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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 1,189 records · Page 66Linked to original sources

[Arterial administration of SMANCS and other antitumor agents dissolved in lipiodol for various malignant solid tumors].

Selective deposition of lipiodol in primary and metastatic liver cancer, lung cancer, gallbladder cancer, pancreatic cancer and renal cancer was elucidated by plain X-ray film and CT. Selective delivery of anticancer agent, SMANCS was also proved by measurement of its biological activities of removed specimen. Because of these selective delivery of anticancer agent and embolization of neovasculature in the tumor, highly effective chemotherapy of unresectable cancer was established. Drug was given via celiac, the hepatic, bronchial or renal artery mostly 1-5 mg in 1-5 ml of lipiodol once every 3-8 weeks. Antitumor effects of this therapy for hepatocellular carcinoma was confirmed based on decrease in AFP levels (92% of the cases), reduction in tumor size (90% of the cases) and histology. In 76 percent of the patients with the other malignant solid tumors reduction in tumor size was recognized. Decrease in CEA level occurred in 88 percent of the cases with metastatic liver cancer and lung cancer. Major side effect was transient fever in about 50% of cases. Mitomycin C and aclarubicin dissolved in lipiodol showed remarkable antitumor effects for experimental liver cancer.

Aclarubicin↗

Two-dimensional gel analysis of a second family of class II molecules by polymorphic HLA-DR4,5, and w9 monoclonal antibodies.

Human Ia-like, class II molecules were isolated by immunoprecipitation with monoclonal antibodies from various HLA-D/DR homozygous cell lines and were analyzed by two-dimensional gel electrophoresis. The monoclonal antibody PLM12 reacted with B cells carrying DR4, DR5, DRw6.2, and DRw9 phenotypes, and its reactivity perfectly correlated with the previously defined TB21 (MB3-like) specificity. Class II molecules detected by PLM12 were structurally distinct from those precipitated by the anti-DR monoclonal antibody NC1 on all HLA-DR4, DR5, DRw6.2, and DRw9 homozygous cell lines and showed polymorphism in heavy and light chains among these cell lines. The monoclonal antibodies PLM2 and PLM9 only reacted with B cells carrying DR5 and DRw6.2 and also detected a distinct set of class II molecules from those precipitated by NC1 but identical to those of PLM12. Thus, PLM2 and PLM9 serologically detected a new subtypic antigen of the PLM12-reactive class II molecules. Furthermore, the antibody NC1 precipitated two light chains and one heavy chain from HLA-DRw6.2 homozygous cell line EBV-Sh. The result indicated the presence of three sets of class II molecules: two in a DR family and another carrying the polymorphic determinants detected by PLM2, PLM9, and PLM12 in a second family.

Animals↗

Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image.

Highly malignant rabbit tumor (VX-2) was implanted at the periphery of the liver in 63 rabbits. Selective delivery of the anticancer agent copoly(styrenemaleic acid) conjugated to neocarzinostatin (SMANCS), which was dissolved in an oil contrast medium (Lipiodol), was performed by injection via the proper hepatic artery. The anticancer effect was also evaluated by various parameters. By using low-kVp X-ray examination of the resected rabbit liver, Lipiodol was found to distribute throughout the entire liver arterial lumina and was retained there for about 24 hr, but disappeared from the normal liver arterial lumina gradually. However, Lipiodol was retained in the tumor tissue and vessels for at least 7 days, whereas it was undetectable in any other organs. A radioactive analogue of Lipiodol, a chloroiodinated fatty acid, was prepared by using [14C]linoleic acid. This analogue was used in the study of the distribution by low-kVp X-ray examination, Sudan III staining, and autoradiography. Lipiodol remained in the tumor vessels as well as the tumor cells. The use of the radioisotope yielded a quantitative profile of Lipiodol accumulation in tumor tissues; approximately 1000 times more at 15 min and 100 times more at 3 days after the injection than that of most other organs or plasma. Its major excretion route appeared to be through the bile and then the feces. The biological activity of SMANCS was also determined and was found to be significant in both tumor and liver even 7 days after injection. No activity was found in any other organ or tissue. The relatively high biological activity of SMANCS in the nontumorous liver adjacent to the tumor may be the result of continuous drug release from SMANCS-Lipiodol in the tumor tissue. By histological examination, massive tumor necrosis and infiltration of the inflammatory cells were found in the rabbits treated with SMANCS-Lipiodol. In the rabbits treated with Lipiodol alone, necrosis of the tumor was only minimal, and no infiltration of inflammatory cells was observed. Survival periods of the treated rabbits (n = 14) were significantly longer than those of controls (n = 10); 23.1 +/- 5.5 (S.D.) days versus 16.1 +/- 2.9 days (p less than 0.005), respectively, even though only one injection was used for this highly malignant tumor. Mean tumor size for both groups at laparotomy was 163.3 +/- 83.0 sq mm and 160.5 +/- 76.5 sq mm, respectively (not significant).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[Tumor selective drug delivery with lipid contrast medium (smancs/lipiodol): sustained antitumor effect, enhanced diagnostic value and quantification of dosage regimen].

A new method for the treatment of solid tumor, in particular, primary and metastatic liver cancer using a hydrophobic-polymer conjugated macromolecular anticancer agent, smancs is described. Smancs was dissolving in a lipid contrast medium, Lipiodol, as an injection into the feeding artery. The marked antitumor effect was observed in both experimental animals and human trials. In the patients with hepatocellular carcinoma, both reductions in tumor size and alpha-feto-protein were observed in 91% of the patients. The survival period of the treated patient with highly advanced stage and inoperable cases was comparable to or better than that of resected cases. No major side effect such as bone marrow suppression or liver toxicity was observed due to selective drug delivery to the tumor. About half of the patients, however, showed a transitory fever (37-39 degrees C) for 1-3 days. The mechanism for such selective tumor targeting of anticancer agent appears to be due to the difference in the vascularity of tumor and normal tissue. Furthermore, we found that lack of lymphatic clearance system in the tumor made the prolonged and selective retention of such lipophilic drug in the tumor tissue possible. Another advantages of this method are found in radiological approaches. Differential diagnosis of primary or metastatic cancer became possible and dosing regimen can be determined since a presence of the contrast medium is restricted to the tumor area and it parallels to that of the drug being dissolved. Insufficiency in X-ray staining indicates a need for subsequent injection. The selective remaining of Lipiodol in the tumor for long period may help follow-up study as well.

Animals↗

[Epidemiology of lung cancer in Nagasaki--especially in relation to radiation exposure].

We investigated the present incidence of lung cancer and its distribution by histologic type in Nagasaki City using Nagasaki Tumor Registry data from the years 1973-1977. The risk of radiogenic lung cancer did not increase significantly in either sex. The difference in relative distribution by histologic type between the exposure and non-exposure groups was not significant. Further analyses should be carried out on the risk present for individuals who were young at the time the bomb was dropped and the effect of exposure distance on the incidence and histologic types of lung cancer in A-bomb survivors.

Adenocarcinoma↗

Molecular identifications of HLA-DR4, MT3, and TB21 antigens on HLA-DR4 homozygous B cell lines.

The HLA-DR locus in the human major histocompatibility complex determines a series of polymorphic cell surface antigens; these antigens are composed of two noncovalently associated glycoproteins of 34,000 daltons and 29,000 daltons and are predominantly expressed on B cells, monocytes, and activated T cells (1). To date, 10 HLA-DR specificities have been well characterized by using alloantisera obtained from multiparous women (2). In addition to these DR antigens, two other B cell alloantigen systems (MT and MB) were proposed on the basis of the serologic data (3,4); the MB1 or MT1 specificities are found in association with DR1, DR2, and DRw6, whereas MT2 is associated with DR3, DR5, DRw6, and DRw8; MT3 is associated with DR4, DR7, and DRw9, and MB3 or MT4 is associated with DR4, DR5, and DRw8, respectively (3, 4). We have also described that the TB21 antigen is expressed in association with DR4, DR5, and DRw9 (5). The HLA-DR, MB, MT, or TB antigens are collectively referred to as class II antigens. The number of human class II antigens has been of primary concern because of their similarity to murine Ia antigens and especially because of their close relationship to certain diseases. With the aid of immunochemical means and alloantisera, it has been demonstrated that at least two loci control human class II molecules (6-10). The data presented in this report show the existence of three class II molecules carrying well-known allospecificities, DR4, MT3, and TB21, on HLA-DR4 homozygous cell lines.

Antigen-Antibody Reactions↗

[The mutagenicity evaluation of MT-141, a new cephamycin].

Mutagenicity of MT-141, a new cephamycin, was evaluated by in vitro and in vivo assays. MT-141 did not induce mutations of the test strains, Escherichia coli WP2 (uvr A) and Salmonella typhimurium TA1535, TA1537, TA1538, TA100 and TA98, with and without metabolic activation in vitro. In bone marrow micronucleus assay with male mice, MT-141 showed no induction of micronucleated polychromatic erythrocyte at 6 hours and 30 hours after administration. In addition MT-141 was found not to cause any dominant lethal effects on male mice for 8 weeks after administration.

Animals↗

Identification of the MT3 molecule from HLA-DR4, 7, and w9 homozygous cell lines.

Human B lymphoblastoid cell lines are known to express several class II antigens. The MT3 specificity defined by alloantisera is in linkage disequilibrium with DR4, DR7, and DRw9, and is called a "supertypic" specificity. To identify the MT3 molecule, immunoprecipitates of HLA-DR and MT3 antigens from extracts of three metabolically labeled HLA-DR homozygous cell lines (Wa;DR4, L-Pi-tot;DR7, L-KT12;DRw9) were analyzed by two-dimensional gel electrophoresis. The light chains of the MT3 antigens from DR4, DR7, and DRw9 homozygous cell lines were indistinguishable from one another in charge and m.w. The light chains of the MT3 antigens differed from those of DR4, DR7, and DRw9 antigens, whereas the heavy chains of the MT3 and DR antigens were indistinguishable. The MT3 antigen appears to share the same heavy chain as the DR antigens. However, this antigen would constitute a new human class II molecule distinct from the DR antigen. These data also raised the possibility that the light chains of the MT3 molecules may be the products of a new locus different from the DR locus.

B-Lymphocytes↗

A case of congenital nephrotic syndrome associated with partial deficiency of lecithin cholesterol acyltransferase (LCAT) and hypothyroidism.

The case of a 3 year-old boy with congenital nephrotic syndrome is reported, in whom decreased LCAT activity and hypothyroidism were also present. Renal biopsy confirmed a diffuse proliferative glomerulonephritis with a large number of foam cells in the capillary lumen of the glomerulus and the interstitium, which stained positively with acid phosphatase indicating the presence of macrophage with phagocyted lipid vacuole. The histological picture was similar to that of familial LCAT deficiency, but the reported case is one of secondary LCAT deficiency as a result of urinary loss of the enzyme. Replacement therapy with thyroid hormones resulted in improvement in growth and development.

Child, Preschool↗