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T Katsuya

Publications and source records attributed to T Katsuya.

At least 73 records · Page 4Linked to original sources
PubMed1995

Linkage and haplotype analysis of familial early-onset Alzheimer disease in Japanese population.

Linkage and haplotype analysis of eleven early-onset Alzheimer disease (AD) families was performed in relation to D21S210 and microsatellite DNA polymorphisms localized on chromosome 14q24.3. Linkage analysis of eight informative families out of eleven early-onset AD families disclosed the highest LOD score of 3.45 (theta = 0.00) at D14S77, while the locus of beta/A4 amyloid protein precursor gene was formally excluded within 10 cM from D21S210, given the evidence of recombinations in five families. Transmission disequilibrium study between the patients and controls without dementia indicated significant differences at D14S43 (p = 0.0001) and D14S71 (p = 0.02). Association study between genotypes linked or related to onset of AD and those of control also revealed a significant difference at D14S43 (p < 0.05), suggesting the existence of linkage disequilibrium. Moreover, the haplotypes at D14S43 linked with the onset of AD indicated a significant relationship with the mean age at onset. These results support that the major locus of early-onset familial AD is located on 14q24.3, and its close linkage to D14S43 and the existence of allelic heterogeneity were suggested.

Age of Onset↗
PubMed1995

Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia.

Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. The present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk factors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance and 57 with noninsulin-dependent-diabetes mellitus (NIDDM), and compared various aspects of glucose, insulin, and lipoprotein metabolism in the three ACE genotypes. In general, normal subjects with the DD genotype had a lower body mass index, were more insulin sensitive (as assessed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride and cholesterol concentrations were lowest and HDL cholesterol concentrations highest in the DD group. However, the only statistically significant differences were between the ID and DD groups; the latter had lower values for body mass index, was more insulin sensitive, and had a lower plasma insulin response to oral glucose. Similar but insignificant trends were noted in the patients with NIDDM. The present results show that subjects with the ACE/DD genotype are not at increased risk for CHD because of insulin resistance, relative hyperglycemia and hyperinsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Gap junction protein locus on chromosome 18 cosegregates with body weight in the spontaneously hypertensive rat.

To detect genetic predisposing factors for hypertension, we screened the genome of the spontaneously hypertensive rat (SHR). We determined the genotypes of all F2 rats at polymorphic sites between the two strains, using the DNA of F2 rats derived from mating of SHR and Wistar-Kyoto rats (WKY). Cosegregation analysis was conducted to assess whether the genotypes of polymorphic markers associate with any phenotypic parameters such as directly measured blood pressure, heart rate or body weight. All measurements in F2 rats were performed at 15 weeks of age. Two polymorphic markers on chromosome 18 cosegregated with body weight. Gap junction protein (heart connexin 43) gene showed the most significant association with body weight as a recessive trait, but no association was noted with other parameters. We conclude that the gap junction protein locus is a new candidate for the determinant gene of body weight in SHR.

Analysis of Variance↗
PubMed1995

[Familial Alzheimer's disease in Japanese population].

We ascertained 56 related cases with early onset familial Alzheimer's disease (EOFAD; mean age of onset < 65 years) and 10 related cases with late onset familial Alzheimer's disease (LOFAD; mean age of onset > or = 65 years) through a questionnaire administered to neuro-psychiatric and medical school hospitals in Japan and through a review of cases in Japanese literature. Mean age of onset and death (+/- S.D.) of EOFAD were 43.4 +/- 8.6 years (n = 94) and 51.1 +/- 10.5 years (n = 85), respectively. Distributions of the age-onset were relatively constant within a family but significantly different between families. Our result may suggest that clinical differences between families represent genetic heterogeneity at the molecular level. Six out of 32 related cases of with EOFAD showed the 717 Val-->Ile mutation of beta/A4 amyloid precursor protein (APP) gene. This result suggests that the frequency of this mutation in Japanese population is higher than in Caucasian and allelic the existenced heterogeneity, in Japanese EOFAD.

Adult↗
PubMed1994

Differential regulation of brain angiotensin II in genetically hypertensive and normotensive rats after nephrectomy.

To investigate the role of tissue angiotensin II (Ang II) in the maintenance of hypertension after nephrectomy in spontaneously hypertensive rats (SHR), Ang II levels were measured in various tissues of both 12-week-old SHR and normotensive control, Wistar-Kyoto rats (WKY), 48 h after nephrectomy or sham operation. Ang II was determined by radioimmunoassay coupled with high performance liquid chromatography. Nephrectomy caused a decrease of plasma renin activity and plasma Ang II concentration in both SHR and WKY. Aortic Ang II levels were significantly lowered by nephrectomy only in WKY, and not in SHR. Ang II levels in hypothalamic block, brainstem and cerebellum of SHR increased after nephrectomy, whereas those of WKY were unchanged. Intracerebroventricular administration of ceronapril, an angiotensin converting enzyme inhibitor, significantly decreased sustained high blood pressure in SHR 48 h after nephrectomy compared with vehicle administration, whereas intravenous administration had no effect. These results suggest that in spite of the important role of the renal renin-angiotensin system in maintenance of high blood pressure in SHR, control mechanisms may switch to other systems after nephrectomy, and that the increased brain Ang II levels after nephrectomy may be related to these mechanisms.

Angiotensin II↗
PubMed1993

A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat.

Recent advances in molecular biology have allowed the study of the candidate genes for essential hypertension. To identify the genes responsible for basal blood pressure in the spontaneously hypertensive rat strain, the rat model of genetic hypertension, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 progeny obtained from SHR and Wistar-Kyoto rats, a reference normotensive strain. Our investigation revealed that a locus on the chromosome 4 cosegregates with the blood pressure in SHR, especially at neuropeptide Y locus. The degree of cosegregation with all values of blood pressure without sodium loading was moderate but consistent. We propose that neuropeptide Y locus on chromosome 4 is a new candidate for the hypertensive effect in original SHR.

Animals↗
PubMed1993

Association analysis of a polymorphism of the angiotensin converting enzyme gene with essential hypertension in the Japanese population.

An association study of the insertion/deletion (I/D) polymorphism located in intron 16 of the ACE gene with essential hypertension in the Japanese population was performed. The 287 bp I/D polymorphism was detected by polymerase chain reaction. Derived allele frequencies for insertion and deletion were not significantly different between 133 hypertensive and 104 normotensive subjects. A significant relationship between I/D polymorphism and plasma ACE activity was observed in the normotensive group, but not in hypertensives. These results suggest that I/D polymorphism of the gene is not implicated in Japanese hypertensive subjects, and that studies involving various ethnic groups are important.

Adult↗
PubMed1993

[Molecular genetic analysis of sporadic Alzheimer's disease].

The authors report the clinical findings and the results of molecular genetic analysis of 8 patients with sporadic Alzheimer's disease. Differential diagnosis was carried out on the basis of familial history, laboratory data, brain imaging analysis using CT, MRI and SPECT. According to the clinical stage criteria made by Cummings and Benson, 6 cases were in stage 1 and the remaining 2 in stage 2. Recently, it was reported that affected members from 6 Japanese kindreds with familial Alzheimer's disease (FAD) had missense mutation in exon 17 of the gene for beta/A4 amyloid precursor protein (APP). Amino acid substitution (Val-Ile) at codon 717 by this mutation was considered to be responsible for FAD in these kindreds. We used genomic DNA from 8 sporadic cases to determine whether the disease in these families is associated with an APP 717 mutation and the mutated codons, 102, 117, 129, 178, and 200, on the gene for proteinase-resistant prion protein (Prp) which causes transmissible dementia, Creuzfelt-Jacob disease (CJD) and Gerstmann-Sträussler syndrome (GSS). The results showed that there were no mutations on these genes in 8 patients. It would be necessary to analyze DNA from patient with sporadic Alzheimer's disease to examine the mutations found in the APP gene and Prp gene of heredity Alzheimer's disease patients.

Aged↗
PubMed1993

[Cosegregation studies in spontaneously hypertensive rats].

SHR (spontaneously hypertensive rat) is the most popular genetic hypertensive model rat. Using the F2 progeny obtained from SHR and normotensive rats, for example, WKY (Wistar-Kyoto rat), many cosegregation studies to find the genes responsible for blood pressure have been done. In this review, we present some studies using F2 rats concerning candidate genes, renin, kallikrein, sodium potassium-ATPase, heat shock protein 70, angiotensin converting enzyme, phospholipase C-delta 1 and SA gene to show whether these genes really associate with blood pressure. We discuss the signification of these genes in the process of producing SHR and stroke-prone SHR from WKY. We hope these studies will lead to identify the mechanism of human essential hypertension.

Animals↗
PubMed1992

Hypotensive effect associated with a phospholipase C-delta 1 gene mutation in the spontaneously hypertensive rat.

To identify the genes responsible for blood pressure in the spontaneously hypertensive rat strain, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 rats obtained by crossmating SHR with Wistar-Kyoto rats, a parental normotensive strain. Our investigation revealed that the phospholipase C-delta 1 polymorphism, which resulted in missense mutation, cosegregates with the lower blood pressure in SHR, and that PLC-delta 1 gene is located on chromosome 8. On the other hand, we found the lack of cosegregation between blood pressure and the nerve growth factor receptor gene, which is linked to a hypertensinogenic gene locus (denoted as BP/SP-1) on chromosome 10. We propose that PLC-delta 1 gene itself of closely linked gene on chromosome 8 is a new candidate with the hypotensive effect, and that BP-SP1 locus does not directly contribute to blood pressure elevation in original SHR.

Animals↗
PubMed1992

[Affected siblings with Alzheimer's disease had missense mutation of codon 717 in amyloid precursor protein gene].

Using reverse genetic techniques, the gene responsible for familial Alzheimer's disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's disease (AD). Recently a missense mutation in the APP (amyloid precursor protein) gene (generally this mutation was called APP717) was detected in 2 Caucasian AD families and the same mutation was found in 3 Japanese AD families. We experienced brother's cases who were diagnosed as AD. Both of them and one normal person of the next generation had APP717. The first symptom of the elder brother (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his clinical course there were characteristic findings such as the mirror sign, pseudodialog and jargon which has been rarely described in the Japanese literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD pathologically and physical findings of brain CT, SPECT (single photon emission computed tomography) and EEG supported this diagnosis clinically. The first symptom of the younger brother (case 2) was also forgetfulness at 45 years old, then severe dementia was advanced, at last he died of pneumonia at age 53 old. On the other hand the mother of the brothers died of severe dementia, so it was suspected that brothers died of severe dementia, so it was suspected that she had had AD. The clinical courses and pathological findings were thought to be typical of AD, namely there were no significant differences in comparison with other cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗
PubMed1992

[Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation and the mutated genes for the prion protein].

Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been described in the literature, while only 21 Japanese FAD families have been reported to date. Here we report the clinical findings and the result of molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3. The proband in OS-2 family has developed loss of recent memory and place disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her younger brother had dementia at 42 years and her mother and other 3 siblings had also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3 family showed declining recent memory at 49 years and developed dysphagia, gait disturbance and emotional incontinent with cerebral atrophy at 52 years. His father and elder brother demonstrated dementia signs at 60 and 54 years old, respectively. Recently it was reported that affected members from 2 Caucasian kindreds with FAD had missense mutation in exon 17 of the gene for amyloid precursor protein (APP). Patients from three different Japanese kindreds with FAD also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile) at codon 717 by this mutation is responsible for FAD in at least some kindreds. We used genomic DNA from 4 affected members of 2 families to determine whether the disease in these families is associated with a APP717 mutation and the mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The 717Val----Ile substitution in amyloid precursor protein is associated with familial Alzheimer's disease regardless of ethnic groups.

Alzheimer's disease (AD) is a devastating neurological disorder and the leading cause of dementia among aged individuals. The human amyloid beta protein, which is a cleavage product of amyloid precursor protein (APP), is a major component of the amyloid deposited in the brain of patients with AD. By using PCR direct sequencing of exon 17 (encoding part of the beta protein) of the APP gene, we have found that a Japanese AD patient harbours a C to T substitution, responsible for a valine to isoleucine change at position 717, heterogeneously. The mutation is exactly the same as that found in a Caucasian AD family by Goate et al. (1). Furthermore, the mutation was shown to co-segregate with AD in his family. These results suggest that the Val----Ile change in the APP causes AD, regardless of ethnic background.

Alzheimer Disease↗
PubMed1991

Substrain comparison of genetically hypertensive rats using DNA fingerprinting, and genetic analysis of blood pressure in the inbred rats.

Using DNA fingerprinting, genetic heterogeneity or homogeneity was studied between substrains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats maintained in Japan. Using human myoglobin minisatellite 33.15 as a probe, we did not detect any inter- or intra-substrain genetic heterogeneities in HinfI digests of SHR or WKY rat DNA. However, analysis of Sau3AI digests of rat DNA using mouse C-6 gene as a probe revealed intra-substrain heterogeneity of 1-2 DNA bands in one of the WKY rat substrains. In the other substrains of SHR and WKY rats, there existed no intra-substrain heterogeneities, but several inter-substrain heterogeneities were observed in both SHR and WKY rats. In another experiment using the inbred substrains of SHR and WKY rats which have been confirmed as genetically homogeneous, we produced F1 and F2 rats, and biometrically analyzed their systolic blood pressure. The results suggested that there may be 1-4 dominant antihypertensinogenic genes with high heritability of 0.6-0.7.

Animals↗
PubMed1991

Effects of repeated administration of buprenorphine on ambulatory activity in mice.

Effects of repeated administration of buprenorphine, given 5 times at intervals of 3-4 days, were investigated by ambulatory activity in mice. Buprenorphine (0.3 and 1 mg/kg sc) significantly increased the activity, and tolerance to the effect tended to be produced during the repeated administration schedule. The mice that experienced the repeated administration of buprenorphine exhibited an increased sensitivity to the ambulation-increasing effect of methamphetamine (2 mg/kg) in parallel with the doses of buprenorphine. However, no significant modification of the sensitivity to buprenorphine was produced in the mice that had experienced the repeated methamphetamine administration. Furthermore, the established reverse tolerance to methamphetamine was not significantly modified by the repeated treatment with buprenorphine (0.1, 0.3 and 1 mg/kg).

Animals↗