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Biomedical subjects

Y Oguchi

Publications and source records attributed to Y Oguchi.

177 records · Page 10Linked to original sources

Multicenter genetic study of retinitis pigmentosa in Japan: I. Genetic heterogeneity in typical retinitis pigmentosa.

A nationwide, multicenter study of typical retinitis pigmentosa (RP) was carried out in collaboration with 18 hospitals throughout Japan to obtain current information for genetic counseling. We analyzed the genetic heterogeneity of RP based on the parental consanguinity of 434 probands registered during a 6-month period in 1990. A gradual decline in the frequency of consanguineous marriage was recognized among the normal parents of RP patients. The relative frequencies of inheritance patterns were estimated as: autosomal recessive, 25.2%; autosomal dominant, 16.9%; X-linked, 1.6%; and simplex, 56.3%. A comparison of these results with previous reports in Japan revealed a decline in the relative frequency of autosomal recessive cases and an increase in simplex cases. This suggests a decrease in the incidence of autosomal recessive retinitis pigmentosa in Japan, as well as the necessity for exhaustive investigations aimed at identifying inheritance patterns for RP patients seeking genetic counseling.

Adolescent↗

Multicenter genetic study of retinitis pigmentosa in Japan: II. Prevalence of autosomal recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with autosomal recessive (AR), autosomal dominant, and X-linked modes of inheritance. Autosomal recessive retinitis pigmentosa (ARRP) is the most common form in Japan. A genetic analysis was done to determine the prevalence of ARRP indirectly, to provide an estimation of changing trends in the overall prevalence of RP. Data on the frequency of consanguinity and marriage year of normal parents of 59 ARRP patients were obtained from a nationwide multicenter survey of typical retinitis pigmentosa conducted in 1990. The gene frequency of ARRP was 0.01145 (Dahlberg's formula). In 1990, the number of young symptomatic ARRP patients decreased, while the number of patients aged 40 years and older increased. The total number of symptomatic ARRP patients in 1990 was nearly 21% higher than in 1970. Despite a dramatic decline in consanguinity in recent decades in Japan, the number of ARRP patients has increased. This increase is attributed to greater longevity and overall population growth. Our results suggest that the total number of RP patients has not decreased, and may even have increased.

Adolescent↗

Animal pharmacological effects of 24R,25-dihydroxyvitamin D3 one of the endogenous substances regulating calcium metabolism.

Lewis lung carcinoma was found to cause hypercalcaemia in tumour-bearing mice. 24R,25-Dihydroxyvitamin D3, a naturally occurring steric epimer, significantly prolonged the survival time of mice with Lewis lung carcinoma. It also had an analgesic effect in mice with Lewis lung carcinoma and increased the strength of bone weakened by the carcinoma which causes abnormal calcium metabolism and results in hypercalcaemia.

24,25-Dihydroxyvitamin D 3↗

Effects of the protein-bound polysaccharide preparation, PSK on spontaneous breast cancer in mice.

The protein-bound polysaccharide preparation, PSK was tested for its ability to suppress carcinogenesis in spontaneous tumours in C3H/OuJ mice. They were divided into two groups of 40 individuals each. A normal diet was given to one group, establishing a control population, while the other group had 2% PSK added to their feed. Amount of feed consumed, body weight and tumour size were recorded weekly for 1 year. Within 15 weeks, 90% of the control population had developed tumours. In the test group the incidence of cancer and the number of tumours was significantly suppressed, and survival rates were improved. The amount of feed consumed and body weights of control and test groups were about the same.

Administration, Oral↗

Mechanism of action of the antitumour effect of K18.

K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G less than K18 less than melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I] K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.

Animals↗

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18).

K18 (3-[p-(N,N-bis(2'-chloroethyl)amino)- phenyl]-L-alanine conjugated with human immunoglobulin) is a newly developed antitumor agent. LD50 values of K18 in animals were quite high, suggesting its low acute toxicity. This drug showed anti-tumorigenicity not only on an experimental animal tumor (Walker 256), but also on a human tumor transplantable into nude mice (RCC-13). A distribution study clarified the unique properties of K18 to accumulate and remain in the tumor site with a high rate.

Animals↗

Antitumor effect of K18 on metastatic models.

K18 is a newly synthesized antitumor agent which is the conjugate form of human immunoglobulin with p-di (2-chloroethyl)-amino-L-phenylalamine (melphalan). The antitumor effect of K18 on two animal metastatic models was investigated: (a) Lewis lung carcinoma was transplanted into thigh muscle of mice, followed by the reaction of the primary lesion, or the tumor was transplanted through the tail vein: (b) a renal model was also created, where colon-26 was inoculated into the renal capsule of BALB/c mice. Oral administration of K18 resulted in the decrease in the number of nodules in the lung in the case of tumor transplantation through tail vein.

Animals↗

Antitumor effect of 24R,25-dihydroxyvitamin D3.

24R,25(OH)2D3, one of the endogenous active metabolites of vitamin D3, showed suppressive effects on the proliferation of various tumor cells in vitro and a prolonging effect on the survival of P-388 bearing mice in vivo. Lewis lung carcinoma was found to cause hypercalcemia in tumor bearing mice. K-DR (24R,25(OH)2D3 (prepared by Kureha Chemical Ind.) significantly prolonged the survival of mice with Lewis lung carcinoma. K-DR also showed a suppressive effect on the growth of human osteosarcoma transplanted in nude mice.

24,25-Dihydroxyvitamin D 3↗

Tumor and tissue distribution of 125I-labeled natural and antitumor antibodies in murine experimental tumor systems.

The binding and tissue distribution of 125I-labeled rabbit anti-sarcoma 180 (S-180) immunoglobulin G (IgG) (RAS-180G), normal rabbit IgG (NRG) and ICR mouse IgGs from normal (NMG) and S-180-bearing ICR mice (AS-180G) were studied in ICR mice bearing S-180. 125I-labelled IgGs preparted from normal (NC57G) or Adenocarconoma 755 (Ca 755)-bearing C57BL/6 mice (A755G) were also examined in C57BL/6 mice bearing ca755. Not only RAS-180G and AS-180G but also NRG and NMG persisted in the tumor site. This result suggests that allogeneic natural IgG could be used as a carrier protein for antitumor agents.

Adenocarcinoma↗

Effect of PSK on cytotoxicity against sarcoma-180 in tumor-bearing mice.

The effect of PSK, a protein-bound polysaccharide with antitumor activity, on the host defence mechanism against tumor in sarcoma-180-bearing mice was examined. PSK restored the capacity to generate cytotoxic lymphocytes and complement-requiring cytotoxic antibody in tumor-bearing mice. PSK did not, however augment cytotoxic activity in tumor-free mice.

Adjuvants, Immunologic↗

The effect of a biological response modifier, PSK, on the intestinal immune system in tumor-bearing mice.

We have previously shown that oral administration of PSK not only exerts antitumor activity, but also restores immune response in tumor-bearing mice. In order to analyze the immunomodulative effect of PSK, we investigated the effects of oral PSK on the intestinal immune systems in ICR mice bearing sarcoma 180. Oral administration of PSK increased the number of Peyer's patches that developed relatively well, and led to recovered mitogenic response of lymphocytes from gut-associated lymphatic tissue and responsiveness to oral preimmunization with SRBC in tumor-bearing mice. These results suggest that PSK modulates the immunity in intestinal tract of tumor-bearing mice.

Adjuvants, Immunologic↗

Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: an overview.

PSK, a protein-bound polysaccharide obtained from cultured mycelia of Coriolus versicolor in basidiomycetes, is a biological response modifier, diverse operations of which include an antitumor action. We have previously reviewed recent research which had demonstrated that in animals, PSK has a preventive effect on chemical carcinogen-induced, radiation-induced, and spontaneously developed carcinogenesis (Kobayashi et al., Cancer Epidemiol., Biomarkers & Prev., 2: 271-276, 1993). We now focus on the effects of PSK once the progression of carcinogenesis has begun, and review what is now known of the preventive action of PSK on cancer metastasis. Recent research reports that PSK suppresses pulmonary metastasis of methylcholanthrene-induced sarcomas, human prostate cancer DU145M, and lymphatic metastasis of mouse leukemia P388, and that it has prolonged the survival period in spontaneous metastasis models. PSK also suppresses the metastasis of rat hepatoma AH60C, mouse colon cancer colon 26, and mouse leukemia RL male 1 in artificial metastasis models. PSK influences the steps of cancer metastasis in a number of ways: (a) by suppression of intravasation through the inhibition of tumor invasion, adhesion and production of cell matrix-degrading enzymes; (b) by suppression of tumor cell attachment to endothelial cells through the inhibition of tumor cell-induced platelet aggregation; (c) by suppression of tumor cell migration after extravasation through the inhibition of tumor cell motility; and (d) by suppression of tumor growth after extravasation through the inhibition of angiogenesis, the modulation of cytokine production, and the augmentation of effector cell functions. In addition, PSK has suppressed the malignant progression of mouse tumor cells through superoxide trapping.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolongation of the survival period with the biological response modifier PSK in rats bearing N-methyl-N-nitrosourea-induced mammary gland tumors.

The antitumor effects of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of Coriolus versicolor in basidiomycetes on mammary gland tumors produced in Sprague-Dawley rats by the intravenous injection of N-methyl-N-nitrosourea were investigated. PSK prolonged the survival period of tumor-bearing rats significantly, when given at the dose of 250 mg/kg twice a week for 3 weeks after the tumor reached 100 mm2 in size (p = 0.011 by log rank test and p = 0.023 by generalized Wilcoxon test). These findings suggest that PSK is effective in the prolongation of the survival period in the rat autochthonous tumor model, acting at the growth stage of the tumor during carcinogenesis.

Animals↗

Enhancement of the antitumor effect by the concurrent use of a monoclonal antibody and the protein-bound polysaccharide PSK in mice bearing a human cancer cell line.

The antitumor effects of a monoclonal antibody against a human cancer cell line and a protein-bound polysaccharide, PSK, obtained from cultured mycelia of Coriolus versicolor in basidiomycetes were examined. The IgG2a monoclonal antibody against the human colon cancer cell line colo 205 induced in vitro antibody-dependent macrophage-mediated cytotoxicity against the cancer cells, but only slightly suppressed the in vivo growth of the cancer cells. Concurrent use of PSK with the antibody enhanced the in vitro antibody-dependent macrophage-mediated cytotoxicity as well as the in vivo antitumor activity. These findings suggest that the combined use of a monoclonal antibody and PSK, which have different modes of action, may be useful in the treatment of cancer.

Animals↗