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Biomedical subjects

N Hibi

Publications and source records attributed to N Hibi.

At least 37 records · Page 2Linked to original sources
PubMed1990

Beneficial effect of nipradilol (K-351) on acute myocardial ischemia. Study of the relationship between regional myocardial blood flow and energy metabolism.

To examine the effects of nipradilol on ischemic myocardium, experiments were performed on regional myocardial blood flow (MBF) and energy metabolism in anesthetized, open-chest dogs. Nipradilol at a dose of 0.3 mg/kg was i.v.-administered 10 min after coronary ligation. MBFs at various sites, including ischemic and non-ischemic areas, were determined by the hydrogen gas clearance method. The levels of ATP and creatine phosphate (CP) at the site of MBF determination were measured 60 min after ligation, and mitochondrial function (RCI, QO2) in the ischemic and non-ischemic areas was determined. Following nipradilol administration, aortic pressure and heart rate were significantly lowered. In ischemic areas with MBF below 40 ml/min/100 g, nipradilol had no influence on MBF. However, the tissue level of ATP in nipradilol treated hearts was significantly higher as compared with untreated hearts. In the area of mild ischemia with MBF of 40-60 ml/min/100 g, nipradilol preserved the tissue ATP and CP levels in spite of a decrease in MBF. Moreover, an inhibition of the decrease in mitochondrial respiratory function was observed in ischemic areas with MBF below 20 ml/min/100 g. Thus, nipradilol administered following ischemia preserved ATP content and mitochondrial function in the ischemic myocardium with reduction of heart rate and aortic pressure. This suggests that nipradilol exerts a cardioprotective effect in acute ischemia. It seems that the cardioprotective effect is due to a decrease in myocardial oxygen demand and preservation of mitochondrial function.

Adenosine Triphosphate↗
PubMed1990

[Intraoperative epicardial two-dimensional and pulsed Doppler echocardiography for assessing functional tricuspid regurgitation].

Intraoperative epicardial two-dimensional and pulsed Doppler echocardiography (PDE) were performed for 44 patients undergoing open mitral valve surgery to determine the presence and severity of functional tricuspid regurgitation (TR). The findings of intraoperative epicardial PDE performed before cannulation for extracorporeal circulation were compared with those of preoperative transthoracic PDE test. The findings of intraoperative PDE after cessation of the extracorporeal circulation were compared with postoperative transthoracic PDE and clinical findings. Pansystolic pulsed Doppler signals recorded in the right atrium were defined as TR. The grade of TR was assessed transthoracically and intraoperatively on the basis of its maximum distance from the tricuspid valve orifice. To perform intraoperative echocardiography, the transducer was sterilized with ethylene oxide gas and placed directly on the right atrium. The pulsed Doppler signals were recorded from nine sample volumes set in the right atrium, and the TR was graded. There were no complications using this technique. Intraoperative PDE prior to the extracorporeal circulation was more sensitive and specific for detecting TR (100% and 80%, respectively) than was preoperative transthoracic PDE (92.8% and 46.7%, respectively). All patients without TR by intraoperative PDE before cannulation for extracorporeal circulation had the competent tricuspid valves. The patients who were diagnosed as having no TR by intraoperative PDE after cessation of the extracorporeal circulation had no significant TR during the follow-up period. It was concluded that intraoperative PDE is a practical method which allows surgeons to assess the presence and severity of TR intraoperatively and to evaluate tricuspid valve function after intracardiac procedures.

Adult↗
PubMed1989

Overcoming effect of antibody against rat alpha-fetoprotein (AFP) on the growth of daunorubicin-resistant mutant rat ascites hepatoma cell line AH66.

A daunorubicin (DNR)-resistant variant (AH66DR) of alpha-fetoprotein (AFP)-producing rat ascites hepatoma AH66 was established. AH66DR was 169 times more resistant to DNR than AH66. A growth-inhibitory effect due to the decrease in sugar uptake following treatment of the cell lines with specific antibody against highly purified rat AFP was also observed. Pre-incubation of both lines with antibody prior to the measurement of 2-deoxy-D-glucose (2dG) uptake resulted in a 45-55% decrease in 2dG uptake compared to control cells with a 2-fold reduction of Vmax value while the Km remained unchanged. Upon pre-incubating AH66DR with antibody, an increased intracellular level of DNR concentration with reduction of efflux rate was observed. A significantly superior cytotoxic effect against AH66DR, which reached almost the same level as the cytotoxic effect of DNR against AH66, was found, as compared to various other controls when tumor cells were cultured with a mixture of antibody and DNR. Our in vitro results suggest that the DNR-resistance of the AFP-producing tumor cells may be overcome if the cells are treated with specific antibody.

Animals↗
PubMed1989

Prostate-specific antigenic domain of human prostate specific antigen identified with monoclonal antibodies.

With the use of five murine monoclonal antibodies (1A5, 2A4, 3F1, F5 and 3A12) and an antigen-affinity purified goat polyclonal IgG antibody, the presence of a prostate-specific antigenic domain in human prostate-specific antigen molecule was identified. The results were based upon a series of quantitative competitive inhibition assays of each 125I-labeled monoclonal antibody and polyclonal antibody binding to prostate-specific antigen by unlabeled monoclonal antibodies as inhibitors, and immunohistochemical examination of an extensive panel of human tissue specimens. A cluster of two epitopes that are spatially related or in close topographical proximity and represent a prostate-specific antigenic domain are defined by the monoclonal antibodies 1A5, 2A4, 3F1, and F5, 3A12, respectively.

Animals↗
PubMed1989

The effect of bispecific monoclonal antibody recognizing both hepatoma-specific membrane glycoprotein and anthracycline drugs on the metastatic growth of hepatoma AH66.

A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R tumor cells treated with cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd membrane glycoprotein (HG-90) which is expressed on in vitro cultured hepatoma cell lines AH66 and AH66R. A monoclonal antibody was prepared to the anthracycline drug daunomycin, and it also reacted with adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized daunomycin/adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the therapeutic effect of the A8C bispecific antibody with adriamycin treatment and compared it to the effect of the bispecific antibody to which adriamycin had been conjugated via an albumin (Alb) bridge. The therapy model used was the tumor AH66R in Donryu rats. Tumor bearing rats had their subcutaneous tumors resected on day 10, a time when distant metastases were present. After the surgical resection of the tumor the rats were injected intravenously for two cycles with the bispecific antibodies, followed by the administration of adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and drug treatment. This suggests that the bispecific antibody/drug treatment is potentially more beneficial in the suppression of distant metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local drug concentration of unmodified adriamycin.

Animals↗
PubMed1988

[Evaluation of secondary tricuspid regurgitation by intraoperative epicardial pulsed Doppler echocardiography].

Since 1985, we have evaluated secondary tricuspid regurgitation associated with acquired mitral valve disease in patients undergoing open mitral surgery by intraoperative epicardial two-dimensional and pulsed Doppler echocardiography. We found intraoperative pulsed Doppler echocardiography to be a sensitive, safe technique allowing surgeons to evaluate the severity of tricuspid regurgitation intraoperatively, even in critically ill patients who cannot afford preoperative cardiac catheterization. To assess the severity of tricuspid regurgitation intraoperatively, the transducer was placed directly on the right atrium. The ultrasound beam was transmitted into the right atrium at right angles to the tricuspid valve orifice to record intraoperative four-chamber two-dimensional echocardiograms, which were used to detect the sites of eight sample volumes, one in the right ventricle and seven in the right atrium, for pulsed Doppler echocardiography. The pulsed Doppler signals were recorded in each sample volume before and after cardiac procedures. The pansystolic abnormal signals lasting from tricuspid valve closure to the subsequent opening and consisting of components moving away from the tricuspid valve were interpreted as tricuspid regurgitant flows. Without operative correction of the tricuspid valve, secondary tricuspid regurgitation can resolve following mitral valve surgery alone. However, to our knowledge, there are no published reports of objective findings of intraoperative changes of secondary tricuspid regurgitation. Here we present the unique intraoperative pulsed Doppler echocardiographic features of tricuspid regurgitation before and after cardiac procedures. A 30-year-old woman with preoperative diagnosis of aortic regurgitation, mitral stenosis and severe tricuspid regurgitation underwent aortic and mitral valve replacement. The intraoperative pulsed Doppler echocardiograms recorded after pericardiotomy and before cannulation of the heart showed tricuspid regurgitant flow signal in all of the seven sample volumes in the right atrium, which was interpreted as severe tricuspid regurgitation. After surgical procedures, no regurgitant flow from the tricuspid orifice to the right atrium was detected in the eight sample volumes. This suggested that preoperative secondary tricuspid regurgitation improves without operative procedures for the tricuspid valve. All intraoperative echocardiographic procedures were performed within 5 min, and no arrhythmias or other complications related to this technique were noted. Epicardial pulsed Doppler echocardiography is helpful in assessing tricuspid valve function of patients undergoing mitral valve surgery bef

Adult↗
PubMed1987

Therapeutic effect of treatment with polyclonal or monoclonal antibodies to alpha-fetoprotein that have been conjugated to daunomycin via a dextran bridge: studies with an alpha-fetoprotein-producing rat hepatoma tumor model.

Purified monoclonal mouse or polyclonal horse antibodies (Ab) to rat alpha-fetoprotein (AFP) were conjugated with daunomycin via a dextran bridge. The therapeutic effect of these Ab-daunomycin conjugates on an AFP-producing rat hepatoma which was inoculated s.c. in Donryu rats was studied. Tumors (s.c.) and distant metastases were present by 14 days after tumor inoculation and the serum AFP level was 35 micrograms/ml. The injection of the Ab-daunomycin conjugate, started on day 14, significantly prolonged host survival with inoculated controls having a median survival of 25 days compared to 57 and 60 days for the treated groups. In a second study the Ab-daunomycin conjugates were injected i.v. every other day for five times after the surgical resection of the s.c. tumor. There was a slight therapeutic effect with either antibody or daunomycin alone but treatment with the AFP Ab-daunomycin conjugates significantly prolonged survival and 60% of these treated animals were "tumor free" when sacrificed on day 100. Serial quantitation of the concentration of AFP in the serum of the treated tumor-bearing or in the tumor-resected rats correlated with the therapeutic effectiveness of the Ab-daunomycin conjugates. These experiments show that the optimal treatment with specific antibody-drug conjugates will be in hosts where there is a small residual tumor burden such as may exist following resection of a primary tumor mass. They further show that the serial quantitation of serum AFP can be utilized to determine if residual tumor is present following treatment with Ab-daunomycin conjugates.

Animals↗
PubMed1987

[Present status and future of real-time two-dimensional Doppler echocardiography].

Advent of Doppler echocardiography has provided a great number of informations regarding the intracardiac blood flows. However, conventional pulsed Doppler echocardiography using fast Fourier transform is cumbersome and time-consuming for intracardiac flow imaging despite the capability of localizing the sample volumes in the two-dimensional echocardiograms. Recently, real-time two-dimensional Doppler echocardiography (color flow mapping) has come into clinical practice and made a breakthrough in the diagnosis of cardiovascular disease. Color flow mapping is divided into two different displays; the one is velocity display and the other power display. In velocity display, the direction and magnitude of the mean flow velocity and the spectrum variance are displayed in color, being superimposed on the two-dimensional images in real-time. The flow toward the transducer is depicted as a red color and away from the transducer as a blue color. The velocity spectrum variance represents the turbulence by adding green to red and blue. Additionally, the magnitude of the velocity is displayed by the brightness of color. In power display, the sum of the squared amplitude of the reflected echo signals from blood cells is depicted as red or blue when the flow is directed or away from the transducer, regardless of the velocity. However, this display lacks the display of velocity spectrum variance. Nevertheless, the merits of this display consists in the capability of describing the slower blood flows in wider areas of enlarged chambers. Furthermore, it may have a lower dependence on the incidence of the ultrasonic beams.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Dissection↗
PubMed1987

[Tricuspid regurgitation evaluated by intraoperative epicardial pulsed Doppler echocardiography: investigation of patients with combined valvular diseases].

To evaluate the grade of tricuspid regurgitation (TR) associated with mitral valve disease and to ascertain the operative procedure for the involved tricuspid valve, epicardial pulsed Doppler echocardiography (PDE) was performed during cardiac surgery. Thirty-two patients with mitral valve disease were studied, 17 of whom had only mitral valve lesion; the remaining 15 had combined mitral and aortic valve disease. The patients' ages ranged from 24 to 63 years and averaged 48.3 years. There were nine men and 23 women. Echocardiographic examinations were performed using a Toshiba SSH-60A for parasternal study and a SSH-11A combined with a SDS-10A with a specially-devised flat transducer for intraoperative use. Intraoperatively, the PDE performed was from the right side of the right atrium (RA), referenced by a four-chamber view and a long-axis view of the right ventricular inflow. The sampling volumes were positioned in the inflow of the right ventricle, immediately above the tricuspid valve, the middle and upper areas of the RA, and adjacent to the interatrial septum. PDE was performed before and immediately after the operative procedure and before chest closure. By severity, TR was classified as non -, mild +/-, moderate +, and severe ++, according to the distances attained by the TR signals from the tricuspid valve orifice, and the velocities and durations of the TR signals during systole. The TR signal was recorded in 23 of 32 patients before surgery, whereas it was determined more adequately in 28 patients by intraoperative epicardial PDE. The gradings of TR via the parasternal approach before surgery were as follows: no TR, in nine cases; mild TR, in three; moderate, in 13; and severe, in seven. Intraoperatively, four patients had none; eight had mild TR; 14, moderate TR; six, severe TR before surgical intervention, respectively. In cases with mild or no TR before surgery, TR was rarely detected by contrast echocardiography using saline solution injected into the right ventricle during surgery. The moderate or severe cases before surgery had moderate or severe TR according to the contrast method during surgery, except for one case not operated on for tricuspid valve disease. Tricuspid valve replacement was performed for two patients, and tricuspid annuloplasty or valvuloplasty for eight.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

Human monoclonal antibody recognizing liver-type aldolase B.

A human hybridoma clone (4E3) has been established by fusing lymphocytes from a lymph node taken from a breast cancer patient and human lymphoblastoid cells, LICR-LON-HMy2, by the poly(ethylene glycol) method. 4E3 has been stabilized and continued to secrete IgMk antibody into culture medium (greater than 10 micrograms/ml) for over 1 year. The following characteristics of the antigen strongly suggested that 4E3 recognizes liver-type aldolase B (EC 4.1.2.13): the Mr of the native molecule is 160,000 and that of the subunit is 40,000, and thus it has a tetrameric structure of identical subunits; the antigen is abundant in the liver and kidney of human, mouse and rabbit, and is localized by immunohistochemical methods in the cytoplasm of hepatocytes and in the proximal tubules of the kidney; the antigen is precipitable by 50-80% saturation with (NH4)2SO4; the antigen shows charge-dependent heterogeneity on DEAE-cellulose chromatography. To confirm this notion, aldolase B was purified to homogeneity from the liver of human, mouse and rabbit by phosphocellulose chromatography. During the chromatographic purification, the antigen activity as assayed by enzyme-linked immunosorbent assay (e.l.i.s.a.) was superimposed on the enzymic activity of aldolase. Furthermore, monoclonal antibody 4E3 strongly reacted with purified aldolase B in SDS/polyacrylamide-gel electrophoresis followed by Western blotting and also in e.l.i.s.a. using microplates coated with purified enzyme. The reaction between aldolase B and 4E3 activated the human complement system as assessed by the attachment of C3 to the immune complex of aldolase B and 4E3.

Animals↗
PubMed1986

Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines.

The anticancer drug, DNR, was conjugated to an affinity-purified horse antibody to human AFP (aAFP) via a dextran bridge. The conjugate (immunoglobulin: DNR molar ratio, 1:50) was twice as potent as free DNR in an in vitro cytotoxicity assay against an AFP-producing human yolk sac tumor. The in vivo effect of aAFP, DNR, and the conjugate was tested against the human yolk sac tumor growing in nude mice. The conjugate, at a concentration of DNR containing the equivalent amount of 20 micrograms or 70 micrograms/mouse significantly retarded tumor growth whereas free aAFP showed only a slight inhibition of tumor growth compared to the PBS-treated control. Mice which received 20 micrograms/mouse of free DNR showed a moderate retardation of tumor growth whereas those which received 70 micrograms/mouse of DNR or a mixture of DNR and aAFP showed emaciation and early death due to acute toxicity of the drug. These results suggest that the anti-body-drug conjugate accumulated preferentially on the AFP-producing tumor cells and that cytotoxicity occurred.

Animals↗
PubMed1986

Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human alpha-fetoprotein conjugated with mitomycin C via human serum albumin.

The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) with human serum albumin (HSA) as the intermediate drug carrier. The conjugate (aAFP:HSA:MMC molar ratio, 1:1:30) retained full antibody binding activity as determined by a competitive binding radioimmunoassay. In a cytotoxicity test in which the AFP-producing human yolk sac tumor TG-1 cells were preincubated with test materials for 2 h followed by an additional 48-h culture in fresh medium, the conjugate was 20-fold more cytotoxic than free MMC at an equivalent MMC concentration of 100 ng/ml. The in vivo antitumor effect of the conjugate was tested against the human yolk sac tumor JOG-9 growing in athymic nude mice. When the tumor-bearing mice were treated with a total of 6 injections given on 2 consecutive days and then every other day starting 8 days after SC tumor inoculation [2 (equivalent MMC) microgram/head per injection], the conjugate retarded tumor growth more effectively than free MMC and normal horse immunoglobulin conjugate.

Adolescent↗
PubMed1986

[The development of a convenient enzyme-immunoassay method to detect human serum ferritin].

We have developed an enzyme-immunoassay (EIA) method which is easily and conveniently handled to detect human serum ferritin instead of using the radioisotopes. Rabbit anti human liver ferritin antiserum was adsorbed to a 96 well microplate. Then, sera from patients were put into each well following the addition of peroxidase-labelled rabbit anti human liver ferritin antiserum. Therefore, this is composed of so-called "sandwich" method. One of the beneficial characteristics in this method is to be able to examine many samples at once and easily. Based on this principle, this is clinically useful for screening the abnormal level of serum ferritin from various patients.

Ferritins↗
PubMed1986

[Mitral stenosis of the postoperative state evaluated by echocardiography].

Echocardiography was performed to compare pre- and postoperative findings and to evaluate the postoperative state in 109 patients with mitral stenosis (MS) including 22 who underwent closed mitral commissurotomy (CMC) (34.3 +/- 6.9 y.o.); 71, open mitral commissurotomy (OMC) (42.9 +/- 8.7 y.o.); and 16, mitral valve replacement (MVR) (44.5 +/- 8.9 y.o.). Echocardiographic examinations were performed using a Toshiba SSL-51H with a mechanical sector scanner or an SSH-11A with a phased-array electronic sector scanner, one or two weeks before and about one month after surgery, and were reviewed yearly. The results were as follows: The E-F slope of the anterior mitral leaflet (AML) and mitral valve orifice area (MVA) were significantly increased after cardiac surgery in both the CMC and OMC groups. The amplitude of the mitral valve was slightly increased in the CMC group, but was unchanged in the OMC group. Before surgery, the left atrial dimension (LAD) was larger in the MVR group than in the other two groups, and it was significantly decreased after surgical intervention in all three groups. The aortic dimension (AOD) was slightly increased in the majority of patients, and the ratio of the aortic dimension to the sum of the aortic and left atrial dimensions [AOD/(AOD + LAD)] was significantly increased after cardiac surgery due to the improvement of cardiac function and the resolution of the left atrial enlargement. Repeated echocardiography facilitated follow-up of the state of the mitral valve and of cardiac performance, and is considered useful in determining indication for reoperation.

Adult↗
PubMed1985

Hormonal regulation during secretion of alpha-fetoprotein in hepatoma cells grown in synthetic medium.

The variant cell line of H4-II-E-C3 cells derived from the Reuber H-35 hepatoma cells has been established using protein- and lipid-free synthetic medium. This H4-II-E-C3-V line can synthesize and secrete considerable amounts of alpha-fetoprotein (AFP) and albumin. The addition of 5 X 10(-7) M dexamethasone to the medium stimulated the excretion of AFP without increasing total AFP synthesis, whereas 8.7 X 10(-8) M insulin inhibited the excretion of AFP without a significant inhibition of intracellular AFP synthesis. However, neither dexamethasone nor insulin altered either the cellular or secreted levels of albumin. Cells were pulse labeled with [35S]methionine and then chased after addition of excess unlabeled methionine. AFP appeared in the medium after 10 min, and 50% of the protein was secreted after 110 min. The rate of secretion of AFP was much slower than that of albumin, 50% of which was secreted after 25 min. Dexamethasone, 5 X 10(-7) M, caused a marked enhancement in the rate of AFP secretion, with 50% released after 75 min. Insulin, 8.7 X 10(-8) M, by contrast, caused a marked delay in AFP secretion with only 20% released after 180 min and then a plateau was approached. Since the intracellular AFP was excreted 55% after 180 min the remaining 25% of newly made AFP was suggested to be degraded during secretion. The kinetics of movement of AFP during secretion and endoglycosidase H treatment of intracellular and secreted AFP suggested that insulin impeded the transport of AFP from the rough endoplasmic reticulum to the Golgi apparatus.

Animals↗
PubMed1985

Pleiotropic phenotypic expression in cybrids derived from mouse teratocarcinoma cells fused with rat myoblast cytoplasts.

Cybrid clones were isolated by fusing mouse embryonal carcinoma (PCC4) cells with cytoplasts of rat myoblastic cells (L6TG X CAPr). Although some clones were similar to PCC4 (Type II), a high proportion (88%) were differentiated; the differentiated cells had a mesh-like arrangement (Type I) or were flat with many projections (Type III). Protein patterns of both Type I and Type III cells changed markedly from that of PCC4 cells. Type III cells lacked alkaline phosphatase and expressed endo A and B proteins predominantly. One Type III clone produced alpha-fetoprotein and plasminogen activator (visceral endoderm-like), while another clone consisted of trophectodermal cell-like giant cells. Therefore it was shown that introduction of the somatic cell cytoplasm induces differentiation of teratocarcinoma stem cells, suggesting a cytoplasmic element (or elements) regulating gene expression.

Alkaline Phosphatase↗