Biomedical subjects
Publications and source records attributed to N Hibi.
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The inhibitory effects of horse antiserum against rat alpha-fetoprotein (AFP) on the uptake of 2-deoxy-D-glucose (2dG) by the AFP-producing rat ascites hepatoma AH66 cells was studied. AH66 cells cultured in medium containing 20% heat-inactivated antiserum had a 1.5-fold lower rate of sugar uptake than did AH66 cells which were cultured in medium containing 20% heat inactivated normal horse serum. The inhibition of 2dG uptake by antiserum was dependent on both the concentration and the exposure time of antiserum. Preincubation of AH66 tumor cells for 2 and 6 h with antiserum prior to the measurement of 2dG uptake resulted in a 70.1% and 58.2% decrease in 2dG uptake compared to control cells. Antiserum did not inhibit the rate of phosphorylation of 2dG by tumor cells. Kinetic constants for the uptake of 2dG in both AH66 cells treated with antiserum to AFP and in control cells were calculated from Lineweaver-Burk plots. The Km remained constant at approximately 1.2 mM, but the Vmax was twice as small for the cells treated with antiserum as for the control cells (571 vs 923 nanomoles/2 X 10(5) cells/min). These studies suggest that the inhibition of 2dG uptake by treatment with antiserum was the result of a decrease in the number of transport sites, or a decrease in the amount of carrier protein for the sugar which was present on the surface of the plasma membrane of the AH66 cells.
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A highly sensitive sandwich enzyme-immunoassay (EIA) for human muscle carbonic anhydrase isozyme III (CA-III) has been developed using microplate as a solid-phase and peroxidase as a labelled enzyme. The assay can detect levels as low as 2 ng/ml when 20 microliter of sample sera were used. Sera from patients with various neurological diseases were studied using this method, and elevated serum CA-III levels were found in patients with Duchenne muscular dystrophy, limb-girdle dystrophy, fascioscapulohumeral dystrophy, polymyositis and amyotrophic lateral sclerosis. The values correlated well with the results of radioimmunoassay (RIA), with a correlation coefficient of 0.92 (P less than 0.001). We feel EIA is preferable to RIA for its simple methodology.
For its selective accumulation into tumor cells, the antitumor drug adriamycin (ADM) was attached to specific antibodies reactive against alpha-fetoprotein, a carcinoembryonic protein, and the antibody and antitumor activities of the resulting conjugate were investigated. Using the glutaraldehyde or carbodiimide binding methods, preparations containing 4-5 moles of ADM per mole of antibody were obtained. They retained 60-75% of the original antibody activity. Upon incubation of AH-66 ascites hepatoma cells with the conjugates, an increased number of dead cells and inhibited uptake of 3H-thymidine by the cells were observed. The conjugates were more effective against tumor cells than the free drug, and it was further presumed that the cytotoxic action of ADM on normal cells could be reduced by binding it to a macromolecular protein.
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Antibiotics having antitumor activity (anticancer drugs) also possess inevitable side effects on normal proliferating cells. In order to overcome these side effects, targeting chemotherapy has been developed using antibodies to specific tumor-associated antigens. In this experiment, polyclonal or monoclonal antibodies to AFP (aAFP) were selected for coupling to anticancer drugs such as daunomycin and adriamycin. Dextran (M.W. 10,000) was used as an intermediate drug carrier to increase the number of drug molecules bound indirectly to aAFP. This aAFP-dextran-anticancer drug conjugate produced a striking effect on AFP-producing tumor cells in vivo as well as in vitro using both rat AFP-producing hepatoma AH66 and human ovarian tumor growing in nude mice. The aAFP-dextran-adriamycin conjugate was administered to patients with hepatoma. Although the effect of the conjugate was unclear, long-term suppression of serum AFP level was observed in one case. No obvious side effect encountered.
We visualized the Valsalva sinus aneurysm ruptured into the right ventricle using two-dimensional echocardiography, and analyzed the blood flow by pulsed Doppler technic. Cross-sectional echocardiography was performed on 11 patients with right sinus aneurysm protruding into the right ventricle. The age of the examined subjects ranged from 17 to 40 years. Ten of the 11 revealed a ruptured aneurysm of the right sinus of Valsalva into the right ventricle. Nine of the 11 had ventricular septal defect and five were associated with aortic regurgitation. Pulmonic regurgitation was recognized in one case. The diagnosis was made by cardiac catheterization and angio-cardiography in all cases and was confirmed by cardiac surgery in nine patients. In this study, we employed an electronic (SSH-11A) or mechanical sector scanning system (SSL-51H) for cross-sectional echocardiography. In order to clearly visualize an aneurysm, the cross-section of the left ventricular long-axis was obtained from a slightly lower and more sagittal position than the standard method. In addition, the short axis cross-section of the aortic root was also examined. Furthermore, a pulsed Doppler technic was applied to three patients using a Doppler unit SDS-10A combined with SSH-11A. In all patients, an aneurysm of the right sinus of Valsalva was seen to protrude into the right ventricle by two-dimensional echocardiography. Furthermore, the ruptured orifice of the aneurysm was clearly visualized in ten cases. The shape of the aneurysm was tubular in ten cases and saccular in the remaining one. A continuous blood flow of wide band pattern was recorded in the right ventricle near the ruptured orifice in two of the examined three cases and a disturbed diastolic flow was noted in a saccular aneurysm. In conclusion, two-dimensional echocardiography is useful to visualize an aneurysm of the right sinus of Valsalva ruptured into the right ventricle and a pulsed Doppler technic is greatly contributed in detecting localized disturbed flow due to the ruptured aneurysm.
We discussed the left ventricular deformity in atrial septal defect (ASD) using two-dimensional echocardiography and elucidated the mechanism responsible for the production of mitral valve prolapse (MVP) associated with ASD. Two-dimensional echocardiography was performed for 78 cases with ASD, ranging in age from three to 64 years. The diagnosis was made by cardiac catheterization in all patients and was verified by surgical intervention in 66 cases. Two-dimensional images were obtained using an electronic sector scanning system of Toshiba (SSH-11A). The recording was made with 8 mm cinematography and an ordinary 35 mm camera. The major diameter/the minor diameter of the short-axis cross-section of the left ventricle was defined as the left ventricular distortion ratio (LVDR). The LVDR in early diastole was significantly larger than those in end-diastole and end-systole (p less than 0.001, n = 33). Furthermore, in end-diastole, the left ventricle showed a greater distortion ratio than that in end-systole (p less than 0.001, n = 33). The left ventricular short-axis area (LVSAA) corrected for the body surface area (BSA) was significantly greater both in early diastole and end-diastole than that in end-systole (p less than 0.001, n = 33). In early diastole, there was a poor correlation between the LVDR and the pulmonic to systemic flow ratio (Qp/Qs) (r = 0.44, p less than 0.05, n = 33). Similarly, the LVDR was poorly related with the right ventricular dimension (RVD) in early diastole (r = 0.43, p less than 0.05, n = 30).(ABSTRACT TRUNCATED AT 250 WORDS)
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Using the indirect immunoperoxidase method, we studied the localization of carbonic anhydrase-III (CA-III) in frozen sections of biopsies of human skeletal muscle which had no definite pathology. CA-III was found to be localized in Type-I muscle fibers when compared with serial sections stained with myosin ATPase and other reactions. Our finding was in accordance with the biochemical data so far reported. It was though that CA-III could be used as a marker for abnormal Type-I muscle fibers in several neuromuscular diseases.
Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP antibodies were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested for their antitumor activity in vitro and in vivo. They were equally cytotoxic to the rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates by either intraperitoneal or intravenous injection. Daunomycin conjugates with horse-anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than were the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal Ig. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls only slightly delayed tumor development.
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Prostatic acid phosphatase (PAP) was purified from human seminal plasma by precipitation with ammonium sulfate and by serial chromatographies with concanavalin A-Sepharose, Sephadex G-100, and carboxymethyl-cellulose. The purified enzyme was found to be homogeneous by polyacrylamide gel electrophoresis, both with and without sodium dodecyl sulfate. The purified enzyme also gave a single precipitin line upon immunoelectrophoresis, when reacted with rabbit antiserum to seminal plasma. A simple method was developed for the preparation of monospecific antibody to PAP. In addition, a new immunoenzymatic assay system for PAP is reported, utilizing filter paper discs as a solid-phase to which monospecific antibody to PAP was covalently coupled. By this method, serum PAP in a range of 1 to 7,000 ng/ml could be accurately measured within 4 hr.
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Daunomycin was covalently attached via a dextran bridge to specific antibodies against rat alpha-fetoprotein produced in a horse. The effect of this conjugate on an alpha-fetoprotein-producing tumor was investigated in terms of cytotoxicity and inhibition or retardation of tumor development. Under the experimental conditions used, the covalent conjugate was by both criteria more efficient than either daunomycin alone or a mixture of daunomycin and specific antibodies or a conjugate of daunomycin with horse immunoglobulin. These results show that the conjugate may be useful as a specific cytotoxic agent against alpha-fetoprotein-producing tumors.
Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.
The interatrial septum (IAS) has not been readily appreciated by M-mode echocardiography, but cross-sectional echocardiography has the capability of recording the shape and location of the IAS. Thirty-five patients with secundum atrial septal defect (ASD) were studied with cross-sectional echocardiography for detection of the ASD defect and demonstration of the IAS features following ASD closure. The ASD was shown as an echo dropout at the mid-portion of the septum in those patients examined in the present study in the horizontal cross-sections at the fourth intercostal space. The edge of the remaining IAS sharply demarcated and the defect was constantly demonstrated. In the postoperative patients, the IAS was recognized as a smooth series of echoes and the defect was no longer recognized. A notch echo was demonstrated in patients who underwent direct suture of the defect, and two notch echoes were recorded in patients who had a patch closure from a cardiac operation. The size of the defect at cardiac operation ranged from 1.5 to 5.0 cm with an average of 3.3 +/- 0.2 cm. The defect was slightly smaller on cross-sectional echocardiograms than at the time of operation. As the defect grew larger, the right ventricular dimension and the Qp/Qs became larger as well. Postoperatively, the right ventricular dimension was remarkably decreased, and the paradoxical movement of the interventricular septum (IVS) was normalized in the majority of the patients. Cross-sectional echocardiography is useful to diagnose ASD, to measure the size of the IAS defect, and to follow the clinical course.