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Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 289 records · Page 16Linked to original sources
PubMed1996

Ten-year experience with the Carpentier-Edwards pericardial xenograft in the tricuspid position.

We reviewed the cases of 66 patients who underwent 67 tricuspid valve replacements with Carpentier-Edwards pericardial xenografts between April 1985 and January 1994. Average patient age at time of operation was 52 years (range 8 to 71 years). Concomitant mitral or aortic valve replacements were performed in 46 patients. There were 10 operative deaths and 6 late deaths. Actuarial survival at 9 years was 75.4% +/- 5.7%. Prosthetic valve endocarditis occurred twice in one patient. Reoperations for tricuspid regurgitation and for concomitant procedures (maze operation and repair for leak of the mitral prosthesis) were performed in two patients. In both cases, examination of the explanted prostheses showed that the tricuspid regurgitation was the result of nonstructural dysfunction caused by fibrous pannus formation on the cusps of the ventricular side. Among the survivors, 47 patients (92%) were in functional class I or II. Prosthetic valve function was studied by color Doppler echocardiography. Among 38 patients, tricuspid regurgitation more than grade 3/4 or transprosthetic gradient more than 5 mm Hg was found in 11. One patient had right heart failure and the others had no symptoms. In 10 years of experience with the Carpentier-Edwards pericardial xenograft, mortality and morbidity after tricuspid valve replacement were satisfactory. Echocardiographic examination revealed subclinical prosthetic dysfunction in 35% of patients who were followed up for longer than 5 years, however, and we believe that these patients should receive careful follow-up.

Adolescent↗
PubMed1996

Detection and identification of metabolites of microcystins formed in vivo in mouse and rat livers.

The hepatic metabolism of microcystins (MCs), potent cyclic peptide hepatotoxins produced by cyanobacteria, was studied by i.p. injection in mice and rats. An immunoaffinity purification method using an anti-MC-LR monoclonal antibody showed a remarkable effect on the removal of contaminants in the hepatic cytosol and enabled us to analyze MCs and their metabolites by HPLC and Frit-FAB LC/MS. At 3, 6, and 24 h post-injection of MC-RR, a small percent of the applied dose was detected in all of the mouse livers together with several metabolites. Among them, GSH and Cys conjugates of MC-RR were identified at 3 and 24 h, respectively, by comparison with the chemically prepared standards, indicating that the thiols of GSH and Cys nucleophilically bound to the Mdha moiety of MCs. Another metabolite was presumed to be formed by both epoxidation followed by hydrolysis and sulfate conjugation in the Adda moiety and GSH conjugation in the Mdha moiety. In rat livers, MC-LR showed almost the same behavior as that of MC-RR in mouse livers. These results suggest that the conjugation of GSH with MCs may play a role in the metabolic pathway leading to detoxification of MCs.

Animals↗
PubMed1996

Fas ligand in human serum.

The Fas ligand (FasL), a member of the tumor necrosis factor family, induces apoptosis in Fas-bearing cells. The membrane-bound human FasL was found to be converted to a soluble form (sFasL) by the action of a matrix metalloproteinase-like enzyme. Two neutralizing monoclonal anti-human FasL antibodies were identified, and an enzyme-linked immunosorbent assay (ELISA) for sFasL in human sera was established. Sera from healthy persons did not contain a detectable level of sFasL, whereas those from patients with large granular lymphocytic (LGL) leukemia and natural killer (NK) cell lymphoma did. These malignant cells constitutively expressed FasL, whereas peripheral NK cells from healthy persons expressed FasL only on activation. These results suggested that the systemic tissue damage seen in most patients with LGL leukemia and NK-type lymphoma is due to sFasL produced by these malignant cells. Neutralizing anti-FasL antibodies or matrix metalloproteinase inhibitors may be of use in modulating such tissue damage.

Animals↗
PubMed1996

Effects of myeloid cell growth factors on alkaline phosphatase, myeloperoxidase, defensin and granulocyte colony-stimulating factor receptor mRNA expression in haemopoietic cells of normal individuals and myeloid disorders.

The mRNA expression of alkaline phosphatase (ALP), myeloperoxidase (MPO), defensin and G-CSF receptor (G-CSFR) in bone marrow cells of normal individuals and myeloid disorders, with or without in vitro stimulation by myeloid cell growth factors, i.e. G-CSF, GM-CSF and IL-3, were examined as markers for myeloid cell differentiation in both mononuclear cell (MNC) and polymorphonuclear cell (PMN) fractions. Without any stimulation, ALP mRNA was expressed only in PMNs, G-CSFR mRNA in PMNs were expressed stronger than in MNCs; both MPO and defensin mRNA were expressed to the same degree in both fractions. With stimulation, the ALP mRNA expression in both fractions was strongly enhanced by G-CSF, but the expression was inhibited by GM-CSF and/or IL-3. MPO mRNA expression was stimulated by G-CSF and/or GM-CSF in MNCs. G-CSFR mRNA expression was enhanced by G-CSF in both fractions. Defensin mRNA expression was inhibited by G-CSF. In cases of myelodysplastic syndrome and chronic myelogenous leukaemia which display a suppressed maturation of myeloid cells, our results demonstrated an almost normal response to these growth factors. Our results suggest that studies on these myeloid marker mRNA expressions would provide more knowledge about the differentiation state and cytokine reactivity of myeloid cells in normal individuals as well as various disorders.

Adult↗
PubMed1996

An aggressive nasal lymphoma accompanied by high levels of soluble Fas ligand.

Fas ligand (FasL), either in the membrane bound form or soluble form, has cytotoxic activity against Fas-expressing cells. We report a case of nasal lymphoma accompanied by liver damage and pancytopenia. The serum level of soluble FasL (sFasL) was very high on admission, but rapidly decreased to normal levels after chemotherapy for lymphoma. Liver damage and pancytopenia also improved with the decrease in serum sFasL. Since Fas is expressed on both hepatocytes and haemopoietic cells, these facts suggest that FasL was expressed on lymphoma cells and directly associated with pathogenesis of liver damage and pancytopenia through its cytotoxic activity.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

Fas-induced apoptosis, and diseases caused by its abnormality.

Homeostasis of multicellular organisms is controlled not only by proliferation and differentiation of cells but also by cell death. Physiological cell death mostly proceeds by apoptosis, a process which includes condensation and segmentation of the nuclei and cytoplasm, and often extensive fragmentation of chromosomal DNA into nucleosome units. Molecular and cellular characterization of Fas, a cell-surface protein recognized by cytotoxic monoclonal antibodies, has led to its definition as a receptor for a Fas ligand (FasL). FasL binds to Fas, which results in target cell apoptosis. A family of cysteine proteases seems to be sequentially activated during the Fas-mediated apoptosis. The phenotypes of the loss-of-function mutants of Fas and FasL indicate that this system is involved in T cell-mediated cytotoxicity, in down-regulation of immune responses, and probably in the turnover of senescent cells. Malfunction of the Fas system causes hyperplasia in peripheral lymphoid organs and the liver, accelerating autoimmune diseases and tumorigenesis, whereas exaggeration of the system leads to tissue disruption.

Amino Acid Sequence↗
PubMed1996

High concentrations of immunoreactive inhibin in the plasma of mares and fetal gonads during the second half of pregnancy.

Plasma concentrations of immunoreactive (ir)-inhibin were measured in seven pregnant mares from around Day 140 of gestation to Day 2 after parturition using a heterologous bovine-based radioimmunoassay (RIA). Concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol-17 beta, progesterone and relaxin were also measured in the same samples. A marked increase in plasma concentrations of ir-inhibin, FSH and LH occurred between Day 220 and Day 300 of gestation but the concentrations of all three hormones returned to baseline by about Day 320 (three weeks before parturition). In contrast, circulating concentrations of the three placental hormones, oestradiol-17 beta, progesterone and relaxin, increased during the final weeks of pregnancy and then decreased markedly to basal values within two days of parturition. There was a positive correlation between circulating concentrations of ir-inhibin and FSH (r = 0.75, P < 0.01) rather than the expected negative correlation. ir-inhibin was not detected in homogenates obtained at Day 190 of pregnancy and form term placenta, but high concentrations of ir-inhibin were present in homogenates of fetal and newborn gonads. Despite the high concentrations of ir-inhibin in these homogenates, they failed to exert any suppressive bioactivity on FSH secretion by rat pituitary cells cultured in vitro. Furthermore, immunohistochemical staining revealed the presence of inhibin in the interstitial cells of equine fetal gonads at Day 190 of gestation. These findings demonstrate for the first time that high concentrations of ir-inhibin, LH and FSH are secreted into the peripheral circulation of the mare during the second half of pregnancy. However, ir-inhibin present in the plasma of pregnant mares appears to be biologically inactive. This hormone is not presumed to be of placental origin but it is proposed that either the enlarged fetal gonads or the maternal ovaries, or both of these organs, may be a source of inhibin in response to the coincident increase in circulating concentrations of LH and FSH.

Animals↗
PubMed1996

The binocular fusion of human vision on stereoscopic displays--field of view and environment effects.

This paper points out that the fusional limits of binocular stereoscopic viewing are an important factor, not only determining the reproduction range of stereoscopic images, but also the conformity between the stereoscopic display and stereoscopic vision. Experimental results showed that fusional limits increase in proportion to the field of view angle, and that they are affected not only by the size of the viewing target, but also by the effects that the environment has on the target. These findings explain the differences between binocular vision in real space and binocular vision in a stereoscopic display. Finally, the conditions under which observers are able to view images of stereoscopic displays without excessive visual strain are discussed.

Attention↗
PubMed1996

Stereopsis with normal and reversed binocular parallax using a head mounted display in normal and strabismic subjects.

A virtual reality system using a head mounted display (HMD) was constructed for the purpose of finding out how human beings perceive the three-dimensional world. Four ophthalmologically normal subjects and 4 strabismic patients (2 with exotropia, 2 with esotropia) were examined. They wore the HMD and viewed some familiar objects (e.g. human face) and an unfamiliar object (e.g. tangled ropes) under normal parallax, reversed parallax, and monocular conditions. They also attempted the ring and hook test under each condition. They recognized the normal familiar objects under each condition, but some normal subjects were confused when they perceived unfamiliar objects. The normal subjects barely passed the ring and book test under the reversed parallax condition. The results of the strabismic subjects showed change under each condition. Stereoptic ability in normal and strabismic patients were considered based on the above. Also considered were some stereoptic keys, binocular parallax, monocular stereoptic keys such as shadows, shades, texture, etc., the near reflex and the fact that the objects were familiar. It was found that the strabismic patients used monocular stereoptic keys more than normal people to supplement their lack of binocular parallax perception.

Adult↗
PubMed1996

Detection of microcystins, a blue-green algal hepatotoxin, in drinking water sampled in Haimen and Fusui, endemic areas of primary liver cancer in China, by highly sensitive immunoassay.

An epidemiological survey for the causes of a high incidence of primary liver cancer (PLC) in Haimen city, Jian-Su province and Fusui county, Guangxi province in China, found a close correlation between the incidence of PLC and the drinking of pond and ditch water. With an aim to clarify whether microcystins (MC), a hepatotoxic peptide produced by water bloom algae, contaminate the drinking water in the endemic areas of PLC in China, a highly sensitive enzyme-linked immunosorbent assay with a detection limit of 50 pg/ml, was introduced to monitor the MC. Three trials to survey the drinking water were carried out in 1993-1994. Samples, 1135 in total, were collected from different sources such as: ponds, ditches, rivers, shallow wells and deep wells in Haimen city. The first survey in September 1993 found that three out of 14 ditch water specimens were positive for MC, with a range of 90-460 pg/ml. Several toxic algae such as Oscillatoria agardhii were present in some of the ditches. In the second trial, samples were collected from five ponds/ditches, two rivers, two shallow wells and two deep wells monthly for the whole year of 1994. These data showed that MC was highest in June to September, with a range of 62-296 pg/ml. A third trial on the 989 different water samples collected from the different types of water sources in July 1994 revealed that 17% of the pond/ditch water, 32% of the river water, and 4% of the shallow-well water were positive for MC, with averages of 101, 160 and 68 pg/ml respectively. No MC was detected in deep well water. A similar survey on 26 drinking water samples in Fusui, Guangxi province, demonstrated a high contamination frequency of MC in the water of ponds/ditches and rivers but no MC in shallow and deep wells. These data support a hypothesis that the blue-green algal toxin MC in the drinking water of ponds/ditches and rivers, or both, is one of the risk factors for the high incidence of PLC in China. Based on previous findings on the epidemiology of PLC and the present results from the mass screening of MC in the drinking water, an advisory level of MC in drinking water was proposed to below 0.01 microg/l. The combined effect of a potent hepatocarcinogen AFB1 and an intermittent intake of MC in drinking water in the summer season was discussed as an etiology of PLC.

Antibodies, Monoclonal↗
PubMed1996

A novel phenylserine dehydratase from Pseudomonas pickettii PS22: purification, characterization, and sequence of its phosphopyridoxyl peptide.

A novel phenylserine dehydratase [EC 4.2.1.-], which catalyzes the deamination of L-threo-3-phenylserine to yield phenylpyruvate and ammonia, was purified to homogeneity from a crude extract of Pseudomonas pickettii PS22 isolated from soil. The enzyme was a monomer having a molecular mass of about 38 kDa and contained 1 mol of pyridoxal 5'-phosphate per mol of enzyme. The enzyme exhibited absorption maxima at 279 and 416 nm. No appreciable spectral change was observed over the pH range of 6.0 to 8.0. The maximal reactivity was obtained at about pH 7.5. The enzyme was highly specific for L-threo-3-phenylserine (Km, 0.21 mM). L-erythro-3-Phenylserine, L-threonine, L-serine, and D-serine were inert. The enzyme was inhibited by phenylhydrazine, hydroxylamine, p-chloromercuribenzoate, and HgCl2, but not by L-isoleucine, L-threonine, or L-serine. AMP, ADP, and ATP did not affect the enzyme activity. The N-terminal amino acid sequence was not similar to those of biosynthetic and biodegradative L-threonine dehydratases and L-serine dehydratases. The isolated tryptic phosphopyridoxyl peptide, however, contained a pyridoxal 5'-phosphate-binding consensus amino acid sequence of amino acid dehydratases.

Amino Acid Sequence↗
PubMed1996

Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis.

OBJECTIVES: To investigate Fas in peripheral lymphocytes from HIV-1-positive patients at different disease stages with respect to the extent of apoptosis. DESIGN: The study included analysis of Fas involvement in T-cell apoptosis observed during HIV-1 infection. Because ligation of Fas can result in costimulation of proliferation or the induction of apoptosis in uninfected cells, we evaluated the effect on T cells of Fas activation by monoclonal antibodies (MAb) of different specificity from both UB2 and CH11 clones and activation by the Fas ligand (Fas-L). METHODS: Fas was measured by FACS in peripheral blood and in phytohaemagglutinin (PHA)-driven cultures derived from 59 HIV-1-positive individuals with different Centers for Disease Control and Prevention stages. The percentage of apoptotic cells was detected by propidium iodide cell staining. The effect of Fas ligation was assessed in peripheral T cells from patients and healthy controls by a proliferative test measuring the 3H-thymidine uptake. RESULTS: FACS analysis revealed that Fas was predominantly expressed in advanced disease, although it was promptly exposed in PHA cultures from asymptomatic individuals. In several instances, Fas overexpression was associated with substantial subdiploid DNA content in cells from severely lymphopenic patients. The proliferative assay showed a significant inhibition of 3H-thymidine uptake in T cells from all patients following Fas ligation by the immunoglobulin (Ig) G1 MAb from the UB2 clone. This was in contrast to the apparent cell activation detected in controls and the weak suppression observed in Fas-positive cell lines. In addition, the IgM anti-Fas and recombinant Fas-L concentrations inducing a moderate inhibition of fresh T cells from controls strongly depressed the proliferative rate of cells from patients. CONCLUSIONS: Our data suggest that Fas overexpression parallels the progression of the disease and that the increased susceptibility of T cells from HIV-1-infected individuals to undergo apoptosis may include a Fas pathway. Functionally exhausted T cells in advanced HIV-1 infection are primed to apoptosis because of their high sensitivity to Fas stimulation even using the IgG1 MAb, which is unreactive to the death domain of Fas. This suggests that the increased sensitivity of Fas is apparently unrelated to its trimeric ligation and supports the hypothesis that Fas pathway plays a role in increasing the lymphocyte apoptosis during the disease.

Adult↗
PubMed1996

Immunogenicity of peptides coupled with multiple T-cell epitopes of a surface protein antigen of Streptococcus mutans.

A surface protein antigen (PAc) of Streptococcus mutans, in particular the A-region of the molecule, has been noted as a possible target of effective dental caries vaccine. We have previously shown that two peptides of 19 amino acids (residues 361-379, NAKATYEAALKQYEADLAA, and residues 301-319, ANAANEADYQAKLTAYQTE), which correspond to parts of the A-region, contain both T- and B-cell epitopes for the induction of cross-reacting antibodies to the PAc. In this study, for development of an appropriate antigen as a peptide vaccine for use in prophylactic dentistry, we analysed in detail the localization of the T- and B-cell epitopes of PAc(361-379) peptide and the T-cell epitope of PAc(301-319) peptide in B10 congenic mice. In four murine major histocompatibility complex (MHC) haplotypes (H-2f,d,a and k), PAc(361-377) peptide showed T- and B-cell epitopes forming a cluster. It was found that the antibody which was induced by the immunization with the peptide was strongly cross-reactive with recombinant (r)PAc. Meanwhile, PAc(305-318) peptide, recognised by five strains of mice of different MHC haplotypes (H-2f,d,a,k and s), also bore multiple T-cell epitopes. PAc(361-377) peptide coupled to PAc(305-318) significantly elevated cross-reacting antibody levels compared to immunization with PAc(361-377) only in four H-2 haplotypes. Moreover, a peptide with PAc(305-318) coupled to the N-terminal region of PAc(361-377) produced significant cross-reacting antibody against rPAc, even in B10.S mice which had not responded to immunization with PAc(361-379) peptide. Therefore, it was suggested that coupling among the peptides forming a cluster might be effective in increasing immunogenicity. These results may provide us with a useful strategy for the design of peptide-based vaccines for S. mutans in the future.

Amino Acid Sequence↗
PubMed1996

Endothelins contract guinea-pig pulmonary artery and enhance its adrenergic response via ET(A) receptors.

1. This study has pharmacologically characterized endothelin (ET) receptor subtype(s) mediating contraction and enhancement of adrenergic contraction in guinea-pig pulmonary artery. Isometric tension of the isolated endothelium-denuded ring preparations was measured in the presence of indomethacin (10(-5) mol/L) and N(G)-nitro-L-arginine methyl ester (L-NAME; 3 x 10(4) mol/L) to exclude a mechanism via endothelium, cyclo-oxygenase-generated eicosanoids and nitric oxide. 2. In the additional presence of tetrodotoxin (TTX; 3 x 10(-7) mol/L), ET-1 (10(-11)-10(-7) mol/L) concentration-dependently contracted the preparations. The rank order of potency to contract the preparations among ET receptor agonists was ET-1, sarafotoxin (STX)6b > ET-3 > IRL 1620, STX 6c. BQ-123 (7 x 10(-7)-7 x 10(-6) mol/L) concentrations-dependently shifted the concentration-contraction curve for ET-1 to the right in a parallel manner. Pretreatment with STX 6c (3 x 10(-7) mol/L for 30 min) did not significantly desensitize contractions to ET-1, ET-3 or IRL 1620 (P > 0.05; t-test, 10 d.f). 3. ET-1 (10(-10)-10(-9) mol/L) and STX 6b (10(-9)-10(-8) mol/L) significantly enhanced the electrical field stimulation-induced contraction in a BQ-123-sensitive manner (P < 0.05: t-test, 24-38 d.f), while ET-3 (10(-11)-10(-8) mol/L) and STX 6c (10(-11)-10(-7) mol/L) did not affect contractions. ET-1 (10(-11) mol/L) significantly enhanced contractions to exogenous noradrenaline in the presence of TTX (3 x 10(-7) mol/L) (P < 0.05; t-test, 16 d.f.). 4. These data indicate that the BQ-123-sensitive ET(A) receptor mediates both contraction and enhancement of adrenergic contractions in the guinea-pig pulmonary artery.

Animals↗
PubMed1996

Clinical implications of hypertrophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene.

OBJECTIVE: The disease-bearing genes for hypertrophic cardiomyopathy (HCM) in HCM families have been identified as the beta-myosin heavy chain, alpha-tropomyosin, and cardiac troponin T genes. Three HCM kindreds with three distinct point mutations in the alpha-tropomyosin gene had extensive clinical evaluations. DESIGN AND RESULTS: Single-strand conformation polymorphism gel analysis of polymerase chain reaction amplified products was used to capture each of the nine exons from the alpha-tropomyosin gene to identify mutations in 60 familial HCM patients. Two missense mutations in exon 2 (Ala63Val and Lys70Thr) and one missense mutation in exon 5 (Asp175Asn) were found in three unrelated HCM kindreds. These kindreds were the subject of clinical, electrocardiographic and echocardiographic studies. The morphological appearance of HCM was similar in the three kindreds. All the patients had severe hypertrophy of the left ventricle with asymmetrical septal hypertrophy during the early stage of the disease, which gradually progressed to dilatation of the left ventricle. Moreover, these kindreds showed similar disease penetrance, age of onset, and incidence of premature sudden death. The disease in these kindreds was severe and resulted in frequent sudden deaths. CONCLUSIONS: Among Japanese patients with familial HCM mutations in the alpha-tropomyosin gene are not as rare as reported, accounting for about 5% of all cases. These mutations are characterised by hypertrophy of the left ventricle which then progresses to dilatation and a high incidence of sudden or disease-related death.

Adult↗
PubMed1996

Evaluation of 6.5-mm BENT incision to reduce postoperative astigmatism.

We examined surgically induced astigmatism following 6.5-mm incisions between 9 and 12 o'clock (BENT incision) in 50 cases with cataracts who underwent phacoemulsification-aspiration and 6-mm intraocular lens implantation. The surgically induced astigmatism (n = 50) shifted to against-the-rule astigmatism (ATR; -0.03 +/- 0.95 dpt) 1 day after the operation and then tended to shift to with-the-rule astigmatism (WTR). The results of a group with preexisting ATR (> 2 dpt; n = 4) were similar to the results of the aforementioned group, whereas the results of a group (n = 7) with preexisting WTR (> 2 dpt) were different. Astigmatism in this group shifted to ATR of about 1.0 dpt. This study suggests that the BENT incision procedure can reduce both preexisting WTR > 2.0 dpt and preexisting ATR > 2 dpt.

Aged↗
PubMed1996

Comparison of changes in cardiac structure after treatment in secondary hypertension.

To investigate the role of aldosterone and the renin-angiotensin system in cardiac structure, we performed echocardiography in patients with secondary hypertension. The relation between blood pressure or hormonal influences and left ventricular hypertrophy has not been well established in secondary hypertension. Sixteen patients with primary aldosteronism and 11 with unilateral renovascular hypertension who had completely normalized blood pressure after operation or percutaneous transluminal angioplasty were evaluated by echocardiography before and after surgery or other interventional treatment. Blood pressure was not statistically different between the groups before treatment and was normalized after treatment in both groups. Left ventricular hypertrophy was mild in both groups before treatment, and its degree was not statistically different between the groups. At the end of the follow-up period, all parameters of primary aldosteronism and left ventricular mass index in patients with unilateral renovascular hypertension were significantly reduced. In patients with primary aldosteronism, changes in end-diastolic left ventricular internal dimension correlated positively with changes in left ventricular mass index (r=.58,P<.01). In patients with unilateral renovascular hypertension, changes in mean blood pressure and left ventricular mass index were significantly correlated (r=.77,P<.01). The expanded plasma volume induced by an excess of aldosterone and high blood pressure may play an important role in the increase of left ventricular mass in primary aldosteronism. In unilateral renovascular hypertension, high blood pressure mainly contributes significantly to increased left ventricular mass. Therefore, different factors may modulate the development of left ventricular hypertrophy in patients with secondary hypertension.

Adult↗