Maternal blood levels of cystine aminopeptidase (CAP), human placental lactogen (HPL) and β1 glycoprotein (SP-1) were predicted and evaluated using the expressions and thier charts developed by us to help diagnosis of placental function in women of the third trimester of pregnancy. This study was conducted on the assumption that these placenta-originating substances as markers would behave similarly to the previously reported heat-stable alkaline phosphatase (HSAP). The results realized the following features: (1) CAP, HPL and SP-1, like HSAP, had their normal ranges of values too wide to be based on for diagnosing placental function in general, but it was confirmed that on the individual basis these marker substances could develop adequate “prediction curves” for their values to come well answering to the test in the same way as with HSAP. (2) The expressions for predicted values revealed that these marker substances in their shift in the maternal blood had different critical points start of deviation from exponential rising. Particularly in abnormal pregnancy, their shifting patterns were often dissimilar to one another, with implications that impaired placental function could possibly be confirmed qualitatively by reference to the predicted curve for the values of either of the marker substances.
The sensitivities to various chemotherapeutic drugs of the primary malignant melanoma cell of the esophagus and the malignant melanoma cells established from human skin were studied by determining the incoporation of 3H-thymidine into tumor cells using the tissue culture method. The incorporation of 3H-thymidine was depressed by a low concentration of Actinomycin D in malignant melanoma cells of the esophagus and by a low concentration of Adriamycin or Actinomycin D in the established malignant melanoma cells. When Actinomycin D was clinically used according to the experimental results, the subcutaneously metastasized tumor was remarkably reduced.
A continuous cell line of malignant melanoma has been established. The tumor specimen was obtained from a left axillary lymph node of a malignant melanoma originating in the abdominal skin of a 67-year-old woman. The cell line has been designated TM-1. Explant specimens showed positive dopa staining, but after 2 years and 4 months, or 60 generations of cell passage, the dopa staining is now weakly positive. Treatment with DBcAMP that causes marked morphological changes induces melanin production and lowers the proliferative ability of the cells. These changes were reversible. Transplantation of the cells to nude mice resulted in the formation of large tumors consisting of epithelioid cells and spindle cells. Morphologically, the majority of the cell population in vitro was polygonal epithelioid cells, but the cell passage produced a large number of spindle cells. The shape of the TM-1 cells was examined by scanning electron microscopy. Depending upon the culture conditions, either of these cell types could be predominated, indicating that both cells are of the same origin.
Tumor culture toxohormone (TCT) obtained from cultures of MBQA mouse tumor cells, a line derived from a methylcholanthrene-induced fibrosarcoma (CBA/J origin), suppressed the mitogenic responsiveness of mouse spleen cells (PHA, LPS) as well as the antibody formation to SRBC in vitro. The immunosuppressive activity of toxohormone was readily inactivated by heating at 100°C or treatment with trypsin, but not by DNase and RNase treatment;
The nucleoprotein (NP) antigen isolated from influenza A virus by solubilization with Triton X-100 (TX-100) and further electrophoresis with SDS-cellulose acetate membrane gave a single band on SDS-polyacrylamide gel electrophoresis. Rabbit anti-serum hyperimmunized with the NP reacted only against the NP antigen. Moreover, a well-defined single precipitin line was shown between the NP and human sera. These results suggested that the NP was possible to detect anti-NP antibody in human serum. Immuno double diffusion (IDD) and single radial immunodiffusion (SRD) tests using the NP were established to detect the anti-NP antibody in human sera. During an epidemic caused by antigenic drift strain, anti-NP antibody was detected by the IDD test in the cases which did not show any significant rise in HAT titer. During a mixed epidemic caused by the different strain of HA antigen, the infection ratio in mass population was revealed more convenient and sensitive by SRD than HAI. The anti-NP antibody was detected by IDD for long periods of one year or more after infection. These results suggest that the detection of anti-NP antibody is applicable to serologic studies, particularly serologic diagnosis and serologic surveys of influenza infection in mass population.
Enzyme replacement therapy was performed for a 1-year and 5-month old boy with adenosine deaminase deficiency disease, the first case in Japan. Irradiated fresh red blood cells were administered without any clinical improvement, but there was an increase in the peripheral lymphocytes from 300/mm3 to 1849 /mm3, of which 88% had T cell marker. B lymphocytes did not bear any classes of surface immunoglobulins. The proliferative responses of these lymphocytes to phytohemagglutinin, concanavalin A, pokeweed mitogen and allogeneic cells were examined. More than two-fold increase in response to these mitogens was observed in lymphocytes after treatment as compared with responsiveness before treatment, but these responses still remained to a much lesser degree than that of lymphocytes from controls.
The antimetastatic effect of Triton WR 1339 (TWR), a nonionic detergent, was evaluated in the rats bearing ascites tumor (Yoshida sarcoma or AH 66F). TWR did not inhibit the growth of primary tumor (ascites production). However, a marked inhibition of metastasis was observed in the lung and liver of rats treated with TWR. The results obtained suggest that TWR exerts antimetastatic effect before the entry of tumor cells into vascular channels. With other tests, it was found that TWR inhibits the release of tumor cells from tumor graft.
The incidence of hypertension in past history was investigated in 811 cases of cerebral aneurysm. These cases were compiled from 1, 000 cases of saccular aneurysm in which direct surgical operations for aneurysm were performed at our clinic during the period from June 1961 to September 1975. Of the 811 cases, 365 (45.0%) had hypertension in their past history; 185 (42.7%) out of 433 males and 180 (47.6%) out of 378 females. In the 5th decade of age, the incidence was significantly higher in the females than in the males, but no difference by sex was noted in other age groups. In the males from the 3rd to the 7th decade, the number of hypertensives increased significantly with advancing age, whereas in the females a signfiicant difference was observed only between the 4th and 7th decades, the latter including more hypertensives. The incidence of hypertensives in the aneurysm cases was compared with that in the Japanese population reported by Sasaki. This comparison revealed that in both sexes between the 4th and 6th decades, the incidence was significantly higher in the former, whereas no significant difference was noted between the two in the 7th decade. As to the location of aneurysms, only the multiple aneurysms group had a significantly greater number of hypertensives than single aneurysm group. These results agree with previous reports that cerebral aneurysm may occur more frequently in the hypertensives than in the normotensives.
Tumor cell suspension was filtered through Nuclepore filters of various pore diameters (5.4, 7.9 and 9.3 μm) with positive pressure from 5 to 60 cmH2O at 37°C. The mean diameters of tumor cells of 6 strains ranged from 10.6 to 13.6 μm. Cell suspension of each tumor strain was filtered with characteristically different time. No significant difference was observed among tumor strains in the percentage of cells filtered. The cell viability was almost unchanged by filtration. The filtration time was considered to indicate the passing ability of tumor cells through capillary pores. Leukemic cells such as DBLA 1, DBLA 6 and L 1210 were relatively small in diameter and possessed a high passing ability compared with other nonleukemic tumor cells such as Yoshida sarcoma, AH 109A and AH 100B. The relationship between pressure and flow rate of the cell-free solution was linear, while the pressure-flow rate curves of the tumor cell suspension were convexed to the pressure-axis at low pressure and became linear over the pressure of the yield point. Rheologically, the yield point and the reciprocal of the slope indicate structural viscosity and apparent viscosity of the cell suspension, respectively, they are considered to reflect the rheological properties of tumor cells. Comparing these parameters of the curves in filters of different pore diameters, the viscosity of leukemic cells appeared to be the lowest and the structural viscosity of AH 100B cells was the highest among the tumor strains examined. The distribution and frequency of metastases following intravenous transplantation of these tumor cells suggested that the passing ability of tumor cells plays an important role in organ preference of hematogenous metastasis and leukemic state in leukemia.
To learn the toxicity of xenogeneic tumor-specific immune ribonucleic acid (I-RNA), experimental and clinical studies were carried out. Experimentally, doses of 30 mg/kg, 15 mg/kg, 7.5 mg/kg or 3.75 mg/kg of xenogeneic I-RNA extracted from lymphoid tissues of rabbits sensitized with 105, 000 ×g sediments of human gastric carcinoma tissue were injected intraperitoneally into Wistar rats once a day for 30 days. During the period of the study, changes of physiological and biochemical values were examined. In addition, pathological study was made for each organ after the I-RNA administration. There was no death during the study. In the groups of high dose administration, there were poor increase in body weight, elevation of GOT, GPT and LDH, findings of vacuolar degeneration of hepatic cells, and increase of mesangial matrix and polynuclear glomerulus. Throughout the experiment, the groups given 7.5 mg/kg and 3.75 mg/kg of I-RNA showed no significant difference from control groups. Clinically, 31 cases treated with passive immunotherapy with allogeneic lymphocytes, preincubated with xenogeneic I-RNA, were examined retrospectively for the difference in hematological and biochemical data before and after the therapy. One case showed a transient mild febrile reaction after the therapy. There was no significant difference in hematological and biochemical data. Pathological findings in 3 autopsies after the treatment were reported.
Guinea pigs rendered hypersensitive to tuberculin 2 to 3 weeks (early stage) or 10 to 14 weeks (late stage) after sensitization with complete Freund's adjuvant could be completely desensitized by a single or double injections of a sufficient amount of PPD (purified protein derivative). Lymph node cells from such desensitized animals 48 to 72 hr after the challenge showed a considerable reduction of the ability to produce blastogenic factor and skin reactive factor upon PPD-stimulation, whereas the macrophage migration inhibitory factor activity remained still unaffected. As regards antigen-induced 3H-thymidine incorporation in vitro, lymph node cells from animals desensitized in the late stage after sensitization showed no substantial reduction in the degree of enhanced DNA synthesis upon PPD-stimulation, although the desensitization in the early stage resulted in a significant loss of this activity. These results suggest the possibility that desensitizing challenge does not bring about a uniform and regular effect on every lymphocyte subpopulations relevant to different functions and, in addition, indicate that there are some exceptions to the compartmentalization concept of antigen-reactive lymphocytes.