Biomedical subjects

R Oyama

Publications and source records attributed to R Oyama.

At least 19 recordsLinked to original sources

PubMed2005

The transcriptional landscape of the mammalian genome.

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.

3' Untranslated Regions↗

PubMed2003

Phase II study of exatecan mesylate (DX-8951f) as first line therapy for advanced non-small cell lung cancer.

BACKGROUND: Exatecan mesylate (DX-8951f) is a water soluble analogue of camptothecin that inhibits topoisomerase I. This multi-centre phase II study evaluated the activity of single agent exatecan in previously untreated patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with histologically or cytologically proven stage IIIb or IV NSCLC were treated with exatecan 0.5 mg/m(2) per day by 30 min intra-venous (i.v.) infusion for 5 days every 3 weeks to a maximum of six cycles. Measurable disease was documented prior to study entry and patients were re-staged every two cycles. Pharmacokinetic (PK) sampling was performed during cycle one. RESULTS: 39 patients (32 patients ECOG performance status 0 or 1; 29 male and ten female; mean age 63 years) were entered into the study. Thirty-three completed at least two cycles of exatecan and 11 completed six cycles. Two patients (5.1%, 95% C.I. 0.3-21.3%) had a partial response, 7 (18.0%) minor response and 8 (20.5%) stable disease. Median time to tumour progression (TTP) was 88 days and median overall survival 262 days. The main toxicity was reversible neutropenia. PK analysis of exatecan demonstrated a mean clearance of 2.28 l/h per m(2), volume of distribution 18.2 l/m(2) and mean elimination half-life of 7.9 h. CONCLUSIONS: Exatecan mesylate has limited activity in advanced NSCLC and is not recommended for further evaluation as a single agent in this tumour type. PK data from this trial supports results established in phase I studies.

Adult↗

PubMed2002

A unique early gastric tubular adenocarcinoma arising from a pre-existent carcinoid tumor in a patient with a more than 20-year history of type A gastritis: an immunohistochemical and ultrastructural study.

A unique early gastric tubular adenocarcinoma developed from a pre-existent carcinoid tumor in a patient with a more than 20-year history of type A gastritis, multiple endocrine cell micronests, hypergastrinemia, and a high level of serum antiparietal cell autoantibody. The patient was a 60-year-old Japanese man. The background gastric mucosa around the tumor showed marked atrophy with intestinal metaplasia, in which endocrine cell micronests were frequently observed, and was consistent with type A gastritis. The mass was composed of both adenocarcinoma and carcinoid tumor. The adenocarcinoma was restricted to the lamina mucosa and submucosal area, and constituted a minor component of the tumor mass. The carcinoid tumor was the dominant constituent of the tumor, that invaded continuously the subserosa and muscularis propria. Based on this examination together with the detailed immunohistochemical and ultrastructural studies, the adenocarcinoma was presumed to have developed from the pre-existent carcinoid tumor. Ultrastructurally there were no amphicrine cells in the tumor, containing both endocrine granules and mucin droplets.

Adenocarcinoma↗

PubMed2001

The relationship between the level of expression of intercellular adhesion molecule-1 in placenta and onset of preeclampsia.

OBJECTIVE: To investigate the differences in the expression of intercellular adhesion molecule-1 (ICAM-1) in the placenta and the concentration of soluble ICAM-1 between early-onset and late-onset preeclampsia. METHODS: Preeclampsia was divided into early-onset type (EO: 20 to 31 weeks gestation) and late-onset type (LO: > or = 32 weeks gestation). Post delivery, placentas were obtained from 19 control pregnant women and from 9 EO and 8 LO preeclamptic women. The expression of ICAM-1 in placenta was determined by immunohistochemical staining. Blood samples were taken from 21 non-pregnant women, 16 control pregnant women, 13 EO and 8 LO preeclamptic women, and umbilical cord blood samples from 38 control pregnancies and from 16 EO and 14 LO preeclampsia. The concentration of ICAM-1 was measured by enzyme-linked immunosorbent assays. RESULTS: The expression of ICAM-1 in placenta was higher in LO than in EO preeclampsia (48.2 +/- 8.2% vs 17.9 +/- 5.0%) (p < 0.05). ICAM-1 concentration in umbilical cord blood was higher in EO than in LO preeclampsia (umbilical artery, 150.6 +/- 34.0 ng/ml vs 90.3 +/- 9.4 ng/ ml) (umbilical vein, 128.3 +/- 31.2 ng/ml vs 91.3 +/- 10.2 ng/ml) (p < 0.05). CONCLUSIONS: Significant differences were noted in the expression of ICAM-1 between patients with EO and LO preeclampsia, which suggest that the possibility that EO and LO preeclampsia may have different onset mechanisms.

Adult↗

PubMed2001

Characterization of the oxidized beta-Si3N4 whisker surface layer using XPS and TOF-SIMS.

The change in composition of the surface layer of beta-Si3N4 whiskers was examined after heat treatment in atmosphere. At 873 K, the beta-Si3N4 whisker was barely oxidized. At 1273 K, the oxidation of the surface layers of the whisker occurred easily. With the beta-Si3N4 oxidation, the Si-N bond gradually changed into the Si-N-O bond, and finally became the oxidized layer (amorphous layer) of the whisker surface. It was assumed that the whisker surface has a gradient interface structure which gradually changes from the oxide layer of the whisker's outer surface to the nitride crystal of the inside layer. It was confirmed that impurity elements such as Y and Ca existed mainly in the amorphous region near the interface between the amorphous layer and the crystal layer.

Journal Article↗

PubMed2000

Glutamine synthetase, hemoglobin alpha-chain, and macrophage migration inhibitory factor binding to amyloid beta-protein: their identification in rat brain by a novel affinity chromatography and in Alzheimer's disease brain by immunoprecipitation.

Proteins binding to amyloid beta-protein (Abeta) may modulate the accumulation of Abeta in Alzheimer's disease (AD) brain. We developed a monomeric Abeta column for isolation of the proteins binding to Abeta from rat brain. By amino acid sequence analysis and immunoreactivity with specific antibodies, we identified three new Abeta-binding proteins, glutamine synthetase, hemoglobin alpha-chain, and macrophage migration inhibitory factor as well as serum albumin, beta-tubulin, and glyceraldehyde-3-phosphate dehydrogenase already identified as proteins bound to amyloid beta-protein precursor. In addition, the retained fraction contained both apolipoprotein E and alpha(1)-antichymotrypsin already known as Abeta binding proteins. Furthermore, we detected the complexes of these new binding proteins with Abeta in a soluble fraction of the cerebral cortex of AD brain by immunoprecipitation. Our results suggest that these binding proteins also associate with Abeta, leading to the clearance or the accumulation of Abeta and the neuronal cell damage in human brain.

Alzheimer Disease↗

PubMed2000

Identification and characterization of the point mutation which affects the transcription level of the chromosomal 3-N-acetyltransferase gene of Streptomyces griseus SS-1198.

We determined the molecular basis for the enhanced expression of the aac(3)-Xa gene encoding an aminoglycoside 3-N-acetyltransferase in Streptomyces griseus. A C-->T substitution was identified at the putative promoter of the mutant gene. RNA analyses demonstrated that the substitution caused a marked increase in the production of the gene-specific transcripts. Therefore, it seemed very likely that the aac(3)-Xa gene was activated by the substitution resulting in the emergence of a stronger promoter.

Arylamine N-Acetyltransferase↗

PubMed1996

[Methods and clinical significance of an oral tolerance test of essential trace element, especially an oral zinc tolerance test].

Oral administration of zinc (zinc tolerance test) was performed in 6 healthy adults, 11 patients with chronic hepatitis and 17 patients with liver cirrhosis to evaluate the ability of the digestive organs in patients with chronic hepatic diseases to absorb zinc. That is 300 mg of zinc sulfate powder (ZnSO4 7H2O)--equivalent to 68 mg of zinc--was dissolved in 200 ml of physiological saline solution, and the subjects received oral administration of the solution in a fasting condition during the early morning. The mean levels of serum Zn (ppm) at 0, 1, 2, and 3 hours after the test dose of ZnSO4 were 0.8 +/- 0.06, 1.66 +/- 0.21, 2.73 +/- 0.22 and 2.53 +/- 0.33 in cirrhotic patients, respectively. In most subjects, serum Zn levels peaked at 2 or 3 ours. The increase in serum Zn at 60 minutes during the base line Zn tolerance test was similar in patients and controls. The area under the curve was also significantly decreased in cirrhotic patients. These results will confirm the presence of diminished absorption by the intestinal tract in patients with liver cirrhosis.

Administration, Oral↗

PubMed1996

[Liver diseases and essential trace elements].

The significance of the biochemical and nutritional roles of trace elements is widely recognized, since metals are found as constituent components of many metalloproteins and metalloenzymes. Some trace elements such as copper act as cofactors against hepatic fibrosis in chronic liver diseases, particularly in the biosynthesis of collagen. As the disease progress from chronic hepatitis to liver cirrhosis, serum calcium, magnesium, phosphorus and zinc concentrations decrease, while the copper concentration increases. In the patients with hepatocellular carcinoma, serum concentrations of trace elements are similar to those of liver cirrhosis. In the patients with acute hepatitis, serum calcium, magnesium and zinc concentrations decrease, while phosphorus, iron and copper concentrations decrease. These trace element abnormalities may reflect such pathological conditions as liver dysfunction, cholestasis, hepatic fibrosis or liver regeneration.

Humans↗

PubMed1995

Localization of pheromonal sexual dimorphism in Drosophila melanogaster and its effect on sexual isolation.

Drosophila melanogaster is sexually dimorphic for cuticular hydrocarbons, with males and females having strikingly different profiles of the long-chain compounds that act as contact pheromones. Gas-chromatographic analysis of sexual mosaics reveals that the sex specificity of hydrocarbons is located in the abdomen. This explains previous observations that D. melanogaster males display the strongest courtship toward mosaics with female abdomens. We also show that males of the sibling species Drosophila simulans preferentially court D. melanogaster mosaics with male abdomens. Because the primary male hydrocarbon in D. melanogaster is also the primary female hydrocarbon in D. simulans, this supports the idea that interspecific differences in cuticular hydrocarbons contribute to sexual isolation.

Abdomen↗

PubMed1995

Apolipoprotein E genotype, Alzheimer's pathologies and related gene expression in the aged population.

We have investigated the effect of genotypes of apolipoprotein E (ApoE) on the pathologies found in Alzheimer's disease (AD) and its related gene expression in 38 aged human brains obtained from consecutive autopsied cases. ApoE2/3, -3/3, -3/4, and -4/4 were typed in those aged brains, with ApoE3/3 being most prevalent. The AD pathologies were undetectable in ApoE2/3 brains, but were frequently observed in the other ApoE groups. In ApoE3/3 brains, 55%, 34%, and 24% of the cortical sections examined showed senile plaques (SPs), neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA), respectively. In ApoE4/4 brains, the SP formation was significantly higher. The ApoE genotype neither affected ApoE, APP, or tau mRNA level, nor the differential expression of the latter two. These results suggest that ApoE4/4 accelerates and ApoE2/3 decelerates the development of the AD pathologies in the aged brain, but this is not through alterations of the APP and tau gene expression.

Aged↗

PubMed1994

Down's syndrome: up-regulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination.

Almost all patients > 40 years of age with Down's syndrome (DS) develop the pathology characteristic of Alzheimer's disease: abundant beta-amyloid plaques and neurofibrillary tangles. We have investigated the gene expression of beta-amyloid protein precursor (APP) and tau in DS and age-matched control brains and found that levels of both mRNAs were significantly elevated in DS. Such up-regulation was not observed in two other neuronal proteins. A correlation between total APP and tau mRNA levels was also found in DS brain but distinct from the pattern observed in normal brain. Although a proportionality existed between APP-695 mRNA and three-repeat tau mRNA in DS, the proportionality between APP-751 mRNA and four-repeat tau mRNA, which is normally present, was not observed. Thus, DS brains are primarily characterized by the up-regulation of tau mRNA as well as APP mRNA and disruption of the coordinate expression between APP-751 and four-repeat tau.

Adult↗

PubMed1994

An extracellular quinoprotein oxidase that catalyzes conversion of enacyloxin IVa to enacyloxin IIa.

A new extracellular quinoprotein oxidase named enacyloxin oxidase (ENX oxidase), which is involved in biosynthesis of ENX IIa, a congener of ENX, was found in the culture supernatant of Frateuria sp. W-315 and purified as a homogeneous protein on SDS-PAGE. ENX oxidase was shown to have a molecular mass of 73 kDa by SDS-PAGE and 79 kDa by gel filtration. The enzyme was inhibited by various carbonyl reagents and the activity was stimulated by addition of PQQ. This is the first report on a quinoprotein oxidase that is secreted into the culture medium in the logarithmic growth phase, and acts for biosynthesis of the antibiotic.

Alcohol Oxidoreductases↗

PubMed1993

Ribonuclease activity of sialic acid-binding lectin from Rana catesbeiana eggs.

Sialic acid-binding lectin (SBL) isolated from Rana catesbeiana eggs is a basic protein which agglutinates a large variety of tumour cells and has an amino acid sequence homologous to that of human angiogenin and pancreatic ribonuclease (RNase). Although SBL and angiogenin lack the Cys-65-Cys-72 disulphide bond of pancreatic RNase, the locations of the other three disulphide bonds are similar among the three molecules. SBL was found to exhibit RNase activity, as well as catalytic properties resembling those of bovine RNase A in some respects. For example, SBL hydrolyses poly(uridylic acid) and poly(cytidylic acid) as substrates, and prefers the former. RNase A and angiogenin are strongly inhibited by human placental RNase inhibitor, whereas the RNase activity and tumour cell agglutination activity of SBL are not affected by this inhibitor.

Amino Acid Sequence↗

PubMed1993

Engineering of artificial cell-adhesive proteins by grafting EILDVPST sequence derived from fibronectin.

Fibronectin contains at least two distinct oligopeptide sequences serving as signals for the interaction with cell surface adhesion receptors termed integrins. One of these sequences, Arg-Gly-Asp-Ser (RGDS) tetrapeptide, was shown to be transferred to a truncated form of Staphylococcal IgG-binding protein (hereafter referred to as tSPA) with retention of its cell-adhesive activity [Maeda, T. et al. (1989) J. Biol. Chem. 264, 15165-15168]. We have extended the observation to another cell-adhesive sequence, Glu-Ile-Leu-Asp-Val-Pro-Ser-Thr (referred to as "CS1" sequence), to demonstrate that: i) the tSPA grafted with the sequence mediated adhesion of human lymphoma and rhabdomyosarcoma cells, mouse melanoma cells, but not of hamster fibroblasts; ii) antibodies against integrin alpha 4 and beta 1 subunits specifically inhibited cell adhesion mediated by the CS1-grafted tSPA; iii) a heterodivalent tSPA grafted with both RGDS and CS1 sequences at different sites was more potent in promoting cell adhesion than the monovalent tSPAs grafted with either sequence alone. These results indicate that not only the RGDS but also the CS1 sequence can be transferred to tSPA with retention of its cell-adhesive activity as well as its cell-type specificity, and that the grafted CS1 sequence is recognized by the same integrin isotype as the authentic sequence within intact fibronectin.

Amino Acid Sequence↗

PubMed1993

Improved method for expression of Kunitz-type serine proteinase inhibitor domain of beta-amyloid protein precursor in Escherichia coli and characterization of disulfide bonds of the product.

Kunitz-type serine proteinase inhibitor (KPI) domain of Alzheimer's disease-related beta-amyloid protein precursor (APP) was expressed in Escherichia coli as a fusion protein with a truncated form of Staphylococcus protein A. The fusion protein was purified from the cell culture medium using an IgG Sepharose column. The KPI domain was separated from the protein A portion by cleavage with human alpha-thrombin at the engineered recognition sequence, followed by purification on IgG Sepharose and reversed-phase HPLC columns. The recombinant KPI domain strongly inhibited trypsin; the inhibition constant (Ki) for bovine trypsin was 2.5 x 10(-11) M, comparable to those of the secreted forms of APP with the KPI domain. The recombinant protein contained three intramolecular disulfide bonds, which were determined to be located between Cys-6 (C1) and Cys-56 (C6), Cys-15 (C2) and Cys-39 (C4), and Cys-31 (C3) and Cys-52 (C5) of the recombinant KPI domain, respectively. These positions are highly homologous to those of disulfide bonds in bovine pancreatic trypsin inhibitor. The trypsin-inhibitory activity of the recombinant protein was abolished by preincubation with 0.4 mM dithiothreitol under non-denaturing conditions. By this mild reduction, all the disulfide bonds were completely cleaved. These results clearly indicate that the disulfide bonds play an important role in the function of the KPI domain of APP.

Alzheimer Disease↗

PubMed1993

Beta-amyloid protein precursor and tau mRNA levels versus beta-amyloid plaque and neurofibrillary tangles in the aged human brain.

To learn whether or not the levels of beta-amyloid protein precursor (APP) and tau mRNAs are related to the formation of beta-amyloid and neurofibrillary tangles, we quantified these mRNA levels in three cortical regions of 38 aged human brains, which were examined immunocytochemically for beta-amyloid and tangles. Marked individual variabilities were noted in APP and tau mRNA levels among elderly individuals. The mean APP mRNA level was slightly reduced in the beta-amyloid plaque (+2) group, but not in the plaque (+) group, compared to the plaque (-) group. Some brains in the plaque (-) group showed increased APP expression, the extent of which was not seen in the plaque (+) or (+2) group. The differences in the mean tau mRNA levels were not statistically significant among the tangle (-), (+), and (+2) groups. These results show that beta-protein and tau deposition do not accompany increased expression of the APP and tau genes, respectively, and thus suggest that factors other than gene expression may be at work in the progression of beta-amyloid and/or tangle formation in the aged human brain.

Aged↗

PubMed1992

A novel correlation between the levels of beta-amyloid protein precursor and tau transcripts in the aged human brain.

beta-Amyloid protein precursor (APP) and tau are implicated in the pathogenesis of Alzheimer's disease. We quantified the levels of APP and tau transcripts in the three cortical regions of 38 aged human brains obtained from consecutive autopsied patients. The level of APP mRNA was directly proportional to that of tau mRNA to a remarkable extent, suggesting coordinate expression of the APP and tau genes, whereas much weaker correlations were noted among mRNAs encoding other neuronal proteins. From the previous data on the differential expression of APP and tau mRNAs, the levels of APP-751 and -695 mRNAs were calculated and found to be proportional to those of four-repeat and three-repeat tau mRNAs, respectively, whereas that of APP-770 mRNA was rather constant. These results suggest that the mRNA concentrations of APP isoforms are linked to those of tau isoforms in the aged human brain.

Aged↗