Biomedical subjects
Publications and source records attributed to Y Mishima.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effect of murine alpha/beta interferon (IFN) on experimental metastasis was investigated using B16-F10 melanoma cells. Since the outcome of metastasis of blood-borne tumor cells is mainly determined within the first 24 h after i.v. inoculation of tumor cells, i.p. injection of IFN was focused on this critical early phase. The inhibition of pulmonary metastases by IFN was found to be maximal when given 3 h prior to tumor cell inoculation, while mice with 24-h and 12-h pretreatment and simultaneous IFN treatment also showed a reduction in metastases, but to a lesser extent. However, mice receiving IFN 2 h after tumor cell inoculation did not show any reduction. Tumor cells cultured for 24 h in IFN-containing medium showed no reduction in metastases. Administration of anti-asialo GMl prior to IFN treatment was found to eliminate the inhibitory effect of IFN 3 h pretreatment. However, natural killer (NK) cell activity in vitro measured at 3 h, 13 h and 24 h after IFN administration was enhanced to the same extent, not paralleling the inhibitory effect on pulmonary metastases. These data indicate that prepared host status against blood-borne tumor cells is established by IFN pretreatment, being maximal when injected several hours prior to tumor cell inoculation, and that this effect is substantially dependent on NK cell activity, though the implication of other factors is not excluded.
In moderately colored guinea-pig skin, UVB, PUVA, and allergic contact dermatitis were shown to induce hyperpigmentation that resembled the pigmentary changes observed in mongoloid human skin. Using this model, we examined the effects of chemical agents, including tyrosinase inhibitors and sunscreen agents, on the color changes induced by UV irradiation. The daily exposure of brownish guinea-pig skin to UVB irradiation at a variety of energies for 3 successive days induced clearly visible black pigmentation on the irradiated rectangular areas of the flank within a few days of irradiation, the maximum being reached about 1 week after irradiation, i.e., similar to the changes that occur in pigmented human skin. Split epidermal sheets prepared from untreated pigmented guinea pigs exhibited 200-400 melanocytes/mm2; 1 week after UV irradiation, the applied areas show an increased number of strongly dopa-positive melanocytes with stout dendrites (800-1,000 cells/mm2). UVA irradiation following an intraperitoneal injection of 8-methoxypsoralen (8-MOP) also produced black pigmentation 1 week after irradiation, and this was paralleled by a marked increase in the number of dopa-positive melanocytes in dopa-reacted split epidermal sheets. Allergic contact dermatitis produced by the application of 1-phenylazo-2-naphthol induced hyperpigmentation after an interval of about 14 days in 10 of the 21 allergy-acquiring animals examined. This induced pigmentation was accompanied by an increase in the number of dopa-positive melanocytes as compared to the number seen in controls. In contrast, allergic contact dermatitis produced by the application of dinitrochlorobenzene failed to induce such a high ratio of postpigmentation, with only 3 of the 21 allergy-acquiring animals showing hyperpigmentation and 5 showing depigmentation; in the latter, there was a slight decrease in the number of dopa-positive melanocytes. To study the preventive effect of tyrosine inhibitors on UVB-induced pigmentation, daily topical applications of these compounds were performed after three daily UVB irradiations. Treatment with 10% hydroquinone for 10 days interrupted UVB-induced pigmentation and resulted in a marked reduction in the number of epidermal melanocytes as compared to the number found in UVB-irradiated, untreated control skin.
Antimelanosome-associated monoclonal antibody has recognized the common antigenic determinant of melanosomes and cell surface of pigment cells, and it is suggested that melanosomes play a significant role as an antigen in progressive depigmentary disorders, in which melanocytes are selectively altered and disappear presumably by auto-antibodies in vivo. Mouse myeloma cells were fused with spleen cells from BALB/c mice immunized with a melanosomal fraction separated from human melanotic melanoma cells (Mm-1-JCK). The monoclonal antibody (MoAb) A4F11 has been found to react with premelanosomes, melanosomes, and probably with Golgi-associated endoplasmic reticulum lysosomes, but not with mitochondria, nuclei, and cytosol from human melanoma cells, by immunoelectron microscopy using the saponin permeation method, which was carried out together with indirect radioimmunoassay and quantitative absorption assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using melanosome preparations have revealed the antigen(s) reactive with the MoAb A4F11 in 3 bands corresponding to Mr 50,000, 18,000, and 17,000. Cell binding assay has shown the reactivity of the MoAb A4F11 with the cell surface of human normal melanocytes and melanoma cells, but not with other mammalian melanoma cells or with human nonpigment cells examined. Indirect immunofluorescence on cultured cells and frozen sections has revealed distinct granular reactivity not only with human melanotic melanoma, but also with junctional and intradermal nevi, cultured malignant blue nevus cells, as well as normal melanocytes. The above evidence has indicated the presence of an antigenic determinant common to the intracellular melanogenic compartments and to the cell surface of human pigment cells, regardless of their oncogenic differentiation status.
Specific inhibition of core carbohydrate synthesis has been found to induce selective aberration and melanin loss in melanosomes, accompanied by alteration of the carbohydrate moiety in functioning glycoproteins, tyrosinases. In order to further clarify the biologic significance of glycoproteins in the initiation of melanization, initial melanogenesis which occurs during the recovery period following interrupted melanogenesis induced by glycosylation inhibitors, has been electron microscopically investigated. Changes in the tyrosinase activity of the corresponding melanogenic subcellular compartments have also been studied electron cytochemically. Removal of glycosylation inhibition was carried out after exposure of B-16 melanotic melanoma cells to the inhibitors for 10-20 culture days resulting in the loss of their melanization. Recovery of melanization begins visibly 48 h later, thereafter almost attaining the previous normal level by 72 h. At the electron microscopic level, re-formation of melanosomal matrix with periodicity is observed within premelanosomes 48 h after removal of glucosamine, soon followed by deposition of apparent melanin particles along their periodicity by 72 h. In tunicamycin experiments, melanization within premelanosomes starts after the concentration of the fine threadlike interior becomes less distinct followed by a prominence of multiple accumulation of microvesicles within the interior. Electron microscopic dopa reaction shows that the deposition of dopa melanin is prominent in Golgi-associated endoplasmic reticulum of lysosome and coated vesicles up to 24 h after the removal. Thereafter, predominant localization of dopa melanin in premelanosomes gradually increases and finally becomes almost uniform. These observations suggest 2 possible mechanisms for the involvement of glycosylation in melanogenesis: first, the translocation of tyrosinases may be regulated by the presence of specific carbohydrate moieties; second, melanosomal matrix proteins contain carbohydrates which may contribute to the tyrosinase-accepting function or in vivo melanizing function of tyrosinases after forming particle-bound T3 tyrosinase.
Experimental hyperlipidemia was induced in ddY, C57BL, BALB and ICR strain mice and in Wistar rats. By feeding the animals a high cholesterol diet (HCD) for 2 weeks or by administering a high fat emulsion for a week, plasma level of total cholesterol (TC) increased in these animals. The increment of TC in mice was less than that of TC in rats. In rats, plasma level of triglyceride (TG) increased, but it decreased in mice of all these strains. Plasma level of high density lipoprotein cholesterol (HDL-C) decreased in rats and mice except BALB mice. By feeding these animals a HCD, the relative liver weight increased in rats and mice. In rats, clofibrate (CF), 100 mg/kg/day, decreased TC and TG and increased HDL-C, and nicotinic acid (NA), 100 mg/kg/day, decreased and increased HDL-C. However, in mice, CF decreased TC only in ICR mice fed a HCD. The hypolipidemic effects of gemfibrozil, LK-903 and pirozadil were also studied in rats and ICR mice.
General pharmacological properties of two kinds of Senso-containing drugs were studied. There were no prominent differences in the pharmacological profile between the two prescriptions. Inhibition of writhing (60 mg/kg, p.o.), prolongation of hexobarbital-induced hypnosis, hypothermia, antipyretic effect, and inhibition of acetic acid-induced capillary permeability (600 mg/kg, p.o.) in mice were observed after administration of these drugs. These effects were suggested to originate from cinobufagin, a constituent of Senso. Augmentation of blood sugar level and inhibition of gastric juice secretion (600 mg/kg, p.o.) in rats were also observed after administration of these drugs. These effects were suggested to originate from constituents of Senso other than cinobufagin. Isolated ileum and aorta of guinea pigs and vas deferens and fundus strip preparation of rats contracted, and isolated trachea of guinea pigs relaxed after the application of these drugs. The majority of these effects were suggested to originate from epinephrine-like or serotonin-like compounds, constituents of Senso.
Carcinoma of the colon was induced in rats by injection of a carcinogen 1,2-dimethylhydrazine (DMH), and thymidylate synthetase (TS) and thymidine kinase (TK) activities, which catalyze the biosynthesis of dTMP by the de novo pathway and the salvage pathway of pyrimidine synthesis, respectively, were measured in normal control colon, DMH-treated normal colon, and DMH-induced colon carcinoma with or without administration of two doses of an anti-cancer drug UFT (a combination of tegafur and uracil). TS and TK activities were both increased after treatment with DMH, markedly in colon carcinoma tissue, and to a lesser degree in normal-appearing colon tissue. This phenomenon is well explained by the hypothesis that biochemical alterations of DNA-synthesizing enzyme activities occur as a preliminary step prior to the development of overt cancerous transformation. A low dose of UFT inhibited TS activity but enhanced TK activity, therefore, the salvage pathway may compensate for the reduced level of the de novo synthesis. On the other hand, a large dose of UFT reduced both TS and TK activities, perhaps due to cytotoxic effects of UFT incorporation into RNA.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The present report describes a 53-year-old non-obese man with adiposis dolorosa whose pain was dramatically relieved by the intravenous injection of lidocaine. The patient showed a paradoxical response of growth hormone to thyrotropin-releasing hormone. In addition, in-vitro studies on adipose tissue metabolism revealed the reduced glucose conversion to neutral glycerides in painful adipose tissue. These abnormalities may be related in some ways to the pathogenesis of this disorder.
Vascular and lymphatic invasion of cancer cells, type of histology, histopathological TNM classification, level of tumor invasion, menopausal status, and age were reported as prognostic factors for breast cancer. We determined the discriminatory power of these prognostic factors for predicting breast cancer recurrence in 98 patients with the method of quantification theory type II, using a computer, model Hi-TAC M-150. The discriminatory rate of these combined seven factors for recurrence was 82.609%. We calculated the probability of breast cancer recurrence using the method of quantification theory type II. The probability of breast cancer recurrence (P) was given as follows. P = 1/1 + 7.333e5.468X. The score X is given by the sum of category weight of seven prognostic factors. Averages of P values of patients with recurrence and without recurrence were statistically different (p less than 0.01). The rate of having more than 30% of P values was 78% in 23 patients with breast cancer recurrence, and it was only 3% in 75 patients without breast cancer recurrence. The difference was statistically significant (X2 = 61.83, p less than 0.001). These results suggest that we can discriminate a high-risk patient with breast cancer recurrence using this method.
Explore the source record for details and available documents.
An in vitro processing system of mouse rRNA was achieved using an RNA polymerase I-specific transcription system, (S100) and recombinant plasmids consisting of mouse rRNA gene (rDNA) segments containing the transcription initiation and 5'-terminal region of 18S (or 41S) rRNA. Pulse-chase experiments showed that a specific processing occurred with transcripts of the plasmid DNAs when the direction of transcription was the correct orientation relative to the 18S rRNA coding sequence, but not with transcripts of the DNA templates in which this coding sequence was in the opposite orientation. From the S1 nuclease protection analyses, we concluded that there are several steps of endonucleolytic cleavage including one 105 nucleotides upstream from the 5' end of 18S rRNA. Intermediates cleaved at this site were identified in in vivo processing of rRNA. This result indicates that endonucleolytic cleavage takes place 105 nucleotides upstream from the 5' terminus of 18S rRNA prior to the formation of mature 18S rRNA. Trimming or cleavage of the 105 nucleotides may be involved in the formation of the 5' terminus of mature 18S rRNA.
Explore the source record for details and available documents.