Biomedical subjects
Publications and source records attributed to H Maeda.
An uptake of fluorescein isothiocyanate labeled neocarzinostatin into normal and cancerous epithelial cells from bladder was investigated. Results showed that neocarzinostatin traversed the cell membrane into cytosol and nuclei, and it appeared to have a preferential cytotoxicity for the cancer cell.
Systematic hyalinosis (juvenile hyaline fibromatosis) is characterized by hyalinized skin lesions. Electron microscopic examination of a hyalinized skin tumor from a 19-year-old man with this syndrome revealed that the hyaline was composed of ruthenium red-positive ultrastructures (granules, filaments, and a kind of cross-banded structure), indicating the presence of glycosamino-glycan or glycoprotein, and a small number of thin collagen fibrils. Using a new ruthenium red staining method combined with an enzymatic digestion procedure, it was demonstrated that the cross-banded structure and granules consisted of chondroitin sulfate-proteoglycan and/or glycoprotein, and that the cross-banded structure is probably a noncollageneous aggregate of the granules attached to the parallel-arranged filaments of hyaluronic acid-like nature.
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Fluorescence polarization technique was applied for the assay of angiotensin I (Al) in human plasma. In this assay system, fluorescein labeled Al (F-Al), which retained the original antigenicity, and antibody to Al was allowed to interact in a cuvette in the instruments yielding an increase in the fluorescence polarization (P) value. Non-labeled Al in the sample blocked the binding of F-Al to the antibody resulting lower P value. Log of antigen concentration and P value was found to exhibit reverse linear proportionality between 0.05 ng to 2 ng/ml of antigen (Al) concentration. The present method was compared with standard radioimmunoassay method and the result showed that data were compatible with each other. The calculation of P value is automated and three cavity filter and optics of the instrument gave reliable results. The method is fast (less than 2 min), sensitive (less than 10 picomole/ml) and simple (no separation step before readout of the results).
Recently it has been paid attention whether the liver diseases might induce the disseminated intravascular coagulation (DIC) or not, although it has well known that liver cirrhosis contribute to the hemorrhagic diathesis. In this paper, we studied on the hemorrhagic tendency and hemostatic tests in the patients with liver cirrhosis in order to clarify the coagulation and fibrinolytic activity. We can conclude that the hemorrhagic diathesis occurs due to the complex of decreases in platelet number, platelet functions, clotting factors, and increased fibrinolytic activity. The increased fibrinolytic activity may be primary and the frequency of clinically important DIC is quite low.
The immunosuppressive activity of neocarzinostatin, an antitumor antibiotic with a high molecular weight, was demonstrated, as measured by the local and systemic graft-versus-host reaction in rats. The preincubation of parental strain lymphocytes with doses more than 1 micrograms/ml of neocarzinostatin for at least 10 min at 37 degrees C resulted in the marked suppression of the popliteal lymph node enlargement, when injected subcutaneously into the hind footpads of F1 hybrid rats. The suppressive effect was temperature-dependent and irreversible, because the neocarzinostatin (1 microgram/ml) pretreatment of parental lymphocytes at 4 degrees C was not effective in the suppressive activity, and the reincubation of cells after the removal of the drug from the culture did not result in demonstrable changes in the degree of suppression. The neocarzinostatin pretreatment does not result in visible changes in the oxygen consumption rate and viability of cells in vitro or in the distribution pattern within a regional lymph node, indicating that treated cells may retain the same viability and migration capacity in vivo as do untreated cells. Furthermore, the drug pretreatment resulted in the complete prevention of runting syndrome, when treated parental lymphocytes were injected intravenously into F1 hybrid rats.
A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of Lys-20). The NCS-polystyrene (SMANCS) was purified on a column of Sephadex G-100 in 0.05 M ammonium bicarbonate and the main product was obtained as a single peak. The elemental analysis showed an increased C and a decreased N content. U.v. and i.r. absorption spectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular weight of about 25 000, indicating the numbers of polymers conjugated to be about six units, two of which were found attached to the two amino groups. SMANCS was soluble in organic solvents, in contrast to NCS, and in water. SMANCS exhibited increased chemical and biological stability and appeared to possess similar in vitro biological activity.
Oral (PO) administration of KS-2 to adult DDI mice resulted in a peak serum interferon (IF) titer of 800 units (U)/ml 20 hours after administration with detectable levels persisting until 30 hours. After intraperitoneal (IP) injection, a peak serum IF titer of 1,600 U/ml was detected and it followed the same time course as that of oral administration. The IF induced by KS-2 shared certain physico-chemical properties with the standard preparation of immune IF and was not neutralized by an antiserum against type I IF. In mice infected intranasally (IN) with influenza A2 (H2N2) virus, KS-2 was found to possess significant protective activities. Efficacy of the agent was evidenced by an increase in survivor number, a prolongation of mean survival time, an inhibition of the development of lung consolidation induced by the viral infection and a decrease in virus titer in lung tissues. Both PO and IP administrations of KS-2 protected mice against infection and significant antiviral activities were achieved not only by prophylactic but also chemotherapeutic administration. The protective activities of KS-2 against influenza virus infection in mice are discussed in view of the immunopotentiation of the host animals.
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A highly lymphotropic derivative of a proteinaceous antitumor agent, Neocarzinostatin, was prepared by chemical conjugation of a water-soluble synthetic poly(maleic acid)-styrene oligomer. The derivative of 2.5 X 10(4) dalton exhibited a strong antitumor activity against AH109A and DBLA-6 as well as antimetastatic activity against metastatic AH109A with which experimental lymphatic metastasis was produced in rats. An increased lipophilicity and molecular weight of the derivative appear to be responsible for its improvement as lymphotropic antimetastatic agent.
Effect of a protein antitumor antibiotic, neocarzinostatin (NCS) was examined on Epstein-Barr virus (EBV)-carrying human lymphoid cell lines and normal human lymphocytes. A marked cytotoxic effect of NCS on umbilical cord lymphocytes freshly transformed by EBV was observed, whereas the cells before transformation were affected only very little by NCS. Majority of long-term cultured cell lines were affected only slightly, while shorter-term cultured lines were more susceptible to the effect of NCS. An uptake of FITC-labeled NCS into cells was examined by fluorescence microscopy. The incorporation by the freshly transformed cells was higher than that by the longer-term cultured cell lines. Normal lymphyocytes or heat-killed cells, however, incorporated FITC-NCS very little. On the basis of the known mode of action of NCS on DNA and the present observation, the cytotoxicity of NCS appeared to be exerted within the cells.
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