Biomedical subjects
Publications and source records attributed to K Ohkawa.
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A new diagnostic method, panendomicroscopy, provides an accurate diagnosis and follow-up of normal and abnormal tissues at cellular level. A prospective study of 36 patients presenting with gynaecological symptoms, was undertaken to compare the diagnostic accuracy of cytologic, colposcopic, histologic and panendomicroscopic findings in gynaecology. We have found that panendomicroscopy gave a 95% (19/20) accurate diagnosis of cervical premalignant and malignant conditions, compared to an 80% (16/20) accuracy with traditional Papanicolaou smear and colposcipc screening.
Major molecular species of human alpha-fetoprotein(AFP), which were separated as single components by serial affinity chromatography with concanavalin A(Con-A) and Lens culinaris agglutinin, were further resolved into several bands by affinity electrophoresis with erythroagglutinating phytohemagglutinin of Phaseolus vulgaris lectin(E-PHA). Among the newly separated main molecular species, both Con-A- and E-PHA-reactive AFP(AFP-1X1) was demonstrated, contrary to the known sugar specificity of Con-A and E-PHA, in addition to molecular species of AFP reacting with Con-A but not with E-PHA(AFP-1X0) and of AFP reacting with E-PHA but not with Con-A(AFP-0X1). AFP-0X1 was formed from AFP-0X0, and AFP-1X1 from AFP-1X0 by neuraminidase treatment; thus, AFP-0X1 and AFP-1X1 represent asialylated and AFP-0X0 and AFP-1X0 sialylated molecular species. AFP-1X1' and AFP-0X0' were present as minor components. AFP-0X0' had no affinity for E-PHA, and the affinity increased in the order of AFP's-0X0(or 0X1), -1X1', -1X1 and -0X1. Proportions of those components varied depending on the pathophysiological conditions of AFP production.
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.
In normal pregnancy, the activity of the alternate pathway elevates latently and compensatorily for the suppression of cellular immunity. Aging of the placenta becomes a trigger for the onset of labor and production of C3-a. In cases of hydatidiform mole, abruptio placentae, threatened abortion, and chorionic malignancy, the activity of the complement system is depressed, especially that of C3-activator and alternate pathway. This may in turn result from activation of complement by the pathologic lesion of the chorionic villi. In pathologic lesions of the placenta, activation of alternate pathway can lead to a number of diseases. Immunotherapy is effective in the prevention of malignant transformation of hydatidiform mole. Immunotherapy and combination chemotherapy are markedly effective for treatment of metastatic chorionic malignancy.
Effects of horse antibody (purified IgG) to rat AFP on synthesis with both protein and DNA of rat ascites hepatoma cells were examined. The addition of antibody to the cultures showed a decrease in protein synthesis within several hours; whereas, it showed a transient increase in the incorporation of thymidine into tumor cells approximately in 6-12 hours both in vitro and in vivo. Eventually within 24-48 hours, more than 50% of the cells in culture were killed and inhibited the synthesis of DNA by the antibody treatment. The stimulatory effect of antibody on the synthesis of DNA in the tumor cells was more obviously observed in synchronized cells which were capable to obtain by the treatment with thymidine followed by hydroxyurea. The synchronized tumor cells cultivated with antibody containing medium also exhibited the shortening of the cell cycle from 22 to 12-20 hours. Based on these effects of antibody on tumor cell growth, sequential administration of antibody followed by an anticancer drug (carboquone) was proven to be the most effective immunochemotherapeutic schedule for tumor bearing rats, showing 25-33% long-term survival in comparison with any other controls.
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.
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Trophoblast cells invading into decidual tissue of implantation sites of 21 cases in early stage of gestation were morphologically studied in order to clarify the correlation between integrity of the microfilament system and the various biological statuses. Especially, trophoblast cells of ovum at 15 day post coitus were mainly analyzed, since the migrating direction of the cells could be easily identified. 1. Syncytiotrophoblast cells migrating to maternal vessel were in slender shape toward the vessel. Thin and thick filaments connecting to dense body in tip of the cell run parallel with the cell axis. Thus, it is suggested that trophoblast cell migrates in decidual tissue by the joint work of its own actin and myosin in the tip of the cell. 2. Trophoblast cells making close contact with maternal cell such as endothelial cell, decidual cell and gland cell were relatively stable. The cells mainly put into action to project the cytoplasmic processes by thin filament, beneath the cytomembrane, running parallel with the cytomembrane and by thin filament, in the cytoplasmic process, running parallel with the axis of the cytoplasmic process in order to exchange information with maternal cell or to destroy the maternal cell.
The conditions for the reconstitution of surfactant lipoprotein were investigated using pig pulmonary surfactant. Lipids of surface-active material (SAM) were extracted with ethanol-ether and the residue, containing mainly protein, was extracted first with dilute sodium borate buffer (pH 10.0) (fraction A) followed by extraction with deoxycholate solution (fraction B). The former (A) contained mainly protein having a nominal molecular weight of 34,000 daltons, albumin and globulin, and the latter (B) 34,000 and 15,000 daltons. Reconstitution of lipids and proteins using these two fractions revealed a greater affinity of fraction B to lipids than that of fraction A, when lipids and proteins were dialyzed against pH 7.4 Tris-HCl. Observation by freeze-fracture methods revealed that protein particles were incorporated into liposomes. Protein-lipid ratio of this complex (LB) could be regulated by altering the amount of lipids and protein during the dialysis. Fraction A was incorporated into LB (LBA) by dialyzing LB with fraction A at an acidic pH. With this procedure, protein having a nominal molecular weight of 34,000 daltons was selectively incorporated. In negatively stained preparations, LBA had a granular appearance in the area limited by lipid membrane. We suggest that in the lipid-protein complex of SAM, two different proteins are present; a hydrophobic one in lipids and more hydrophilic ones in the water phase that have a close association with the former.
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Five permanent cell lines were established in vitro from patients with gestational choriocarcinoma. Chromosome study with Q-band technique showed a modal chromosome number per cell in the hypotetraploid range in all cell lines. There were unidentifiable, structurally altered chromosomes in each cell line. BeWo cell line from choriocarcinoma following delivery of a normal male baby lost identifiable Y chromosome, whereas Jar cell line following delivery of a normal male did have a Y chromosome. One of the two cell lines following complete hydatidiform mole had a Y chromosome. The significance of this finding is discussed.
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5'-Nucleotidase activity in the cerebrovascular system in stroke-prone spontaneously hypertensive rats was histochemically investigated. In the hypertensive rats, an enhancement of 5'-nucleotidase activity was observed already in the early stage of hypertension and the enzyme activity increased with advancing age. The enzyme activity appeared earlier and stronger in the larger arteries in the basal portion than the pial arteries in the convexity of the brain and arterioles in the brain parenchyma. The activity in the arterial walls proved to be particularly strong in the thickened parts showing cellular hyperplasia, mainly at the branching portions. The reaction products localized along the plasma membrane, and also in the cytoplasma in some parts where the activity was strong. Relationship between the increased 5'-nucleotidase activity and aging of the cells composing the cerebrovasculature resulted from an accelerated or repeated cell proliferation was discussed.
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To elucidate the mechanism of trophoblastic invasion, implantation sites removed from human uteri of early gestational stages of 7 to 10 week were investigated by electron microscopy. Almost all trophoblast cells which penetrated the fibrinoid layer and invaded into decidual tissue were cytotrophoblast cells, and abundant close-contacts between the cytotrophoblast and decidual cells were recognized in this site. The close-contact patterns which were composed of simple apposition, cytoplasmic projection from both cells and mixture of those without fusion were classified into five types. At the time of close-contact, the decidual cells showed the altered structures in various degrees, but never did they alter so strongly as to appear to have died completely. Thus, it is deduced that the influence from cytotrophoblast cells did not cause the destruction of the decidual cells but only biological inactivation of the cells. It is of great significance to the immunological problem between fetus and mother that the cytotrophoblast cells which are fetal epithelial cells can be in close-contact with decidual cells which are maternal stromal cells. Further confirmation relating to the production and transcellular transfer patterns of the information materials should be awaited in future.