Biomedical subjects
Publications and source records attributed to T Ohkubo.
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Gamma-enolase, otherwise called neuron specific enolase (NSE), is specific for neural and neuro-endocrine systems and is present in the tumors of these systems. Gamma-enolase is also reported to be present, however, in a localized form in the tissues of other nonneural systems in some cases of lung cancer in relatively large number of incidences. We examined immunohistologically specimens of digestive organ cancers. Two principal conclusions were obtained. First, gamma-enolase is not specific for neural and neuro-endocrine systems. Second, gamma-enolase is localized in the epithelium of cancers of some cases following the transformation into cancer.
Fifty-five hematopoietic cell lines, including 19 T-, 16 B-, 5 pre-B-, 5 non-T non-B-, 1 erythroid, and 9 myeloid-monocytoid cells, were screened for production of human hematopoietic survival and stem cell growth factor (SCGF) by enzyme immunoassay using anti-SCGF monoclonal antibody. The KPB-M15 myeloid cell line constitutionally secreted a considerable quantity of SCGF, while other T- or myeloid-monocytoid cell lines did not secrete SCGF. Other biomaterials investigated were fetal calf, horse, and human serum; granulocyte-macrophage colony-stimulating factor and erythropoietin preparations; human placental conditioned medium; lectin (phytohemagglutinin, concanavalin A, and pokeweed mitogen); and mixed leukocyte reaction-stimulated leukocyte-conditioned medium. SCGF was detected only in human placental conditioned medium. SCGF produced by the KPB-M15 cells was a protein with a molecular weight of 20,000. The molecule, highly purified by immunoadsorbent affinity chromatography, retained SCGF activity in vitro, e.g., erythroid burst-promoting activity and granulocyte-macrophage-colony potentiation. With the availability of purified SCGF, it is now possible to study in detail the mechanisms regulating hematopoietic stem cells.
Chronic volume overloaded cardiac hypertrophy was induced by abdominal arteriovenous shunt in 10-week-old male Wistar rats. Ten weeks after the operation, myocardial mechanical examination was performed with isolated left ventricular papillary muscles. Left ventricular myosin isoenzyme pattern was also examined by pyrophosphate gel electrophoresis. In addition, morphological study by electron microscope was performed. In arteriovenous shunt rats, isometric developed tension (T) and its first derivative (dT/dt) were decreased, resting tension (RT) was increased and time to peak tension (TPT) was prolonged as compared to sham-operated control rats (T: 2.4 +/- 0.5 vs 2.8 +/- 0.8 g/mm2, NS. dT/dt: 23.9 +/- 4.8 vs 31.9 +/- 7.0 g/mm2.s, p less than 0.05. RT: 1.2 +/- 0.2 vs 0.9 +/- 0.1 g/mm2, p less than 0.05. TPT: 151.7 +/- 20.2 vs 128.3 +/- 10.3 msec, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7) mol/l) and dibutyryl cyclic AMP (10(-5) mol/l) were both depressed in hypertrophied myocardium, although not significant statistically. Left ventricular myosin isoenzyme pattern was shifted towards VM-3 by chronic volume overload. Electron microscope study revealed increased collagen content in hypertrophied myocardium.
201Tl myocardial imaging can, noninvasively, visualize the various cardiac structures; such as the left ventricle, right ventricle and, occasionally, the atrium. We have noted that certain patients exhibit a prominent appearance of the papillary muscle on a scintigram. Thus, we analyzed 201Tl myocardial scintigrams for evidence of activity which corresponded to the anterolateral (A-PM) and posteromedial (P-PM) papillary muscles. Twenty normal subjects, 81 patients with ischemic heart disease (IHD), 11 with hypertrophic cardiomyopathy (HCM) and 13 with dilated cardiomyopathy (DCM) were examined. Patients with DCM had rest imaging only, while the remaining ones performed exercise studies. The prevalence of a positive A-PM image was not high (9%-23%) and there was no significant difference among groups. The P-PM was seen in only 15% of the normal group and in 18% of the HCM group, while the prevalence was high in the IHD (34.6%) and DCM (53.8%) groups. In the IHD, the positive images of the P-PM were largely from the sub-group with single vessel left anterior descending (LAD) coronary artery disease (78.9%). However, even in the presence of a defect in the left ventricular wall supplied by the LAD coronary artery, the patients with multi-vessel coronary artery disease did not tend to disclose the P-PM on the scintigram (30.8%). Thus, we conclude that positive P-PM imaging on a planar 201Tl myocardial scintigram is frequently observed under some cardiac states and seems to be related to reduced wall motion, sound blood supply to the P-PM and the existence of a defect in the anterior left ventricular wall overlapping the P-PM.(ABSTRACT TRUNCATED AT 250 WORDS)
A patient with acquired von Willebrand disease associated with multiple myeloma (IgG-lambda) is described. Mixture of his plasma or IgG fraction with washed control platelets resulted in the inhibition of aggregation with ristocetin, but mixture of control plasma or IgG fraction with washed patient platelets showed no inhibition of ristocetin-induced aggregation. Although his vWF: Ag, RCo, and factor VIII coagulant activity were all normal, inactivation of RCo was induced in normal plasma by incubation with patient plasma. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. A marked increase of Factor VIII and a rapid return of RCo to the baseline after 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. A transient increase in vWF:Ag after the infusion of DDAVP showed with less anodic forms and in the relative proportion as in normal. Treatment of the underlying disease also led to a correction of the bleeding time, improvement of platelet adhesion and ristocetin-induced aggregation, and normalization of crossed immunoelectrophoresis of vWF:Ag. The present study showed that myeloma-associated IgG interacted specifically with the antigenic sites on the von Willebrand portion of the Factor VIII complex.
The altitude variation of the cosmic-ray neutron energy spectrum and the dose equivalent rate was measured at an average geomagnetic latitude of 24 degrees N by using the high-efficiency multi-sphere neutron spectrometer and neutron dose-equivalent counter developed by the authors. The data were obtained from a 2-h flight over Japan on 27 February 1985. The neutron energy spectra measured at sea level and at altitudes of 4,880 m and at 11,280 m were compared with the calculated spectra of O'Brien and with other experimental spectra, and they are in moderately good agreement with them. The dose equivalent rate increases according to a quadratic curve up to about 6,000 m and then increases linearly between 6,000 m and 11,280 m. The dependence of dose equivalent rates at sea level and at an altitude of 12,500 m on geomagnetic latitude also is given by referring to other experimental results.
Serum and early-morning urinary levels of estrone sulfate during the menstrual cycle were measured by a direct radioimmunoassay without hydrolysis. These levels were high and showed prominent peaks [serum, 2.67 +/- 0.37 ng/ml (mean +/- SE); urine, 5.82 +/- 2.3 micrograms/l] around the day of the preovulatory estradiol-17 beta peak, and increased again during the luteal phase. Following intravenous injection of estrone sulfate, serum estrone sulfate, estrone and estradiol-17 beta were measured. The conversion of estrone sulfate to estrone and/or estradiol-17 beta was very small during their transit in the general circulation.
A patient with acquired von Willebrand's syndrome associated with polycythemia rubra vera is described. Ristocetin cofactor activity was decreased, while the levels of vWF:Ag and VIII:C were normal. Crossed immunoelectrophoretic analysis showed that vWF:Ag was composed of much more anodic component. The mixture study using pooled normal plasma and the patient IgG fractions showed the inhibition of ristocetin cofactor and the decrease of less anodic parts of vWF:Ag in normal plasma. After 1-deamino-8-arginine vasopressin (DDAVP) infusion the marked increases of vWF:Ag, VIII:C and ristocetin cofactor and a rapid return of ristocetin cofactor to the baseline were observed. Transient increase of vWF:Ag after DDAVP infusion showed less anodic forms and in the relative proportion as normal plasma. The present study showed that the patient IgG fractions had the specific inhibitory activity against the antigenic sites on the active subfractions of von Willebrand's factor.
Subcutaneous injection of formaldehyde into mouse hind paw elicited pain responses consisting of licking or biting of the paw, which were observed biphasically. The first and second phases were enhanced by melatonin and melatonin, naloxone, prostaglandin E2, respectively. Mice kept in the dark also exhibited hyperalgesic response. When neurotropin was injected intraperitoneally 30 min prior to those treatments, hyperalgesia was suppressed to the control level. Aspirin inhibited only the second hyperalgesic phase.
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Mouse hybridoma clones were isolated, and found to constitutionally secrete monoclonal antibody (MoAb) immunoglobulins specific for human hematopoietic stem cell growth factor (SCGF). MoAbs were initially screened by dot-blotting and enzyme immunoassay (EIA), and their specificity was confirmed using western blotting and EIA. Protein A-purified MoAb IgG neutralized SCGF activity, namely, granulocyte-macrophage colony potentiating and erythroid burst-promoting activities. The availability of MoAb could extend its application to one-step immunoadsorbent affinity-purification of SCGF as well as analysis on its receptor.
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We performed hemopoietic colony culture assays in 15 patients with aplastic anemia (AA) in order to test the effect of hydrocortisone (HC) on late erythroid colony (CFU-e) formation of the patients' marrow and to correlate the in vitro culture results with the clinical response to corticosteroid therapy. HC enhanced CFU-e growth in four patients. All four patients failed to respond to corticosteroid, but three improved with with androgens. The addition of HC did not increase CFU-e colony formation in 11 patients. However, two of them responded to corticosteroid therapy. Among the nine patients showing no HC effect in vitro, two subsequently improved with androgens and one each with anti-thymocyte globulin and anti-lymphocyte globulin. The results suggest that the in vitro corticosteroid effect may not necessarily correlate with responsiveness to corticosteroid therapy.
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A variety of biologic activities on human hematopoietic stem cells were detected in 12-O-tetradecanoylphorbol-13-acetate-stimulated leukocyte-conditioned medium (TPA-LCM). Partial purification of TPA-LCM demonstrated the presence of human-active granulocyte-macrophage colony-stimulating factor (GM-CSF; Mr 50-70Kd), macrophage-CSF (M-CSF; Mr greater than 100Kd) and possibly a third protein (Mr 24-26Kd) supporting survival and growth of hematopoietic stem cells in vitro. Activities investigated included GM-colony and erythroid burst-potentiation, burst-promoting activity (BPA) and delta granulocyte and delta burst-promoting activities (delta GPA and delta BPA).