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Biomedical subjects

S Nagata

Publications and source records attributed to S Nagata.

At least 451 records · Page 25Linked to original sources
PubMed1993

Cytotoxicity induced by monoclonal antibody to alpha-fetoprotein coadministered with spleen cells of nude mice.

This paper describes an attempt to effectively induce antibody-dependent cell-mediated cytotoxicity (ADCC) in nude mice. A monoclonal antibody against alpha-fetoprotein, 80G, coadministered with spleen cells from other nude mice bearing HuH-7N (xenograft of human hepatoma cell line, HuH-7) significantly suppressed the growth of HuH-7N as compared to treatment with 80G alone. 80G with spleen cells from normal nude mice also had some suppressive effect. In contrast, no effect was observed with each spleen cells alone as well as 80G alone. These results suggest that further supply of effector cells could enhance ADCC activity in nude mice.

Animals↗
PubMed1993

Structure of 85 kDa subunit of human phosphatidylinositol 3-kinase analyzed by using monoclonal antibodies.

An 85 kDa subunit (p85 alpha) of phosphatidylinositol 3-kinase (PI-3K) has one SH3 and two SH2 regions [SH2(N) and SH2(C)], which direct protein-protein interaction. We have established eighteen hybridomas producing monoclonal antibodies against p85 alpha to study the structure-function relationship of this protein. Epitope mapping using a series of deletion mutants expressed in E. coli showed that the monoclonal antibodies bound to at least 5 distinct epitope regions, which were well dispersed on p85 alpha except for its carboxyl-terminus. Monoclonal antibodies against amino-terminal regions and polyclonal antibodies against carboxyl-terminal regions immunoprecipitated p85 alpha expressed in human cells and in E. coli. On the other hand, monoclonal antibodies against the central part of p85 alpha failed to immunoprecipitate p85 alpha efficiently; however, they could immunoprecipitate p85 alpha mutants with deletion of either the amino- or the carboxyl-terminal region. Similar results were obtained by immunocytochemistry using confocal microscopy. These results suggested that steric hindrance prevents binding of monoclonal antibodies to the central part of p85 alpha where SH2(N) is located. The SH2(N) may have a distinct function from SH2(C), which is located at the carboxyl-terminal region and has been shown to mediate the binding of PI-3K to activated growth factor receptors.

Animals↗
PubMed1993

Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic mutation due to an unstable DNA sequence.

The fragile X syndrome is the most common familial form of mental retardation. The mutation causing the syndrome is dynamic mutation due to an unstable DNA (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype of fragile X mutation individuals by Southern blot analysis. In the present study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus cells, of a fetus which was at risk of having fragile X syndrome. In the PstI assay, the Southern blot showed the typical pattern of a female carrier with the full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay showed that the EagI restriction site was not methylated on the mutated X chromosome of chorionic villi, but the sites were totally methylated in the brain and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous female carrier of the dynamic mutation involved in the fragile X syndrome.

Blotting, Southern↗
PubMed1993

Two cases of recurrent hepatic injury associated with early pregnancy: hCG on hepatocytes is a suspected target antigen for lymphocyte attack.

Two cases of recurrent hepatic injury which appeared in the first trimester of pregnancy were studied. Case 1 was a 35 year old woman, gravida 4, para 0, who suffered repeatedly from hepatic injury requiring induced abortions. The patient was healthy before the pregnancies and the plasma aminotransferases increased after 8 weeks gestation and promptly returned to normal after the abortions. No fluctuation of aminotransferases was observed in the menstrual cycle. A liver biopsy immediately after abortion showed spotty necrosis of hepatocytes with mononuclear cell infiltration. Most of the infiltrating cells were cytotoxic T cells that were directly in contact with hepatocytes. Numerous lymphocytic infiltrations were also found in the decidua of the uterine curettage material. The patient's lymphocytes showed conspicuous blast transformation in culture with human chorionic gonadotropin (hCG). The hCG was detected in close vicinity to the injured hepatocytes by immunostaining. Case 2 was a 23 year old woman, gravida 2, para 0, who underwent an induced abortion due to hepatic dysfunction in the first pregnancy. Although hepatic dysfunction reappeared from 10 weeks gestation during the second pregnancy, her health gradually improved with conservative therapy and resulted in a full-term delivery. She lacked allergies to drugs or foods and was healthy when she was not pregnant. These two cases suggest that some hepatotoxic materials appeared transiently in the first trimester. The results of Case 1 suggest strongly that hCG on the hepatocytes was recognized as an antigen and evoked lymphocytic attack.

Adult↗
PubMed1993

NADP(+)-dependent D-threonine dehydrogenase from Pseudomonas cruciviae IFO 12047.

NADP(+)-dependent D-threonine dehydrogenase (EC 1.1.1.-), which catalyzes the oxidation of the 3-hydroxyl group of D-threonine, was purified to homogeneity from a crude extract of Pseudomonas cruciviae IFO 12047. The enzyme had a molecular mass of about 60,000 Da and consisted of two identical subunits. In addition to D-threonine, D-threo-3-phenylserine, D-threo-3-thienylserine, and D-threo-3-hydroxynorvaline were also substrates. However, the other isomers of threonine and 3-phenylserine were inert. The enzyme showed maximal activity at pH 10.5 for the oxidation of D-threonine. The enzyme required NADP+. NAD+ showed only slight activity. The enzyme was not inhibited by EDTA, o-phenanthroline, alpha,alpha'-dipyridyl, HgCl2, or p-chloromercuribenzoate but was inhibited by tartronate, malonate, pyruvate, and DL-2-hydroxybutyrate. The inhibition by these organic acids was competitive against D-threonine. Initial-velocity and product inhibition studies suggested that the oxidation proceeded through a sequential ordered Bi Bi mechanism. The Michaelis constants for D-threonine and NADP+ were 13 and 0.12 mM, respectively.

Alcohol Oxidoreductases↗
PubMed1993

Rapid increase in plasma endothelin concentrations during percutaneous balloon dilatation of the mitral valve in patients with mitral stenosis.

OBJECTIVE: To investigate the relation between plasma concentrations of immunoreactive endothelin and haemodynamic variables before and after percutaneous transvenous balloon dilatation of the mitral valve. DESIGN: Prospective study. SETTING: National cardiovascular centre. PATIENTS: 25 patients with mitral stenosis and 26 healthy volunteers. MAIN OUTCOME MEASURES: Plasma concentrations of immunoreactive endothelin were measured in the pulmonary artery, left atrium, ascending aorta, and femoral vein before and after balloon dilatation of the mitral valve. RESULTS: Peripheral venous concentrations (mean (SD)) of endothelin were higher in the patients with mitral stenosis than in the healthy volunteers (1.76 (0.51) v 1.37 (0.45) pg/ml, p < 0.05) and they correlated with the mean left atrial pressure (r = 0.74, p < 0.01). Balloon dilatation of the mitral valve reduced the mean left atrial pressure without changing the mean right atrial pressure, systemic arterial pressure, heart rate, or cardiac index. Concentrations of plasma endothelin in the femoral vein increased from 1.76 (0.51) to 3.39 (2.46) (p < 0.01), 4.82 (2.34) (p < 0.001), and 2.43 (0.52) pg/ml (p < 0.05) at 15 and 30 minutes and 24 hours after the procedure. The concentration of endothelin in the pulmonary artery also increased from 1.85 (0.85) to 4.32 (1.58) pg/ml (p < 0.01) 30 minutes after the dilatation, whereas there were no appreciable changes in endothelin concentration in the left atrium or ascending aorta. CONCLUSIONS: Plasma endothelin concentrations were higher in patients with mitral stenosis than in healthy volunteers and the increase was proportional to left atrial pressure. After balloon dilatation of the mitral valve there was an abrupt rise in endothelin in the femoral vein and pulmonary artery but no change in left atrial or aortic blood samples. These findings suggest that endothelin may be another vasoactive substance involved in congestive heart failure.

Adult↗
PubMed1993

Characterization of renal aldosterone receptors in genetically hypertensive rats.

To investigate the aldosterone responsiveness of genetically hypertensive rats, we compared characteristics of renal cytosolic aldosterone receptors from the M strain of stroke-prone, spontaneously hypertensive rats (M-SHRSP) with normotensive Wistar-Kyoto rats (WKY). In M-SHRSP, blood pressure was elevated significantly at 6 wk of age, when their plasma aldosterone concentrations were similar to those in WKY. Decreases in urine volume and sodium excretion were also observed in M-SHRSP. At 10 wk of age, M-SHRSP plasma aldosterone concentrations became significantly higher than those in WKY. On the other hand, the concentration of renal cytosolic aldosterone receptors (type I, aldosterone specific) had already increased at 6 wk of age in M-SHRSP, with no difference in affinity, and levels remained increased thereafter. There were no significant differences in molecular weights or ionic charges of either "activated" or "non-activated" aldosterone-receptor complexes between M-SHRSP and WKY, indicating that the molecular properties were similar in both groups. These results suggest that the increased concentration of aldosterone receptors in the kidneys of M-SHRSP might increase their aldosterone responsiveness and contribute to the development of high blood pressure in these animals.

Animals↗
PubMed1993

Hemorrhagic and ischemic cerebrovascular complications of active infective endocarditis of native valve.

Cerebrovascular events complicate the management of infective endocarditis. The purpose of this study is to analyze clinical features of cerebrovascular complications in infective endocarditis and to establish the appropriate time schedule of chemotherapy and cardiosurgical intervention. We studied the clinical data of 123 patients with active infective endocarditis of native valves retrospectively. Thirty-three patients (18 males and 15 females, age 17-57 years) had cerebrovascular complications such as cerebral ischemia (n = 22) or intracranial hemorrhage (n = 11). The majority of complications (21 ischemic and 13 hemorrhagic episodes) occurred prior to or within 1 month after chemotherapy. Fatal neurological deterioration developed after cardiac surgery in 2 patients. Both of them needed emergency cardiac surgery, because of worsening hemodynamic state, which was performed within 5 days after cerebral embolic events. The remaining patients undertaking cardiac surgery did all survive; in whom there were chemotherapeutic intervals of 11 days after ischemic events or of 23 days after hemorrhagic events. These medical records suggest that early cardiosurgical intervention, if necessary, needs at least 2-3 weeks of preceding chemotherapy. In cases undergoing more than 1 month of chemotherapy, cerebrovascular complications may be well managed by medical treatment alone.

Adolescent↗
PubMed1993

Detection of enteroviral genome and its significance in cardiomyopathy.

Myocarditis is an important disease that can lead to dilated cardiomyopathy (DCM). Using the polymerase chain reaction (PCR), we examined whether viral genomes were present specifically in the hearts of viral myocarditis or DCM patients in our autopsy series and compared the results with their clinicopathological features. We applied three different criteria of myocarditis to fully describe the histological features. The presence of a viral genome was detected by PCR but was not specific in DCM or myocarditis. PCR might be helpful in the diagnosis of viral myocarditis, when combined with other clinical information.

Adult↗
PubMed1993

Transesophageal echocardiography for detecting intracardiac thrombi in embolic stroke.

The authors studied 56 patients with cardioembolic stroke to search for intracardiac thrombi by use of transesophageal and transthoracic echocardiography. Forty consecutive patients were examined within four weeks of stroke onset and the remaining 16 in the chronic stage. They also performed ultrafast computed tomography in 9 of them. Underlying heart disease was present in all subjects. Anticoagulant therapy had already been started in 29 at the time of examinations. Using their own criteria for echocardiography, they diagnosed intracardiac thrombus in 7 cases and valvular vegetation in 1. Six thrombi were located in the left atrial appendage, 4 of which were smaller than 10 mm in diameter. These small thrombi were not found by either transthoracic echocardiography or computed tomography. Transesophageal echocardiography appears to be superior to the other two methods, especially for detecting small intracardiac thrombi in the left atrial appendage.

Adult↗
PubMed1993

Immunohistochemical studies on small intestinal mucosa in Kawasaki disease.

To investigate the etiology of Kawasaki disease (KD), the cell surface phenotypes of mononuclear cells and enterocytes in the jejunal mucosa of KD were investigated in a case-control study. Sixteen Japanese patients with KD were enrolled in the study. As disease controls, jejunal tissues from 10 patients with diarrhea due to cow's milk protein intolerance were used. The numbers of cells stained by an immunofluorescent technique were counted and analyzed statistically by t test. Both HLA-DR+CD3+ and DR+CD4+ cells were significantly increased in the lamina propria of KD patients in the acute phase compared with numbers in controls and patients with cow's milk protein intolerance (p < or = 0.01). CD8+ cells were significantly reduced in both the epithelium and the lamina propria of KD patients in the acute phase in comparison with numbers in both controls (p < or = 0.05) and patients with cow's milk protein intolerance (p < or = 0.01). HLA-DR+ cells were significantly increased in both the enterocytes and the lamina propria of KD patients in the acute phase compared with numbers in controls (p < or = 0.01). These cell patterns returned to normal in the convalescent phase of KD. Differences between these cell patterns in KD patients with and without diarrhea were not significant, although these immunohistochemical features tended to be more marked in patients with diarrhea than in those who lacked diarrhea. These results are consistent with what one would expect to find if a delayed-type hypersensitivity reaction had occurred in the small intestinal mucosa of KD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1993

Pathologic features of acquired immunodeficiency-like syndrome in cats experimentally infected with feline immunodeficiency virus.

Five specific pathogen free cats were inoculated with feline immunodeficiency virus (FIV) isolated in Japan to observe changes toward development of acquired immunodeficiency syndrome (AIDS)-like disease. All inoculated cats had lymphadenopathy and mild respiratory disease shortly after inoculation. Following the initial acute phase lasting for more than 40 weeks, the clinical signs gradually diminished in three animals, and the asymptomatic carrier (AC) stage was observed at 45 (1 cat) and 70 (2 cats) weeks postinoculation (p.i.). Two of the three cats developed respiratory signs and diarrhea at 105 or 106 weeks p.i. One cat died at 121 weeks p.i. with severe wasting, with necropsy findings consistent with AIDS-related complex (ARC). The others were surviving at 150 weeks p.i. with mild clinical signs or asymptomatic. Another group of two cats developed more severe illness without the AC phase. One died at 48 weeks p.i. with the ARC illness. The other cat developed marked emaciation with diarrhea at 75 weeks p.i., and died at 100 weeks p.i. with a histologic diagnosis suggestive of terminal immunodeficiency. Histologically, the lymph nodes showed serial changes toward the terminal illness, from follicular hyperplasia at the acute phase to the lymphoid depletion at the ARC and AIDS-like terminal stages. The FIV antigen was demonstrated in the lymph nodes. The virus was isolated from peripheral blood mononuclear cells of all the inoculated animals. These data demonstrated possible etiologic association of FIV with development of AIDS-like disorders in the cat.

Animals↗
PubMed1993

Left main coronary flow velocity associated with stenosis. Evaluation by transesophageal color-guided pulsed Doppler technique.

To quantitatively estimate the extent of left main coronary artery (LMCA) stenosis, flow velocity of the LMCA in 33 patients was analyzed by a transesophageal color-guided pulsed Doppler technique. In 11 of 20 patients with LMCA stenosis, coronary flow velocity could be measured. The peak diastolic flow velocity at the stenotic segments was 90 +/- 32 (SD) cm/s which was significantly greater than that at the nonstenotic segments (n = 13; 34 +/- 8 cm/s; p < 0.01), and was correlated with the angiographically determined percentage of diameter stenosis of the vessel which ranged from 52 to 90 percent (r = 0.77; y = 6.34 square root of x + 10.4; p < 0.01). These results suggest that acceleration of flow velocity at the point of stenosis may be correlated with the severity of the stenosis. Measurement of flow at the point of stenosis by transesophageal color-guided pulsed Doppler technique may facilitate the quantitative assessment of LMCA stenosis, although its sensitivity requires improvement.

Adult↗
PubMed1993

Use of STA-MCA anastomosis for clipping of giant middle cerebral artery aneurysm--case report.

A 50-year-old female developed subarachnoid hemorrhage due to rupture of a giant aneurysm in the left middle cerebral artery (MCA). One month later, direct surgery was performed on the aneurysm. The superficial temporal artery was anastomosed to the cortical artery of the parietal MCA segment. The MCA was exposed and trapped for 40 minutes during barbiturate infusion, with electroencephalographic and somatosensory evoked potential monitoring. During MCA trapping, the aneurysm was collapsed by dome puncture and obliterated by neck clipping. After surgery, she had only mild amnestic aphasia and an infarct in the medial temporal lobe demonstrated by computed tomography. However, cerebral angiography disclosed complete occlusion of the MCA by the displaced aneurysm clip, and perfusion of the distal MCA segments through the anastomosis. The initial bypass procedure prevented a disastrous outcome in this patient and is recommended for direct surgery on MCA aneurysms.

Cerebral Revascularization↗
PubMed1993

Suppression of gene expression of myeloperoxidase (MPO) by gamma-interferon (IFN-gamma) in HL60 cells.

The gene expression of myeloperoxidase (MPO) in HL60 cells, as tested by Northern blot analysis with a MPO gene probe, was markedly suppressed at 9 h after the addition of gamma-interferon (IFN-gamma) (200 U/ml), whereas cytochemically detected MPO activity, cell surface antigen expression, and cell morphology remained unchanged even at 48 h. IFN-gamma of 50 U/ml was sufficient for the suppression at 24 h. When the HL60 cells treated with IFN-gamma (200 U/ml) for 24 h were cultured in the absence of IFN-gamma for another 24 h, the transcript of MPO gene reverted to a level comparable to that of the HL60 cells cultured thoroughly in the absence of IFN-gamma, indicating the reversibility of the suppression. The suppression of MPO expression at RNA level, probably independent of differentiation, is a biological activity exerted by IFN-gamma, which has not been previously reported.

Cell Line↗