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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 613 records · Page 34Linked to original sources

Long-term toxicity and carcinogenicity study of sodium o-phenylphenate in B6C3F1 mice.

Sodium o-phenylphenate (OPP-Na) was given at dietary levels of O (control), 0.5, 1.0 and 2.0% to groups of 50 male and 50 female mice for 96 wk, and all the animals were maintained without OPP-Na for a further 8 wk. Both sexes given 2% OPP-Na and females given 0.5% and 1% OPP-Na showed growth retardation. Serum alkaline phosphatase activity in OPP-Na treated females was significantly increased in a dose-related manner. There were no treatment-related effects on clinical signs, mortality, urinalyses, haematology or organ weights. The incidences of several non-neoplastic and neoplastic lesions achieved statistical significance but none was considered to be related to treatment. There were increased incidences of haemangiosarcomas of the liver in males given 1% and of hepatocellular carcinomas in 1 and 2% males, and haemangiomas and leiomyomas of the uterus, present in the controls, were absent or decreased in all treated females. Therefore, this study did not demonstrate any clear carcinogenic effect of OPP-Na on mice at dietary levels of up to 2%.

Animals↗

Enhancement of N-bis(2-hydroxypropyl)nitrosamine-initiated lung tumor development in rats by bleomycin and N-methyl-N-nitrosourethane.

Potential modification of N-bis(2-hydroxypropyl)nitrosamine (DHPN)-induced lung carcinogenesis by bleomycin and N-methyl-N-nitrosourethane (MNUT) was investigated in male F344 rats. Rats were given 0.2% DHPN for 1 week followed by a weekly i.p. injection of either bleomycin at 2.0 mg/kg body wt or of MNUT at a dose of 1.0 mg/kg body wt for 35 weeks. Animals given DHPN followed by solvent administration alone, either saline or 0.02% ethanol and animals given bleomycin or MNUT without DHPN pretreatment were served as controls. Bleomycin treatment increased the incidence of cancer, whereas hyperplasia, adenoma and cancer of the lung were all significantly elevated after MNUT administration. MNUT alone induced low incidences of lung tumors. Bleomycin also increased the incidence of papillary or nodular hyperplasia of the urinary bladder while it inhibited the development of thyroid tumors. MNUT, however, did not affect tumor development in other organs.

Adenocarcinoma↗

Postoperative deep vein thrombosis--early diagnosis and prophylaxis.

The incidence of postoperative deep vein thrombosis (DVT) was investigated using the 125I-fibrinogen method and measurement of beta-thromboglobulin on surgical and gynecological patients. It was definitely lower in Japan as compared to Western countries. The age of 50 or more and malignant diseases were significant as risk factors for development of DVT. The presence of hypercoagulability before surgery and on the first postoperative day in addition to postoperative impaired fibrinolysis was considered to be the most important factor in development of DVT. The efficacy of the graded compression stocking for the prevention of DVT was confirmed, reducing from 13.5 per cent to 4.0 per cent. Furthermore, the most effective preventive method is the use of an intermittent pneumatic compression device for high risk patients with DVT.

Adult↗

Ribonucleotide reductase and thymidine kinase activities in various cultured cell lines derived from hematologic malignancies.

The activities of ribonucleotide reductase and thymidine kinase, and the thymidine incorporation rate were measured in 16 cultured human hematologic malignant cell lines with different cell proliferation rates. Thymidine kinase activity was significantly higher in myeloid and monocytoid cell lines than in other cell lines, but ribonucleotide reductase activity presented as CDP reductase activity was similar in the different cell lines. The ratio of thymidine kinase to CDP reductase activity was high in monocytoid cell lines. A close correlation was found between the cell proliferation rate and CDP reductase activity, but not thymidine kinase activity or the thymidine incorporation rate. The ratio of thymidine kinase to CDP reductase activity was high in slowly growing cell lines and low in rapidly growing cell lines. These results indicate that in cultured human malignant cells a high potential for proliferation may depend mainly on the de novo pyrimidine pathway of DNA biosynthesis.

Adolescent↗

Induction of forestomach hyperplasia by crude butylated hydroxyanisole, a mixture of 3-tert and 2-tert isomers, in Syrian golden hamsters is due to 3-tert-butylated hydroxyanisole.

Male Syrian golden hamsters were given 1.0% 2-tert- or 3-tert-butylated hydroxyanisole (BHA) or crude BHA for 1 to 4 weeks. The incidence of severe hyperplasia induced in the forestomach was high in the hamsters given 3-tert-BHA or crude BHA for 2 weeks or more, but was almost at the control level in those given 2-tert-BHA. Thus, the 3-tert isomer would appear to be responsible for the tumorigenicity of crude BHA.

Animals↗

Induction of rat mammary gland tumors by 1-nitropyrene, a recently recognized environmental mutagen.

1-Nitropyrene, a direct-acting mutagenic component of extracts of diesel exhaust and ambient air particulates, is one of the major nitroarenes found in products of incomplete combustion. Injection of this compound into newborn Sprague-Dawley-derived CD rats at 100 mumol/kg body weight s.c. once a week for 8 weeks induced 32 and 28% sarcomas, primarily malignant fibrous histiocytomas, at the site of injection in male and female animals, respectively. Mammary tumors, most of which were adenocarcinomas, developed distant from the site of injection in 47% of the females. Similar but lesser responses were observed in animals given one-half this dose. This carcinogenic response is consistent with the systemic effects of structurally related aromatic amines. 4-Nitrobiphenyl, given at equimolar doses, was not tumorigenic in this study.

Animals↗

Nuclear binding and sedimentation properties of two activated forms of glucocorticoid-receptor complexes from rat mammary glands.

Mammary cytoplasmic glucocorticoid-receptor complexes, which had been exposed to a high concentration of ammonium sulfate, were found to be separated into two receptor forms, consisting of DNA-cellulose-bound and non-DNA-cellulose-bound receptors. Experiments under cell-free conditions revealed that not only the DNA-cellulose-bound receptor but also the non-DNA-cellulose-bound receptor have binding abilities to nuclei and to nuclear chromatin. In sucrose density gradient centrifugation, the non-DNA-cellulose-bound receptor sedimented at higher sedimentation coefficients than the DNA-cellulose-bound receptor under all the salt conditions tested. These data strongly suggest that in the mammary glucocorticoid receptor system there exist at least two activated receptor forms with different conformations.

Animals↗

Postoperative deep venous thrombosis in Japan. Incidence and prophylaxis.

The incidence of postoperative deep venous thrombosis was investigated using the iodine-125-fibrinogen method in 256 patients undergoing major surgery. Deep venous thrombosis was found in 49 patients (15.3 percent), and nonfatal pulmonary embolism developed in one of seven patients in whom the thrombus extended to the popliteal vein. The same investigation was performed in 110 patients who wore a graduated compression stocking on one leg, with the other leg serving as a control. Deep venous thrombosis was found in 4 of 110 stockinged legs (3.6 percent) and in 16 of 110 control legs (14.5 percent). The incidence of deep venous thrombosis decreased significantly in patients who wore the stocking. An increase in femoral venous flow velocity was found in the stockinged legs by the Doppler method. The mean velocity of venous return by xenon-133 clearance was significantly greater in the stockinged legs than in the control legs. These findings were considered to support the efficacy of graduated compression stockings for the prevention of deep venous thrombosis.

Adolescent↗

Effect of quercetin on two-stage carcinogenesis of the rat urinary bladder.

The initiating and promoting effects of quercetin on urinary bladder carcinogenesis in male F344 rats were examined histopathologically. No tumor or hyperplasia were observed in rats given 5.0% quercetin as initiator in the diet for 4 weeks followed by 0.001% N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) for 29 weeks. Moreover, administration of 5.0% quercetin diet for 25 weeks after initiation with 0.01% BHBN for 4 weeks did not promote urinary bladder carcinogenesis. Furthermore, no lesions were detected in rats given 5.0% quercetin diet only. These results suggest that quercetin is not carcinogenic to rat urinary bladder.

Animals↗

Effect of phenobarbital on the carcinogenesis of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in rats.

Male Fischer rats were fed a N-[4-(5-nitro-2-furyl]-2-thiazolyl]formamide (FANFT) diet for 6 weeks followed by a phenobarbital (PB) diet for an additional 86 weeks. PB significantly increased the incidence of bladder tumors, but not the incidence of hepatic foci and areas of cellular alterations caused by FANFT. The results suggest that PB may be a weak promoter for bladder carcinogenesis, and that FANFT may not be an initiator for hepatocarcinogenesis.

Animals↗

Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia.

By using human T-cell growth factor (TCGF), 10 cell lines were established from tissue samples of 10 patients with adult T-cell leukemia (ATL). Three cell lines were adapted to growth in medium lacking TCGF. The surface markers of all cell lines were characteristic of inducer/helper T cells, i.e., OKT3+, OKT4+, OKT6-, OKT8-, OKIa1+, and human Lyt2+ and Lyt3+, except that one cell line was OKT3-. The expression of the viral antigen was examined during establishment of 8 of the 10 cell lines. The viral antigen was not expressed in leukemic cells before cultivation. In 5 lines, the viral antigen was detected by immunofluorescent staining after a short period of cultivation. However, 3 cell lines, ATL-6A, ATL-9Y, and ATL-1K did not express the viral antigen during short-term culture: the ATL-6A and ATL-9Y cell lines became positive for the viral antigen after 5 and 2 months of cultivation, respectively; the ATL-1K cell line remained antigen-negative throughout a culture period of 13 months. Southern blot hybridization assay showed that all of the cell lines, including the viral antigen-negative ATL-1K cell line, contained the viral genome. Thus, the retrovirus was associated with all 10 cell lines established from ATL patients, but there was a heterogeneity in the expression time of the retroviral antigen in leukemic cells maintained in vitro. Our findings suggested that the expression of the viral antigen was not required for maintenance of the leukemic state in vivo and for growth of leukemic cells in vitro.

Antigens, Surface↗

Coarctation of the aorta in early infancy. Left ventricular outflow tract obstruction and its clinical implications.

In order to clarify the clinical significance of left ventricular outflow tract obstruction, 11 infants with coarctation of the aorta and ventricular septal defect were subjected to cineangiography (or autopsy) analysis. Three infants without left ventricular outflow tract obstruction were salvaged by aortoplasty using a subclavian flap or a Dacron patch with concomitant pulmonary artery banding. The remaining 8 infants died surgically or nonsurgically, and were confirmed retrospectively to have had left ventricular outflow tract obstruction. It seems worthwhile to stress that the presence of an abnormal muscle bundle in the left ventricle can be demonstrated angiographically, especially by the axial technique. From our present study, though the number of cases examined is limited, we have an impression that left ventricular outflow tract obstruction may be a determining factor with regard to the appropriateness of pulmonary artery banding in the two-stage operation for infantile coarctation associated with a large ventricular septal defect.

Aortic Coarctation↗

Copper-binding proteins in the liver and kidney from the patients with Menkes' kinky hair disease.

Copper-binding proteins in the tissues from the patients with Menkes' kinky hair disease were examined by gel filtration on a Sephadex G-75 column. In the kidney, major part of copper was found to bind to low molecular weight protein, which corresponded chromatographically to metallothionein. This copper-binding protein contained a large amount of copper and a small amount of zinc. Cu: Zn ratio of this protein was different from that of metallothionein found in the fetal liver. In the liver of the same patient, however, there was no increase of copper bound to this protein.

Brain Diseases, Metabolic↗

Monoclonal antibody studies in B(non-T)-cell malignancies.

Tumor cells suspensions prepared from 129 B- or non-T cell malignancies were investigated with a panel of 10 monoclonal antibodies and conventional surface marker techniques. Surface immunoglobulin (sIg) and B1 antigen proved to be the most useful markers for B-cell lineage. Six major subtypes of acute lymphoblastic leukemia (ALL) of non-T cell nature are now recognized by these immunological techniques, including null-ALL, Ia-ALL, lymphoid stem cell ALL, pre-pre-B ALL, pre-B ALL and B-ALL. In cases of chronic leukemias and lymphomas of non-T cell nature, 80% of the tumor was defined by sIg and 88% by B1 antigen as definitely of B-cell lineage. The clonal character was also defined in 68% of the tumor on the basis of the detection of predominant single light chain in sIg. Ia-like antigen was detected in almost all cases (96%). Leukemic cells from all cases of chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (CLsCL) and hairy cell leukemia (HCL) reacted with OKIa1 and anti-B1, and leukemic cells from most of them with anti-pan T monoclonal antibody (10.2). In more than half of CLL and CLsCL, leukemic cells were reactive with J5, OKM1, 9.6 and OKT8, but not with OKT3, OKT4 and OKT6. HCL cells had almost the same reactivity with these monoclonal antibodies as CLL and CLsCL cells except that J5 remained unreactive. These results indicated that Japanese CLL, CLsCL and HCL were different from Western ones at least with respect to surface marker characteristics. In cases of lymphomas, heavy chains of sIg were expressed in polyclonal fashion, especially in follicular lymphoma and diffuse lymphomas of medium sized cell type and large cell type, indicating that lymphomas of these types may originate from follicular center cells of the heavy chain switching stage. Anti-T monoclonals were also reactive with lymphoma cells. In about half of follicular lymphomas and diffuse lymphomas of the medium sized cell type, lymphoma cells reacted with 10.2, and less frequently with 9.6, OKT4 and OKT3. On the other hand, only in one or two cases of diffuse lymphoma of the large cell type and of immunoblastic sarcoma (IBS), did tumor cells react with 10.2 and 9.6, but this was exceptional. In more than 25% of IBS, tumor cells also reacted with OKT8, but not with OKT4 and OKT3. These results indicated that anti-T monoclonals are no longer specific for T-cell lineage.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

Two novel cultured cell lines, A3/Kawakami and A4/Fukuda, derived from malignant lymphoma of B(non-T)-cell nature of the gastrointestinal tract.

A3/Kawakami was derived from ascitic lymphoma cells of a 68-year-old female patient with malignant lymphoma (non-Hodgkin's lymphoma, diffuse, large cell type) of the stomach and A4/Fukuda was derived from ascitic lymphoma cells of a 52-year-old female patient with double cancer of the colon (well-differentiated papillary adenocarcinoma and non-Hodgkin's lymphoma, diffuse, large cell type). The fresh ascitic lymphoma cells in the case of A3/Kawakami were surface immunoglobulin-positive, but the cultured A3/Kawakami cells no longer expressed any distinct markers. In the case of A4/Fukuda, the fresh ascitic lymphoma cells and cultured cells did not express any specific surface markers. Only 20% of A4/Fukuda cells were reactive with OKI1. However, a small amount of IgM could be detected in the cell extract and concentrated culture supernate of A4/Fukuda. In addition, A4/Fukuda cells heterotransplanted into anti-thymocyte sera-treated newborn hamster or athymic nude mice with a BALB/c genetic background were found to have weak surface immunoglobulin and distinct cytoplasmic immunoglobulin (gamma, mu). These data suggest that A4/Fukuda cells share the characteristics of the late differentiation stage of B-cell lineage (intermediate between mature B-cells and plasma cells). It was found that monoclonal antibodies, OKT4 and anti-Leu 3a, which are known to react specifically with inducer/helper T-cells, reacted to both A3/Kawakami and A4/Fukuda cells. The karyotypes of both A3/Kawakami and A4/Fukuda cells were very complicated but included some marker chromosomes such as 14q+.

Aged↗