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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 127 records · Page 7Linked to original sources
PubMed1996

Immunohistochemical investigation of human leukocyte antigen (HLA)-DR-positive astrocytes in adrenoleukodystrophy brain.

We investigated immunohistochemically the expression of human leukocyte antigen (HLA)-DR in postmortem brain tissue of two adult patients with adrenoleukodystrophy (ALD). In addition to microglia and macrophages, a significant number of star-like cells were stained positively for HLA-DR in demyelinating lesions of both patients. Such cells congregated in the peripheral zone of the lesions. A mirror image analysis as well as double immunostaining for HLA-DR and glial fibrillary acidic protein established that these cells were a subset of reactive astrocytes. Together with other reports demonstrating that astrocytes express HLA-DR only under very limited conditions, the results of this study suggest the involvement of immune and inflammatory responses in the pathological processes of ALD.

Adrenoleukodystrophy↗
PubMed1996

Ventral tegmental injection of nicotine induces locomotor activity and L-DOPA release from nucleus accumbens.

Effects of nicotine systemically or locally on locomotor activity and L-3,4-dihydroxyphenylalanine (L-DOPA) release were studied using microdialysis in the nucleus accumbens of freely moving rats. The basal L-DOPA release was Ca2(+)-dependent and tetrodotoxin-sensitive. Systemic nicotine (1 mg/kg s.c.) increased locomotor activity and L-DOPA release preferentially in the nucleus accumbens as compared with the striatum. Injection of nicotine (30 micrograms) into the ventral tegmental area increased locomotor activity and L-DOPA release from the nucleus accumbens. These increases were antagonized by prior injection of mecamylamine into the ventral tegmental area. Nicotine induces locomotor activity and L-DOPA release from the nucleus accumbens via nicotinic receptors in the ventral tegmental area. The release may be relevant to behavioral actions of nicotine.

Animals↗
PubMed1996

Secondary lymphoid malignancy in two children with neuroblastoma.

Secondary lymphoid malignancy, particularly acute lymphoblastic leukemia (ALL), is rare. We report one case of ALL and another case of mediastinal lymphoblastic lymphoma developed after treatment for neuroblastoma. The secondary ALL characterized by short latency period and an 11q23 translocation apparently was induced by etoposide treatment. The pathogenesis of the secondary lymphoma is less certain and may be related to previous treatment with cyclophosphamide and radiotherapy, host susceptibility, or chance occurrence. One child died of progressive lymphoma and the other remains in remission 1 year following allogeneic bone marrow transplantation. Additional studies are needed to determine the risk, pathogenesis, and optimal treatment for secondary lymphoid malignancy.

Child↗
PubMed1996

Effect of combination therapy of troglitazone and sulphonylureas in patients with Type 2 diabetes who were poorly controlled by sulphonylurea therapy alone.

The clinical efficacy of troglitazone, a new oral hypoglycaemic agent was investigated in Type 2 diabetes in combination with sulphonylureas. Two hundred and ninety-one patients with Type 2 diabetes (age 21-81 years) whose previous glycaemic control by sulphonylureas was judged stable but unsatisfactory (fasting plasma glucose (FPG) > 8.3 mmol I-1) were randomly allocated into the troglitazone treatment group (troglitazone group, n = 145) or the placebo treatment group (placebo group, n = 146). They were treated by test drugs for 12 weeks in combination with the same dose of sulphonylureas before the trial. One hundred and twenty-two patients who received troglitazone and 126 patients who received placebo were evaluated for efficacy. The baseline characteristics did not differ significantly between the two groups. In the troglitazone group, FPG and HbA(1c) decreased significantly after the treatment (before vs after, FPG: 10.8 +/- 2.0 mmol I(-1) vs 9.2 +/- 2.5 mmol I(-1), p< 0.001; HbA(1c): 9.2 +/- 1.4% vs 8.5 +/- 1.5%, p< 0.001). FPG and HbA(1c) did not change after the treatment in the placebo group (before vs after, FPG: 10.5 +/- 1.7 mmol I(-1) vs 10.7 +/- 2.2 mmol I(-1); HbA(1c): 9.0 +/- 1.5% vs 9.2 +/- 1.6 %). Serum total cholesterol and HDL-cholesterol did not change in either group, however, serum triglyceride significantly decreased in the troglitazone group. No serious adverse events occurred in either group. In conclusion, troglitazone 400 mg day(-1) had a significant hypoglycaemic effect in combination with sulphonylureas without any serious adverse events. Troglitazone, developed as an insulin action enhancer, can be a useful hypoglycaemic agent in the treatment of patients with Type 2 diabetes who are not well controlled by sulphonylureas alone.

Administration, Oral↗
PubMed1996

Association between HLA and islet cell antibodies in diabetic patients with a mitochondrial DNA mutation at base pair 3243.

Islet cell antibodies (ICA), autoantibodies to glutamic acid decarboxylase (GAD) and HLA genotypes were examined in 31 patients with diabetes and a mitochondrial gene mutation located at base pair 3243 (mtDNA 3243 mutation). ICA was detected in 42% (13/31) of these patients compared to 0 of 90 among healthy control subjects. The ICA showed a "non-restricted" pattern of staining in all 13 ICA-positive patients. In a sensitive radioligand assay only 2 of 31 (6%) diabetic patients with the mutation were positive for both GAD65 autoantibodies and ICA, while the remaining 29 patients were GAD65 antibody negative. The ICA-positive patients had an increased frequency of the HLA-DQA1*0301 allele compared to control subjects (p < 0.05). Of the diabetic patients with the mutation 45% (14/31) had progressive clinical course of beta-cell failure. These results indicate that patients with an mtDNA 3243 mutation may develop islet autoimmunity associated with ICA and GAD autoantibodies. We hypothesize that the presence of HLA-DQA1*0301 in individuals with the mtDNA 3243 mutation increases the risk for diabetes and associated autoantibodies against islet cell antigens.

Adult↗
PubMed1996

Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review.

A 57-year-old woman showed progressive sensory aphasia as an initial symptom, and then developed total aphasia within 6 years and, finally, severe dementia. Neuropathologically, the cerebral cortex was most severely affected in the superior and transverse temporal gyri, and subsequently in the inferior frontal gyrus, especially in the pars opercularis. The degeneration in the subcortical grey matter was most severe in the substantia nigra, and it was moderate to mild in the ventral part of thalamus, globus pallidus and striatum. Cytopathologically, in addition to achromatic ballooned neurons, massive taupositive types of cytosekeletal abnormalities were observed both in neurons and glia, mainly in the degenerating region. This cytoskeletal pathology coincided with that reported in corticobasal degeneration (CBD). On Bodian staining, only a few neurofibrillary tangles were found in the entorhinal pre-alpha layer and substantia nigra. Pick's bodies and senile plaques could not be found. This case is thought to represent a type of CBD, but with its cortical lesion focus located in the speech area instead of the frontoparietal region. A survey of 28 pathologically evaluated cases of CBD revealed two similar cases, both of which began with progressive aphasia and presented cortical degeneration in the superior temporal gyrus. An overview of CBD cases clarified the features in another group of cases, in which the cerebral accentuated focus was shifted forward from the central region, clinically resembling Pick's disease. The clinical manifestations in CBD seem to be the expression of these diverse cortical lesions. Primary progressive aphasia may include cases of CBD with involvement of the language center.

Aphasia, Primary Progressive↗
PubMed1996

Neuropathological evaluation and apolipoprotein E gene polymorphism analysis in diffuse Lewy body disease.

We performed a quantitative neuropathological investigation of senile plaques and neurofibrillary tangles in the brains of 14 Japanese patients with diffuse Lewy body disease (DLBD), and examined apolipoprotein E (APOE) gene polymorphism in these patients. Most DLBD brains had as many senile plaques as those with Alzheimer-type dementia (ATD), but fewer neurofibrillary tangles. The APOE epsilon 4 allele frequency in DLBD was 39.3%, similar to that previously reported in pathologically diagnosed ATD. DLBD and ATD are clinically and pathologically distinct, but may have common mechanisms with regard to the formation of amyloid deposition based on these findings. Future investigation of the pure form of DLBD may clarify the association between Lewy body dementia and APOE.

Aged↗
PubMed1996

Age-related ubiquitin-positive granular structures in non-demented subjects and neurodegenerative disorders.

The distribution and nature of age-related ubiquitin-positive granular structures (UPG) were examined in non-demented brains. In addition, their appearance pattern in some neurodegenerative disorders was investigated. In the transentorhinal cortex, they were distributed among cell islands of layer pre-alpha and in layers II and IIIab. In the amygdala, they were preferentially located in the accessory basal and basal nuclei. UPG were first observed in the transentorhinal cortex of non-demented middle-aged brains and increased in frequency and extended to other regions with increasing age. In Alzheimer-type dementia (ATD), they decreased with advance of the clinical stage. In diffuse Lewy body disease (DLBD), they decreased, accompanying linear neuritic structures. With the double-immuno-staining, UPG were frequently overlapped with neurofilament-positive granules. The multipolar cells of layer pre-alpha and pyramidal cells of layers IIIc and V were also immunostained with anti-neurofilament antibody, and the obliquely ascending fibers of these cells were found frequently to continue to these neurofilament-positive granules. Using ubiquitin immunoelectron microscopy, UPG appeared to derive from degenerating terminal axons. These findings suggest that UPG originate mainly from the recurrent collateral ascending axons in layers II-IIIab and from projecting axons in the amygdala. The occurrence of UPG in the limbic system is an important morphological hallmark of aging. In addition, further studies on the appearance pattern of UPG in ATD and DLBD may clarify whether a difference in the degenerative process of both disorders exists.

Adolescent↗
PubMed1996

High glycosylated hemoglobin levels increase the risk of progression to diabetes mellitus in subjects with glucose intolerance.

The relationships between HbA1c level and oral glucose tolerance test (OGTT) at the initial visit and the incidence of diabetes after 5 years of follow-up were investigated in 819 subjects participating in a general health examination. The 100 g OGTT was performed. In order to use WHO criteria, the blood glucose levels of 100 g OGTT corresponding to those of 75 g OGTT were adopted according to the recommendations of the Japan Diabetes Society. Subjects other than diabetic type and IGT (impaired glucose tolerance) were divided into a normal group (fasting blood glucose < 100 mg/dl, 1-h blood glucose < 160 mg/dl, a 2-h blood glucose < 120 mg/dl) and a borderline group (the remaining subjects). In IGT, the incidence of diabetes in the low- (< or = 6.3%), intermediate- (6.4-6.7%) and high-HbA1c (> of = 6.8%) groups were 10.4%, 23.1% and 52.5%, respectively (high vs intermediate and low, P < 0.001; intermediate vs low, P < 0.05). In the borderline group, the incidence were 2.8%, 14.3% and 28.6%, respectively (high and intermediate vs low, P < 0.001). The results showed that the combination of HbA1c level and OGTT enables more precise prediction of progression to NIDDM in subjects with glucose intolerance.

Adult↗
PubMed1996

Electron microscopic serial-sectioning/reconstruction study of parvalbumin-containing neurons in the external plexiform layer of the rat olfactory bulb.

Neurons containing a calcium-binding protein parvalbumin in the external plexiform layer of the rat olfactory bulb were identified light microscopically with the pre-embedding immunocytochemistry and were subsequently analysed with the electron microscopic serial-sectioning and three-dimensional reconstructions. In the present study we chose several different types of parvalbumin-immunoreactive neurons identified light microscopically as Van Gehuchten cell type, superficial short-axon cell type and multipolar cell type. Parvalbumin-immunoreactive somata were similar to one another in their ultrastructural characteristics, showing nuclear indentations, moderately developed Golgi apparatus and abundant mitochondria; these structural features appeared to resemble those of the short axon cells around the glomeruli and in the granule cell layer reported in previous electron microscopic studies. All neurons analysed in the present study made symmetrical synapses on to dendrites and somata of presumed mitral/tufted cells and received asymmetrical synapses from them, and occasionally formed reciprocal synapses with them. On the parvalbumin-immunoreactive processes, the asymmetrical synapses nearly equalled the symmetrical ones in number and about 30-50% of them were identified as reciprocal pairs. In contrast, no presynaptic sites were observed on parvalbumin-immunoreactive somata, and thick portions (more than approximately 2 microns in diameter) of the proximal dendrites, where they were occasionally postsynaptic in some asymmetrical and symmetrical synapses from parvalbumin-immunonegative profiles. Characteristically, parvalbumin-immunoreactive process frequently make direct contacts with one another; processes regarded light microscopically as arising from a soma or a dendrite or parvalbumin-immunoreactive neurons were sometimes revealed to be separate but directly contacting processes with electron microscopic examinations. Although puncta adherentia were occasionally observed between these contact sites, so far neither gap junctions nor chemical synapses were observed. Until now, it has been believed that in the external plexiform layer only granule cells form reciprocal synapses with mitral/tufted cells. However, the present study clearly demonstrates that interneurons different from granule cells, namely GABAergic neurons containing a calcium-binding protein parvalbumin, also make reciprocal synapses with mitral/tufted cells in the external plexiform layer. Therefore, neuronal processes making reciprocal synapses with mitral/tufted cells in the external plexiform layer cannot be determined a priori as granule cell processes.

Animals↗
PubMed1996

Dementia with Lewy bodies.

Dementia with Lewy bodies is a generic term which was proposed at the first International Workshop on Lewy Body Dementia (Newcastle upon Tyne, 1995). It is an all encompassing term that includes various types of disorder such as diffuse Lewy body disease, senile dementia of Lewy body type, and Lewy body variant of Alzheimer's disease. Epidemiological, clinical, neuropathological, biochemical, molecular biological, and therapeutic contributions to the understanding of dementia with Lewy bodies are reviewed.

Alzheimer Disease↗
PubMed1996

A neuropathologic study of long-term, Economo-type postencephalitic parkinsonism with a prolonged clinical course.

In this report, the neuropathologic features of five autopsied cases of postencephalitic parkinsonism of the Economo-type (PEPE) with a mean age of 66.6 years and a mean duration of the illness of 53.6 years are described. All five patients had presented with personality changes and severe parkinsonism. In addition, four patients had also had ocular symptoms. A pronounced chronic progression of the symptoms characterized all five cases. Active degenerating lesions were found in the substantia nigra (patients 3, 4 and 5) and the oculomotor nucleus (patient 5) which might explain the clinical observation of chronic active disease in these patients. We found that the intraneuronal neurofibrillary tangles (NFT) were immunoreactive to paired helical filaments (PHF), tau and ubiquitin; but ghost tangles demonstrated immunoreactivity only to glial fibrillary acid protein (GFAP). The ghost tangles consisted of dispersed bundles of abnormal tubules, and electron-dense glial filaments would surround and occasionally invade the ghost tangles. The present study suggests that NFT in PEPE are similar in their immunohistochemistry and ultrastructure to those observed in the case of Alzheimer-type dementia.

Age of Onset↗