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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 1,081 records · Page 60Linked to original sources

Progressive sinobronchiectasis associated with the "bare lymphocyte syndrome" in an adult.

A Japanese adult lacking the expression of HLA-A, HLA-B, and HLA-C antigens on the lymphocyte (the "bare lymphocyte syndrome") had recurrent sinopulmonary infections and diffusely progressive bronchiectasis. Class I antigen and beta 2-microglobulin on the lymphocytes of the patient, his siblings, his father, and healthy subjects were assayed by using monoclonal antibodies against these surface markers. Class I antigen and beta 2-microglobulin were not found on the lymphocytes of the patient and the Daudi cells. In addition, lymphocytes of his siblings showed low fluorescence intensity. The HLA molecule on the lymphocyte plays an important role at the stage of recognition of immunogenic antigens. These results might suggest a correlation between sinobronchiectasis and the deficiency of HLA molecules, and the importance of the HLA system in the immune defense mechanism.

Adult↗

A kindred of familial combined hyperlipidemia (FCHL) with proband showing type V hyperlipoproteinemia.

A case of familial hyperlipidemia incidentally found through a 16 year-old high school girl with type V hyperlipoproteinemia and abdominal bouts consistent with this type of hyperlipemia is reported for the first time in Japan. The laboratory findings of the plasma of her father revealed typical hyperlipoproteinemia of type IIa. Nineteen of her 26 kindred were investigated. Type V was seen only in the proband, type IIa in father, paternal grandmother, two paternal aunts, and two paternal cousins, type IV in three paternal cousins. The serum apolipoprotein (apo A-I, A-II, B, C-II, C-III, and E) concentrations were determined by the single radial immunodiffusion technique. The apolipoprotein concentrations were not different from those of normolipidemic control subjects except for apo B, which was higher in the hyperlipidemic members, and apo C-II, C-III, and E, which were higher in the proband.

Adolescent↗

Stimulation of macrophage by polyanions and its conjugated proteins and effect on cell membrane.

Lipophilic anionic copolymer (styrene-maleic acid; SMA) conjugates of albumin and antitumor protein neocarzinostatin (NCS) (smancs) were found to stimulate the release of H2O2 and O-2 from the peritoneal macrophages obtained from mice which had been pretreated with the heat-killed preparation of Streptococcus pyogenes (OK-432) in vivo. Some alkyl esters of SMA exhibited effects similar to protein-polymer conjugates. Among them, butyl-SMA was the most effective followed by ethyl-SMA, whereas hydrolyzed SMA showed no effect. This activity was dose-dependent but exhibited a bell-shape profile. These results suggest that the aliphatic ester residue in SMA as well as the main chain of the copolymer may be important for the activation of macrophages. A strong antitumor effect of smancs reported elsewhere may be attributed partly to the activation of macrophages in addition to the direct damage to the cellular DNA by the NCS component. A preliminary investigation of the subcellular mechanism of macrophage activation was carried out in view of membrane fluidity by the fluorescence polarization method. The results showed that the apparent decrease in the cell membrane fluidity and the degree of macrophage activation paralleled the same dose range and at similar time courses. This indicated the interaction of SMA component and macrophage cell membrane.

Animals↗

[Targeting of anticancer chemotherapy utilizing the characteristic nature of the neovasculature of solid tumors].

We have been able to achieve targeting of anticancer treatments using the differences between the neovasculature of solid tumors and the vasculature of normal tissues. The first of these differences was as follows; We discovered that when the lipid contrast medium, Lipiodol, was administered arterially, it remained selectively in the solid tumor for a long time. Using this characteristic nature of Lipiodol, we achieved targeting of anticancer chemotherapy by arterial administration of oily anticancer drugs solubilized in Lipiodol. Remarkable anticancer effects against various malignant solid tumors were observed using this targeting chemotherapy. The second of the above differences, studied by Suzuki, is responsiveness to angiotensin II, in which the blood flow in the tumor can be increased using this vasoconstrictor. With Angiotensin II, a larger volume of oily anticancer drugs could be delivered to the tumor. The third difference is the permeability of the neovasculature to drugs of high molecular weight and the duration that these drugs remain in the extracapillary space. The high-molecular-weight anticancer agent, SMANCS (m.w. 17,000) dissolved in 5% glucose solution, was administered intravenously, and its histological antitumor effects on gastric cancer and esophageal cancer were clearly observed.

Angiotensin II↗

A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs.

We previously found that a polymer conjugated to the anticancer protein neocarzinostatin, named smancs, accumulated more in tumor tissues than did neocarzinostatin. To determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins of various molecular sizes (Mr 12,000 to 160,000) and other properties. In addition, we used dye-complexed serum albumin to visualize the accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of these mice, and a ratio of the protein concentration in the tumor to that in the blood of 5 was obtained within 19 to 72 h. A large protein like immunoglobulin G required a longer time to reach this value of 5. The protein concentration ratio in the tumor to that in the blood of neither 1 nor 5 was achieved with neocarzinostatin, a representative of a small protein (Mr 12,000) in all time. We speculate that the tumoritropic accumulation of these proteins resulted because of the hypervasculature, an enhanced permeability to even macromolecules, and little recovery through either blood vessels or lymphatic vessels. This accumulation of macromolecules in the tumor was also found after i.v. injection of an albumin-dye complex (Mr 69,000), as well as after injection into normal and tumor tissues. The complex was retained only by tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis.

Albumins↗

[CT image of the liver cancer after administration of SMANCS/lipiodol].

A new type of anticancer agent with an amphiphilic nature, poly (styrene-co-maleic acid)-conjugated neocarzinostatin [SMANCS], was dissolved in the lipid contrast medium Lipiodol [SMANCS/LPD]. This medium was injected intra-arterially and was found to be an invaluable tool for highly sensitive CT image analysis of tumors. Following administration, CT images revealed high-density areas which corresponded to the location and size of liver cancer, the smallest being 4 mm in diameter. The deposition pattern of SMANCS/LPD in liver cancers by CT was classified into 3 types. In type A, Lipiodol was distributed relatively evenly in the tumor lesion, while in type B it was accumulated predominantly around the tumor periphery, the central portion remaining low in density. A for cases exhibited a type C pattern which was a mixture of types A and B. Type A was found essentially in primary liver cancer, and types B and C in secondary liver cancer. Thus, the CT pattern was found to be useful for differential diagnosis. For a sufficient therapeutic effect, 0.08 ml of SMANCS/LPD per cm2 of the maximal CT cross-section of the tumor area was found to be necessary. As a routine protocol after SMANCS/LPD administration, CT scanning was recommended for primary liver cancer initially at one week and then once every month. Secondary liver cancer required more frequent CT follow-ups after administration, on the 3rd day, after one and two weeks, and every month, due to the relatively rapid disappearance of the stain than in primary liver cancer.

Antibiotics, Antineoplastic↗

[Stability of high molecular weight anticancer agent SMANCS and its transfer from oil-phase to water-phase. Comparative study with neocarzinostatin].

SMANCS is a conjugate protein of copolymer of styrene-maleic acid [SMA] (molecular weight: 1,500) and an antitumor protein neocarzinostatin [NCS] (molecular weight: 11,700). It has an approximate molecular weight of 15,000. We report here stability of SMANCS in oil and in water, and NCS in water, under various physical conditions such as exposure to heat, UV, pH, and ultrasonic treatment. Then, we carried out an experiment of transfer of SMANCS in lipid contrast medium [lipiodol] (oil phase) to water phase (blood and physiological saline) in vitro. Results are summarized as follows: In aqueous condition, SMANCS is far more stable than NCS against the exposure to heat and UV, though it is inactivated by excessive exposures. SMANCS in an oily medium was found much more stable even at higher temperatures than in the aqueous phase. Both SMANCS and NCS are the most stable at pH 4.9-6.0. SMANCS dissolved in oil transferred to water phase slowly, having T1/10 of 24 hours (in case of lipiodol). This helps maintaining the anticancer effect of the drug in vivo for a long period of time. SMANCS in lipiodol was found to exert its action against cultured tumor cells as in an aqueous solution.

Antibiotics, Antineoplastic↗