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Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 505 records · Page 28Linked to original sources
PubMed1991

The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.

Mouse anti-Fas monoclonal antibody has a cytolytic activity on human cells that express the antigen. Complementary DNAs encoding the cell surface antigen Fas were isolated from a cDNA library of human T cell lymphoma KT-3 cells. The nucleotide sequence of the cDNAs revealed that the molecule coding for the Fas antigen determinant is a 319 amino acid polypeptide (Mr 36,000) with a single transmembrane domain. The extracellular domain is rich in cysteine residue, and shows a similarity to that of human tumor necrosis factor receptors, human nerve growth factor receptor, and human B cell antigen CD40. Murine WR19L cells or L929 cells transformed with the human Fas antigen cDNA were killed by the anti-Fas antibody in the process known as apoptosis.

Amino Acid Sequence↗
PubMed1991

Bone modulation in sustained hematopoietic stimulation in mice.

To understand the etiology of bone modulation and hypercalcemia observed in granulocytosis of a tumor-bearing animal model and to gain insight into the implication of sustained hematopoietic stimulation on the bone tissue, in vivo responses of normal mouse hematopoietic and bone tissues to long-term injections of recombinant human and murine granulocyte colony-stimulating factor (G-CSF), murine granulocyte-macrophage CSF (GM-CSF), and human erythropoietin were quantitatively analyzed. Osteoclast activation was estimated by the osteoclast-endosteal ratio, determined by morphometric analyses of femoral sections. Medullary and bone areas were measured on transverse ground bone sections of the tibia. Recombinant murine G-CSF provoked marked granulocytosis associated with significant increases in the number of marrow granulocytes and their progenitors, and caused expansion of granulopoietic marrow into fatty marrow. The bone of G-CSF-treated mice showed a significant increase in endosteal osteoclast numbers with medullary area enlargement and a reduction in the bone thickness; indicative of endosteal bone resorption. Although GM-CSF had little effect on granulopoiesis, it caused peritoneal macrophages to increase and induced similar bone changes as those observed in G-CSF treatment. Enhanced erythropoiesis stimulated by erythropoietin was also associated with evidence of endosteal bone resorption. Bone changes induced by these growth factors were not associated with hypercalcemia. These animal studies document association of bone modulation in sustained stimulation of hematopoiesis, and implicate important physiologic effects of hematopoietic growth factors on skeletal tissue in vivo.

Animals↗
PubMed1991

Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture.

We are interested to know whether expression of a lineage-specific growth factor receptor is deterministic to lineage commitment during hematopoiesis. For this purpose, we introduced the human c-fms gene into the multipotential stem cell clone LyD9 and two myeloid progenitor clones, L-GM3 and L-G3, cells that differentiate in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF, respectively. Although LyD9 cells have differentiation potential to become macrophages, c-fms transfectants of LyD9 and L-GM3 cells did not differentiate in response to human macrophage (M)-CSF. However, c-fms transfectants of L-G3 cells differentiated to neutrophils in response to human M-CSF. These results indicate that the M-CSF receptor requires a specific signal transduction pathway to exert its differentiational and proliferative effects. Furthermore, the M-CSF receptor can convey a granulocyte-type differentiation signal possibly by cooperating with the G-CSF receptor signal transduction pathway. The c-fms-transfected LyD9 cells as well as the original LyD9 cells differentiated predominantly into GM-CSF- and G-CSF-responsive cells by coculturing with PA6 and ST2 stromal cells, respectively. The results indicate that differentiation lineage is not affected by premature expression of the M-CSF receptor. Instead, the stromal cell used for coculture apparently controls lineage-selective differentiation of the multi-potential stem cell line.

Animals↗
PubMed1991

Site-directed mutagenesis of the beta subunit of tryptophan synthase from Salmonella typhimurium. Role of active site glutamic acid 350.

To investigate the functional role of glutamic acid 350 in the active site of the beta subunit of tryptophan synthase from Salmonella typhimurium, we have replaced this residue by glutamine or alanine by use of site-directed mutagenesis. The mutant alpha 2 beta 2 complexes were expressed, purified, crystallized, and characterized by spectroscopic and kinetic studies with several substrates. We find large alterations in the substrate and reaction specificity of each mutant form of the alpha 2 beta 2 complex. Since the two mutant enzymes are virtually inactive in reactions with L-serine but are active in reactions with beta-chloro-L-alanine, glutamic acid 350 may facilitate the beta-elimination of the weak hydroxyl leaving group of L-serine. The mutant alpha 2 beta 2 complexes are more active than the wild type enzyme in the beta-elimination reaction with beta-chloro-L-alanine. These enzymes are irreversibly inactivated by beta-chloro-L-alanine, whereas the wild type enzyme is not. These altered properties may result from a change in the conformation of the active site, from a change in the orientation of the coenzyme relative to active site residues, or from a change in the solvent accessibility of the active site. The alteration in the active site may enhance the release of amino acrylate from the Schiff base intermediate by hydrolysis or by transamination.

Amino Acids↗
PubMed1991

Molecular cloning of cDNA and a chromosomal gene encoding GPE1-BP, a nuclear protein which binds to granulocyte colony-stimulating factor promoter element 1.

Granulocyte colony-stimulating factor (G-CSF) is produced from macrophages in response to lipopolysaccharide (LPS). GPE1, a cis-acting element of the G-CSF gene promoter, functioned as an LPS-inducible element. We isolated cDNA and a chromosomal gene encoding the mouse GPE1-binding protein (GPE1-BP). A 150-amino acid protein deduced from the cDNA has a basic domain and a leucine zipper motif, and seems to be identical to that of recently isolated Ig/EBP. The nuclear extract from COS cells transfected with the cDNA showed GPE1-binding activity. Transcripts were ubiquitously detected, and may be spliced from two exons of a single gene.

Amino Acid Sequence↗
PubMed1991

Effects of percutaneous transvenous mitral commissurotomy on levels of plasma atrial natriuretic peptide during exercise.

To clarify the factors that influenced the secretion of human atrial natriuretic peptide (ANP) during exercise, we studied the relations between the changes in ANP, transmitral pressure gradient, heart rate and blood pressure at exercise in 16 patients with mitral stenosis before and after percutaneous transvenous mitral commissurotomy (PTMC). Before PTMC, ANP levels increased from 107 +/- 70 to 183 +/- 96 pg/ml during exercise testing (p less than 0.01), concomitant with the increment in mean transmitral pressure gradient, heart rate and systolic blood pressure. After PTMC, ANP levels also increased from 78 +/- 43 to 117 +/- 64 pg/ml, concomitant with the increment of those parameters. However, increments of ANP, mean transmitral pressure gradient and heart rate after PTMC were lower than those before PTMC. Because the most important factor influencing the secretion of ANP was unclear, the differences between these parameters were calculated at submaximal exercise before and after PTMC. There was a significant relation only between the change in ANP and mean transmitral pressure gradient (r = 0.70, p less than 0.01). These results suggest that the most important factor influencing the secretion of ANP during exercise is the change in transmitral pressure gradient in patients with mitral stenosis.

Atrial Natriuretic Factor↗
PubMed1991

Balloon diameter of the Inoue balloon catheter during percutaneous transvenous mitral commissurotomy: clinical and experimental study.

To determine adequate and effective balloon diameters of the Inoue balloon catheter, we reviewed clinical results and characteristics of the Inoue balloon catheter, especially the relationship between the intra-balloon pressure and the balloon diameter, experimentally and clinically, in 46 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Mitral valve area increased from 1.1 +/- 0.3 to 2.1 +/- 0.3 cm2 in all patients after PTMC. Based on balloon diameter settings, mitral valve area increased from 1.3 +/- 0.4 to 2.3 +/- 0.5 cm2 in patients treated with a balloon setting greater than 26 mm in diameter, from 1.1 +/- 0.3 to 2.0 +/- 0.5 cm2 in patients with a balloon setting at 26 mm in diameter, and from 1.1 +/- 0.4 to 1.7 +/- 0.4 cm2 in those treated with a balloon setting less than 26 mm in diameter, with an increase in mitral valve area of 1.0 +/- 0.6, 0.9 +/- 0.4, and 0.7 +/- 0.2 cm2, respectively. There was a significant difference between the increase in mitral valve area at a setting of 26 mm in diameter and that observed at a setting less than 26 mm in diameter. We next investigated differences between balloon diameter settings and actual balloon diameters measured from cineangiograms at maximum balloon inflation. The ratio of actual balloon diameter to a setting diameter of less than 26 mm was smaller than that of 26 mm. To evaluate the reason for the difference, we investigated the relationship between intra-balloon pressure and balloon diameter. In the prototype Inoue balloon catheter, intra-balloon pressure increases from 1.0 kg/cm2 at 20 mm in diameter to 2.2 kg/cm2 at 30 mm in diameter at atmospheric pressure. In conclusion, the increase in mitral valve area was inadequate when the balloon was less than 26 mm in diameter because of inadequate intra-balloon pressure. We, therefore, recommend a balloon size set above 26 mm to obtain adequate intra-balloon pressure when using the Inoue balloon catheter.

Catheterization↗
PubMed1991

Molecular cloning and expression of a cDNA encoding the secretin receptor.

Secretin is a 27 amino acid peptide which stimulates the secretion of bicarbonate, enzymes and potassium ion from the pancreas. A complementary DNA encoding the rat secretin receptor was isolated from a CDM8 expression library of NG108-15 cell line. The secretin receptor expressed in COS cells could specifically bind the iodinated secretin with high and low affinities. Co-expression of the secretin receptor with the alpha-subunit of rat Gs protein increased the concentration of the high affinity receptor in the membrane fraction of the transfected COS cells. Secretin could stimulate accumulation of cAMP in COS cells expressing the cloned secretin receptor. The nucleotide sequence analysis of the cDNA has revealed that the secretin receptor consists of 449 amino acids with a calculated Mr of 48,696. The secretin receptor contains seven putative transmembrane segments, and belongs to a family of the G protein-coupled receptor. However, the amino acid sequence of the secretin receptor has no significant similarity with that of other G protein-coupled receptors. A 2.5 kb mRNA coding for the secretin receptor could be detected in NG108-15 cells, and rat heart, stomach and pancreatic tissue.

Amino Acid Sequence↗
PubMed1991

Functional domains of the granulocyte colony-stimulating factor receptor.

The granulocyte colony-stimulating factor (G-CSF) receptor has a composite structure consisting of an immunoglobulin(Ig)-like domain, a cytokine receptor-homologous (CRH) domain and three fibronectin type III (FNIII) domains in the extracellular region. Introduction of G-CSF receptor cDNA into IL-3-dependent murine myeloid cell line FDC-P1 and pro-B cell line BAF-B03, which normally do not respond to G-CSF, enabled them to proliferate in response to G-CSF. On the other hand, expression of the G-CSF receptor cDNA in the IL-2-dependent T cell line CTLL-2 did not enable it to grow in response to G-CSF, although G-CSF could transiently stimulate DNA synthesis. Mutational analyses of the G-CSF receptor in FDC-P1 cells indicated that the N-terminal half of the CRH domain was essential for the recognition of G-CSF, but the Ig-like, FNIII and cytoplasmic domains were not. The CRH domain and a portion of the cytoplasmic domain of about 100 amino acids in length were indispensable for transduction of the G-CSF-triggered growth signal.

Amino Acid Sequence↗
PubMed1991

Lateral ventricular arteriovenous malformations: natural history and surgical indications.

The authors report 21 cases of lateral ventricular arteriovenous malformation (AVM) focusing on their natural history and surgical indications. Eighteen of 21 patients (86%) had bleedings prior to admission. We performed definitive surgery in 9 patients and conservative treatment in 12 patients. In 7 of 9 patients (78%) in the operative group and in 5 of 12 patients (42%) in the non-operative group, the nidus of the AVM was less than 4 cm in diameter. The other 2 AVMs in the operative group, more than 4 cm in diameter, were located in the temporal lobe and widely extended to the temporal horn of the lateral ventricle. The nidi of the AVMs were totally removed in all 9 cases in the operative group. All patients have been doing well except one who had a mental breakdown 6 years after surgery. In 10 patients in the non-operative group, AVMs were located in the left cerebral hemispheres. Three patients in the non-operative group had rebleeding of the AVM. Two of the 12 patients in the non-operative group (17%) died of the recurrent haemorrhages. The rate of bleeding of the lateral ventricular AVM seems to be higher than that of the cerebral cortical AVM, but the mortality due to recurrent bleeding might be similar between the two. The operative indications we made depended on the sizes and locations of the AVMs. For AVMs in the temporal horn, even though they were large, we performed total removals of the nidi and had good results. We did not perform any definitive surgery for AVMs more than 4 cm in diameter except for those in the temporal horn. The mortality and morbidity of the 21 cases were 10% and 14%, respectively. Patients with AVMs in the temporal horn and patients with small AVMs in the frontal horn were good candidates for definitive surgery. We undertook conservative treatment for patients with large AVMs, and the results were acceptable.

Adolescent↗
PubMed1991

Acute reduction of mitral valve area after percutaneous balloon mitral valvuloplasty: assessment with Doppler continuity equation method.

Mitral valve areas before and after balloon mitral valvuloplasty were serially determined by the Doppler continuity equation method in 16 patients. Ultrasound examinations were performed before and immediately after balloon inflation and 24 hours, 1 week, and 1 month after valvuloplasty. Mitral valve area determined by the Doppler continuity equation method correlated well with that determined at catheterization by the Gorlin formula, not only before but also immediately after balloon inflation (y = 0.87 x + 0.05, standard error of estimate = 0.22 cm2, r = 0.90). Serial calculation of mitral valve area by the Doppler continuity equation method showed a slight but significant decrease in the valve area at 24 hours after balloon mitral valvuloplasty but no change after that. We conclude that the Doppler continuity equation method provides an accurate estimation of mitral valve area before and even after balloon valvuloplasty. Mitral valve area dilated by balloon inflation is decreased slightly within 24 hours after the procedure, which corroborates valve stretch as one mechanism for increasing mitral valve area with balloon valvuloplasty. Estimation of mitral valve area immediately after balloon mitral valvuloplasty may overestimate the long-term efficacy of the procedure.

Cardiac Catheterization↗
PubMed1991

Estrogen-insulin synergism in induction of prolactin in growth hormone-producing cells.

Insulin suppresses growth hormone expression and induces prolactin (PRL) biosynthesis in MtT/S cells cultured in a medium supplemented with normal sera. Incorporation of [35S]amino acids into immunoprecipitable PRL became detectable at 15 h of culture with insulin (500 ng/ml) and increased up to 48 h. Northern blot hybridization demonstrated a concurrent induction of PRL mRNA. However, insulin failed to induce PRL in a medium supplemented with steroid-depleted sera. Either pre- or cocultivation of cells with 10 pM to 10 nM 17 beta-estradiol (E2), which did not induce PRL by itself, restored the insulin-mediated PRL biosynthesis in a dose-dependent manner. Diethylstilbestrol was as effective as E2, whereas testosterone, progesterone and corticosterone were without effect. The E2 action was partially suppressed by tamoxifen. These results suggest that estrogen is required for the insulin-mediated induction of PRL biosynthesis in MtT/S cells.

Animals↗
PubMed1991

Assignment of the human granulocyte colony-stimulating factor receptor gene (CSF3R) to chromosome 1 at region p35-p34.3.

The gene for the granulocyte colony-stimulating factor (G-CSF) receptor (CSF3R) was localized on the p35-p34.3 region of human chromosome 1 by in situ hybridization using human G-CSF receptor cDNA as the probe. Polymerase chain reaction using oligonucleotides specific for the human CSF3R produced a specifically amplified DNA fragment with DNA from mouse A9 cells that contained human chromosome 1 but not other human chromosomes. Localization of the CSF3R on chromosome 1 was further confirmed by the spot-blot hybridization of sorted human chromosomes.

Animals↗
PubMed1991

Application of Doppler color flow imaging to determine valve area in mitral stenosis.

This study was undertaken to examine whether Doppler color flow imaging could accurately estimate the valve area in mitral stenosis. Doppler color flow assessments were performed in both an in vitro model and in 30 patients with mitral stenosis undergoing cardiac catheterization. In the experimental Doppler study using a circuit model, color jet width correlated well with actual orifice diameter (r = 0.99). In the clinical Doppler study, the mitral valve orifice was assumed to be elliptic and the mitral valve area was calculated from the following equation: (pi/4) (a x b), where a = color jet width at the mitral valve orifice in the apical long-axis view (short diameter) and b = the width in the 90 degrees rotated view (long diameter). Mitral valve area was also determined by two-dimensional echocardiography and the pressure half-time method, and the results for all three noninvasive methods were compared with those obtained at cardiac catheterization. By Doppler color flow imaging, mitral valve area could be determined in all patients and there was a significant correlation between the Doppler jet and catheterization estimates of mitral valve area (r = 0.93). Valve area determined by two-dimensional echocardiography correlated well with catheterization measurements in 26 patients (r = 0.84). However, the area could not be determined in 4 (13%) of the 30 patients because of technical problems. Although there was a fair correlation between the valve area determined by the pressure half-time method and catheterization (r = 0.79), this method tended to overestimate valve area in patients with aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1991

Granulocyte colony-stimulating factor and its receptor.

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein of Mr of about 20,000, which stimulates proliferation and differentiation of progenitor cells of neutrophils. Recent clinical application of G-CSF has proven that this hormone is effective in treatment of patients suffering from neutropenia. In the last few years, the biochemical and molecular nature of the G-CSF receptor has been characterized. The G-CSF receptor is a glycoprotein of Mr 100-130,000, and is expressed on the cell surface of various myeloid cells. A homodimer of this polypeptide can bind G-CSF with a high affinity, and transduce G-CSF-triggered growth signals into cells. Its extracellular domain contains a sequence of about 200 amino acids which can be found in various cytokine receptors. In addition, it contains an immunoglobulin-like domain and three fibronectin type III domains. The overall structure of the beta-chain (gp130) of the interleukin 6 receptor was found to be very similar to that of the G-CSF receptor.

Amino Acid Sequence↗
PubMed1991

Evaluation of EC-IC bypass for patients with atherosclerotic occlusive cerebrovascular disease: clinical and positron emission tomographic studies.

The authors report clinical evaluations of extracranial-intracranial (EC-IC) bypass surgery for patients presenting with misery perfusion on positron emission tomography (PET) due to atherosclerotic occlusive cerebrovascular disease. Seven patients underwent PET both before and after undergoing EC-IC bypass surgery. Three of the 7 patients had transient ischaemic attacks (TIAs) and 4 had minor strokes. Five of the 7 had unilateral superficial temporal-middle cerebral artery (STA-MCA) anastomosis, one had bilateral STA-MCA anastomoses and one had STA-MCA anastomosis on one side and carotid endarterectomy on the other side. PET showed postoperative improvement in regional cerebral blood flow and metabolism in 5 of the 7 patients. In the remaining 2 patients, one showed no remarkable changes on PET and the other showed exacerbation on PET due to postoperative cerebral infarction. All three patients who had TIAs had no further TIAs after surgery. Two of the 3 patients postoperatively showed improvement in misery perfusion on PET. In the 4 patients who had minor strokes, 2 showed clinical improvements. One of the 2 showed improvement not only in motor function but also in the higher cortical functions such as verbal and performance intelligence quotients. Changes on PET correlated to the clinical improvement in 4 of 7 patients. The EC-IC bypass is therefore effective in patients with haemodynamic hypoperfusion syndromes by improving the state of low perfusion.

Adult↗
PubMed1991

Production of monoclonal antibodies by the use of pH-dependent vesicular stomatitis virus-mediated cell fusion.

To explore an alternative fusion method to generate monoclonal antibody (MAb)-producing hybridomas, we have tested whether pH-dependent vesicular stomatitis virus (VSV)-mediated cell fusion is applicable for generation of hybridomas. VSV-mediated cell fusion induced by acid treatment resulted in several specific MAb-producing hybridomas, almost all of which stably produced MAbs. This method is quite simple and offers a potential alternative to other fusion methods. In addition, the fusogenic proteoliposomes prepared by the reconstitution of the solubilized glycoprotein of VSV were also demonstrated to have the ability to generate MAb-producing hybridomas by the same pH-dependent cell fusion.

Animals↗