Heterogeneity of human cataractous and normal lens gamma-crystallins.
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Biomedical subjects
Publications and source records attributed to T Kodama.
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Cytosol of the benign hypertrophic human prostate was prepared in a low salt medium and then the concentration of salt was increased to 0.4 M with KCl (0.4 M KCl-cytosol). This preparation showed a high affinity binding to R 1881 and the binding was specific for androgens. These results suggest that the binding of the preparation to R 1881 was due mainly to the cytosolic androgen receptor. The R 1881 binding component in the 0.4 M KCl-cytosol was sedimented at 3S by sucrose density gradient centrifugation. The small sedimentation coefficient of the binder seems to be due to the high concentration of salt and not to degradation by proteolytic enzymes in the preparation. The molecular weight, Stokes radius and frictional ratio of this binding component were 32,000, 25.9 A and 1.24, respectively.
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Spontaneously hypertensive rats (SHR) that develop hypertension and arterial lesions resembling human periarteritis nodosa were found to possess a selective depression of T cell functions with an appearance of natural thymocytotoxic autoantibody (NTA). The relationship between T cell depression and hypertension in these animals was investigated. The immune responsiveness of T cell-depressed SHR was completely recovered by histocompatible thymus grafts and was partially restored by histoincompatible allogeneic or xenogeneic thymus grafts or by injection of thymus extracts. Transplantation of compatible thymus tissues into neonatal SHR produced long-lasting recovery of immune functions. When complete immunologic restoration was achieved, significant suppression of high blood pressure was obtained. The SHR that showed high blood pressure were always accompanied with high NTA titers and arterial lesions. Thymus grafts or thymus extracts significantly decreased the titers of NTA. The development and dissemination of arterial lesions, which may cause increased blood flow resistance, were completely prevented by compatible thymus grafts into neonatal SHR. These results suggest that thymus grafts and thymus extracts may suppress the development of hypertension by preventing or curing the periarteritis nodosa in SHR.
The relation between the excretion of urinary steroids and the therapeutic effect of ovariectomy on tumors was investigated in female Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary cancer. Ovariectomy significantly reduced the excretion of urinary androgen, 11-deoxy-17-oxosteroid (11-DOOS), but hardly affected that of urinary corticosteroid, 17-deoxy-corticosteroid (17-DOCS). The responsiveness of tumors to ovariectomy was positively correlated with both pre-operative 11-DOOS and pre-operative ratio of 11-DOOS to 17-DOCS, and negatively correlated with pre-operative 17-DOCS. The extent of tumor regression after ovariectomy was associated with the decrease of urinary androgen. A similar correlation was observed between the decrease in the ratio 11-DOOS/17-DOCS and tumor suppression during cyclophosphamide treatment (medical ovariectomy). These results indicated that the tumor response to ovariectomy was related to a shift of the endogenous hormone balance from a relative dominance of androgen to relative dominance of corticosteroid. The significance of the hormonal findings is discussed in the light of the steroid metabolism in human breast cancer.
The biochemical properties of preneoplastic antigen (PN antigen) were investigated in order to resolve inconsistencies in previous reports. First of all, epoxide hydrase was purified biochemically from the liver of phenobarbital-treated rats and anti epoxide hydrase serum was prepared in rabbits. Immunochemically, in Ouchterlony double diffusion, PN antigen had the same antigenicity as epoxide hydrase. From an immunoprecipitation study using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and crossed immunoelectrophoresis, it was found that PN antigen may be composed of epoxide hydrase and at least one more protein (mol. wt. 27,000). However, the biochemical and biological properties of the protein binding to epoxide hydrase were not determined. The existence of PN antigen (epoxide hydrase and its binding protein) may be associated with microsomal membrane alterations during chemical carcinogenesis.
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Abrin is known as a cytotoxic lectin. Immunization with Meth-A tumor cells which were treated in vitro with abrin induced a strong antitumor immunity in syngeneic BALB/c mice. The immunizing effect was stronger than that produced by an irradiated Meth-A tumor cell vaccine. Studies on the mechanisms of the immunizing effect with the abrin-treated tumor cells demonstrated that abrin acts as an immunoadjuvant. Furthermore, the regression of a growing Meth-A tumor was observed after abrin was injected into the tumor, while the induction of a strong antitumor immunity also occurred. It appears, therefore, that the antitumor effects of abrin are attributable to two kinds of activity: cytotoxicity and adjuvant activity.
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The incidence of tumor metastases was studied in WKA/Hok rats after cryosurgery and surgical excision of primary tumors. When rats with syngeneic fibrosarcoma, KMT-17, were treated by cryosurgery 5 days after transplantation of the tumor, 15 out of 31 rats (48.4%) died with tumor metastases. In contrast only 4 out of 34 (11.8%) died with tumor metastasis after surgical excision. Because tumor cells either in the regional lymph nodes or in the peripheral blood were already detectable in about half of the rats treated by either cryosurgery or surgical excision, mechanical and physical control of enhanced metastasis by cryosurgery is ruled out. The development of anti-tumor immunity was delayed in the rats treated by cryosurgery as compared with that in rats treated by surgical excision. This was investigated by means of Winn's assay. A marked reduction of tumor metastasis was seen after the surgical removal of cryonecrotized tumor tissue, while implantations of cryonecrotized tumor tissue into the rats treated by surgical excision resulted in an increment of metastasis. The mechanism of the enhanced metastasis observed in this experimental investigation is discussed from an immunological point of view.
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Post-operative antitumor immunity was studied by comparing the results following cryosurgery and surgical excision of 3-methylcholanthrene-induced primary autochthonous tumors in WKA/Hok rats. Immunity was tested by challenge with the autochthonous tumors on the 4th and 21st days post-operatively. Antitumor resistance which developed following cryosurgery was found in 7 out of 14 rats (50%) challenged after 4 days and in 2 out of 13 rats (15%) challenged after 21 days. Following surgical excision, however, resistance was found in 13 out of 18 rats (72%) challenged after 4 days and in 10 out of 17 rats (58%) challenged after 21 days. Therefore, the development of antitumor immunity by surgical excision was more effective than by cryosurgery (P less than 0.02). In addition, the enhancement of autochthonous tumor growth as compared with that of the control rats was clearly demonstrated after cryosurgery in 4 out of 14 rats (29%) challenged 4 days afterwards and in 3 out of 13 rats (23%) challenged 21 days afterwards. After surgical excision, however, this was seen in only 3 out of 18 rats (17%) challenged 4 days afterwards, and in 0 out of 17 rats (0%) challenged 21 days afterwards. These results suggest not only that the development of antitumor immunity is delayed but also that the tumor growth is more likely to be enhanced by cryosurgery than by surgical excision.
A 43-year-old woman and her 47-year-old brother were studied because of corneal opacity. They showed a marked decrease in plasma high density lipoproteins (HDL) and a decrease in the ester ratio of plasma total cholesterol. Discoidal particles were found in the HDL2 fraction (d 1.063-1.125). A marked heterogeneity of low density lipoproteins was disclosed in both patients by electron microscopy. Apoprotein analysis revealed an increase in apo E and a decrease in apo A-I and A-II in both patients. These abnormalities were similar to the data reported in other cases with hereditary lecithin : cholesterol acyltransferase (LCAT) deficiency. However, several interesting dissimilarities have been disclosed as compared with the previously reported cases. Neither patient had proteinuria, and their kidney functions were within the normal limits. The ester ratios of plasma cholesterol of both patients were the highest among the cases reported thus far. Their plasma LCAT activities were 14.4 and 15% of the normal mean values determined by Glomset-Wright's common-substrate method. The enzyme activities determined by Stokke-Norum's self-substrate method were 40.2 and 29% respectively. These results may indicate that this inherited disorder is not characterized by absence of plasma LCAT or presence of inhibitory factors in plasma, but by the presence of partially inactive LCAT in patients' plasma.
The purpose of this investigation was to clarify the relation between the therapeutic efficacy of cyclophosphamide and the activity of the endogenous and exogenous corticosteroid hormones using ICR female mice with ascitic Ehrlich tumor. A single ip injection of the drug, 3 mg/mouse, was given to each mouse 36 hr after tumor inoculation (1 X 10(6) tumor cells, ip), and the drug effect was assessed in terms of the number of 1-month survivors with and without tumor. The clock time of drug administration which produced minimal therapeutic efficacy chronologically coincided with the dark period (8 PM approximately 8 AM) and/or with a stage of increased plasma corticosterone in mice. In support of this, concomitant administration of corticosterone (hydrocortisone or corticosterone) significantly depressed the anti-tumor effect of the drug. Evidence is presented to indicate that the adverse effect of corticosteroids is related to an accelerated metabolism of cyclophosphamide within the host. The drug effect for a given total dose was improved by the use of hourly partitioned injections in place of a single injection. It was concluded that the therapeutic efficacy of cyclophosphamide is dependent on the time of exposure to drug action on the scale of hours, but not days, and that the anti-tumor effect of the drug can be suppressed by increased activity of endogenous and exogenous corticosteroid hormones through acceleration of the drug metabolism.
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