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Biomedical subjects

F Takaku

Publications and source records attributed to F Takaku.

At least 361 records · Page 20Linked to original sources
PubMed1988

Induction of anomalous killing activity from antigen-specific CTL clones by adding high doses of human recombinant interleukin 2.

Four out of six long-term murine cytotoxic T lymphocyte (CTL) clones specific for trinitrophenyl (TNP)-modified spleen cells could develop an anomalous cytotoxicity against syngeneic and allogeneic tumor cells upon stimulation with TNP-modified spleen cells and high doses of human recombinant interleukin 2 (rIL-2). On FACS analysis, hyperactivated CTLs were positive for Thy-1, Ly 2 and LFA-1, but negative for L3T4 and asialo GM1. The staining profile of the cells with each antibody indicated that the CTL clones consisted of just one cell type. Monoclonal anti-Ly 2.2 and anti-LAA (lymphokine-activated cell-associated antigen) antibodies inhibited cytolysis of CTL and hyperactivated CTL clones against TNP-modified spleen cells, but failed to inhibit the anomalous killing of the hyperactivated CTL. The cold target competition test suggested the degeneracy of antigen specificity. The present study demonstrated that the CTL clone acquired a new specificity for tumor target cells upon stimulation with a high dose of rIL-2.

Animals↗
PubMed1988

A study of DNA polymorphism in the apolipoprotein B gene in a Japanese population.

A Japanese group comprising 53 hyperlipidemic and 54 normolipidemic subjects was genotyped for DNA restriction fragment length polymorphisms (RFLPs) at the apo B gene locus. The polymorphisms with XbaI and PvuII were present at allelic frequencies of 0.04 (X1 allele) and 0.96 (X2 allele), 0.94 (P1 allele) and 0.06 (P2 allele), respectively. Unlike the previous reported association of the X1 allele with hypercholesterolemia found in Caucasians there was no difference in the frequency of the X1 allele between normolipidemic and hypercholesterolemic Japanese. Among the Japanese, two RFLPs appear to be in linkage equilibrium and can be used in conjunction as a haplotype. There is no strong population association in our patient group between any allele of the RFLPs studied and hyperlipidemia.

Adult↗
PubMed1988

Serum erythropoietin titers in the aged.

Erythropoietin (Epo) titers in the aged (from 70 to 89 years) were determined by a radioimmunoassay. Epo levels in normal elderly subjects were not different from levels in the young volunteers. The serum Epo levels in elderly patients with anemia were inversely related to hemoglobin levels; their regression coefficient was not worse than that found in young patients. It is suggested that the reactivity of Epo production to anemia in the aged may not be worse than that reactivity in the young.

Aged↗
PubMed1988

Production of granulocyte colony-stimulating factor by acute myelomonocytic leukemia cells.

Two patients with acute myelomonocytic leukemia (AMMoL) were tested to determine whether or not their cells produced granulocyte colony-stimulating factor (G-CSF). Using the NFS-60 bioassay method, relatively high levels of G-CSF were demonstrated in the serum pre-treated with acid-dialysis and in the media conditioned by leukemia cells. Northern blot analysis for G-CSF using cDNA as a probe revealed that G-CSF production was increased at the mRNA level in the cells. No rearrangement at the DNA level, however, was observed by genomic Southern analysis. Our data indicate that the leukemic cells in AMMoL probably have the capacity to synthesize and secrete G-CSF.

Aged↗
PubMed1988

Radioimmunotherapy of transplanted small cell lung cancer with 131I-labelled monoclonal antibody.

Monoclonal antibody TFS-4 has previously been shown to react selectively with human small cell lung cancer (SCLC). We evaluated the use of 131I-labelled TFS-4 for the treatment of established human SCLC transplanted in nude mice. The specific accumulation of the antibody in the transplanted tumour was recorded by both scintigraphic and biodistribution studies. Administration of 200 microCi 131I-labelled TFS-4 inhibited tumour growth when compared with the same radiation dose of the control monoclonal antibody. The therapeutic effect was dose-dependent and complete disappearance of the tumour was observed transiently in one out of the three animals following the administration of 500 microCi 131I-labelled TFS-4.

Adenocarcinoma↗
PubMed1988

Down-regulation of hepatic LDL receptor protein and messenger RNA in fasted rabbits.

Rabbits fasted for 9 and 14 d exhibited 6- and 8-fold increase in plasma cholesterol level, respectively. As one of the mechanisms causing hypercholesterolemia in fasted rabbits, the decreased activity of hepatic low-density lipoproteins (LDL) receptor has been reported (Stoudemire, J.B., Renaud, G., Shames, D.M., & Havel, R.J. (1984) J. Lipid Res. 25, 33-39). In order to demonstrate the down-regulation of hepatic LDL receptor on a molecular basis, we carried out immunoblotting of the liver membranes with a specific antibody against LDL receptors and blot hybridization of hepatic RNAs with cDNA of LDL receptor. Immunoblotting showed that LDL receptors in fasted rabbits were markedly decreased, and blot hybridization of RNAs showed a significant decrease in mRNA level of hepatic LDL receptor in fasted rabbits. Further, significant decreases both in LDL binding to liver membrane and in hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in fasted rabbits were demonstrated. From these results, we concluded that hypercholesterolemia in fasted rabbits is caused by the impaired catabolism of LDL due to down-regulated biosynthesis of hepatic LDL receptor.

Animals↗
PubMed1988

Effect of beta-adrenergic blockade on plasma levels of atrial natriuretic peptide during exercise in humans.

Effect of beta-adrenergic blockade on plasma levels of atrial natriuretic peptide (ANP) during treadmill exercise was studied in 9 healthy volunteers. Plasma ANP levels increased during exercise. The mean plasma ANP concentration on 12-min exercise (32.5 +/- 3.7 pg/ml, mean +/- SEM) was significantly higher than the control (16.7 +/- 1.0 pg/ml). After exercise, the levels decreased and the mean plasma ANP concentrations in the recovery period were higher in subjects in the sitting position than in subjects who kept standing. Prior administration of a long-acting propranolol, 160 mg daily for 3 consecutive days, augmented ANP release during exercise. The mean plasma ANP concentrations on 9- and 12-min exercise (34.5 +/- 3.1 and 64.9 +/- 15.0 pg/ml, respectively) were significantly higher than those in the corresponding exercise stage without propranolol. Plasma ANP levels in the recovery period also increased after the administration of propranolol and the subjects in the sitting position again had higher plasma levels than those in the standing position. These results suggest that increased central blood volume during exercise elevates atrial pressure to stimulate ANP secretion, and that greater atrial distension and pressure due to reduced ventricular contractility by beta-adrenergic blockade facilitates ANP release to a greater extent.

Adrenergic beta-Antagonists↗
PubMed1988

Morphologic changes of neutrophils in myelodysplastic syndrome treated with recombinant human granulocyte colony-stimulating factor.

Two cases of myelodysplastic syndrome (MDS) were treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In both cases, an increase of peripheral neutrophil counts was noted with a peak within 12 hr after the rhG-CSF administration. Neutrophils with ring shaped or hypersegmented nuclei were noted in the peripheral blood during the treatment, and they disappeared promptly after discontinuation of the therapy. The results indicate that the rhG-CSF might have mobilizing and differentiating effects on neutrophils derived from the MDS clone.

Adult↗
PubMed1988

Clinical application of phorbol diester-induced leukemic cell differentiation for the definite diagnosis of acute leukemias.

Seventy-three patients with acute leukemias or chronic myelogenous leukemias in blast crisis were evaluated as to the susceptibility of their leukemic cells to differentiation induction by a chemical agent, 12-O-tetradecanoyl phorbol-13-acetate (TPA). Leukemic cells of myeloid origin treated with TPA showed monocyte-macrophage-lineage differentiation morphologically and functionally, whereas those of lymphoid origin did not. We applied these differentiation phenomena for the clinical diagnosis of three leukemia cases in whom it was difficult to determine whether the leukemic cells were of non-lymphoid or lymphoid origin, although all the regular diagnostic procedures available had been performed. We successfully diagnosed these three cases by utilizing the above differentiation phenomena. Furthermore, this technique was clinically beneficial as to the choice of adequate chemotherapy in each of these leukemia cases. These findings confirm that the responsiveness to TPA of leukemic cells is of clinical usefulness for the definite diagnosis of acute leukemias.

Acute Disease↗
PubMed1988

Effects of type beta transforming growth factors on haematopoietic progenitor cells.

The effects of type beta transforming growth factors (TGF-beta s) on normal human and murine haematopoietic progenitor cells were examined using bone marrow colony assays. In erythroid colony assays, TGF-beta 1 inhibited human CFU-E derived colony formation, BFU-E derived burst formation, and murine BFU-E derived burst formation in a dose dependent manner between 0.1 and 5.0 ng/ml. However, murine CFU-E derived colony formation was unaffected even at a concentration of 5.0 ng/ml TGF-beta 1. In myeloid colony assays, different sensitivity of progenitor cells to the inhibitory effects of TGF-beta s was observed between both species. TGF-beta 1 inhibited murine granulocyte-macrophage colony (GM-colony) formation and granulocyte colony (G-colony) formation in a dose dependent manner between 0.1 and 5.0 ng/ml, but had no remarkable effects on human GM-colony and G-colony formation. TGF-beta 2 also had similar inhibitory effects on haematopoietic progenitor cells, while its inhibitory effect was less potent than that of TGF-beta 1. Thus our data suggest that TGF-beta may be involved in negative regulation of haematopoiesis and that its inhibitory action may be restricted in lineage and/or species specific manner.

Animals↗
PubMed1988

Rhabdomyosarcoma with bone marrow metastasis simulating acute leukemia. Report of two cases.

Rhabdomyosarcoma manifested as a systemic disease is very rare and cases showing diffuse metastasis in the bone marrow are most unusual. Recently we encountered two cases of rhabdomyosarcoma with diffuse bone marrow metastasis which were clinically manifested as acute leukemia. The first patient was a 15-year-old female, who was admitted in 1982 with pancytopenia and many large primitive cells in bone marrow aspirates, hematological malignancy being diagnosed. Thereafter the bilateral breasts showed rapid swelling and a biopsy specimen revealed the histological features of typical alveolar rhabdomyosarcoma. The primary site of the neoplasm remained undetermined during the course. At autopsy, it was disclosed that the neoplasm originated from the left thigh and showed generalized metastasis. The second patient was a 38-year-old man, who was admitted in 1986 because of a nasal polyp obstructing the nasal cavity, and persistent nasal bleeding. Peripheral blood samples showed leukoerythroblastosis and thrombocytopenia, and large primitive cells were found in bone marrow aspirates, so that hematological malignancy was initially diagnosed. A biopsy specimen of the nasal polyp showed proliferation of large round cells and electron microscopy demonstrated the ultrastructural features of rhabdomyosarcoma.

Acute Disease↗
PubMed1988

Evolution, expression, and chromosomal location of a novel receptor tyrosine kinase gene, eph.

Partial sequence analysis of the genomic eph locus revealed that the splicing points of kinase domain-encoding exons were completely distinct from those of the other protein tyrosine kinase members reported, suggesting that this is the earliest evolutionary split within this family. In Northern (RNA) blot analysis, the eph gene was expressed in liver, lung, kidney, and testis of rat, and screening of 25 human cancers of various cell types showed preferential expression in cells of epithelial origin. Overexpression of eph mRNA was found in a hepatoma and a lung cancer without gene amplification. Comparison of cDNA sequences derived from a normal liver and a hepatoma that overproduces eph mRNA demonstrated that two of them were completely identical throughout the transmembrane to the carboxy-terminal portions. Southern blot analysis of DNAs from human-mouse hybrid clones with an eph probe showed that this gene was present on human chromosome 7.

Animals↗
PubMed1988

Measurement of angiotensin-converting enzyme activity in intact human alveolar macrophages and effect of smoking.

Serum angiotensin-converting enzyme (ACE) activity is known to be elevated in various granulomatous conditions such as sarcoidosis, whose characteristic epithelioid cells are thought to belong to the macrophage series. It was recently shown that alveolar macrophages had ACE activity in their sonicated and homogenate forms. We investigated ACE activity of human alveolar macrophages in the intact form using a sensitive radioimmunoassay of generated angiotensin II. We also investigated the effect of smoking on ACE activity of alveolar macrophages using this method. Alveolar macrophages generated angiotensin II (218 +/- 106 pg/20 min/10(5) cells). More angiotensin II was generated in smokers (246 +/- 119 pg/20 min/10(5) cells) than in nonsmokers (160 +/- 50 pg/20 min/10(5) cells) (p less than 0.05). These data showed that ACE activity of macrophages is higher in smokers than nonsmokers.

Angiotensin I↗
PubMed1988

Atrial natriuretic peptide distribution in fetal and failed adult human hearts.

The distributions of atrial natriuretic peptide (ANP) in human hearts during the developmental stage and in adult pathological states was examined with an antibody specific to human alpha-ANP. With immunoblotting and immunofluorescence methods, we found that a 17-kDa protein, which is a pro ANP, was expressed in human fetal ventricles, in which the numbers of myofibers containing ANP granules were more abundant in the subendocardial region than the subepicardial region. As determined by radioimmunoassay, the content of immunoreactive ANP (per milligram protein) in the developing heart was greatest in the left atrium and occurred decreasingly in the right atrium, right ventricle, and left ventricle, respectively. Because ANP content in the left ventricle declined during the progress of gestation in developing hearts and because it was very low, if ever detectable, in normal adult hearts, ventricular ANP expression appears to be developmentally regulated from the early gestational stage. However, it was reexpressed in the ventricles of patients who had suffered from severe congestive heart failure. In this situation, we found that the ventricular ANP expression was more marked in patients with dilated cardiomyopathy than in patients with severe valvular disease. Interestingly, in the ventricles of patients with dilated cardiomyopathy, ANP contents were higher in the left ventricular free wall than in the right ventricular free wall, although the left ventricular subendocardium contained more ANP than the subepicardium, showing a transmural gradient similar to that expressed in fetal ventricles. Thus, the expression of ANP in human ventricles is developmentally regulated from the early gestational stage, and even adult ventricular myofibers can synthesize ANP during severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Expression of cellular oncogenes in the myocardium during the developmental stage and pressure-overloaded hypertrophy of the rat heart.

Proto-oncogenes have been revealed to participate in normal cell proliferation as well as in cell transformation. Since cardiac myocytes are terminally differentiated, they cannot divide except in the fetal period. To determine the role of cellular oncogenes in the growth of the heart, the expression pattern of eight cellular oncogenes during the developmental stage and pressure-overloaded hypertrophy of the rat hearts were examined in vivo. Northern blot analysis was performed with eight oncogene probes (myc, fos, Ha-ras, src, erbA, erbB, sis, myb). Pressure overload increased the levels of cellular (c-) fos, c-myc, and c-Ha-ras. An increase of c-fos and c-myc was detected at 30 minutes and 2 hours, respectively; the levels peaked at 8 hours, and they returned to baseline by 48 hours after aortic constriction. However, the level of c-Ha-ras showed a gradual increase. During the course of development, the expression of c-myc was detectable only in the embryonic stage, whereas the expression of c-fos was not detected in the fetal period, was increased after birth, and peaked in 200-day-old adults. The expression of c-Ha-ras was almost the same throughout the development. Cellular oncogenes were expressed in the heart in response to pressure overload and in a stage-specific manner. These results suggest that cellular oncogenes may participate in the normal developmental process and hypertrophy of hearts and that the cellular hypertrophy induced by pressure overload may share a similar mechanistic pathway with cell proliferation.

Animals↗
PubMed1988

Differences in response of myosin isozyme transition of ordinary and specialized myocardium to overload.

To investigate the response of myosin isozyme transition in specialized myocardium to cardiac overload, we examined immunohistochemically the distribution of myosin isozymes in sinus node cells of overloaded canine atria, using the monoclonal antibodies CMA19 and HMC14, which are specific for atrial myosin heavy chain (alpha-HC) and ventricular myosin heavy chain (beta-HC), respectively. Overloading in canine right atria was induced by artificial tricuspid valve regurgitation and pulmonary stenosis. Right atrial mean pressure rose to 15-20 mm Hg (n = 4) 2 months after surgery. In the working myocardium, cardiac overload caused redistribution of myosin isozymes, alpha-HC to beta-HC. Compared with the normal right atria, fewer myocytes were labeled with CMA19, but more were labeled with HMC14. However, the reactivity of sinus node cells with CMA19 and HMC14 was not changed between normal and overloaded right atria, indicating no redistribution of myosin heavy chain isozymes, alpha-HC to beta-HC. These results suggest that isozymes in myosin heavy chains in the specialized myocardium are protected from overload effects by their firm cytoskeletal framework or other mechanisms.

Animals↗