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Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 325 records · Page 18Linked to original sources
PubMed1997

T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not responsible for sporadic late-onset Alzheimer's disease in Japanese population.

To investigate whether presenilin 1 (PS1) gene, a major causative gene of familial early-onset Alzheimer's disease (AD), also contributes to the etiology of sporadic AD, we evaluated associations between Japanese AD and polymorphisms located at 14q24.3. While the D14S43 and FOS loci showed no association with either early- or late-onset AD, late-onset AD carrying no APOE-epsilon4 allele was associated with the G allele of the T/G polymorphism located at intron 9 of the PS1 gene (P = 0.016). Considering another study showing a positive association between AD and the T allele, this polymorphism is associated with, but not responsible for sporadic late-onset Alzheimer's disease.

Age of Onset↗
PubMed1997

Immotile phenotype of an Escherichia coli mutant lacking the histone-like protein HU.

The histone-like protein HU in Escherichia coli are encoded by the hupA and hupB genes. A hupA-hupB double deletion mutant has now been shown to express an immotile phenotype. The motility of hupA or hupB single mutants was similar to that of wild-type cells. SDS-polyacrylamide gel electrophoresis revealed that the amount of flagellin in the hupA-hupB double deletion mutant was markedly reduced compared with the wild-type strain suggesting that the immotile phenotype of the double deletion mutant is caused by a loss of flagella.

Bacterial Outer Membrane Proteins↗
PubMed1997

Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features.

The contiguous 874.423 base pair sequence corresponding to the 50.0-68.8 min region on the genetic map of the Escherichia coli K-12 (W3110) was constructed by the determination of DNA sequences in the 50.0-57.9 min region (360 kb) and two large (100 kb in all) and five short gaps in the 57.9-68.8 min region whose sequences had been registered in the DNA databases. We analyzed its sequence features and found that this region contained at least 894 potential open reading frames (ORFs), of which 346 (38.7%) were previously reported, 158 (17.7%) were homologous to other known genes, 232 (26.0%) were identical or similar to hypothetical genes registered in databases, and the remaining 158 (17.7%) showed no significant similarity to any other genes. A homology search of the ORFs also identified several new gene clusters. Those include two clusters of fimbrial genes, a gene cluster of three genes encoding homologues of the human long chain fatty acid degradation enzyme complex in the mitochondrial membrane, a cluster of at least nine genes involved in the utilization of ethanolamine, a cluster of the secondary set of 11 hyc genes participating in the formate hydrogenlyase reaction and a cluster of five genes coding for the homologues of degradation enzymes for aromatic hydrocarbons in Pseudomonas putida. We also noted a variety of novel genes, including two ORFs, which were homologous to the putative genes encoding xanthine dehydrogenase in the fly and a protein responsible for axonal guidance and outgrowth of the rat, mouse and nematode. An isoleucine tRNA gene, designated ileY, was also newly identified at 60.0 min.

Base Sequence↗
PubMed1997

A high-density STS map based on a single contig of YAC and P1 clones in the chromosome 8p12-p21 region.

We have constructed a yeast artificial chromosome (YAC) and P1 contig in the 8p12-p21 region. The contig comprises 16 overlapping YAC clones and 44 overlapping P1 clones. Twelve dinucleotide-repeat polymorphic sequence-tagged site (STS)-markers that were previously isolated mainly from these YAC and P1 clones were genetically mapped. A total of 46 nonpolymorphic STS markers were newly established mainly from the YAC and P1 clone end fragments, and 28 of the 46 nonpolymorphic STSs, as well as the 12 polymorphic STSs, were also mapped physically onto the contig based on STS content analysis of YAC pools and of the P1 and YAC clones. As a result, the YAC and P1 clones were assembled into a single contig covering a minimum of 1.5 Mb physically and 2.8 cM genetically with 12 polymorphic and 28 nonpolymorphic STSs within the 8p12-p21 region. Average STS spacing in the contig was estimated to be 40 kb/STS. In addition, further characterization of the contig suggested that this contig includes a region where genetic recombination occurs frequently. Thus, the resulting cloned region, together with densely mapped STS markers on the contig, should help to promote our understanding of this region.

Bacteriophage P1↗
PubMed1997

Elevated amyloid beta protein(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase (Erk1/2)-dependent pathway in rat pheochromocytoma PC12 cells.

The deposition of amyloid beta protein (A beta) in the cerebral cortex is the pathological characteristic of Alzheimer's disease (AD), and patients with AD suffer from progressive memory loss. Transgenic experiments have revealed that long-term memory is dependent on cyclic AMP-response element binding protein, CREB. CREB phosphorylation at serine-133 is essential for its transcriptional activity. Here we demonstrated that A beta(1-40), at a concentration more than 1 microM, induced CREB phosphorylation at serine-133 in rat pheochromocytoma PC12 cells. A beta(1-40) induced phosphorylation of p44 and p42 MAP kinases (Erk1 and Erk2) at tyrosine-204, and PD98059, a MEK1 inhibitor, inhibited A beta(1-40)-induced CREB phosphorylation at serine-133. We conclude that elevated A beta(1-40) level induces CREB phosphorylation at serine-133 via p44/42 MAP kinase-dependent pathway.

Amyloid beta-Peptides↗
PubMed1997

Expression of a novel isoform of Vav, Vav-T, containing a single Src homology 3 domain in murine testicular germ cells.

Vav is a signal transducing molecule containing C-terminal Src homology 3 (SH3)-SH2-SH3 domains, and has been thought to be expressed exclusively in hematopoietic and trophoblastic cells. By Northern blot analysis, vav transcripts of unique sizes, 4.8 kb and 1.0 kb, were detected in the testis among various tissues examined. From a mouse spermatocyte cDNA library, a novel isoform of vav (vav-T) was cloned, which corresponded to a part of the 4.8 kb transcript. Vav-T had an alternative 5' sequence up to the middle of SH2-coding region, and encoded 163 amino acids with a single SH3 domain. Northern blot analysis of fractionated testicular cells and in situ hybridization histochemistry demonstrated that vav-T transcripts were expressed in the differentiating germ cells, especially spermatocytes. A 24 kD protein was detected by anti-Vav antibodies in the testis, but not in the spleen or bone marrow. Transcripts of heterogeneous nuclear ribonucleoprotein K, known to associate with the most C-terminal SH3 domain of Vav, were also detected in the differentiating male germ cells. These results demonstrate expression of previously nondescribed Vav-isoform in the testicular germ cells, and suggest that it interacts with RNA-binding proteins and plays an important role in spermatogenesis.

Amino Acid Sequence↗
PubMed1997

Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population.

The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS mutation involves a member (WRN) of the RecQ family of helicases and may perturb DNA replication, repair, recombination, transcription, or chromosomal segregation [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls suggesting that a polymorphic WRN variant is associated with increased risk for MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence intervals: 1.23 to 6.86). The variant was not significantly associated with NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity, turnover, macromolecular interactions or, alternatively, could be markers for haplotypes influencing WRN regulation or reflecting gene action at linked loci. However, given the caveats implicit in genetic association studies, it is imperative that the present results be replicated in independent populations.

Adult↗
PubMed1997

Malignant lymphoma of the kidney.

BACKGROUND: Primary renal lymphoma (PRL) is a rare disease, making information including etiologic factors for PRL extremely limited. METHODS: Clinical and pathologic findings of PRL in Japan are presented and compared with those from Western countries. The presence of Epstein-Barr virus (EBV) genomes in the tumor was also evaluated. Eight cases of PRL were collected from a review of the "Annual of the Pathological Autopsy Cases in Japan (1976-1992)". These cases fulfilled the following criteria: (1) presence of renal mass without extrarenal lymphomatous involvement at admission and (2) absence of a leukemic blood picture. For histologic and immunohistochemical studies, 10% formalin-fixed and paraffin-embedded histologic specimens were used. Presence of Epstein-Barr virus (EBV) genome was examined by polymerase chain reaction (PCR) and in situ hybridization (ISH). RESULTS: There were five males and three females; age at admission ranged from 15 to 79 years (median 57 yr). Abdominal and/or flank pain were the most common presenting symptoms. No particular past history was present in any of the patients. Histologically, tumor cells in all cases showed a diffuse pattern of proliferation: large cell type in six cases, mixed cell type and small lymphocytic type in 1 each. Immunohistochemistry revealed B-cell nature of lymphoma cells in all cases. Neither PCR nor ISH showed the presence of EBV genome in any cases. CONCLUSIONS: PRL is non-Hodgkin's lymphoma of predominantly large cell type with a B-cell immunophenotype. EBV etiology is unlikely in PRL.

Adolescent↗
PubMed1997

Granulocyte colony stimulating factor-producing tongue carcinoma.

BACKGROUND: Leukocytosis without infection in patients with malignancies is known as the leukemoid reaction. The mechanisms involved in this phenomenon remain uncertain. METHODS: We describe the clinical, biochemical and immunohistochemical findings in a patient with recurrent tongue carcinoma accompanied by marked leukocytosis as high as 96200/ mm3. RESULTS: The serum granulocyte colony stimulating factor (G-CSF) concentration was increased to 204 (normal: < 30) pg/ml, which paralleled to the elevation of white blood cell (WBC) count and the tumor growth. The G-CSF content of the tumor tissue was also elevated (131 pg/mg protein) compared to that in control patients (6.63 +/- 2.63 pg/mg protein). Production of G-CSF from the tumor was evidenced by immunohistochemical staining with monoclonal antibody against human recombinant G-CSF. CONCLUSIONS: We suggest that the G-CSF production of the tumor participates in the mechanisms of the leukemoid reaction.

Aged↗
PubMed1997

alpha 1-Antichymotrypsin as a risk modifier for late-onset Alzheimer's disease in Japanese apolipoprotein E epsilon 4 allele carriers.

In the Japanese population, sporadic late-onset Alzheimer's disease (LOAD) cases had significantly higher frequencies of the A allele of alpha 1-antichymotrypsin (ACT) gene as well as the epsilon 4 allele of apolipoprotein E (APOE) gene than controls. The odds ratio for LOAD in APOE4 carriers with the ACT-A allele was more than six times that in APOE4 carriers without the ACT-A allele (21.1 vs 3.2). These results indicate that the ACT-A allele is a risk modifier for LOAD in APOE4 carriers.

Age of Onset↗
PubMed1997

Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets.

Rabs are prenylated, membrane-bound proteins involved in vesicular fusion and trafficking. We isolated the complete cDNAs of two rab isoforms, rab27a and rab27b, from human melanoma cells and melanocytes, Rab27a is the human homolog of a rat megakaryocyte rab called ram p25. Rab27b corresponds to a small GTP-binding protein, c25KG, which was previously purified from platelets but whose cDNA had not been cloned. Sequence comparisons with known rabs indicate that rab27a and rab27b comprise a melanocyte/platelet subfamily within the rab family. In addition, rab27a was expressed in a large variety of cell and tissue types, excluding brain, and rab27b manifested itself primarily in testis. Bacterially expressed and purified rab27a and rab27b exhibited GTP-binding activity and can now be used for antibody production and studies of the substrate specificities of geranylgeranyl transferase. In addition, the expression of rab27a and rab27b in both melanocytes and platelets makes them candidates for involvement in mouse and human disorders characterized by the combination of pigment dilution and a platelet storage pool defect.

Amino Acid Sequence↗
PubMed1997

The mechanism of protection from 5 (N-ethyl-N-isopropyl)amiloride differs from that of ischemic preconditioning in rabbit heart.

We investigated the effects of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on infarction in isolated rabbit hearts and cardiomyocytes. Thirty min of regional ischemia caused 29.6 +/- 2.8% of the risk zone to infarct in untreated Krebs buffer-perfused hearts. Treatment with EIPA (1 microM) for 20 min starting either 15 min before ischemia or 15 min after the onset of ischemia significantly reduced infarction to 5.4 +/- 2.0% and 7.0 +/- 1.0%, respectively (p < 0.01 versus untreated hearts). In both cases salvage was very similar to that seen with ischemic preconditioning (PC) (7.1 +/- 1.5% infarction). Unlike the case with ischemic preconditioning, however, protection from EIPA was not blocked by 50 microM polymyxin B, a PKC inhibitor, or 1 microM glibenclamide, a KATP channel blocker. Forty-five min of regional ischemia caused 51.0 +/- 2.9% infarction in untreated hearts. Ischemic preconditioning reduced infarction to 23.4 +/- 3.1% (p < 0.001 versus untreated hearts). In these hearts with longer periods of ischemia pretreatment with EIPA reduced infarction similarly to 28.8 +/- 2.1% (p < 0.01 versus untreated hearts). However, when EIPA was combined with ischemic PC, no further reduction in infarction was seen (23.8 +/- 3.5% infarction). To further elucidate the mechanism of EIPA's cardioprotective effect, this agent was also examined in isolated rabbit cardiomyocytes. Preconditioning caused a delay of about 30 min in the progressive increase in osmotic fragility that occurs during simulated ischemia. In contrast, EIPA had no effect on the time course of ischemia-induced osmotic fragility. Furthermore, EIPA treatment did not alter the salutary effect of ischemic preconditioning when the two were combined in this model. We conclude that Na+/H+ exchange inhibition limits myocardial infarction in the isolated rabbit heart by a mechanism which is quite different from that of ischemic preconditioning. Despite the apparently divergent mechanisms, EIPA's cardioprotective effect could not be added to that of ischemic or metabolic preconditioning in these models.

Amiloride↗
PubMed1997

Intravenous co-infusion of adenosine and norepinephrine preconditions the heart without adverse hemodynamic effects.

OBJECTIVE: A simple intervention is needed that could protect the heart against infarction during limited-access coronary artery bypass grafting. Adenosine and norepinephrine can precondition the heart with resulting protection, but adverse hemodynamic effects prevent clinical application. Because heart rate, blood pressure, and contractility effects of these two drugs are diametrically opposite, a mixture might be beneficial. METHODS: A superficial branch of the left coronary artery of rabbits was surrounded with a suture. Infarction was produced in all hearts by a 30-minute coronary artery occlusion. Infarct size after reperfusion was measured and is presented as a percentage of the risk zone. The effect of 5-minute intravenous co-infusion of adenosine (20 mg/kg) and norepinephrine (0.1 mg/kg) 15 minutes before ischemia was examined. In addition, the protective effect of three sequential intravenous bolus injections of adenosine at either 0.2 or 0.4 mg/kg was evaluated. RESULTS: Thirty minutes of regional ischemia caused infarction of 40% +/- 4% of the risk zone. The combination of adenosine and norepinephrine caused no change in blood pressure but rather protected the heart, with infarction of only 9% +/- 2% of the risk zone (p = 0.0001 vs control). Adenosine-norepinephrine co-infusion still protected the heart when the interval between infusion and ischemia was extended to 60 minutes, but it did not protect with a 120-minute interval. Intravenous bolus injections of adenosine resulted in cardiac slowing and marked hypotension. Boluses of 0.2 mg/kg resulted in a minimal, but significant, reduction in infarct size, whereas the higher dose provided no protection. CONCLUSION: Adenosine-norepinephrine co-infusion provides a feasible and safe parenteral method for preconditioning the heart.

Adenosine↗
PubMed1997

Molecular and epidemiological studies of Werner syndrome in the Japanese population.

Werner syndrome (WS) is an autosomal recessive genetic disease characterized by many age-related features. The gene responsible for WS (WRN) has been isolated and contains a helicase domain, but its function is unknown. Six different mutations throughout the WRN gene have been reported in the Japanese population. We have studied whether patients with a specific mutation exhibit distinct phenotypes from others. Fourteen patients with different mutations showed almost the same signs and symptoms and, therefore, the C terminal part of the product appears to be crucial for its functions, although other parts may be important as well. Haplotype analyses using 13 microsatellites covering the 2.8-3.0 cM WRN region showed that two out of six different mutations had founder chromosomes. These two founder chromosomes may be evenly distributed throughout the western part of Japan, suggesting that these mutations go back to a time earlier than 1400 years ago.

Chromosome Mapping↗
PubMed1997

Interphase detection of BCL6/IgH fusion gene in non-Hodgkin lymphoma by fluorescence in situ hybridization.

We characterized a t(3;14)(q27;q32) translocation in nine patients with B-cell, non-Hodgkin lymphoma (B-NHL) by fluorescence in situ hybridization (FISH). Fluorescence in situ hybridization with immunoglobulin heavy chain (IgH) and BCL6 gene probes detected t(3;14) rapidly and accurately, including complex t(3;14) in three patients; one with t(3;12;8;14)(q27;p13;q24.1;q32) and two with t(3;?;14)(q27;?;q32). Among these nine patients, seven escaped from cytogenetic detection by our G-banding analysis. Double-color FISH with IgH (Y6) and BCL6 (cosB5-1) showed fusion of BCL6 and IgH genes on der(3)t(3;14) in all nine patients, suggesting that der(3) may play a critical role in the development of lymphoma carrying complex as well as standard t(3;14) translocations. BCL6/IgH fusion gene was also demonstrated in interphase nuclei at a frequency of 23% to 91.5% over the cut-off value in control studies (9.0 +/- 2.76%). The breakpoints assessed by FISH with two cosmid clones containing BCL6 probes, cosB5-1 and cosB5-2, were within the cluster region in seven patients including one with complex type, but were not evaluated in two patients with t(3;?;14), because of the loss of partner chromosome. Using double-color FISH with these two BCL6-specific probes, none of an additional 32 patients in whom mitotic spreads were available showed 3q27 translocations. Fluorescence in situ hybridization with IgH and BCL6 gene probes is a rapid and sensitive method to detect t(3;14) in routine cytogenetic studies.

Aged↗
PubMed1997

Haplotype analysis of congenital myotonic dystrophy patients from asymptomatic DM father.

We report a family with congenital myotonic dystrophy (CDM) transmitted from an asymptomatic DM father; we analyzed the haplotype of this family by using polymorphism within and by flanking the DM protein kinase locus. One patient with congenital DM was homozygous for all markers studied, except for the expanded CTG repeats. Two other patients with congenital DM were heterozygous. One patient with congenital DM who was homozygous had greater clinical severity and more expanded CTG repeats than other CDM patients who were heterozygous. The asymptomatic father had a DM protomutation.

Child↗