8-(Dicyclopropylmethyl)-1,3-dipropylxanthine: a potent and selective adenosine A1 antagonist with renal protective and diuretic activities.
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Animals↗
Biomedical subjects
F Suzuki
Publications and source records attributed to F Suzuki.
Demonstration of right and left atrial dissociation by atrial rapid pacing or extrastimulation during fast-slow (uncommon) form of atrioventricular nodal reentrant tachycardia.
Some recent works suggest that extranodal atrial fibers may form part of the reentry circuit in the atrioventricular (AV) nodal reentrant tachycardia (AVNRT). This hypothesis is based on the fact that the perinodal dissection successfully abolished AVNRT while preserving intact AV conduction. Apart from the surgical success, the electrophysiological evidence supporting this hypothesis has not been demonstrated, especially in the uncommon (fast-slow) form of AVNRT. We present some electrophysiological evidence suggesting atrial participation in eight patients with the fast-slow form of AVNRT. During the tachycardia, rapid pacing or extrastimulation was done from the orifice of the coronary sinus (CS) and the right atrium (RA), while recording the electrograms of the CS and the low septal RA. In seven patients, right and left atrial dissociation was demonstrated during pacing from the RA, while in the remaining one this was demonstrated from the CS. The interatrial dissociation will be unlikely if the intranodal reentry circuit connects with the atria via a single upper common pathway. This suggests that the upper turnaround of the reentry circuit involves atrial tissue and that the extranodal accessory pathway with long conduction times may form the ascending limb of the circuit (atrionodal reentry). Alternatively, the reentry circuit is entirely intranodal and two or more connecting pathways are present between the atria and the circuit.
Adult↗
Effects of various growth and differentiation factors on expression of parathyroid hormone receptors on rabbit costal chondrocytes in culture.
In our preliminary report we demonstrated PTH receptors on rabbit costal chondrocytes in culture. In the present study regulation of expression of PTH receptors of the chondrocytes by various growth and differentiation factors and its relation to the synthesis of glycosaminoglycan (GAG), a differentiated phenotype of chondrocytes, were investigated. Treatment with retinoic acid decreased GAG synthesis in cultured chondrocytes and the number of PTH receptors, measured by binding of [125I]-[Nle8,18,Tyr34]bovine PTH-(1-34) amide to the cells. However, the affinity of the receptors did not change. The decrease in the number of PTH receptors was dose and time dependent and parallel to the decrease in GAG synthesis. When chondrocytes that had been treated with retinoic acid were cultured in the absence of retinoic acid for 3 days, both their GAG synthesis and their number of PTH receptors were restored. Epidermal growth factor and fibroblast growth factor also decreased both the number of PTH receptors and GAG synthesis in the cells. However, these treatments did not change their affinity. Treatment with insulin-like growth factor-I, (Bu)2cAMP, and transforming growth factor-beta resulted in increases in GAG synthesis as well as in the number of PTH receptors without any change in their affinity. In addition, the PTH-stimulated cAMP level in chondrocytes pretreated with retinoic acid, epidermal growth factor, and fibroblast growth factor was lower than that in control cells. On the other hand, the PTH-stimulated cAMP level in chondrocytes pretreated with insulin-like growth factor-I and transforming growth factor-beta was higher than that in control cells. These observations suggest that the increase in the number of PTH receptors on chondrocytes is closely related to expression of the differentiated phenotype of chondrocytes and that the number of the receptors is a good marker of the differentiated phenotype of chondrocytes.
Animals↗
Analysis of transforming genes in indirectly induced radiogenic thymomas in mice.
The expression of oncogenes was studied in 12 types of 178 mouse tumors induced by radiations and chemicals. DNA was analyzed in tumors in which the overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not in sarcomas induced by radiation. Activation of oncogenes by small mutations and the inactivation of tumor suppressor genes has to be taken in account in the radiation induction of mouse tumors. We therefore made further analyses of radiogenic thymomas. Loss of heterozygocity was revealed in directly induced thymomas by the deletions of allele specific minisatellite bands. Analysis of a hypervariable minisatellite locus also revealed that these thymoma cells suffered high recombinogenic activity during tumorigenesis. In addition, transfection of cellular DNA to normal Golden hamster cells identified the activated K-ras oncogene in the directly induced radiogenic thymomas. Indirectly induced radiogenic thymomas were tested similarly. Transformed cells from secondary transfection experiment were positive for the mouse-specific repetitious sequences, but devoid of mouse ras oncogenes. Indirectly induced radiogenic thymomas originate from unirradiated normal thymus cells transplanted in irradiated hosts. The spontaneous activation of oncogenes yet to be identified may therefore be involved in the development of this tumor.
Animals↗
[Growth factors of chondrocytes].
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Animals↗
[Cancer cells and carcinogenesis].
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Cell Transformation, Neoplastic↗
[A case of paragonimiasis Miyazakii with bilateral pleural and pericardial effusion].
A 38-year-old man was admitted to our hospital for further examination of bilateral pleural and pericardial effusion. He had complained of dyspnea on exertion occurring six months after ingestion of raw freshwater crabs, Patomon dehaani. X-ray films and CT scan of the chest taken on admission revealed massive bilateral pleural and pericardial effusion. High serum IgE level and eosinophilia were noted on laboratory examination. Antibody against Paragonimus Miyazakii antigen was detected in patient's serum as well as pleural and pericardial fluids by the Ouchterlony test. The patient was treated effectively by Bithionol.
Adult↗
[Clinical analysis of 35 patients with renal injury].
Because of the increase of abdominal trauma owing to traffic accident, the number of renal injury is increasing. Between May 1, 1986 and December 31, 1989, thirty-five cases with renal injury were treated in our hospital. The cases were classified as contusion, minor laceration, major laceration and vascular injury by the clinical findings and the radiographic evaluation. Contusion had 22 patients, who were treated conservatively except one with preexisting hydronephrosis. Four patients of minor laceration were all treated conservatively. In four cases of major laceration nephrectomy was performed, the other five cases were healed conservatively. There were two death cases caused by other organ injuries. The extent of associated injuries influenced the prognosis, rather than the degree of renal damage. Thirty-three cases except two survived with no complication. In cases of major injury same were managed conservatively, other required surgical treatment. Sometimes it is difficult to determine which treatment should be done. Indication for surgical treatment is discussed.
Accidents, Traffic↗
[Biliary intervention for malignant obstructive jaundice. Treatment through PTCD fistula].
Currently, diagnosis of obstructive jaundice has become easier with CT and USEG, and percutaneous transhepatic cholangio -drainage (PTCD) for obstructive jaundice has also become much safer using USEG control. We have performed PTCD in 277 cases, from December 1976 to May 1989 at Saitama Cancer Center with specially designed thin needle. And using a PTCD fistula, we have been attempted radiotherapy for 7 cases of the bile duct cancer using Remote After Loading System (RALS), and hyperthermia for 5 cases of bile duct cancer using antenna of microwaves. From autopsy cases, we evaluated treated lesion pathologically, and we obtained the following results. Dosage of biliary RALS need up to 50 Gy at the point of 1 cm from 60Co ++source. Biliary hyperthermia using microwave seem to be unsuccessful, and further improvement to the antenna of microwave were necessary. Furthermore, we have attempted biliary endoprosthesis 27 cases, for better quality of life to the patients with malignant obstructive jaundice. These method seems to be effective in prolonging patient's lives, comparing of cases in which PTCD of an external fistula has been performed.
Adult↗
Induction of angiogenesis in chick yolk-sac membrane by polyamines and its inhibition by tissue inhibitors of metalloproteinases (TIMP and TIMP-2).
Treatment of yolk-sac membranes of 4-day-old chick embryos with spermine or spermidine resulted in angiogenesis in the membranes. The angiogenic activity of spermine was stronger than that of spermidine. Putrescine, polylysine and histamine did not induce angiogenesis in the membranes. Administration of putrescine, spermidine and spermine increased their respective levels in yolk-sac membranes, but no interconversion of these amines was observed. The increases in spermidine and spermine levels in yolk-sac membranes preceded induction of angiogenesis. The angiogenesis induced by spermine was inhibited by tissue inhibitors of metalloproteinases, that is, TIMP and TIMP-2. These findings suggest that spermine and spermidine are angiogenesis factors in yolk-sac membranes of chick embryos and that matrix metalloproteinases represented by collagenase are involved in their action.
Animals↗
Tumor angiogenesis and polyamines: alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro.
alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membrane and subsequently the growth of the tumor on the chorioallantoic membrane. These inhibitions were reversed by exogenous putrescine and spermidine. DFMO also inhibited rapid neovascularization in yolk sac membrane of 4-day-old chick embryos and the inhibition was reversed by exogenous putrescine and spermidine. DFMO strongly inhibited DNA synthesis and proliferation of bovine pulmonary artery endothelial (BPAE) cells in culture and decreased their ornithine decarboxylase activity and intracellular polyamine concentrations. Addition of putrescine to the culture medium of DFMO-treated BPAE cells restored their intracellular putrescine and spermidine concentrations and their DNA synthesis and proliferation. Addition of spermidine to cultures of DFMO-treated BPAE cells restored their intracellular spermidine concentration and their DNA synthesis and proliferation. DFMO inhibited the proliferation of B16 melanoma cells in culture but the inhibitory effect was much less than that on BPAE cells. When one-half the monolayer of confluent cultures of BPAE cells had been peeled off, addition of DFMO to the cultures inhibited the proliferation and extension of the BPAE cells into the vacant area but had no effect on stationary cells in the remaining half of the monolayer, suggesting that it inhibited induction of proliferation of endothelial cells. These findings suggest that the antitumor activity of DFMO against solid tumors is probably due more to its inhibition of tumor-induced angiogenesis by inhibition of proliferation of endothelial cells induced by polyamine depletion than to a direct effect on tumor cell proliferation.
Animals↗
Role of natural killer cells and macrophages in the nonspecific resistance to tumors in mice stimulated with SMANCS, a polymer-conjugated derivative of neocarzinostatin.
Copoly(styrene-maleic acid)-conjugated neocarzinostatin (SMANCS), a lipophilic derivative of the proteinaceous antitumor antibiotic neocarzinostatin, has been reported to stimulate a nonspecific resistance to tumors (NSRT) in solid tumor-bearing mice, in addition to its chemotherapeutic antitumor effect through the arrest of DNA synthesis by direct DNA strand scission. In the present study, splenic or peritoneal effector cells were used to investigate the ability of SMANCS to augment natural killer (NK) cell activity and to generate cytostatic macrophages (A-M phi). Splenic NK cell activity augmented by SMANCS was characterized by cytotoxicity to various target cells, nylon wool nonadherence, and sensitivity to treatment with anti-asialo-GM1 antiserum or monoclonal anti-Thy-1.2 antibody followed by complement. The A-M phi generated by SMANCS stimulation were characterized by their adherence to a plastic surface coated with fetal calf serum and their ability to phagocytize carbonyl-iron. The maximum level of NK cell activity in the spleens of mice was detected 3 days after i.v. injection of SMANCS, and the highest activity of the peritoneal A-M phi was demonstrated in mice 4 days after SMANCS treatment. On the other hand, the NSRT of mice stimulated with SMANCS was not detectable in mice treated with carrageenan or trypan blue, whereas SMANCS-stimulated NSRT was observed in mice treated with anti-asialo-GM1 antiserum. The NSRT that was stimulated with SMANCS was also demonstrated in mice homozygous for the beige mutation and their non-beige littermates, when NK cell-resistant EL-4 thymoma was used as a tumor target. These results suggest that the expression of NSRT of mice stimulated with SMANCS may require the function of A-M phi, although NK cell activity was also augmented in spleens of mice by administration of SMANCS.
Animals↗
Induction of interleukin 3 and tumor resistance by SSM, a cancer immunotherapeutic agent extracted from Mycobacterium tuberculosis.
Interleukin 3 (IL-3) activity was demonstrated when inguinal lymph node cells obtained from Bacillus Calmette-Guérin-sensitized mice (BCG-ILNC) were stimulated in vitro with SSM, an immunomodulator extracted from Mycobacterium tuberculosis. The IL-3 activity was first detected on Day 1 in culture fluids of BCG-ILNC stimulated with SSM, reached a peak on Day 3, and then gradually decreased. The activity was completely neutralized by treatment with anti-murine IL-3 monoclonal antibody (mAb). When BCG-ILNC were treated with anti-Thy 1.2 or anti-Lyt 1.2 mAb followed by complement, IL-3 was not produced in the culture fluids. However, IL-3 in the culture fluids was detected when BCG-ILNC were treated with anti-Lyt 2.2 mAb, anti-asialo-GM1, or anti-mouse immunoglobulin antiserum followed by complement. These results suggested that Lyt 1+ T-cells appeared to be required for the production of IL-3 from BCG-ILNC stimulated with SSM. In addition, low but significant IL-3 activity was also observed in sera of mice treated with SSM. However, serum IL-3 activity was not detected in mice treated with both SSM and Thy 1.2 or Lyt 1.2 mAb, whereas the activity was induced by SSM in mice treated with anti-Lyt 2.2 mAb or anti-asialo-GM1 antiserum. On the other hand, the in vivo growth of IMC tumors inoculated in BALB/c x DBA/2 F1 mice was significantly decreased by intralesional injection of culture fluids containing IL-3, as well as by SSM itself. This antitumor activity of the culture fluids was not altered when it was treated with mAbs for interleukin 1, interleukin 2, or anti-mouse gamma-interferon antiserum. The antitumor activity of the fluid was only eliminated when it was treated with anti-mouse IL-3 mAb. Since nonspecific resistance to tumors in mice stimulated with SSM appears to require Lyt 1+ T-cells, these results suggest that, in part, nonspecific resistance to tumors of mice stimulated with SSM may be developed through IL-3, which was produced by Lyt 1+ T-cells after SSM stimulation.
Animals↗
Developmental brain abnormalities accompanied with the retarded production of S-100 beta protein in genetic polydactyly mice.
The homozygotes of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) exhibit various brain malformations including exencephaly in about 20%. In the present report, the brains of homozygotes (Pdn/Pdn) which were not exencephalic were examined morphologically and biochemically. Homozygous newborn brains showed hydrocephaly, some gyri on the cerebral hemisphere, absence of the corpus callosum, absence of the commissura anterior, absence of the fornix and commissura fornicis, protuberance of the cortical tissue from the brain surface, and abnormal architecture of the hippocampus. An irregular mass of olfactory nerve was observed on the cribriform plate, and the olfactory bulb was deficient. From these findings, we considered Pdn/Pdn as a kind of arhinencephalic mouse. Nervous tissue-related proteins, S-100 alpha, S-100 beta, creatine kinase B (CK-B), neuron-specific gamma-enolase, guanosine triphosphate binding proteins (Go alpha, Gi2 alpha and G beta) were immunoassayed in the cerebrum of Pdn/Pdn embryos and newborns. Among the protein analysed, only S-100 beta of Pdn/Pdn showed a significantly lower level than that of +/+ cerebrum during the observation period. The newborn brains were examined immunohistochemically using S-100 alpha, S-100 beta, CK-B, Go alpha and NSE antibodies. We could find no differences in the staining patterns among the Pdn/Pdn, Pdn/+ and +/+ brains.
Animals↗
Sensitive enzyme immunoassay for human Cu/Zn superoxide dismutase.
A highly sensitive enzyme immunoassay method for measurement of human Cu/Zn superoxide dismutase (SOD) was established. Antisera were raised in rabbits by injecting SOD purified from human erythrocytes, and antibodies to SOD were purified by the use of Cu/Zn SOD-coupled Sepharose 4B. The assay system consisted of polystyrene balls with immobilized monospecific antibody F(ab')2 fragments and the same antibody Fab' fragments labeled with beta-D-galactosidase from Escherichia coli. The assay was highly sensitive, and the minimum detection limit was 3 pg or 0.1 fmol/assay tube. Serum Cu/Zn SOD levels of normal healthy subjects (36.3 +/- 15.6, n = 120, 16-64 years old) were not related to age and sex. It was confirmed that Cu/Zn SOD levels in erythrocytes and blood plasma were significantly enhanced in patients with Down syndrome. Immunoreactive Cu/Zn SOD was detectable in all the tissues examined and was present at high concentrations in brain, adrenal gland, liver, heart and kidney.
Adult↗
Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage.
The growth-promoting actions of cartilage extracts (CE) on rabbit cultured chondrocytes were studied to assess the role of local acting growth factors in the generation and expansion of highly differentiated cells. In the present study, DNA synthesis and proteoglycan synthesis in the cultured chondrocytes were monitored by flow cytofluorometry and double-isotope autoradiography by using [3H]thymidine and [35S]sulfate. We report here that actions of the same set of growth factors extracted from cartilage evokes differential cellular responses depending upon cell density. Growth factors in the optimal dose of CE (2 micrograms/ml) or epidermal growth factor (EGF, 40 ng/ml) did not reveal such a cell density-dependent effect on cellular proliferation. However, growth factors in CE induced proteoglycan synthesis selectively in nonproliferating and expressing cells in confluent culture.
Animals↗
Effects of tumor necrosis factor alpha on proliferation and expression of differentiated phenotypes in rabbit costal chondrocytes in culture.
Tumor necrosis factor alpha (TNF alpha) decreased the synthesis of glycosaminoglycan (GAG) in rabbit costal chondrocytes in culture, but did not stimulate the release of GAG from cell layers. Like chondrocytes cultured in control medium, chondrocytes cultured in the presence of TNF alpha produced putative "cartilage-specific" proteoglycans identified by density gradient centrifugation under dissociative conditions. Although TNF alpha decreased the synthesis of the proteoglycans, it did not change their monomeric size, which is a marker of cartilage phenotypes. Moreover, TNF alpha did not affect the responsiveness to parathyroid hormone, insulin-like growth factor I, or transforming growth factor beta, which is known to stimulate GAG synthesis in cultured chondrocytes. TNF alpha decreased the alkaline phosphatase activity in the chondrocytes dose dependently. On the other hand, it stimulated their DNA synthesis slightly, but significantly. The stimulatory effect of TNF alpha on DNA synthesis was potentiated by fibroblast growth factor, epidermal growth factor, and fetal bovine serum. These findings suggest that in the presence of hormones and growth factors, TNF alpha promotes the proliferation of chondrocytes while suppressing their further differentiation at the stage of synthesis of cartilage-specific proteoglycans.
Alkaline Phosphatase↗
Enhancement of S-100 beta protein in blood of patients with Down's syndrome.
The human gene encoding the beta subunit of S-100 protein (S-100 beta) was mapped on chromosome 21. In order to confirm the expression of gene-dosage effect of S-100 beta in patients with Down's syndrome (DS), concentrations of immunoreactive S-100 alpha and S-100 beta proteins were determined in the blood plasma and lymphocytes fraction of the patients and control subjects. Cu/Zn-superoxide dismutase (SOD), a protein that is known to show the gene-dosage effect on the trisomy of chromosome 21, also was immunoassayed in the same blood samples as control proteins. In blood plasma, S-100 beta protein as well as Cu/Zn SOD was enhanced (P less than 0.001) in the patients (160 +/- 70 pg S-100 beta/ml and 87 +/- 83 ng SOD/ml, N = 44) as compared with control individuals (76 +/- 25 pg/ml, and 18 +/- 11 ng/ml, respectively, N = 28). However, concentrations of S-100 alpha in blood plasma of DS patients were similar to those of normal subjects. Concentrations of S-100 beta in lymphocyte fractions of DS patients (24.7 +/- 10.9 ng/mg protein) were also higher (P less than 0.001) than those of control subjects (10.1 +/- 5.8 ng/mg protein). These results indicate that gene-dosage effect of S-100 beta levels are expressed in DS patients.
Adolescent↗