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Biomedical subjects

N Nagata

Publications and source records attributed to N Nagata.

At least 235 records · Page 13Linked to original sources
PubMed1995

[Dissection of the pseudointima followed by lethal obstruction of the prosthetic graft--a case report].

One-year-old boy who previously had modified Van Praagh procedure for interruption of the aortic arch (Celoria-Patton type A) and double inlet left ventricle with ventriculoarterial discordance was admitted for progressive cyanosis. He underwent reconstruction of the left pulmonary artery and additional left common carotid-left pulmonary artery shunt. During this procedure, severe hypotension of the lower extremities and heart failure occurred for unknown cause. He died on the 7 postoperative day for lung bleeding with disseminated intravascular coagulopathy. Autopsy revealed dissection of the pseudointima and obstruction of the prosthetic graft (interposed between the main pulmonary artery and the descending aorta). This complication seems very rare but a great care should be taken when a prosthetic graft is manipulated later.

Aorta, Thoracic↗
PubMed1995

Mitral valve repair using continuous warm blood cardioplegia.

To achieve satisfactory mitral valve repair, we applied continuous warm blood cardioplegia to seven children with congenital heart disease associated with mitral valve insufficiency. All patients had mild to moderate mitral valve regurgitation before the operation. The competency of the mitral valve was assessed by injecting test solution into the left ventricle through the mitral valve orifice with the heart beating under warm blood perfusion into the aortic root proximal to the cross-clamp. Repair of the mitral valve was performed under normothermic cardiac arrest with continuous antegrade perfusion of warm blood cardioplegia. In all patients, these two procedures could be alternated with ease and safety simply by varying the potassium concentration of cardioplegia. While satisfactory valve repair was obtained with the initial procedure in 4 cases, repair was repeated twice in two and three times in one. There were no operative deaths and no complications directly related to the procedure. Postoperative echocardiography demonstrated good mitral valve function with none to trivial regurgitation in six patients (86%). Continuous warm blood cardioplegia is a useful and safe tool for mitral valve repair.

Child↗
PubMed1995

[Clinical studies in five cases of Swyer-James syndrome].

We encountered five patients with Swyer-James syndrome. All were men, and ranged in age from 20 to 70 years (mean, 41 years). Their chest X-ray films showed left unilateral hyperlucency. Examinations revealed bilateral involvement in 3 cases and irregularity of involved regions in 2 cases. Chest CT scans revealed the distribution and severity of affected regions in greater detail than did other radiologic exams. Delayed clearance of xenon is a sign of air trapping, which is characteristics of this syndrome. Thus, 133Xe inhalation scintigrams were useful to detect air trapping, especially when mediastinal shift was not apparent on chest X-ray films. Bronchial damage is believed to cause this syndrome, and the present findings support this view. It is noteworthy that all five of these patients were men, and that in all five the affected lung was on the left. Moreover, although "respiratory tract infection is considered to be a very important" factor, many patients had no history of airway infection in childhood. Thus, some congenital factor or factors may contribute to the development of this syndrome.

Adult↗
PubMed1994

Structural analysis of proteoglycan macrophage colony-stimulating factor.

Proteoglycan macrophage colony-stimulating factor (PG-M-CSF) was recently reported as a high molecular type of macrophage colony-stimulating factor (M-CSF). We analyzed its structure by determining the expression of mutant M-CSF cDNA in Chinese hamster ovary cells. PG-M-CSF contained two types of molecules, a homodimeric 150-200-kDa subunit and a heterodimeric form of a 43-kDa subunit and the 150-200-kDa subunit. The 150-200-kDa subunit carries a chondroitin sulfate chain, and its amino-terminal amino acid sequence was identical to that of the 43-kDa subunit, which is known to form the conventional M-CSF molecule (85-kDa M-CSF). The results obtained with the carboxyl-terminal deleted mutants showed that the PG-M-CSF-specific 150-200-kDa subunit had a large part of the precursor sequence at its carboxyl terminus removed in the 43-kDa subunit by proteolytic processing. The expression of mutagenized cDNA, in which Arg220 was replaced by an alanine residue, resulted in the disappearance of the 43-kDa subunit but not that of the 150-200-kDa subunit, indicating that Arg220-Pro-Pro-Arg is essential to process PG-M-CSF to 85-kDa M-CSF. Truncated mutation analysis showed that the carboxyl terminus of the 150-200-kDa subunit lay downstream of Arg412. We also showed that the chondroitin sulfate binding site in the 150-200-kDa subunit was Ser277, since conversion of Ser277 to the alanine residue resulted in complete loss of the chondroitin sulfate substitution.

Amino Acid Sequence↗
PubMed1994

Experimental carcinogenesis in the rat intestine induced by two different carcinogens--evaluation of carcinogenic action and its effect on ornithine decarboxylase activity.

Carcinogenesis in the rat intestine induced with 1,2-dimethylhydrazine (DMH), N-methyl-N-nitrosourea (MNU), and their combinatorial use was studied. Intestinal tumors, including both adenoma and adenocarcinoma, were induced in all the rats given the carcinogens. The tumor frequently occurred in the intestinal tract extending from the duodenum to the colon in the DMH treated group. In the MNU treated group, the tumor occurred in the colon, especially on the distal side. Distribution of tumors in the group treated with both carcinogens was similar to that seen in the MNU-treated group. Neither obvious macroscopic nor histological differences were observed between groups treated with these carcinogens. In addition, we investigated the effect of carcinogens on ornithine decarboxylase (ODC) activity in rat colon. Tumor tissues showed a remarkably high level of enzyme activity compared with the normal-appearing mucosa, and there was a correlation between the level of the ODC activity and the histological grade of malignancy. ODC activity in the normal-appearing mucosa of the carcinogens-treated rats was significantly higher than that of control rats, and the number of tumors per rat was correlated with the level of ODC activity. These results indicate that mucosal ODC may be a pertinent biological marker for local carcinogenic activity.

1,2-Dimethylhydrazine↗
PubMed1994

Direct interaction of proteoglycan macrophage colony-stimulating factor and basic fibroblast growth factor.

The proteoglycan form of macrophage colony-stimulating factor (PG-M-CSF), but not M-CSF with a molecular weight of 85 kD (85-kD M-CSF), bound to immobilized basic fibroblast growth factor (bFGF), and, conversely, bFGF bound to immobilized PG-M-CSF, but not to the 85-kD M-CSF. PG-M-CSF has an additional amino acid sequence at its carboxyl terminus (part of a precursor sequence that is removed in 85-kD M-CSF by proteolytic processing) and it has one or two chondroitin sulfate glycosaminoglycan chains at the carboxyl terminus. Enzymatic removal of the chondroitin sulfate chain from PG-M-CSF had no effect on the binding between PG-M-CSF and bFGF. Ligand blotting analysis with radioiodinated bFGF showed that bFGF specifically bound to the polypeptide that corresponded to the carboxyl terminus of PG-M-CSF and was produced in Escherichia coli transfected with its gene. The exogeneous addition of heparan sulfate, which has strong affinity for bFGF, efficiently inhibited the binding between PG-M-CSF and bFGF. These results show that PG-M-CSF binds bFGF through its carboxyl terminal peptide and that the binding sites for PG-M-CSF and heparan sulfate on bFGF are located close together. PG-M-CSF also significantly reduced the mitogenic action of bFGF on Balb/c 3T3 mouse fibroblastic cells. Therefore, we conclude that PG-M-CSF not only binds bFGF, but also neutralizes the activity of the growth factor.

3T3 Cells↗
PubMed1994

Dystrophin-related protein is found in the central nervous system of mice at various developmental stages, especially at the postsynaptic membrane.

Dystrophin deficiency is known to be the cause of X-linked Duchenne muscular dystrophy (DMD). A recently cloned B3-cDNA shares 80% homology with the C-terminus and actin-binding portion of dystrophin. This autosome-derived gene product is called dystrophin-related protein (DRP). DRP is known to exist in fetal muscles even in mdx mice, an animal model for X-linked DMD, but not in mature mouse muscles. We raised a polyclonal antibody against a B3-unique amino acid sequence (Ab-LDP) and investigated the existence and distribution of DRP in the central nervous system (CNS) tissues of mdx and normal control B10 mice at various stages of development using immunoblotting and immunohistochemical methods. The former shows that DRP exists in the CNS of both B10 and mdx mice, regardless of the developmental stage, with the exception that the 420 kDa DRP band of the 15-day fetus is faint. In immunohistochemical studies, the choroid plexus, some neurons, glial cels, pia mater, and blood vessels were stained with Ab-LDP. Staining intensity did not differ between B10 and mdx mice or between developmental stages except that the 15-day fetus stained only faintly. This is in contrast to the results obtained for muscles in which DRP localized to muscle membrane in embryo decreases and is assembled at the neuromuscular junction in adults. In addition, an electron microscopic study on the cerebral cortex from adult B10 mice was also performed and revealed Ab-LDP staining of the postsynaptic membrane of dendrite and the rough endoplasmic reticulum of neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation. Complete prevention of recurrence of autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor.

MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells and show a recurrence of autoimmune diseases within 5 mo of conventional allogeneic bone marrow transplantation. We recently have found that the MHC preference exists between hemopoietic stem cells and stromal cells; when bones are engrafted, donor-derived stromal cells present in the engrafted bones can migrate into the recipient bone marrows, which are replaced with both donor-derived stromal cells and hematopoietic cells. Based on these findings, we attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the transplantation of both bone marrow cells and bone (as a source of stromal cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6 bone marrow cells plus bone grafts. The mice survived more than 48 wk after this treatment. Immunohistologic studies revealed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as lupus nephritis and rheumatoid arthritis. Sera from these mice showed normal levels of circulating immune complexes and rheumatoid factors. Normal functions of both T cells and B cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition, to our surprise, spleen cells from treated mice showed completely normal in vitro primary anti-SRBC responses. These results indicate that stromal cells in allogeneic bone marrow transplantation play a crucial role not only in the prevention of graft failure but also in the successful cooperation among APCs, T cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of interstitial pneumonia or fatty liver due to the side effects of radiation, it should be noted that this strategy allows a reduction in the radiation dose (9.5 Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any symptoms of autoimmune diseases.

Animals↗
PubMed1994

Focal segmental glomerular sclerosis, a type of intractable chronic glomerulonephritis, is a stem cell disorder.

The etiopathogenesis of focal and segmental glomerular sclerosis (FGS) remains unknown. Using a new animal model for FGS (FGS mouse), we demonstrate here that bone marrow transplantation from normal mice to FGS mice with a high grade of proteinuria (+ + +) ameliorates FGS, and that the transplantation of bone marrow cells or purified hemopoietic stem cells (HSCs) from FGS mice induces FGS in normal mice. These findings strongly suggest that FGS is a stem cell disorder; the abnormalities may be genetically programmed at the level of HSCs.

Animals↗
PubMed1994

Role of mesenchymal cells in the neovascularization of the rabbit phallus.

The neovascularization of the rabbit phallus at ages between prenatal days 15 and 21 was investigated by light- and electron microscopy, computer-aided light microscopic reconstruction, and immunocytochemistry. The phalli are embedded by an abundance of mesenchymal cells, which are in contact with the neighboring ones or with the endothelial lining of growing capillaries. They often form solid cell cords that eventually make contact with the growing capillaries. The computer-aided reconstruction of the serial light micrographs reveals that these cell cords are involved in connecting the adjacent capillaries. The incorporation of such mesenchymal cell projections into the endothelial lining, occasionally conjugated with simple attachment devices, is frequently observed by transmission and scanning electron microscopy. The contact areas between the mesenchymal and endothelial cells show immunoreactions of fibronectin. These results indicate the successive transformation of mesenchymal cells to endothelial cells of the growing capillaries. As endothelial cells of the growing capillaries show mitotic proliferation, such vasoformative mesenchymal cells seem to be involved in the acceleration of the neocapillarization of the rabbit phallus. Fibronectin actively produced in the mesenchymal cells may participate in their migration and the mechanical linkage with the endothelial cells.

Animals↗
PubMed1994

Glucocorticoid regulation of calcitonin receptor in mouse osteoclast-like multinucleated cells.

Abundant multinucleated cells (MNCs) are formed in cocultures of mouse osteoblastic cells and marrow cells in the presence of 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3], and these cells have the properties of osteoclasts (OCs). In this study using the mammalian OCs, we tried to clarify the role of glucocorticoids (GCs) in calcitonin receptors (CTR) and CT-responsive cAMP production in OCs. Dexamethasone (DEX) dose and time dependently enhanced the specific binding of [125I]salmon calcitonin (sCT). When the MNCs were preincubated with DEX for 24 h, the effect was evident at 10(-9) M and the maximum effect was obtained at 10(-7) M. The effect developed over 12-48 h at doses of 10(-9) and 10(-6) M DEX. The numbers of CTR-positive mononuclear cells and MNCs were not altered by the DEX treatment. Prednisolone and triamcinolone reproduced the DEX effect, but 17 beta-estradiol, progesterone, testosterone, aldosterone, and 1 alpha, 25(OH)2D3 did not. RU486, a GC receptor antagonist, attenuated the effect of DEX to enhance the specific binding of [125I]sCT. From a Scatchard plot analysis, DEX enhanced CTR number (212 +/- 64%) with a minimal change in the affinity to sCT. Autoradiographic studies using [125I]sCT showed that DEX enhanced the density of the grains on the tartrate-resistant acid phosphatase (TRAP)-positive MNCs and mononuclear cells, but not on other types of cells. DEX preincubation also enhanced sCT-stimulated but not prostaglandin E2- or forskolin-stimulated cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of glycyrrhizin, cyclosporin A, and tumor necrosis factor alpha on infection of U-937 and MRC-5 cells by human cytomegalovirus.

Reactivation of latent or persistent human cytomegalovirus (HCMV) infection of monocytes or macrophages occurs under immunosuppressive conditions. We investigated the effect of glycyrrhizin (GL), cyclosporin A (CsA), and tumor necrosis factor-alpha (TNF-alpha) on the viral DNA synthesis and antigen expression of HCMV in U-937 and MRC-5 cells. Although GL inhibited the viral antigen expression of HCMV in human monocytic cell line U-937 and human embryonic lung cell line MRC-5 in the study, as determined by flow cytometry and immunofluorescence assay, immediate early HCMV DNA was detected by the polymerase chain reaction. CsA or TNF had no inhibitory effect on HCMV in U-937 or MRC-5 cells. The HCMV infection model with U-937 or MRC-5 cells is of use for clarifying not only the mechanism of persistent infection but also the anti-HCMV effect of chemical agents.

Antigens, Surface↗
PubMed1994

Analysis of human cytomegalovirus-infected peripheral blood mononuclear cells from infants with liver dysfunction by flow cytometry and the polymerase chain reaction.

Perinatal human cytomegalovirus (HCMV) infection often involves the hepatobiliary tract, but infected individuals usually remain asymptomatic. We investigated the role of CD8+ lymphocytes in 13 infants with liver dysfunction associated with perinatal HCMV infection. In three patients more than 40% of CD8+ cells were positive for HCMV immediate early antigen (IEA) and late antigen (LA) by flow cytometry after selection of T lymphocytes subpopulations. In the other 10 infants, 20% to 30% of CD8+ cells were positive for HCMV IEA and LA. HCMV IE DNA was detected in CD8+ cells from one infant, in CD4+ cells from one infant, and in both CD4+ and CD8+ cells from three infants. HCMV infection of CD8+ cells may play an important role in the process of perinatal primary infection.

Antigens, Viral↗
PubMed1994

Increased cell surface expression of a newly identified heterodimer on activated blastic T cells.

A hybridoma (F6C7) was established by fusing NS1 cells with spleen cells of MRL/Mp-+/+ (MRL/+) mice suffering from lpr-GVHD. This F6C7 mAb (IgG2b, kappa) stains a broad spectrum of blood cells at varying intensities in mice and rats. In normal (BALB/c) mice, granulocytes and B cells are highly positive for F6C7-reactive Ag (F6C7-Ag). Thymocytes and peripheral (CD4+ and CD8+) T cells show negative to low intensities. These staining profiles are similar in C57BL/6, AKR/J, C3H/HeJ, and MRL/+ mice. When spleen cells were activated in vitro, a blastic cell population of autoactivated CD4+ and CD8+ T cells showed increased F6C7-Ag expression. Alloactivated CD4+ blastic T cells also showed increased expression of F6C7-Ag, whereas alloactivated CD8+ blastic T cells as well as Con A-activated CD4+ and CD8+ blastic T cells remained at the level of small (nonblastic) cells. These findings suggest that the surface expression of F6C7-Ag is up-regulated in some activation processes of T cells, particularly in autoactivation. Young (2-month-old) MRL/Mp-lpr/lpr (MRL/lpr) mice show staining profiles of F6C7-Ag similar to those of normal mice, except that many more blastic (CD4+ and CD8+) T cells show high F6C7-Ag expression than those of normal mice. A small but significant number of CD4+F6C7-Ag(high) and a much higher number of CD8+F6C7-Ag(high) blastic T cells were observed in the spleen cells of MRL/+ mice suffering from lpr-GVHD. These blastic T cells may exert autoreactivity and participate in the initiation of autoimmune diseases, lymphadenopathy, and lpr-GVHD. Immunoprecipitation and SDS-PAGE revealed that F6C7-Ag is a heterodimer comprised of approximately 78- and 70-kDa molecules without disulfide bonds.

Animals↗
PubMed1994

Development of a transcutaneous blood-constituent monitoring method using a suction effusion fluid collection technique and an ion-sensitive field-effect transistor glucose sensor.

The paper describes a method for the transcutaneous monitoring of blood constituents. It combines the use of a suction effusion fluid (SEF) collecting technique with a silicon on sapphire/ion-sensitive field-effect transistor (SOS/ISFET) biosensor. SEF is directly collected by a weak evacuation through skin from which the stratum corneum has been removed. An SEF collecting cell with a stainless-steel mesh at the bottom is kept in a weak vacuum condition, and SEF is sucked up through the mesh and deposited in a reservoir above. An ISFET glucose sensor is able to detect glucose concentrations in very small SEF samples through the use of two small ISFETs and an immobilised enzyme membrane. The reliability of transcutaneously obtained SEF was first confirmed in an experiment using rabbits. A clinical analyser was used to determine levels of glucose, urea nitrogen and creatinine in SEF obtained transcutaneously; these results are compared with results obtained by the same analyser directly from sera. The ISFET glucose sensor was successfully tested on human subjects for the monitoring of blood glucose levels. During these tests, glucose level changes in the SEF followed actual blood glucose level changes with a slight time delay. Results suggest the feasibility of non-invasive, transcutaneous monitoring of low molecular weight substances in the blood without the use of ordinary blood sampling.

Animals↗
PubMed1994

Leiomyoblastoma causing acute gastric outlet obstruction in an infant.

A 1-year-old boy had acute gastric outlet obstruction, the cause of which was a prepyloric submucosal mass. The mass and the ulcerated overlying mucosa were excised. The histological diagnosis was leiomyoblastoma with parenchymatous hemorrhage. Apparently, he is the youngest patient reported to have this disease.

Acute Disease↗
PubMed1994

Monoclonal antibody-based enzyme-linked immunosorbent assay for glycyrrhizin and its aglycon, glycyrrhetic acid.

Monoclonal antibodies (MoAbs) specific for glycyrrhetic acid (GA) were prepared and characterized. Obtained MoAbs (AGA-1, AGA-3, and AGA-6) reacted with GA dose-dependently, but not with glycyrrhizin (GL), carbenoxolone, and steroids. Next, an enzyme-linked immunosorbent assay (ELISA) system using AGA-1 was established. The standard curve showed good linearity between 0.01 and 1000 ng/ml of GA, and the detection limit was 5 pg/ml. Recovery, and intra- and interassay variations of this assay system was satisfactory. GL was also measurable quantitatively after acid-hydrolysis of the samples. The developed ELISA system would be useful to determine GL and GA in biological samples or drugs as an alternative method to high performance liquid chromatography (HPLC).

Antibodies, Monoclonal↗