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Biomedical subjects

A Sakamoto

Publications and source records attributed to A Sakamoto.

At least 199 records · Page 11Linked to original sources
PubMed1994

Pseudo-noncompetitive antagonism by BQ123 of intracellular calcium transients mediated by human ETA endothelin receptor.

The family of endothelins, endothelin-1 (ET-1), ET-2 and ET-3, act on two subtypes of receptors called ETA and ETB receptors. BQ123 is an ETA-selective competitive antagonist. In this study, however, BQ123 inhibited ET-1-induced transients of cytosolic Ca2+ concentrations ([Ca2+]i) in an apparently noncompetitive manner in mouse L cell stably expressing cloned human ETA receptor. BQ123 (3-30 nM) did not change the EC50 of ET-1 (6.6 nM), but reduced the maximum responses down to 15.0%. In an non-equilibrium binding assay which mimicks the conditions of [Ca2+]i transient assay (cells were incubated with [125I]ET-1 only for 30 s), BQ123 (30 nM) constantly decreased the specific [125I]ET-1 binding to approximately 13% of that without the antagonist. Thus, the apparent noncompetitive antagonism by BQ123 of ETA receptor-mediated [Ca2+]i transient is due to the assay condition where the interactions of the agonist, antagonist and receptor remained non-equilibrium state.

Animals↗
PubMed1994

The HBP-1 family of wheat basic/leucine zipper proteins interacts with overlapping cis-acting hexamer motifs of plant histone genes.

The type I element (CCACGTCANCGATCCGCG) is a cis-acting element that is essential for the transcriptional regulation of the wheat histone H3 (TH012) gene. The sequence CCACGTCA in the type I element resembles various plant regulatory elements that share an ACGT core sequence, which can be recognized by different basic/leucine zipper (bZIP) proteins. Here we describe the isolation and characterization of wheat cDNA clones encoding three novel bZIP proteins, designated HBP (histone promoter-binding protein)-1a(1), HBP-1a(c14), and HBP-1b(c1). These proteins specifically bind to the ACGT core sequence and, together with previously identified HBP-1a(17) and HBP-1b(c38), constitute a protein family, named the HBP-1 family. Based on their structural characteristics and DNA binding specificities, members of the HBP-1 family can be grouped into HBP-1a and HBP-1b subfamilies. The HBP-1a isoforms are characterized by their N-terminal proline-rich domain and a C-terminal bZIP domain, which binds to the CCACGT motif. In contrast, the HBP-1b isoforms have a bZIP domain at the N terminus, which binds to the ACGTCA motif, and a glutamine-rich domain at the C terminus. All members of both subfamilies interact with the CCACGTCA sequence, but their DNA binding specificities and affinities differ. Since HBP-1a isoforms form heterodimers in all pairwise combinations, heterodimer formation among these bZIP proteins may generate an expanded repertoire of regulatory potential for gene expression in plants.

Amino Acid Sequence↗
PubMed1994

Observer disagreement in histological classification of ovarian tumors in Japan.

Histological slides of 789 cases of ovarian tumor registered by the Japanese Gynecologic Oncology Group, sponsored by the Ministry of Health and Welfare, Japan, were reviewed by three certified pathologists in order to evaluate the observer disagreement among the pathologists and the reproducibility of the histological classification. In 53.0% of the cases, all observers agreed upon the diagnosis. At least two of them agreed in 88.4% of the cases. The observer disagreement was highest for low potential malignancy (borderline malignancy) tumors (44.4%), including serous, mucinous, and endometrioid tumors. The results of the study clearly indicate the necessity of establishing a slide review system in order to obtain reliable data for comparative research. Moreover, the histological criteria, especially of tumors of borderline malignancy, should be more clearly defined to obtain high reproducibility of ovarian tumor diagnosis.

Carcinoma↗
PubMed1994

Prevention of insulitis and diabetes in beta 2-microglobulin-deficient non-obese diabetic mice.

beta 2-Microglobulin (beta 2m)-deficient non-obese diabetic (NOD) mice were established by crossing beta 2m-deficient 129/Sv mice with NOD mice, and used to examine the possible involvement of MHC class I molecules and CD8+ T cells in the development of insulitis and diabetes. In these mice, MHC class I molecules were not expressed, resulting in no generation of CD8+ T cells. None of eight lines of beta 2m-deficient NOD mice (-/-) established developed overt diabetes by 32 weeks, while control littermates (+/+) became diabetic by 22 weeks. histological studies showed no significant lymphocyte infiltration of the islets (insulitis score: 0.03 +/- 0.03) in any of the beta 2m-deficient NOD mice (-/-) compared with littermate NOD mice (+/+) with overt insulitis (1.42 +/- 0.28). These findings support the notion that the expression of MHC class I molecules and/or CD8+ T cells plays an essential role in the infiltration of CD4+ T cells in islets as well as the development of diabetes in NOD mice.

Animals↗
PubMed1994

Stepwise participation of p53 gene mutation during dedifferentiation of human thyroid carcinomas.

The spectrum of p53 gene mutations was investigated in thyroid carcinomas with respect to histopathological classification. In all histological subtypes of thyroid carcinoma that had previously revealed positivity in immunohistochemical staining for p53 protein, single-stranded conformation polymorphism analysis and direct sequencing were performed to detect point mutations between exons 5 and 8. In well differentiated papillary and follicular carcinomas, in which we had already known that 11.1 and 14.3% of the cases, respectively, revealed p53 overexpression as determined by immunohistochemistry, genetic aberrations were undetectable. In poorly differentiated carcinoma, in which 40.9% had revealed overexpression, two of six cases revealed point mutations at codon 244 in exon 7 and at codon 278 in exon 8. In undifferentiated carcinoma, in which 63.6% had revealed overexpression, four of six cases examined showed point mutations at codon 157 in exon 5, at codon 248 in exon 7, and at codon 273 and a two-base insertion between codons 266 and 267 in exon 8. These results strongly suggest the crucial role of p53 gene aberration and protein overexpression in a biologically aggressive subtype, possibly as a stepwise participation in the process of tumor dedifferentiation in human thyroid carcinomas.

Amino Acid Sequence↗
PubMed1994

[Changes in luminal diameter of internal thoracic arteries five years after coronary artery bypass grafting].

Five years after coronary artery bypass grafting, 23 internal thoracic arteries (ITAs) were reexamined angiographically, and their luminal diameters were compared with those of one month after the operation. Proximal diameter, just below the subclavian artery, and distal diameter, just above the anstomosis, were measured. One month after surgery, these were 2.38 +/- 0.48 mm and 1.69 +/- 0.39 mm, respectively. After five years, the proximal diameter had not changed significantly (2.48 +/- 0.47 mm), but the distal diameter had increased to 1.96 +/- 0.58 mm (p < 0.05). Especially when there was no competitive flow with the ITA, the distal diameter showed a marked increase from 1.80 +/- 0.35 mm to 2.27 +/- 0.42 mm (p < 0.01). Twelve ITAs were grafted to coronary arteries having less than critical stenosis, and five of them showed distal narrowing or so-called string sign after five years. This seemed to be a form or physiological atrophy resulting from competitive flow, and the patients had no anginal pain in spite of their poor ITA runoff. When coronary artery stenosis is less than 75%, a choice is difficult between an ITA or a saphenous vein graft. We think that the graft must be selected considering the possibility of stenosis progression, if the jeopardized area is important for the patient. An ITA graft would be advisable in such cases.

Aged↗
PubMed1994

[A case of eosinophilic pneumonia with elevated levels of carcino-embryonic antigen (CEA)].

A 70-year-old woman was admitted for productive cough and infiltrative shadows in the right lower lung field on chest X-ray film. Eosinophilia (17%) in blood, an abnormally high percentage of eosinophiles (7%) in bronchoalveolar lavage fluid and eosinophilic infiltration with proliferated goblet cells in transbronchial lung biopsy specimens led to the diagnosis of eosinophilic pneumonia. Laboratory data on admission also revealed a high level of CEA (17.1 ng/ml) in serum. After administration of prednisolone (30 mg/day), the symptoms ameliorated and the CEA levels were normalized. The proliferated goblet cells were immunohistochemically positive for CEA, which suggests that the high levels of CEA were caused by excessive CEA secretion from the goblet cells associated with eosinophilic pneumonia. These studies showed that serum CEA also may be a marker for disease activity in eosinophilic pneumonia.

Aged↗
PubMed1994

T-cell receptor V beta repertoire of L3T4+ regulatory T cells in anti-L3T4 antibody-induced tolerant NOD mice.

In ongoing studies, we have found that short-term administration of anti-L3T4 monoclonal antibodies (mAb) prevents the development of overt diabetes in non-obese diabetic (NOD) mice. In the present work, we asked whether L3T4+ T cells or Lyt-2+ T cells can suppress the diabetes in these mice. L3T4+ T cells or Lyt-2+ T cells were sorted using a magnetic cell sorter, then were transferred into cyclophosphamide-induced male NOD mice. We obtained evidence that the L3T4+ but not Lyt-2+ T cells did inhibit the diabetes, thereby indicating that the former can regulate diabetes in anti-L3T4 mAb-induced tolerant NOD mice. Further analysis on T-cell receptor (TCR) V beta genes on splenic T cells from anti-L3T4 mAb-treated NOD mice revealed that V beta 4-positive T cells expanded predominantly, while L3T4+ T cells represented heterogeneity of the TCR V beta gene, hence, V beta 4-positive Lyt-2+ T cells generate predominantly. Our findings suggest that both L3T4+ and Lyt-2+ T cells renew and function as regulatory cells, through clonotypic interaction in tolerant NOD mice.

Animals↗
PubMed1994

[Delayed sternal closure for life-threatening massive bleeding during re-open heart surgery].

Delayed sternal closure (DSC) was used for 4 patients undergoing various cardiac reoperations to control perioperative hemorrhage. DSC was performed 48-72 hours later. All patients left the hospital alive and in good condition. The only recognized complication was an abscess formation around the bleeding area, which was successfully treated with systemic antibiotics. The remaining 3 patients manifested no infections. In two of these patients, hemodynamic instability was continued because of right ventricular outflow tract obstruction by compression of the packs which were left over the bleeding area. The function of coagulation of the blood was recovered except prothrombin time (PT) at the time of definitive closure of the chest. Recovery of the function of coagulation was useful in deciding the timing of DSC than hemodynamic state.

Aged↗
PubMed1994

[Surgical treatment of active infective endocarditis].

From January, 1978, through December, 1990, surgical treatment for active infective endocarditis was performed in 11 patients. There were 8 men and 3 women who ranged in age from 19 to 54 years with a mean age of 38.8 years. Two patients had ventricular septal defects and 1 patient had rheumatic valve disease. In all patients, the infecting organism was isolated from blood, including streptococcus in 7, staphylococcus in 2, and gram-negative rods in 2. The indication for operation at the active phase was uncontrolled infection in 7 and progressive heart failure in 4. The operation was performed at 7 to 150 days with a mean of 53 days after diagnosis. Operative findings showed vegetations in all cases and perforations of the valve in 6. There were no operative deaths. Perioperative complications developed in 5, whose indication for operation was uncontrolled infection. Complications consisted of 1 prosthetic valve endocarditis, 1 pulmonary suppuration, 1 ruptured mycotic aneurysm of the hepatic artery, 1 ruptured mycotic aneurysm of the popliteal artery, and 1 pyogenic spondylitis. All were successfully treated surgically or with antibiotic therapy. There were no complications in patients whose indication for operation was progressive heart failure. We conclude that the risk of embolism is high in patients undergoing surgery at the active phase of infective endocarditis because of uncontrolled infection; thus, such patients should be carefully monitored for emboli.

Adult↗
PubMed1994

[A case of idiopathic chylothorax--successful pleurodesis with OK-432].

A 73-year-old woman was referred to our hospital because of left pleural effusion. Chyle was obtained by thoracocentesis. Because there was no organic lesion to cause chylothorax, idiopathic chylothorax was diagnosed. Her condition improved by chest-tube drainage and pleurodesis with intrapleural injection of OK-432. We report a rare case of idiopathic chylothorax and conclude that pleurodesis with intrapleural injection of OK432 is very useful for the treatment of idiopathic chylothorax.

Aged↗
PubMed1993

Liposome targeting to rat brain: effect of osmotic opening of the blood-brain barrier.

To determine whether sulfatide liposomes can cross the blood-brain barrier (BBB) with or without osmotic treatment by mannitol, we administered liposomes through the internal carotid artery in rats. Sulfatide liposomes could pass the BBB with osmotic treatment, but not without osmotic treatment. Therefore, we propose that the combination method of administration of the reticuloendothelial-system avoiding liposomes with osmotic treatment can be useful for treatment of various kinds of brain diseases.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

The putative zinc-finger protein WZF1 interacts with a cis-acting element of wheat histone genes.

A nonamer motif (CATCCAACG) that is one of the cis-acting elements identified in the proximal promoter region of some wheat histone genes is included in the region that interacts with the wheat DNA-binding protein, HBP (histone gene-binding protein)-2. To obtain structural and functional information about this DNA-binding protein, we attempted to isolate a cDNA clone encoding HBP-2 on the basis of its ability to bind to a nonamer-containing 38-bp DNA fragment. Southwestern screening of a wheat cDNA library with concatenated 38-residue oligonucleotides as the probe produced one candidate clone. Nucleotide sequence analyses of this cDNA clone and the corresponding genomic clone showed that the protein deduced from the nucleotide sequence consisted of 261 amino acids and contained a set of zinc-finger motifs similar to those found in many eukaryotic transcription factors. The protein, named WZF1 (wheat zinc-finger protein 1), which was expressed from the cDNA in Escherichia coli cells, bound specifically and metal-ion-dependently to the nonamer-containing oligonucleotide. The WZF1 mRNA was highly expressed in the root apexes of wheat seedlings, but less so in the proximal portion of young leaves; whereas, histone H3 mRNA was highly expressed in both tissues. The expression patterns of the WZF1 and histone H3 genes in the early stages of germination differed, expression of the WZF1 gene being almost constant but not that of the H3 gene. The relationship of WZF1 and HBP-2 and the possible role of WZF1 in the histone gene expression were discussed.

Amino Acid Sequence↗
PubMed1993

Distinct subdomains of human endothelin receptors determine their selectivity to endothelinA-selective antagonist and endothelinB-selective agonists.

The endothelin (ET) family of peptides acts via two subtypes of G-protein-coupled heptahelical receptors termed ETA and ETB, which have distinct rank orders of affinity to endothelin receptor agonists and antagonists. To delineate which portions of the receptor molecules determine ligand selectivity, we have constructed a series of chimeras between human ETA and ETB receptors and characterized the chimeric receptors expressed in heterologous cell lines by competitive radioligand binding analysis and by measuring agonist-induced transients of intracellular Ca2+. We demonstrate that the binding determinant for the ETB-selective agonists ET-3, BQ3020, and IRL1620 residues within the region spanning the putative transmembrane helices IV-VI and the adjacent loop regions. In contrast, the transmembrane helices I, II, III, and VII plus the intervening loop regions specify the selectivity for BQ123, an ETA-selective antagonist. BQ123 exhibited no detectable agonistic activity in all wild-type and chimeric receptors tested. A chimeric receptor that has the transmembrane helices IV-VI (and adjacent loops) from the ETB receptor inserted into the remaining regions from the ETA receptor binds both the ETA- and ETB-selective ligands with high affinities. Moreover, BQ123 competitively inhibits the binding of the amino-terminally truncated ETB agonists, 125I-BQ3020 and 125I-IRL1620, to this chimeric receptor, suggesting that BQ123 is a mimic of the carboxyl-terminal linear portion of endothelins. These findings indicate that there are at least two separable ligand interaction subdomains within the endothelin receptors.

Amino Acid Sequence↗
PubMed1993

Chromosomal locations of the genes for histones and a histone gene-binding protein family HBP-1 in common wheat.

The chromosomal locations of the genes in common wheat that encode the five histones and five members of the HBP (histone gene-binding protein)-1 family were determined by hybridizing their cloned DNAs to genomic DNAs of nullitetrasomic and telosomic lines of common wheat, Triticum aestivum cv. Chinese Spring. The H1 and H2a genes are located on different sets of homoeologous chromosomes or chromosome arms, namely, 5A, 5B and 5D, and 2AS, 2BS and 2DS, respectively. Genes for the other histones, H2b, H3 and H4, are found in high copy number and are dispersed among a large number of chromosomes. The genes for all members of the HBP-1 family are present in small copy numbers. Those for HBP-1a(1) are located on six chromosome arms, 3BL, 5AL, 5DL, 6AL, 6BS and 7DL, whereas those for each HBP-1a(c14), 1a(17), 1b(c1), and 1b(c38) are on a single set of homoeologous chromosome arms; 4AS, 4BL, 4DL; 6AS, 6BS, 6DS; 3AL, 3BL, 3DL; and 3AS, 3BS, 3DS, respectively. The genes for histones H1 and H2a, and for all members of the HBP-1 family except HBP-1a(1) are assumed to have different phylogenetic origins. The genes for histone 2a and HBP-1a(17) are located in the RFLP maps of chromosomes 2B and 6A, respectively. Gene symbols are proposed for all genes whose chromosomal locations have been determined.

Aneuploidy↗
PubMed1993

Inhibition of lipid peroxidation by some dihydropyridine derivatives.

The efficacy of dihydropyridine derivatives in inhibiting lipid peroxidation was studied using modified Buege and Aust's method. The method first involves keeping a decapitated rat head at 37 degrees C for 30 min in order to induce global ischemia. Then, the cortex is removed and homogenized, and the homogenate is subsequently exposed to air for 30 min for reoxygenation. Finally, the amount of thiobarbituric acid-reactive substances (TBAR) is measured. With this method, nisoldipine, nimodipine, nitrendipine, nifedipine and nicardipine were all shown to have an antioxidant activity that correlated with their lipophilicity, which was determined by their octanol/water partition coefficients.

Journal Article↗