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Biomedical subjects

K Kosaka

Publications and source records attributed to K Kosaka.

At least 145 records · Page 8Linked to original sources
PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗
PubMed1996

Small doses of subcutaneous insulin as a strategy for preventing slowly progressive beta-cell failure in islet cell antibody-positive patients with clinical features of NIDDM.

We report a pilot study to determine the preventive effect of small doses of insulin injected subcutaneously on slowly progressive beta-cell damage in islet cell antibody (ICA)-positive patients with apparent NIDDM. Ten NIDDM patients who were ICA' were divided into two groups of five. In the insulin group (age: 51 +/- 8 years [mean +/- SD], sex: 3 men and 2 women), intermediate-type insulin (3-16 U/day) was given once or twice daily as a subcutaneous injection. The sulfonylurea (SU) group (age: 48 +/- 11 years, sex: 3 men and 2 women) was initially treated with a SU agent. Changes in beta-cell function, as indicated by serum C-peptide responses and blood glucose values during a 100-g oral glucose tolerance test, as well as ICA and GAD antibody status, were evaluated for up to 30 months in both groups. ICA status became negative in four of five patients in the insulin group. ICA status did not become negative in any of the patients in the SU group (P = 0.047 vs. insulin group). ICA status was persistently positive in two patients whose beta-cell function eventually progressed to an insulin-dependent state and fluctuated in the remaining three patients. In the insulin group, GAD antibody status became negative in one of four initially GAD antibody-positive NIDDM patients. In the SU group, GAD antibody status was persistently positive in three NIDDM patients (NS vs. insulin group). The serum C-peptide response improved significantly within 6 and 12 months in the insulin group, whereas it decreased progressively in the SU group. The changes in C-peptide response were significantly different between the two groups at 6, 12, 24, and 30 months. Two-hour blood glucose and HbA1 values were unchanged in the insulin group, but they increased in the SU group. Subcutaneous small doses of insulin, resulting in a high rate of negative conversion of ICA and an improved serum C-peptide response, may be effective in treating ICA+ NIDDM patients who are at high risk for slowly progressive beta-cell failure.

Autoantibodies↗
PubMed1996

Effects of troglitazone: a new hypoglycemic agent in patients with NIDDM poorly controlled by diet therapy.

OBJECTIVE: To investigate the clinical efficacy of troglitazone, a newly developed oral hypoglycemic agent, in patients with NIDDM. RESEARCH DESIGN AND METHODS: There were 284 NIDDM patients (20-82 years of age) whose glycemic control while on a diet was judged stable but was judged unsatisfactory (fasting plasma glucose [FPG] > or = 8.3 mmol/l) when entered into a multicenter and double-blind study with parallel groups study. They were randomly allocated into two groups, the troglitazone group (the T group: 400 mg/day p.o.) and the placebo group (the P group), and were treated with test drugs for 12 weeks. RESULTS: We evaluated efficacy in 136 patients of the T group and 126 patients of the P group. There was no significant difference in any of baseline characteristics between the T and P groups. In the T group, FPG and HbA1c decreased significantly after treatment (before versus after, FPG 10.1 +/- 1.6 vs. 8.8 +/- 1.9 mmol/l, P < 0.001; HbA1c: 8.6 +/- 1.5 vs 8.1 +/- 1.7%, P < 0.001). FPG and HbA1c did not change after treatment in the P group (before versus after, FPG 10.1 +/- 1.8 vs. 9.9 +/- 2.1 mmol/l; HbA1c 8.5 +/- 1.5 vs. 8.6 +/- 1.6%). Of 136 patients in the T group, 62 (45.6%) were classified as responders. Serum triglyceride level also decreased in the T group but not in the P group. Body weight increased slightly only in the T group. There were no differences in changes in blood pressure between the two groups. No serious adverse events occurred in either group. CONCLUSIONS: Troglitazone at 400 mg/day decreased FPG and HbA1c significantly in NIDDM patients who had failed to respond to diet therapy. Troglitazone, developed as a drug to enhance insulin action, can be a useful hypoglycemic agent for the treatment of NIDDM.

Adult↗
PubMed1996

A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR.

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10%-25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be a important genetic abnormality in PMD and affect myelin formation.

Base Sequence↗
PubMed1996

Insulin response to oral glucose load is consistently decreased in established non-insulin-dependent diabetes mellitus: the usefulness of decreased early insulin response as a predictor of non-insulin-dependent diabetes mellitus.

We studied the plasma insulin response during a 100 g oral glucose tolerance test (OGTT) in subjects with NIDDM and various other conditions associated with glucose intolerance. The criteria for definite diabetes and previously definite diabetes is proposed for those whose fasting blood glucose (FBG) is, or has been, greater than 140 mg dl-1 in the past. A diabetic type glucose tolerance with FBG lower than 140 mg dl-1 was called 'equivocal diabetes'. Insulin response was almost invariably lower in definite diabetes and previously definite diabetes compared to control groups with similar degree of glucose intolerance even in the states of non-diabetic glucose tolerance. This was in contrast to other conditions which are often associated with glucose intolerance such as corticosteroid treatment, post-gastrectomy, liver diseases, in which insulin response is increased with the impairment of glucose tolerance as far as the FBG remains below 140 mg dl-1. The low insulin response in definite diabetes can be represented by a decreased insulinogenic index, the ratio of increment of plasma insulin (muU ml-1) to that of blood glucose (mg dl-1) 30 min after the glucose load. Insulin response was judged to be low when this index was less than 0.5. Low insulin response was a reproducible feature, better than the category of glucose tolerance. It was highly correlated with acute insulin response (AIR) elicited by intravenous glucose injection. The prevalence of low insulin responders was high among groups with a family history of NIDDM. Diabetes with elevated FBG occurred more frequently in low insulin responders than in normal insulin responders. Fasting and 2-h insulin levels are lower in definite diabetes than in control groups with similar blood glucose levels. The so-called inverted-U shape relationship of plasma insulin to blood glucose was not so apparent in definite diabetes. We conclude that a low insulin response to oral glucose, as represented by a low insulinogenic index, is an important inherent characteristic in definite diabetes and probably plays a predominant role in the pathogenesis of NIDDM in most Japanese patients.

Blood Glucose↗
PubMed1996

A prospective study of health check examinees for the development of non-insulin-dependent diabetes mellitus: relationship of the incidence of diabetes with the initial insulinogenic index and degree of obesity.

A total of 1788 non-diabetic subjects, screened by a general health check, had either glycosuria or marginal elevation of fasting blood glucose and/or HbA1c. They were followed by repeated 100 g oral glucose tolerance tests for up to 8 years. Their initial mean age was 52 years and the mean BMI was 23.2. Low insulin secretory response was defined when the insulinogenic index, a ratio of increment of plasma insulin to that of plasma glucose 30 min after oral glucose load, was lower than 0.5. Cumulative incidence of diabetes with fasting blood glucose (FBG) exceeding 120 mg dl-1 was significantly higher in impaired glucose tolerance (IGT) than in non-IGT, and in each of IGT and non-IGT groups, the incidence was significantly higher for low than normal insulin responders. The mean initial plasma insulin response in subjects who developed diabetes was significantly lower than in those who remained non-diabetic with the same category of glucose tolerance at baseline irrespective of the degree of glucose intolerance. The mean baseline BMI did not differ whether or not they developed diabetes, but a few cases who developed diabetes despite normal initial insulin response were much more obese. Fasting insulin levels did not correlate with FBG during the course of development of diabetes. We suggest that defective insulin secretion plays a predominant role in the non-obese subtype of NIDDM which includes the majority of Japanese patients, while both insulin resistance and insulin secretory defect are important in the obese subtype for the development of diabetes.

Arizona↗
PubMed1996

[Impaired glucose tolerance--current concept and its classification].

In this paper, I pointed out a few basic problems related to oral glucose tolerance test (OGTT), and reviewed historical perspective focusing on the changes of diagnostic criteria of glucose intolerance and the application of OGTT to the diagnosis of diabetes mellitus. I also commented on the historical values of the NIH proposal on "the diagnosis of diabetes mellitus and other categories of glucose tolerance" (1979), and the recommendation of both WHO Expert Committee on Diabetes Mellitus (1980) and Japan Diabetes Society Committee on Diagnosis of Diabetes Mellitus (1982). Furthermore, I discussed perspectively the problems remained to be solved in the future.

Diabetes Mellitus↗
PubMed1996

[Worsening factors for the progression of impaired glucose tolerance to diabetes mellitus learning from prospective studies].

Although non-insulin-dependent diabetes mellitus (NIDDM) is essentially a genetic disorder, environmental factors after birth including modernization-westernization and its related life style changes play an important role for the development of diabetes. Former prospective studies have indicated high prevalence of diabetes among the subjects with greater impairement of glucose tolerance, family history of diabetes, history of gestational diabetes and obesity. Beside these, more attention has been paid to the elevation of serum fatty acids and food composition as the provocative factors. In some populations, insulin resistance has been suggested to be a major cause of diabetes. In contrast, we have shown that most of the Japanese patients with NIDDM have impaired early insulin response after glucose loading and this should be important as a predictor for NIDDM.

Body Mass Index↗
PubMed1996

Treatment of hypervascular small hepatocellular carcinoma with ultrasound-guided percutaneous acetic acid injection: comparison with segmental transcatheter arterial embolization.

OBJECTIVE: To compare the efficacy of ultrasound-guided percutaneous acetic acid injection and segmental transcatheter arterial embolization for hypervascular small hepatocellular carcinoma. METHODS: The prognosis of 40 patients with one to three angiographically hypervascular hepatocellular carcinoma smaller than 3 cm in diameter treated with either percutaneous acetic acid injection (25 patients) or transcatheter arterial embolization (15 patients) during the past 4.5 yr were analyzed retrospectively. RESULTS: After initial therapy, none of 25 patients treated with percutaneous acetic acid injection developed ascites, whereas 5 of 15 (33%) patients treated with transcatheter arterial embolization developed it (p < 0.01). All tumors became smaller once after each therapy. However, local recurrence (reenlargement of the original tumor) occurred in 1 of 29 (3%) tumors treated with percutaneous acetic acid injection and 11 of 22 (50%) tumors treated with transcatheter arterial embolization (p < 0.005). During the follow-up, 4 of 25 (16%) patients treated with percutaneous acetic acid injection and 10 of 15 (67%) patients treated with transcatheter arterial embolization died. The 1-, 2-, and 3-yr survival rate was 100, 94, and 83%, respectively, in patients treated with percutaneous acetic acid injection and 72, 65, and 39% in patients treated with transcatheter arterial embolization (p < 0.005). The cancer-free survival rate was also significantly better in the former than in the latter group (p < 0.005). CONCLUSIONS: Percutaneous acetic acid injection is superior to segmental transcatheter arterial embolization in the treatment of hypervascular small hepatocellular carcinoma.

Acetic Acid↗
PubMed1995

Wortmannin inhibits the activation of MAP kinase following vasopressin V1 receptor stimulation.

Treatment of rat 3Y1 fibroblasts with vasopressin (AVP) results in a transient activation of MAP kinase as potent as with EGF and serum. An antagonist of vasopressin receptor V1, but not an antagonist of V2, inhibited the AVP-induced activation of MAP kinases, indicating that AVP activates MAP kinases through V1 receptor. Prolonged TPA treatment of cells resulted in partial MAP kinase activation, indicating the presence of PKC-independent pathway. The pathway was inhibited by wortmannin, an inhibitor of PI3-kinase. The results suggest that wortmannin-sensitive molecules such as PI3-kinase, are involved in the V1 receptor-mediated activation of the MAP kinase pathway independent of TPA-sensitive PKC.

Androstadienes↗
PubMed1995

Immunohistochemical investigation of tau-positive structures in the cerebral cortex of patients with progressive supranuclear palsy.

We have investigated tau-positive structures immunohistochemically in the cerebral cortex of patients with progressive supranuclear palsy (PSP). In addition to neurofibrillary tangles, a variety of tau-positive structures occur. They are particularly abundant in the precentral gyrus and other frontal cortices. Double immunostaining has demonstrated that coil-like structures (coiled bodies) are located in the oligodendroglial cell bodies. Three forms of tau-positive astrocytic inclusions are discerned: those with tuft-like profiles, thorn-like structures, and concentric clusters of short stubby fibers. The concentric clusters of tau-positive fibers are present in some, but not all, PSP brains. They appear to be identical to 'astrocytic plaques' previously reported in patients with corticobasal degeneration (CBD). PSP and CBD might share a common pathological background which causes abnormal accumulation of tau protein in neurons and glial cells of neuroectodermal origin.

Aged↗
PubMed1995

Novel nonsense proteolipid protein gene mutation as a cause of X-linked spastic paraplegia in twin males.

We report a third mutation of the proteolipid protein gene in male Japanese patients with X-linked spastic paraplegia. Although the proteolipid protein gene encodes two myelin proteins, proteolipid protein and DM 20, our W144X mutation resides in the latter part of exon 3 (exon 3B), which is spliced out in DM 20. This mutation may reserve the function of DM 20. Findings in our patients support that this form of spastic paraplesia is allelic to Pelizaeus-Merzbacher disease and that the mild clinical phenotype of this disorder may be related to a mutation within exon 3B of the PLP gene.

Adult↗
PubMed1995

Phosphatidylinositol 3-kinase is involved in TRE-dependent gene expression in response to arginine vasopressin.

We identified arginine vasopressin (AVP) as a potent activator of TPA-response element (TRE)-dependent gene expression in rat 3Y1 fibroblasts. In order to examine the involvement of phosphatidylinositol 3-kinase (PI3-kinase) in TRE-mediated gene expression, we examined the effect of the overexpression of PI3-kinase mutant. The overexpression of p110 alpha, the catalytic subunit of PI3-kinase, enhances TRE-reporter expression in response to AVP. On the other hand, the overexpression of the p110-EcoS mutant, which contains the binding site for the regulatory p85 subunit but lacks the catalytic domain, results in decreased TRE reporter expression in response to AVP. These results suggest that PI3-kinase is involved in TRE-dependent gene expression in response to AVP.

Animals↗
PubMed1995

Fas antigen expression in brains of patients with Alzheimer-type dementia.

Fas antigen (CD95) is a cell surface protein that mediates apoptosis. We have investigated the immunohistochemical localization of Fas antigen in postmortem brain tissue from control subjects, patients with Alzheimer-type dementia (ATD), and from a few patients with diffuse Lewy body disease, progressive supranuclear palsy and adrenoleukodystrophy. In all brains, including controls, vascular endothelial cells and residual blood plasma were weakly stained. In ATD brains, senile plaques and a small number of star-like cells were brains of patients with neurological diseases other than ATD. In double immunostaining for Fas and glial fibrillary acidic protein (GFAP), a small number of cells were positive for both antigens. The majority of Fas-positive astrocytes were, however, negative for GFAP. This implies the downregulation of GFAP production in these cells. Doubly labeled astrocytes were also found around senile plaques, suggesting that the Fas immunoreactivity in senile plaques was derived from astrocytic membranes. The results of this study indicate that Fas antigen is expressed by a subset of reactive astrocytes in degenerative neurological diseases. Such astrocytes may undergo the Fas-mediated apoptotic process.

Aged↗
PubMed1995

A mutation in the beta 3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects.

The Trp 64 Arg mutation in the beta 3-adrenergic receptor (beta 3AR) gene was investigated in 350 Japanese subjects. This mutation was not associated with non-insulin-dependent diabetes mellitus (NIDDM). In 191 subjects without NIDDM, body mass index (BMI) was significantly higher in subjects homozygous for this mutation than in those homozygous for the normal allele (24.7 +/- 1.4 vs 22.1 +/- 0.2 kg/m2, p = 0.009). Moreover, the frequency of the mutant allele in obese subjects (BMI > 26.4) was significantly higher than that in non-obese subjects (BMI < 22) (0.37 vs 0.15, p = 0.009). The presence of this mutation was also accompanied by significantly higher fasting (p = 0.000) and 2 hrs (p = 0.018) serum insulin levels during an oral glucose tolerance test. The beta 3AR may be one of the loci contributing to obesity and hyperinsulinemia/insulin resistance in Japanese subjects.

Adult↗
PubMed1995

Investigation of tau-2 positive microglia-like cells in the subcortical nuclei of human neurodegenerative disorders.

An anti-tau monoclonal antibody tau-2 was demonstrated to react with the cells which characteristically appeared in the subcortical nuclei of certain neurodegenerative disorders. These cells had rod-like cell bodies and elongated processes, whose morphology was consistent with that of reactive microglia (tau-2 positive microglia-like cells; TPMC). TPMC were diffusely scattered in the subcortical nuclei, especially the putamen, irrelevant to focal tissue injury such as infarcts and amyloid deposits. TPMC were positively immunostained with anti-ferritin antibody, but negatively with LN3, anti-GFAP, other kinds of anti-tau and anti-neurofilament antibodies. TPMC were found in some cases of Alzheimer type dementia and diffuse Lewy body disease, but not in the cases of Parkinson's disease, Pick's disease and control without neurological disorder. Similar microglia-like cells were found around infarctic foci and amyloid cores of senile plaques, regardless of the disorder. They were, however, different from TPMC in that they were positively immunostained with LN3.

Aged↗