[Changes in demand for hospital care of the elderly aged 75 or more].
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Age Factors↗
Biomedical subjects
N Nishi
Publications and source records attributed to N Nishi.
[Disturbances of visual perception and the lesions on spastic diplegia].
In a study of 12 cerebral palsy with spastic diplegia, the relationship between their disturbances of visual perception and their lesions was discussed. All of them were performed Frostig Developmental Test of Visual perception and Tanaka-Binet Intelligence Test. Six of them showed disturbances of visual perception on Frostig Test. Subtest II, figure-ground, was the lowest of all subtests. The mean of perceptual quotient was under that of intelligence quotient significantly (p less than 0.05 t-test). MRI examination was performed to all and the lesions were detected at 10 of them. Six who showed disturbances of visual perception had the lesions and two who showed good visual perception had no lesions. The lesions were periventricular white matter and extended to semioval center and subcortical white matter at parietal and occipital lobes. Anatomically, their lesions correspond to superior longitudinal bundle and vertical occipital bundle and their bundles have important functions as the pass way of visual perception. Therefore, it was suggested that the disturbances of visual perception detected at spastic diplegia were based on the lesions and the mechanism was disconnection of higher visual pass way.
Brain↗
Effect of chitin heparinoids on the activation of peritoneal macrophages and on the production of monokines in mice.
Sulfonated derivatives of chitin which showed anticoagulant activity (chitin heparinoids) were studied with regard to the activation of mouse peritoneal macrophages and the production of monokines. In comparison with 70% deacetylated chitin (DAC-70), which was the most adjuvant-active derivative of chitin, all chitin heparinoids were less effective for the augmentation of cytolytic activity of peritoneal macrophages. The number of macrophages was hardly increased or decreased by intraperitoneal injection of chitin heparinoids, and the activity of circulating colony-stimulating factor was not changed by their treatment. Only N-sulfonated DAC-70 stimulated the production of interleukin-1 by thioglycolate-induced peritoneal macrophages in vitro. However, its effect was weaker than that of DAC-70. Chitin heparinoids showed no or weak mitogenic activity on normal mouse spleen cells.
Adjuvants, Immunologic↗
Inhibition of the metastasis of murine malignant melanoma by synthetic polymeric peptides containing core sequences of cell-adhesive molecules.
We investigated that the antimetastatic and antiadhesive activities of peptides based on Arg-Gly-Asp adhesive signal in fibronectin could be augmented by their polymerization. Poly(Arg-Gly-Asp), which consists of a repetitive sequence of Arg-Gly-Asp, inhibited lung metastases in C57BL/6 mice more effectively than Arg-Gly-Asp tripeptide was able to do, when coinjected or separately injected with B16-BL6 cells. The adhesion of tumor cells to fibronectin was specifically inhibited by adding poly(Arg-Gly-Asp) but not unrelated peptides. In contrast, poly(Arg, Gly, Asp), in which three amino acids are randomly arranged, showed neither inhibition of lung metastases nor any adhesive ability to attach to tumor cells. The inhibitory effect of polymeric peptides containing the Arg-Gly-Asp sequence on lung metastases decreased according to the decreasing repeat units of the Arg-Gly-Asp core sequence. Polymeric peptides with Arg-Gly-Asp entrapped within the liposome membranes also caused a remarkable reduction of metastatic colonies. In a spontaneous metastasis model, multiple i.v. administrations of poly(Arg-Gly-Asp) after tumor inoculation caused the significant reduction of metastatic colonies in the lung but did not affect the growth (size) of primary tumor. We found that the polymerization (multivalency) of the Arg-Gly-Asp core sequence was able to augment the inhibition of tumor lung metastases in experimental and spontaneous metastasis models as well as the cell-adhesive property more effectively than a monovalent unit of Arg-Gly-Asp peptide.
Amino Acid Sequence↗
The androgen-dependent rat prostate protein, probasin, is a heparin-binding protein that co-purifies with heparin-binding growth factor-1.
Rat prostate extracts contain an abundant 20-22 kilodalton heparin-binding protein with near identical chromatographic properties, but only 0.2-1% of the mitogenic activity, of bovine brain heparin-binding growth factor-1 (acidic fibroblast growth factor). Amino terminal amino acid sequence (met-met-thr-asp-lys-asn-leu-lys-lys-lys-ile-glu-gly-asn-trp-arg-thr-val -tyr- leu-ala-ala-ser-?-val-glu-lys-ile-asn-glu-gly-ser-pro) and immunochemical analysis revealed that the protein is identical to the androgen-dependent protein "probasin".
Amino Acid Sequence↗
Biological activities of synthetic polypeptides containing a repetitive core sequence (Arg-Gly-Asp) of cell adhesion molecules.
A unique polypeptide containing the repeated structure of core sequence from cell adhesion molecules, poly(Arg-Gly-Asp), was successfully prepared by the polymerization procedure with diphenylphosphoryl azide. This polypeptide dramatically inhibited the aggregation of platelets induced by adenosine diphosphate (ADP) or malignant melanoma cells.
Adenosine Diphosphate↗
Inhibitory effect of a synthetic polypeptide, poly(Tyr-Ile-Gly-Ser-Arg), on the metastatic formation of malignant tumour cells.
A new type of polypeptide containing the repeating sequence of cell attachment site in laminin, poly(Tyr-Ile-Gly-Ser-Arg), was synthesized by the polymerization procedure with diphenylphosphoryl azide (DPPA). We found that this polypeptide inhibited the metastatic formation in the lung of malignant tumour cells far more effectively than pentapeptide.
Amino Acid Sequence↗
Inhibition of tumour cell adhesion by anti-metastatic polypeptide containing a repetitive Arg-Gly-Asp sequence.
Anti-cell adhesive activity was examined by the synthetic polypeptide, containing repetitive Arg-Gly-Asp sequence of cell attachment site from fibronectin, poly (Arg-Gly-Asp). The attachment of tumour cells to fibronectin substrate was specifically inhibited by adding poly (Arg-Gly-Asp) in cell surface receptor-mediated and divalent cation-dependent manners, but not by unrelated peptides. In our previous study, the lung metastatic formation of tumour cells was dramatically reduced by intravenous co-injection of anti-cell adhesive poly (Arg-Gly-Asp) with B16-BL6 melanoma cells. These findings suggest that polypeptide-mediated inhibition of pulmonary metastasis is partly due to interference with tumour cell adhesion to the substrates including fibronectin in target organs or tissues.
Amino Acid Sequence↗
Macrophage activation and host augmentation against Sendai or herpes simplex virus (HSV) infections with synthetic polypeptides in mice.
Poly-L-Lys (mean mol. wt; 12,000), poly-L-Arg (5000) and poly-L-Orn were found to activate peritoneal macrophages effectively in vivo in 14 synthetic homo polypeptides. The ability of sequential poly(L-Arg-L-X) (5000) to activate macrophages was less than that of poly-L-Arg. Neither (L-Arg)12 nor (L-Arg)6 by themselves activated macrophages, but poly-D-Arg (5000) did, as also did poly-L-Arg; this suggests that the polycationic character of poly-L-Arg plays a role in the activation of macrophages. The intranasal administration of poly-L-Lys, -L-Arg, -L-Orn, -D-Arg, all of which activated macrophages, augmented host resistance against Sendai virus infection in mice. The protection afforded by poly-L-Arg seemed to depend on its mol. wt: the order of protection was poly-L-Arg greater than (L-Arg)12 greater than (L-Arg)6. The intranasal administration of poly-L-Arg 3 days before the infection was effective, while that 1 day before infection was not. There was no difference between the groups in the titer of interferon produced by the infection of Sendai virus given with poly-L-Arg either 3 days before or 1 day before the infection. The administration of poly-L-Arg 3 days before the infection caused a significant decrease of the virus titer in the lung 6 days after the infection when compared with the control or the mice given 1 day before. The intravenous administration of 2-chloroadenosine (2-Cl-Ade), which is a selective inhibitor of macrophages, into the mice which had received poly-L-Arg intranasally 3 days before the infection caused a significant decrease in the survival rate of the mice, indicating that the macrophages activated with poly-L-Arg are likely to be an important element in affording the protection. Subcutaneous administration of poly-L-Arg revealed protective activity against systematic infection with herpes virus-type 1.
2-Chloroadenosine↗
Antimetastatic effects of synthetic polypeptides containing repeated structures of the cell adhesive Arg-Gly-Asp (RGD) and Tyr-Ile-Gly-Ser-Arg (YIGSR) sequences.
We have investigated the inhibitory effect on experimental or spontaneous lung metastases of polypeptides which contain repetitive structures of the Arg-Gly-Asp (RGD) or Tyr-Ile-Gly-Ser-Arg (YIGSR) sequence derived from adhesion molecules, and studied their biological characterisation after administration. In the spontaneous metastasis model, multiple intravenous (i.v.) administrations of poly (RGD) and poly (YIGSR) resulted in a reduction of lung tumour colonies, although the monomer peptides, RGD or YIGSR, had no effect under these conditions. The treatment with poly(RGD) substantially prolonged the survival time for mice injected i.v. with B16-BL6 cells as compared to the treatment with RGD and random poly(R, G, D). Tumour cell adhesion to the fibronectin-substrates was remarkably inhibited by adding poly(RGD) freely in solution. Poly(RGD) was found to inhibit completely the ability of platelets to enhance tumour cell adhesion to fibronectin-substrate and tumour cell-elicited platelet aggregation in vitro, but poly(R, G, D) had no such effect. We also found that poly(RGD) led to a decrease in the arrest and retention of tumour cells after its co-injection with radiolabelled tumour cells and that the radiolabelled polypeptide can be at least decomposed into small fragments during circulation. Poly(RGD) was found to be still active in inhibiting experimental lung metastasis even when the contributions of NK cells or macrophages were removed from this system after pretreatment with anti-asialo GM1 serum, 2-chloroadenosine or carrageenan. The results indicate that the poly(RGD)-mediated inhibition of tumour metastasis may be due to the interference of the adhesive interaction of tumour cells with a specific site in the target organs. Derivatives of polypeptides which contain RGD and/or YIGSR sequences derived from cell adhesion proteins may thus provide a promising approach for the control and prevention of cancer metastasis.
Amino Acid Sequence↗
The inhibition of murine lung metastasis by synthetic polypeptides [poly(arg-gly-asp) and poly(tyr-ile-gly-ser-arg)] with a core sequence of cell adhesion molecules.
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Animals↗
Regulation of a bifunctional mRNA results in synthesis of secreted and nuclear probasin.
Probasin, a rat prostatic protein, is statistically related to members of a protein family that includes serum, cellular, and nuclear proteins. In vivo, probasin appears both in the secretions and in the nucleus of prostatic epithelial cells. Using primer extension and S1 nuclease protection assays we detected only one probasin mRNA. Thus, the localization of this protein to two separate cellular regions must be encoded by this one mRNA. Furthermore, in vitro translation of synthetic probasin mRNA demonstrated that a protein containing a signal peptide and a protein lacking a signal peptide were synthesized by initiation at different AUG codons. These data are consistent with a mechanism of translational regulation of a eukaryotic bifunctional mRNA.
Amino Acid Sequence↗
Inhibitory effect of chitin heparinoids on the lung metastasis of B16-BL6 melanoma.
Structure-function studies for the antimetastatic activity of chemically modified chitin heparinoids composed of N-acetyl glucosamine units were performed in an experimental lung metastasis model. 6-O-Sulfated chitin (S-chitin) significantly inhibited the lung tumor colonization in proportion to the degree of sulfation. However, 6-O- and N-sulfated but partially N-deacetylated chitin (S-chitosan), and 6-O-carboxymethylated chitin (CM-chitin) had no effect. 6-O-Sulfated CM-chitin (SCM-chitin), which exhibited fairly low levels of anticoagulant activity, was also more effective than intact heparin. Furthermore, SCM-chitin with a high degree of sulfation (SCM-chitin III) caused a marked decrease of the number of lung tumor colonies in the spontaneous lung metastasis model. These results strongly suggest that 6-O-sulfate and N-acetyl groups in the glucosamine unit were required for the anti-metastatic effect of chitin heparinoids as well as heparin, and SCM-chitin III may be of therapeutic benefit for the prevention of tumor metastasis.
Animals↗
[A case of hepatocellular carcinoma effectively treated by intraarterial infusion of CDDP and other agents].
It is very common for intraarterial infusion therapy of some anticancer agent to be effective against hepatocellular carcinoma. In this case, the patient was a 74-year-old man who suffered from very advanced hepatocellular carcinoma with tumor thrombus of the intrahepatic portal vein and IVC. He was treated with intraarterial infusion of CDDP, Etoposide, 5-FU, through a catheter placed in the proper hepatic artery. CDDP (30 mg/day) and Etoposide (60 mg/day) were given once every 5 days, and then 5-FU(250 mg/day) was infused daily for 26 days. The patient underwent this protocol study twice in 3 months. After the intraarterial infusion, transarterial embolization using CDDP (100 mg) powder added to lipiodol and aluminum stearate as suspension was done a month later. The tumor regression rate was 84% after intraarterial infusion of CDDP, Etoposide and 5-FU. The tumor thrombus in the intrahepatic portal vein and IVC had completely disappeared. We could not find lipiodol accumulated in the tumor after TAE. Thus, we assumed that the remaining tumor was a necrotic scar and that a complete response was obtained in the patient. There were some side effects, such as nausea, vomiting, pancytopenia and gastritis but no severe complication occurred.
Aged↗
Comparative analysis of growth factors in normal and pathologic human prostates.
Growth factors, as detected by DNA synthesis stimulating activity for BALB/c 3T3 cells, in normal, benign hypertrophic and cancerous human prostates were analyzed. The total content (units per gram of tissue) in benign hypertrophic prostate was two to four times higher than those in normal and cancerous prostates. In all the three groups, heparin-binding growth factor, growth factor adsorbed to heparin-Sepharose in the presence of 0.5 NaCl. accounted for about 80-95% of the total growth factor content. Qualitative analysis using a heparin-Sepharose column revealed two types of heparin-binding growth factor in the prostates, one eluted from the column at 1.2-1.3 M NaCl and the other at 1.5-1.8 M NaCl. The latter was the predominant type in all groups. In addition to the growth factors detected with BALB/c 3T3, a growth factor with specific action upon MC3T3-E1 mouse osteoblasts was found in prostatic cancer, but not in normal and benign hypertrophic prostates.
Animals↗
Partial purification of a major type of rat prostatic growth factor: characterization as an epidermal growth factor-related mitogen.
The dorsolateral prostate of rats contains a mitogen that shares several properties with epidermal growth factor (EGF), which was designated as prostatic EGF-related mitogen (PEM). PEM was purified about 2,100-fold using molecular-sieve and ion-exchange chromatography. Final preparation stimulated DNA synthesis in BALB/c 3T3 cells at a concentration as low as 1.5 ng/ml and competed with 125I-EGF for binding to cell surface receptors. PEM had a molecular weight of about 14,000 and an isoelectric point of about 4.5, being heat- and acid-stable but inactivated by dithiothreitol. The primary cultured rat dorsolateral prostate epithelial cells required EGF for maximum growth. Partially purified PEM fully substituted for EGF in the primary culture system at a concentration as low as 90 ng/ml. However, the activity of PEM was hardly suppressed by antimouse EGF antiserum. These findings suggest that PEM is a member of the EGF family but has a higher molecular weight (high molecular weight EGF).
Animals↗
Production of IGF-II-related peptide by an anaplastic cell line (AT-3) established from the Dunning prostatic carcinoma of rats.
AT-3 cells, one of anaplastic cell lines established from the Dunning prostatic carcinoma of rats, were able to grow under serum-free conditions in a state of suspension detached from a substratum. Radioimmunoassay using monoclonal antibody against rat insulin-like growth factor II (IGF-II) revealed the presence of IGF-II-related peptide in acid-ethanol extracts of lyophilized serum-free media conditioned by AT-3 cells. The peptide contents in the culture media increased with increase in cell number; 71 ng at 3.0 X 10(6) cells and 449 ng at 4.6 X 10(7) cells. IGF-II-related peptide was hardly detectable in acid-ethanol extracts of AT-3 cells harvested after 13-days culture. These results indicate that AT-3 cells produce IGF-II-related peptide and may release it into the culture media.
Animals↗
Proliferation of epithelial cells derived from rat dorsolateral prostate in serum-free primary cell culture and their response to androgen.
Primary cultured epithelial cells derived from the rat dorsolateral prostate proliferated in serum-free nutrient medium WAJC 404 supplemented with mitogens: insulin (650 nM), cholera toxin (120 pM), epidermal growth factor (EGF) (2.5 nM), dexamethasone (300 nM), and bovine pituitary extract (25 micrograms/ml). The culture consisted of two types of epithelial cell colonies: one originated from single cells or small cell aggregates and the other was epithelial cell outgrowth from small tissue fragments attached to a substratum. There were differences in requirements for the mitogens between the two types of colonies. Requirements for cholera toxin, bovine pituitary extract, and dexamethasone were higher in the former type of colonies, and those for EGF were higher in the latter type of colonies. Proliferation of the epithelial cells in either type of colony was suppressed more than 50% by 1 nM dihydrotestosterone. This suppressive effect was not mediated by stromal component in the tissue fragments, and was counteracted by cyproterone acetate, indicating specific and direct action of the androgen on prostate epithelial cells. The results suggest that there is discrete participation of polypeptide growth factors and androgen in proliferation and differentiation, respectively, of prostate epithelial cells in vivo.
Androgens↗