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Biomedical subjects

I Kawamura

Publications and source records attributed to I Kawamura.

At least 91 records · Page 5Linked to original sources

A new antitumor antibiotic, FR900840. III. Antitumor activity against experimental tumors.

FR900840 [2S)-2-amino-2-carboxyethyl (3R)-2-diazo-3-hydroxybutyrate), a new antibiotic with antitumor activity was isolated from the fermentation broth of Streptomyces sp. No. 8727. Its antitumor activity was examined in three mouse tumor systems and ten human tumor systems. FR900840 had no clear effect on mouse ascitic tumors, P388 and L1210, and the B16 melanoma line, but had prominent antitumor effects on several human solid tumors. Its antitumor activity against A549 human lung adenocarcinoma was stronger than those of vinblastine, doxorubicin and cisplatin. These results suggest that FR900840 may become a useful prototype antitumor drug.

Adenocarcinoma↗

Treatment of autoimmune MRL/lpr mice with anti-B220 monoclonal antibody reduces the level of anti-DNA antibodies and lymphadenopathies.

The predominant accumulating cells in the lymphoid tissue of MRL/lpr mice have been shown to carry the B220 cell marker. This antigen is expressed on B cells and on T-cell precursors. In order to know the pathogenic involvement of cells carrying this marker, we treated MRL/lpr mice periodically with RA3-6B2, a specific anti-B220 monoclonal antibody, or rat IgG2b as a control. After 12 weeks of treatment, a significant reduction (P less than 0.01) in the size of the lymph nodes and spleen was observed only in the group treated with RA3-6B2 monoclonal antibody. This reduction was mainly due to a decrease in the Thy-1.2+ and B220+ subpopulations. Anti-DNA and anti-Sm antibody titres were also reduced significantly (P less than 0.01) after the therapy. Proliferative response to mitogens (Con A, PHA, LPS) and IL-2 production was not improved after the anti-B220 treatment. These results suggest a pathogenic role of lymphocytes carrying the B220 marker in the autoimmune disease of MRL/lpr mice.

Animals↗

[A case of mitochondrial encephalomyopathy with cardiomyopathy due to decreased complex I and IV activities].

We reported a girl with mitochondrial encephalomyopathy, who had various neuromuscular symptoms including dilated cardiomyopathy, generalized convulsions, myoclonus, muscular weakness and growth retardation. Lactate levels in the serum and CSF were elevated. Muscle biopsy showed scattered ragged-red fibers, and complex I (NADH-CoQ reductase) and complex IV (cytochrome c oxidase) were markedly reduced. Although she was treated with coenzyme Q, DL-carnitine and sodium succinate, she died of progressive congestive heart failure at 9 10/12 years of age.

Cardiomyopathy, Dilated↗

Immunomodulatory effects of cholera toxin in mice.

Immunomodulatory effects of cholera toxin (CT) were investigated in a murine model using various immunological parameters. C3H/HeN mice were injected with 2 micrograms of CT at various intervals (from 6 h to 21 days) before the immunological assays. Thymocytes were markedly decreased in their absolute number, and the phenotypes in such cells were clearly shifted from Thy1.2high+ PNAhigh+ to Thy1.2low+ PNAlow+ 2-4 days after the CT treatment. Spleen T cells were relatively increased, while surface IgM positive B cells were rather decreased. Natural killer activity and in vivo and in vitro cytotoxic T lymphocyte activity were markedly suppressed during the early stages after the CT treatment but recovered completely within 21 days. Mixed lymphocyte reaction was profoundly suppressed at least for the 1st week after the CT treatment. Furthermore, EL-4 tumor of C57BL/6 origin grew progressively and killed the recipient C3H mice when such tumor cells were inoculated 6 h after the CT treatment. On the contrary, a marked augmentation of direct (IgM) and indirect (IgG) plaque-forming cell responses to sheep red blood cells was seen after CT treatment. Delayed footpad reaction to SRBC was also augmented after CT treatment. As the mechanisms, both direct augmentation of CD4+ T cells and direct suppression of CD8+ T cells appeared to occur at a time due to the CT treatment. An indirect effect of CT through the release of the endogenous steroids was dismissed in the present study. Taken together, CT appears to have differential immunomodulatory effects on various immune effector cells through various mechanisms.

Animals↗

Antiestrogenic and antitumor effects of droloxifene in experimental breast carcinoma.

The pharmacological effects of droloxifene [E)-a [p-[2-(dimethylamino)ethoxy]phenyl]-a'-ethyl-3-stilbenol, FK435), a new antiestrogen drug, were studied and compared with those of tamoxifen in animals and in vitro cultured cells. Droloxifene showed about 20-fold and 3-fold higher affinity to estrogen receptors (ER) in the rat uterus and human ER positive MCF-7 breast carcinoma cells, respectively, than tamoxifen, and was more active in decreasing uterine weight of mature rats and 17 beta-estradiol-treated immature rats. Tamoxifen increased uterus growth in immature rats, but droloxifene did not, suggesting that droloxifene has no estrogenic effects. Both drugs inhibited the growth of in vitro cultured MCF-7 cells, with droloxifene being the more active agent, but this effect of both drugs was countered by 17 beta-estradiol. Neither drug, however, had effects on the in vitro growth of human ER negative MDA-MB-231 breast carcinoma cells. In vivo, both drugs inhibited the growth of MCF-7 carcinoma implanted subcutaneously in BALB/c nu/nu mice, but not the growth of human ER negative MX-1 breast carcinoma. The results suggest that droloxifene has antitumor effects on human ER positive breast cancers, and would be useful for the treatment of estrogen-dependent breast cancers.

Animals↗

The Perrault syndrome: clinical report and review.

We report on two Japanese sisters with Perrault syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They also had ataxic gait, pes equinovarus, nystagmus, limited extraocular movements, and short stature. One older affected sister had partial growth hormone deficiency. Our review included 21 patients from 8 families, including our patients; 16 are women with ovarian dysgenesis and deafness, 3 deaf males without gonadal defect, one a woman with ovarian dysgenesis without deafness, and one a girl with deafness in whom ovarian function was not evaluated. Perrault syndrome may not be uncommon; some cases may have gone unrecognized, especially when a single child in a family is affected.

Adolescent↗

Fatty metamorphosis in hepatocellular carcinoma: radiologic features in 10 cases.

We describe the sonographic, CT and angiographic findings in 10 cases of hepatocellular carcinoma in which extensive fatty metamorphosis occurred within the tumors. Fatty change was diffuse in smaller tumors (less than 3.5 cm) and focal in larger tumors (greater than 3.5 cm). Fatty metamorphosis characteristically caused a low-attenuation area on CT (less than -10 H) and a highly echogenic area on sonography. The sonographic appearance of small hepatocellular carcinomas with fatty metamorphosis was identical to the findings in cavernous hemangioma or focal fatty change of the liver. CT correctly revealed the presence of fat in these hepatocellular carcinomas. In these cases, hepatic arteriography showed no tumor stain; however, CT arteriography (dynamic CT during injection of contrast medium into the hepatic artery) was useful in showing the tumor, its capsule, and its internal septa. In the diagnosis of large hepatocellular carcinoma, the presence of intratumoral fat is not likely to be problematic, but small tumors that are diffusely infiltrated by fat must be distinguished from such benign conditions as focal fatty change, lipoma, and angiomyolipoma.

Aged↗

Staining in the liver surrounding gallbladder fossa on hepatic arteriography caused by increased cystic venous drainage.

In 8 patients with gallbladder disease in whom no extension of the disease to the liver was confirmed by surgery, wedge-shaped (segmental) staining of the liver just adjacent to the gallbladder fossa (gallbladder bed) on hepatic arteriography was seen. This was always accompanied by definite visualization of the cystic veins with the drainage directed to the gallbladder bed and became most dense following the peak of the opacification of the cystic veins. We therefore concluded that the increased cystic venous drainage to the intrahepatic portal vein causes the staining in the nondiseased gallbladder bed on hepatic arteriography.

Angiography↗

Antigen-specific augmentation factor involved in murine delayed-type footpad reaction. IV. Effect of delayed-type hypersensitivity augmentation factor on in vitro induction of DTH.

We found an antigen-specific factor capable of augmenting delayed-type hypersensitivity (DTH) in the serum of mice sensitized with heterologous erythrocytes to induce a delayed footpad reaction (DFR), or in the culture supernatant of the mixture of sensitized T cells and specific antigens. This factor (DTH augmentation factor; DAF) was confirmed to augment DTH in transferred recipients. In this paper, such an activity of DAF was further investigated using the system with in vitro induction and local transfer of DTH. DAF also augmented the primary in vitro induction of DTH, when spleen cells from mice transferred with the DAF-containing serum 12 hr previously or spleen cells incubated with the DAF-containing serum on ice for 2 hr were cultured with heterologous erythrocytes. DAF acted on the induction phase of DTH and augmented a typical DTH which was dependent on Thy-1-positive T cells. DAF showed antigen specificity, but was not assigned to conventional immunoglobulin. The activity of DAF was detected when nylon-wool nonadherent cells were incubated with DAF prior to the culture of those cells and antigens, but not detected when only nylon-wool adherent cells were incubated with DAF. Thus, DAF exerted its effect through binding to acceptor cells which were included in nylon-wool nonadherent spleen cells from normal mice.

Animals↗

Transfer of resistance to primary infection of Listeria monocytogenes and early induction of delayed hypersensitivity by sera from L. monocytogenes-infected mice.

We found a new phenomenon which differs from previous reports on experimental listeriosis, that is, failure of passive transfer of serum from Listeria monocytogenes-infected mice to convey resistance to the bacterium. Transfer of immune serum from L. monocytogenes-infected mice markedly augmented resistance to the bacterium, and mechanisms of the transfer of L. monocytogenes-immune serum were investigated. Transfer of immune serum prevented L. monocytogenes lethality. This effect of the immune serum was transferred dose dependently. Augmentation of resistance to L. monocytogenes also appeared in elimination of bacteria from the spleen. The growth of bacteria within 2 days in the spleen was not inhibited. Transfer of the immune serum augmented and accelerated induction of a delayed footpad reaction. Delayed hypersensitivity-dependent accumulation of mononuclear cells, detected by focus formation reaction in the liver, was also augmented. In contrast, polymorphonuclear cell accumulation in the liver was suppressed. Development of delayed hypersensitivity reactions was correlated with the elimination of bacteria in the spleens. These effects of the immune serum were expressed antigen specifically; however, the effector molecule(s) in the immune serum differs from immunoglobulin molecules.

Animals↗

Hepatic artery embolization of experimental hepatic tumors with absolute ethanol.

Hepatic artery embolization with absolute ethanol (HAEE) was done in rats and rabbits with experimentally induced liver tumors, and its effects on liver parenchyma and tumors were analyzed microscopically in comparison with those of controls. HAEE with 0.1 ml in rats brought massive tumor necrosis and minimal damage to liver parenchyma. But HAEE with 0.15 ml in rabbits induced moderate to massive necrosis of liver parenchyma with minimal to moderate tumor necrosis. Damage to the intrahepatic bile ductules was also seen in both animals. Many problems should be resolved before clinical use.

Animals↗

Use of an intravenous branched chain amino acid enriched diet in the tumor-bearing rat.

The purpose of this study was to determine whether a branched chain amino acids (BCAA) enriched intravenous feeding would have an effect on nitrogen retention in the host tissue, without stimulating tumor growth in the malignant tumor bearing animal. NEDH/c rats with an implanted fibrosarcoma were put on one of two total parenteral nutrition regimens, one of an amino acid formula containing 25 per cent BCAA, by weight and the other containing 50 per cent BCAA. Nitrogen retention in the two tumor-bearing groups was similar, although it was 47 per cent greater than observed in the non-tumor bearing animals (p less than 0.05). Skeletal protein synthesis was significantly reduced by the presence of the tumor in rats on the 25 per cent BCAA formula (from 10.1 per cent/day to 6.1 per cent/day) but was increased to 7.9 per cent/day by the 50 per cent BCAA formula. The BCAA enriched intravenous feeding does not enhance tumor growth and supports skeletal protein synthesis, at least in this experimental model.

Amino Acids, Branched-Chain↗

Activation of tumoricidal properties in macrophages and inhibition of experimentally-induced murine metastases by a new synthetic acyltripeptide, FK-565.

The effect of FK-565, a novel low molecular weight (MW) acyltripeptide, on tumoricidal properties of murine macrophages is reported here. Peritoneal macrophages (PMs) harvested from C57BL/6 mice and beige mice were rendered cytotoxic to syngeneic B16 melanoma cells following their interaction in vitro with FK-565. Maximal and reproducible activation of tumoricidal properties in PM were obtained by interaction in vitro with 25 micrograms/ml of FK-565 for a 24 h period, and as little as 0.5 microgram/ml of FK-565 was sufficient to induce significant cytotoxicity. Murine PMs activated by FK-565 in vitro were cytotoxic to syngeneic and xenogeneic tumor cells, but did not affect allogeneic nontumor cells. The PMs were also activated to kill B16 melanoma cells by intraperitoneal injections of FK-565 (10 mg/kg). Multiple injections of FK-565 into mice also slightly but significantly inhibited lung metastases. These results suggest that FK-565 has potential as an effective immunopotentiator in immunotherapy.

Adjuvants, Immunologic↗

"Zero-position" functional shoulder orthosis.

The "zero-position" of the shoulder joint described by Saha (1961) is recognized as a mechanical position between scapula and humerus, and the "scapular plane" is widely accepted as a mechanical plane at the shoulder joint. On the basis of biomechanical concepts of the "zero-position" and the "scapular plane", the authors designed the "zero-position" functional shoulder orthosis. This orthosis has been successfully fitted to more than 75 patients for the postoperative management of rotator cuff injuries, and to 3 patients for the treatment of scapular neck fractures. It is introduced here, together with biomechanical considerations, structure, functional and clinical results.

Biomechanical Phenomena↗