at the middle of the EPL extended dendrites to the nidus, where their small tuft-like complicated branches made synapses with perinidal cells. The present study showed that the basic components of the olfactory bulb are not necessarily constant in all mammals.

Animals↗
PubMed1999

A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a Japanese family with presenile familial Alzheimer's disease. Mutation in brief no. 254. Online.

Over fifty missense mutations in the presenilin-1 (PSEN1) gene have been reported in families with presenile familial Alzheimer's disease (FAD). We describe a novel missense mutation (G209R) within the predicted fourth transmembrane domain of the PSEN1 in a Japanese family with presenile FAD. The affected cases showed similar disease histories with the mean age at onset of 49.6 +/- 3.1 years and rapid progressive dementia characterized by memory impairment, amnestic aphasia, disorientation and personality change, but lacking parietal focal symptoms such as apraxia or agnosia. Compared with the previously reported cases of same Gly209 mutation (G209V), the clinical features of the G209R-FAD cases appear to be less critical than those of G209V-FAD cases, although the Gly to Arg mutation is considered to be less conservative than the Gly to Val mutation. These findings may suggest the possible existence of other genetic and/or environmental factors or the possibility that these two different Gly209 mutations may underlie different pathomechanisms in the development of presenile FAD.

Alzheimer Disease↗
PubMed1999

Pelizaeus-Merzbacher disease: three novel mutations and implication for locus heterogeneity.

We report a mutational and polymorphic analysis of the proteolipid protein gene in members of 27 Japanese families with Pelizaeus-Merzbacher disease. We found causative mutations in 6 members of 27 families (22.2%); 5 of the 6 mutations, including two novel mutations, Leu45Arg and 231 + 2T --> G, resulted in the typically severe clinical symptoms. Paradoxically, the Cys219Tyr mutation, presumed to disrupt the tertiary structure of proteolipid protein by removing the disulfide bond between Cys200 and Cys219, was associated with a mild clinical presentation wherein the patient could walk with assistance and speak. It was inferred that the structural change prevented the toxicity associated with a gain of function mutation. Moreover, in one family 3 patients exhibited a intragenic polymorphism that did not segregate with the disease, suggesting a locus heterogeneity for Pelizaeus-Merzbacher disease.

Adult↗
PubMed1999

Changes in serotonergic neurons in the brain of pyrithiamine-induced acute thiamine-deficient mice.

We examined changes in 5-hydroxytriptamine (5-HT, serotonin) neurons in pyrithiamine-induced thiamine deficiency in mice immunohistochemically. Extensive decreases in the densities of 5-HT-immunoreactive fibers were detected in the lateral septal nucleus, the thalamus, the medial mammillary nucleus, the dorsal and the median raphe nuclei, the raphe obscurus nucleus, the tegmental area, the cerebellum and the vestibular nucleus, though only a small decrease was detected in the inferior colliculus. Most remarkably, degenerative winding fibers were detected between the deep mesencephalic nucleus and the ventral tegmental area. Increases in intensity of 5-HT immunoreactivity in the dorsal raphe nucleus and decreases in the number of 5-HT-immunoreactive cell bodies in the dorsal and the median raphe nuclei were detected. These results demonstrated the differential vulnerability of 5-HT neurons in thiamine-deficient mice. This is the first report to demonstrate changes in 5-HT neurons immunohistochemically throughout the brain of pyrithiamine-induced thiamine deficient mouse.

Animals↗
PubMed1999

Heterogeneous relationship of early insulin response and fasting insulin level with development of non-insulin-dependent diabetes mellitus in non-diabetic Japanese subjects with or without obesity.

The aim of this study was to investigate the association of insulin secretion and insulin resistance with the development of non-insulin-dependent diabetes mellitus (NIDDM) in obese (body mass index (BMI) > or = 25 kg/m2) and non-obese Japanese. Subjects were selected from persons participating a health survey, and a 100 g oral glucose tolerant test was performed. A total of 1604 non-diabetic subjects were followed for 2-8 years (mean 4.5 years). The fasting insulin level and the homeostasis model insulin resistance index (HOMA-R = fasting glucose [mmol/l] x fasting insulin [microU/ml]/22.5) were used as the index of insulin resistance, and insulinogenic index (the ratio of increment of insulin to that of blood glucose 30 min after glucose load) as a measure of early insulin response. Cox's proportional hazards analysis in the whole group showed that BMI, fasting blood glucose (FBG) and 2-h blood glucose (2-h BG) were positive predictors, and age and insulinogenic index were negative predictors of diabetes. Sex, family history, fasting insulin level and HOMA-R were not predictive of developing diabetes. In subgroup analysis, the same variables as in the whole group were predictors in non-obese, whereas only FBG and 2-h BG predicted diabetes in obese subjects. Fasting insulin level and HOMA-R were not predictive of diabetes both in non-obese and obese subjects. Eleven obese subjects, who developed diabetes despite a normal initial insulinogenic index, had significantly higher BMI, fasting insulin level and HOMA-R, compared with 258 obese subjects who did not develop diabetes. We conclude that most cases of diabetes in Japanese begin with decreased insulin secretion, but a small group of diabetes patients may start with insulin resistance, especially obese subjects.

Adult↗
PubMed1999

Recent advances in dementia research in Japan: Alzheimer-type dementia.

In a previous article, recent reports by Japanese researchers on non-Alzheimer-type degenerative dementias were reviewed. In the present article, recent Japanese reports on Alzheimer-type dementia (ATD) are reviewed. Alzheimer-type dementia has received great attention and has been studied from various viewpoints in Japan as well as in Europe and the Americas. In Japan, although it was believed that vascular dementia was the most frequent dementia in the elderly, ATD has recently been shown to be the most predominant type of dementia. Such a great number of papers on ATD have been reported in Japan that mainly the clinical, neuropathological, biochemical and molecular biological research papers alone are reviewed here.

Adult↗