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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 109 records · Page 6Linked to original sources
PubMed1997

Close relationship between spongiform change and ubiquitin-positive granular structures in diffuse Lewy body disease.

The origin of spongiform change seen in diffuse Lewy body disease (DLBD) cases was elucidated, as compared with Alzheimer-type dementia (ATD) cases. Spongiform change was composed of numerous vacuoles in the neuropil, predominantly in layers II-IIIab of the transentorhinal cortex and in the intermediate area of the accessory basal amygdaloid nucleus. The distribution of spongiform change was identical to that of ubiquitin-positive granular structures (UPG) in non-demented cases. The degree of spongiform change was correlated with loss of the large pyramidal neurons in layers IIIc and V of the transentorhinal cortex and with the disappearance of their ubiquitin-positive granular processes. With electron microscopy, the early vacuoles of spongiform change appeared to arise in the presynaptic terminals as well as in the postsynaptic terminals and dendritic processes. These findings indicate that the vacuoles derive from degeneration of terminal axons of the large pyramidal neurons. The occurrence of spongiform change characteristic to DLBD suggests that the large pyramidal neurons degenerate more rapidly in DLBD than in ATD.

Aged↗
PubMed1997

Synthesis and cataleptic effects of optically active dihydrohaloperidols and dihydrobromoperidols.

Optically active dihydrohaloperidols and dihydrobromoperidols, the major metabolites of haloperidol and bromoperidol, clinically used as neuroleptic drugs in humans, were asymmetrically synthesized by Jaen's method. The motor effects of all the reduced haloperidol and bromoperidol metabolites were evaluated by the mouse catalepsy test. The results indicate that administration of the optically active dihydrohaloperidols and dihydrobromoperidols as well as haloperidol and bromoperidol can cause significant motor deficits in mice.

Animals↗
PubMed1997

6-Pyruvoyl-tetrahydropterin synthase deficiency with generalized dystonia and diurnal fluctuation of symptoms: a clinical and molecular study.

We report the case of a 44-year-old woman with a partial 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency, whose predominant clinical symptom was generalized dystonia with marked diurnal fluctuation. Dystonia was present in the eyelids, oromandibular region, trunk, and extremities (Meige syndrome plus double hemiplegia-like dystonia). A marked and sustained positive response to levodopa was observed. A molecular genetic study revealed a homozygous mutation (I114V) in the 6-PTS gene. This study indicates that genetic abnormality in the 6-PTS gene may be a hereditary dystonia disorder. We speculate that our patient has residual 6-PTS activity in the central nervous system, such as in the liver, and we suggest that residual, but insufficient production of tetrahydrobiopterin may play an important role in causing diurnal fluctuation of symptoms.

Adult↗
PubMed1997

Hippocampal pathology in diffuse Lewy body disease using ubiquitin immunohistochemistry.

Various ubiquitin-positive structures in the hippocampus in diffuse Lewy body disease (n=12) and non-demented aged subjects (n=3) were investigated immunohistochemically. These structures were composed of ubiquitin-positive granular structures (UPG), ubiquitin-positive neuritic structures (UPN), spheroidal structures, neuritic plaques, neurofibrillary tangles (NFT), Lewy bodies (LB) and ubiquitin-positive neurons. UPG, UPN, spheroidal structures and neuritic plaques were distributed with special reference to the hippocampal pathway assumed in this study. This pathway was thought to run along the stratum oriens, mostly perforating the stratum pyramidale at many sites of the subiculum and CA1-3, and to end partly in the CA2-3 and the subiculum of the uncus (UPG or UPN). After perforating the stratum pyramidale and giving off terminal branches (ubiquitin-positive neurons or neuritic plaques with degenerative neurites), it was thought to run along the stratum radiatum and continue along the stratum moleculare of the dentate gyrus, forming synapses with the apical dendrites from the stratum pyramidale and the stratum granulosum (spheroidal structures or neuritic plaques). These findings suggest that many of the ubiquitin-positive structures may be caused by degeneration of terminal or distal axons of this pathway. NFT and LB also had a somewhat orderly distribution with reference to this pathway.

Aged↗
PubMed1997

Migration of small and large cells from the grafts of embryonic olfactory bulbs, transplanted into the anterior wall of the lateral ventricle.

Embryonic olfactory bulbs (OBs) were transplanted into the anterior wall of the lateral ventricle (ALV) of juvenile and adult host mice. Neurons originated from the transplanted OBs were detected immunohistochemically by using mouse Thy-1 allelic system. Within the OBs of both host groups, a substantial number of Thy-1.2-positive small presumed granule cells were observed. Furthermore, Thy-1.2 labeled large cells, although far smaller in number, were encountered in some cortical areas, including the anterior olfactory nucleus of the juvenile host group, but not within the host OBs. These results indicated that both small and large cell precursors had the capacity to migrate from the host ALV, but only the small cell precursors could migrate tangentially into host OBs.

Animals↗
PubMed1997

Differentiation of chemically defined neuronal populations in the transplanted olfactory bulb without olfactory receptor innervation.

Olfactory bulbs (OBs) from embryonic day 15 and 17 and postnatal day 1 mice were transplanted into the lateral ventricle of juvenile host mice without bulbectomy, and fine structural and chemical features of neurons and glia in the OB transplants were investigated immunocytochemically and electron microscopically. In the OB transplants there were neither clearly defined glomeruli nor layers, nor olfactory marker protein immunoreactive elements. However, chemically defined neuronal populations resembling those in the normal OBs such as those immunoreactive for gamma-aminobutyric acid (GABA), tyrosine hydroxylase and Ca(2+)-binding proteins (calbindin-D28K, calretinin, parvalbumin) were observed. Electron microscopically, dendrodendritic and somatodendritic reciprocal synapses, that is, synapses characteristic of the OB, were occasionally observed in the OB transplants. These results indicated that at least some embryonic or newborn mouse OB neurons and/or precursor cells could exhibit chemical properties and form typical synaptic contacts observed in normal OB, even when they received no inputs from olfactory receptor cells.

Animals↗
PubMed1997

Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb--II. Prominent differences in the intraglomerular dendritic arborization and their relationship to olfactory nerve terminals.

In the glomerular layer of the rat main olfactory bulb, we previously reported three chemically defined interneuron groups: GABA-like immunoreactive, calretinin-immunoreactive and Calbindin-D28k-immunoreactive groups [Kosaka K. et al. (1995) Neurosci. Res. 23, 73-88]. In the present study, we analysed the structural features of these three neuron groups using confocal laser scanning light microscopy, focusing on their dendritic arborization pattern, especially on their close apposition to olfactory receptor terminals labeled by olfactory marker protein. Each glomerulus consisted of two zones, the olfactory nerve zone and the non-olfactory nerve zone. The former was mainly occupied by olfactory nerve preterminals and terminals as well as their targets, postsynaptic fine dendritic portions of intrinsic neurons. The latter non-olfactory nerve zone was occupied mainly by olfactory marker protein-negative profiles. Processes of GABAergic neurons and those of one of their subpopulations, tyrosine hydroxylase-immunoreactive neurons, were numerous both in the olfactory nerve and non-olfactory nerve zones, resulting in their frequent close apposition to olfactory marker protein-immunoreactive elements. Combined confocal laser scanning light microscopic electron microscopic examination revealed synaptic contacts from olfactory nerve terminals on tyrosine hydroxylase-immunoreactive processes at these sites of close apposition. In contrast, calretinin-immunoreactive and Calbindin-D28k-immunoreactive processes, particularly Calbindin-D28k-immunoreactive ones, were distributed almost exclusively in the non-olfactory nerve zone, as if they avoided the olfactory nerve zone, showing a net or honeycomb pattern. Thus, calretinin-immunoreactive and Calbindin-D28k-immunoreactive processes were not or very rarely closely apposed to olfactory nerve terminals. These findings suggested that there might be some differences among chemically defined interneuronal groups in their synaptic contacts from olfactory nerves. Further quantitative image analysis clearly exhibited the prominent differences among these neuron groups in their intraglomerular dendritic arborization in relation with the olfactory nerve zone, i.e. the percentages of the area in the olfactory nerve zone occupied by GABAergic and tyrosine hydroxylase-immunoreactive processes were about 10%, respectively, whereas those of calretinin-immunoreactive and Calbindin-D28k-immunoreactive processes were only about 1% and 0.3%, respectively. These findings suggested that so-called periglomerular cells in glomeruli might be heterogeneous not only in their chemical nature, but also in their dendritic arborization pattern and synaptic contacts from olfactory nerve terminals.

Animals↗
PubMed1997

Recovery of pancreatic beta-cell function in hemochromatosis: combined treatment with recombinant human erythropoietin and phlebotomy.

A patient with diabetes mellitus caused by secondary hemochromatosis was treated using recombinant human erythropoietin and phlebotomy. A total of 12 g of iron had been infused in the patient because of iron deficiency anemia. Blood glucose level was 17.3 mmol/L, and hemoglobin A1c level was 9.0% at admission. He was treated using phlebotomy (400 mL per week), along with subcutaneous injection of 3,000 U of recombinant human erythropoietin three times a week. After approximately 100 days, a total of 5,500 mL of blood (2.75 g iron) could be removed. Serum ferritin level decreased from 10,000 micrograms/L to 4,807 micrograms/L. Fasting and maximum serum C-peptide immunoreactivity values during 100-g oral glucose tolerance tests were improved from 0.14 nmol/L to 0.42 nmol/L and from 1.84 nmol/L to 2.61 nmol/L, respectively. This case suggests that pancreatic beta-cell recovers in diabetes caused by hemochromatosis by reducing iron overload during a short period.

Aged↗
PubMed1997

Neuroleptic malignant syndrome and hydroxylase gene mutations: no association with CYP2D6A or CYP2D6B.

To examine a possible association between debrisoquine 4-hydroxylase gene mutations and neuroleptic malignant syndrome, we assessed frequencies of wild type and A and B mutant alleles of the CYP2D6 gene in 24 patients with a history of neuroleptic malignant syndrome, 50 patients with neuroleptic-treated schizophrenia but no history of neuroleptic malignant syndrome, and 50 healthy controls. Allele frequencies did not differ significantly between these groups. Homozygotes for CYP2D6A and for CYP2D6B, which indicate a poor-metabolizer phenotype for the CYP2D6 substrate, were not detected among the neuroleptic malignant syndrome cases. This result indicates no excess of poor CYP2D6 metabolizers in neuroleptic malignant syndrome. The aetiology of neuroleptic malignant syndrome is not explainable in terms of CYP2D6 gene mutations.

Alleles↗
PubMed1997

Mutations in the proteolipid protein gene in Japanese families with Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelinating disorder of the CNS resulting from abnormalities in the proteolipid protein (PLP) gene. Exonic mutations in the PLP gene are present in 10 to 25% of all cases. In investigating genotype-phenotype correlations, we screened five Japanese families with PMD for PLP gene mutations and compared their clinical manifestations. We identified two novel nucleotide substitutions in exon 5, at V208N and at P210L, in two families. In the remaining three families, there were no mutations detected. Although all patients satisfied the criteria for the classical form of PMD, two families not carrying the mutations showed milder clinical manifestations than those with the mutations. Since linkage analysis has shown homogeneity at the PLP locus in patients with PMD, our findings suggest that there may be genetic abnormalities other than exonic mutations that cause milder forms of PMD.

Apoproteins↗
PubMed1997

In situ characterization of islets in diabetes with a mitochondrial DNA mutation at nucleotide position 3243.

Changes in the pancreas of diabetic patients with the A-to-G mitochondrial DNA (mtDNA) mutation at nucleotide position 3243 base pair (bp) have not previously been described. The clinical phenotypes of diabetes associated with the mtDNA 3243 mutation range from NIDDM to IDDM. We sought the presence of the mutation and studied volume of beta-, alpha-, and delta-cells, mitochondrial enzyme activity, and presence of apoptosis in diabetic pancreases obtained at autopsy. Pancreases were obtained from 16 patients with IDDM, from 18 patients with NIDDM, and from 11 nondiabetic patients. Mitochondrial enzyme activity was determined for cytochrome c oxidase (COX), the subunits of which are partially encoded by mtDNA, and for succinate dehydrogenase (SDH), the subunits of which are solely encoded by nuclear DNA. The volumes of islet beta-, alpha-, and delta-cells were estimated by computerized morphometry. Pancreatic cells were examined for apoptosis by an in situ end-labeling procedure. The mtDNA 3243 mutation was detected in 1 of 16 (6%) pancreases from the IDDM patients; none of the pancreases from 18 NIDDM patients and 11 nondiabetic patients had the mutation. The single patient with the mtDNA 3243 mutation was a 56-year-old woman with IDDM, aged 39 years at diabetes onset, whose mother was diagnosed with NIDDM. The patient had a history of secondary failure of oral hypoglycemic agents and had a marked decrease in the number of beta-cells. The islet beta-cells and non-beta-cells of the patient showed extremely decreased COX enzyme activity. The islet cells in the patient showed a high activity when examined for SDH. Some pancreatic exocrine cells also showed decreased COX activity with high SDH activity. In IDDM, NIDDM, and nondiabetic patients without the mtDNA 3243 mutation, only weak staining for SDH of the islet cells showed. The percentage of heteroplasmy of the mtDNA 3243 mutation in pancreatic micropunched islet specimens was 63 +/- 5% (mean +/- SD) in the islets, 32 +/- 3% in the exocrine pancreas, and 8 +/- 1% in peripheral polymorphonuclear cells. Apoptotic cells were not observed in the IDDM pancreas in the patient with the mtDNA 3243 mutation. The fact that higher levels of mutated mtDNA at 3243 bp were found in affected islets rather than in other tissue suggests that the distribution of the mutant may determine the effect on islet function. A characteristic decrease in the mitochondrial enzyme with COX activity and accelerated SDH activity of the affected islets may provide new insights into the pathogenesis of mitochondrial diabetes.

Adult↗
PubMed1997

[A study of inner ear autoantibodies in patients with sensorineural hearing loss].

In order to identify the inner ear autoantibodies, sera from 277 patients with sensorineural hearing loss and/or vertigo were reacted with bovine inner ear antigen by the western blotting method. We examined the relationships between the rate of the inner ear autoantibodies and clinical symptoms, course, diagnosis, age and positive tests for antinuclear antibodies. The rate of the autoantibodies which reacted with the 68-kD protein determinant, however, tended to increase with the elevation of hearing threshold. These of autoantibodies also tended to have a high incidence in patients with a fluctuating hearing threshold. Antibody against the 68-kD protein was detected in serum from 64.3% of patients with progressive sensorineural hearing loss. These results indicate that autoimmunological mechanisms involving the 68-kD protein may be one of the causes of sensorineural hearing loss.

Adult↗
PubMed1997

[Parkinsonism in Alzheimer's disease].

Parkinsonism occurs frequently in the patients with Alzheimer type dementia (ATD). The frequency ranges from 9% to 100% of ATD patients, depending on samples, clinical instruments and stages of illness. Several studies have described that rigidity and hypokinesia are the most prevalently observed signs of parkinsonism, and that resting tremor is less. The clinical progress of patients with parkinsonism is more rapid than those of patients without parkinsonism. Patients with parkinsonism are frequently associated with psychiatric symptoms such as depression and delusion. The pathogenesis of parkinsonism in ATD remains to be elucidated, but it should be noted that some cases with parkinsonism correlates with Parkinson's disease pathologic condition, and some have diffuse Lewy body disease.

Alzheimer Disease↗