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Biomedical subjects

O Takatani

Publications and source records attributed to O Takatani.

At least 37 records · Page 2Linked to original sources
PubMed1989

Relationship between the levels of serum thyroid hormones or estrogen status and the risk of breast cancer genesis in Japanese women.

For the purpose of investigating a possible correlation between the genesis of breast cancer and the levels of serum thyroid hormones or the estrogen status, which is one of the potential risk factors for breast cancer in Japanese women, we measured the percentage of free estradiol (E2) and the amounts of sex hormone-binding globulin (SHBG) and thyroid hormones in serum samples from Japanese patients with breast cancer (N = 39) and normal controls (N = 36). The patients were found to have significantly higher free E2 and significantly lower SHBG than controls. Moreover, the serum levels of free triiodothyronine (FT3) and free thyroxine (FT4) were lower in the patients than in controls, while the serum levels of TSH and TBG in the patients were not significantly different from those in controls. The percentage of free E2 in serum was not significantly correlated with the level of any one of FT3, FT4, TSH, and TBG either in the patients or in controls regardless of menstrual status. These results suggest the possibility that the reduction in the serum FT3 and FT4 levels, which is independent of changes in the serum level of free E2, may be one of the risk factors for breast cancer in Japanese women.

Adult↗
PubMed1989

Inhibition by an alkyl-lysophospholipid of the uptake of epidermal growth factor in human breast cancer cell lines in relation to epidermal growth factor internalization.

The effects of 1-O-octadecyl-2-O-methyl-sn-glycerol-3-phosphocholine (ET-18-OCH3), an alkyl-lysophospholipid derivative, on the binding and uptake of labeled epidermal growth factor (EGF) in hormone-dependent (MCF-7 and ZR-75-1) and hormone-independent (BT-20) breast cancer cell lines were investigated at 4 degrees C and 37 degrees C. The total (bound and intracellular) EGF associated with breast cancer cells tested were largely temperature dependent. By pretreatment of the cells with ET-18-OCH3 (10 micrograms/ml) for 12 h, the EGF uptake at 37 degrees C was greatly reduced in both MCF-7 and ZR-75-1 (ET-18-OCH3-susceptible) but not in BT-20 (ET-18-OCH3-resistant) cell lines. The ET-18-OCH3 pretreatment slightly decreased the EGF uptake at 4 degrees C in MCF-7 and ZR-75-1 and had little effect on that in BT-20. The EGF binding at 37 degrees C was unaffected by ET-18-OCH3 in MCF-7 and BT-20 and slightly decreased in ZR-75-1. The EGF binding at 4 degrees C was not changed by ET-18-OCH3 in all cell lines tested. These results suggest that labeled EGF is taken up by the cells in a temperature-dependent manner and ET-18-OCH3 may inhibit this internalization process only in ET-18-OCH3-sensitive human breast cancer cell lines. It is inferrable that the inhibition of the internalization process for EGF may be one of the modes of antitumoral action of ET-18-OCH3.

Antineoplastic Agents↗
PubMed1989

Effects of LTP-inducing tetanic stimulations of the perforant path on the commissural inhibition and facilitation of dentate granule cell discharge.

Effects of diazepam (1 mg/kg, i.p.) on the commissural influences on granule cells were first examined to further assess its GABAergic inhibitory mechanism. Whereas the commissural inhibition at an interval of 5-8 ms of the contralateral dentate-perforant path (CP) combined stimulus was not enhanced by diazepam, the commissural facilitation at a CP interval of 11-20 ms was reduced, suggesting that the GABAergic inhibition is involved in rather a part of the commissural facilitation at a CP interval of 11-20 msec than a part of the 'commissural' inhibition at a shorter CP interval. Based on the results of diazepam, effects of high-frequency stimulations of the perforant path on the commissural inhibition of dentate granule cells were then examined, in relation to their effects on the dentate paired-pulse depression. These stimulations produced the long-term potentiation of the perforant path-dentate excitatory synapse and significant reduction of the paired-pulse depression. The commissural inhibition at a CP interval of 5-8 ms remained unchanged following tetanization. The commissural facilitation at a CP interval of 11-20 ms was, however, slightly enhanced by tetanic stimulations and a statistical significance was obtained at a CP interval of 19 ms. These results imply that tetanic stimulations of the perforant path selectively reduce the GABAergic component of the commissural inhibition, as well as that of the paired-pulse depression.

Action Potentials↗
PubMed1989

Prostaglandins promote osteoclastlike cell formation by a mechanism involving cyclic adenosine 3',5'-monophosphate in mouse bone marrow cell cultures.

We have developed a mouse bone marrow culture system in which multinucleated osteoclast (OC)-like cells are formed within 8 days. Using this culture system, we examined the effect of prostaglandins (PGs), potent bone-resorbing agents, on OC-like cell formation. Four PGs (PGE1 and PGE2 at 10(-8)-10(-5) M, 6-keto-PGF1 alpha at 10(-5) M, and PGF2 alpha at 10(-6)-10(-5) M) significantly stimulated the formation of OC-like cells. The potency of the PGs in inducing OC-like cell formation was the highest in PGE1 and PGE2, followed by PGF2 alpha and 6-keto-PGF1 alpha in that order, and the order was highly correlated with the order of the potency in increasing the production of cyclic adenosine 3',5'-monophosphate (cAMP) in bone marrow cells. Addition of dibutyryl-cAMP also induced OC-like cell formation. Moreover, isobutylmethylxanthine (IBMX), a potent inhibitor of phosphodiesterase, potentiated the OC-like cell formation induced by PGE2, whereas salmon calcitonin greatly inhibited it. Calcitonin induced cAMP production in cultures treated with PGE2, but not in cultures with vehicle. When bone marrow mononuclear cells were cultured on dentine slices in the presence of PGE2, multinucleated OC-like cells were similarly formed and they resorbed calcified dentine, resulting in so-called Howship's lacunae. These results suggest that PGs stimulate resorption of calcified tissues by promoting osteoclast formation. The activity of PGs in inducing OC-like cell formation is considered mediated mainly by a mechanism involving cAMP.

Animals↗
PubMed1989

A case of leiomyosarcoma associated with humoral hypercalcemia of malignancy: demonstration of biological and immunological activities of parathyroid hormone-related protein in the tumor extract.

Hypercalcemia occurred in a patient with leiomyosarcoma when multiple lung metastases developed. Despite normal plasma parathyroid hormone (PTH) levels and low 1,25-dihydroxyvitamin D, this hypercalcemic patient had a marked hypercalciuria and phosphaturia associated with an increased excretion of nephrogenous cyclic AMP (NcAMP). Administration of cisplatin ameliorated both the hypercalcemia and hypercalciuria without any reduction in tumor size of NcAMP excretion. Terminally, acute pancreatitis occurred producing a profound hypocalcemia. In the extract of tumor tissue obtained post mortem, bioactivity stimulating the generation of cyclic AMP in osteogenic cells was demonstrated along with the immunoreactive PTH-related protein (PTH-rP). the first report of a solid non-epithelial malignancy producing PTH-rP and associated with humoral hypercalcemia of malignancy. The hypercalcemia in this case caused acute pancreatitis, which led to a profound hypocalcemia.

Calcium↗
PubMed1989

Treatment of pure red cell aplasia that is resistant to conventional immunosuppressive therapy with intermittent administration of methotrexate.

Two patients with pure red cell aplasia were treated with intermittent administration of methotrexate. One who was refractory to conventional immunosuppressive therapy showed a favorable response to methotrexate within 2 weeks of treatment and entered complete remission. The other also showed an increase in reticulocytes within 3 weeks of methotrexate treatment. Although continuous administration of methotrexate was abandoned in the second case because of its hepatotoxicity, our results suggest that methotrexate may be effective in patients with pure red cell aplasia refractory to conventional immunosuppressive therapy.

Drug Resistance↗
PubMed1989

The tumor cells (FA-6) established from a pancreatic cancer associated with humoral hypercalcemia of malignancy: a simultaneous production of parathyroid hormone-like activity and transforming growth factor activity.

Human pancreatic cancer cells (FA-6) producing bone resorbing factor were established in culture. A biopsied lymphnode from a patient with pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) was transplanted to nude mice, and the cells producing high parathyroid hormone (PTH)-like activity were selected by a limited dilution from outgrowth of the xenografts of the tumor grown in nude mice. The conditioned media contained an activity to stimulate the resorption of mouse calvaria in vitro which was indomethacin-insensitive. The conditioned media had both alpha-type and beta-type transforming growth factor (TGF) activity but no interleukin-1 activity. TGF-alpha activity was co-eluted with PTH-like activity from gel-chromatography at around 15 kDa. The FA-6 cells now established are the first cells of pancreatic cancer associated with HHM producing both PTH-like and TGF-alpha activities along with bone resorbing activity.

Animals↗
PubMed1989

Modulation by retinoids and interferons of alkaline phosphatase activity in granulocytes induced by granulocyte colony-stimulating factor.

We have previously shown that a factor termed NAP-IF has the capacity to induce neutrophil alkaline phosphatase (NAP) in postmitotic granulocytes (PMGs). Recently, this factor found in cystic fluid of a human squamous cell carcinoma was shown to be identical to granulocyte colony-stimulating factor (G-CSF). In this study we examined whether NAP activity inducible with G-CSF could be modulated by other factors that are present in vivo or those that are known to induce differentiation of hemopoietic cells. Purified natural and recombinant G-CSF (nG-CSF and rG-CSF) induced NAP in PMGs from both normal individuals and patients with chronic myelogenous leukemia. Interferons (IFNs) suppressed expression of NAP by G-CSF. IFN-gamma was a potent inhibitor of G-CSF stimulation: IFN-gamma at 100 U/ml inhibited by greater than 90% the induction of NAP by G-CSF. In contrast, retinol (10(-6) M, a nearly physiological concentration) or all-trans-retinoic acid (10(-6) M) significantly enhanced NAP activity in vitro. Furthermore, the simultaneous addition of 10(-6) M retinol partially reversed the inhibitory action of IFN-gamma on the NAP induction by G-CSF. Our results suggest that NAP activity, which is often abnormal in a variety of diseases, may reflect G-CSF levels in vivo perhaps in concert with a number of other factors including IFNs and retinoids.

Alkaline Phosphatase↗
PubMed1989

Attempts at estimating mixed venous carbon dioxide tension by the single-breath method.

The single-breath method was originally proposed by Kim et al. [1] for estimating the blood carbon dioxide tension and cardiac output. Its reliability has not been proven. The present study was undertaken, using dogs, to compare the mixed venous carbon dioxide tension (PVCO2) calculated by the single-breath method with the PVCO2 measured in mixed venous blood, and to evaluate the influence of variations in the exhalation duration and the volume of expired air usually discarded from computations as the deadspace. Among the exhalation durations of 15, 30 and 45 s tested, the 15 s duration was found to be too short to obtain an analyzable O2-CO2 curve, but at either 30 or 45 s, the calculated values of PVCO2 were comparable to the measured PVCO2. A significant agreement between calculated and measured PVCO2 was obtained when the expired gas with PCO2 less than 22 Torr was considered as deadspace gas.

Animals↗
PubMed1989

Parathyroid hormone-related protein and transforming growth factor activities in an extract from a breast cancer associated with humoral hypercalcemia of malignancy.

The pathogeneses of hypercalcemia and hypophosphatemia which developed in a patient with metastatic invasive ductal breast carcinoma were studied. The patient had low plasma levels of immunoreactive parathyroid hormone (PTH) and 1,25(OH)2D, increased nephrogenous cyclic adenosine monophosphate (cAMP) excretion and low TmPO4/GFR, suggesting the presence of humoral PTH-like activity. The tumor extract showed activities which would stimulate bone resorption in vitro and cAMP generation in the osteogenic cell line, MC3T3 E1, and in the rat kidney cortex. In addition, the extract stimulated epidermal growth factor (EGF)-independent colony formation of the NRK 49F cells in soft agar, and inhibited the binding of EGF to A431 cells, indicating it to have transforming growth factor (TGF)-alpha activity. The extract contained appreciable amounts of immunoreactive PTH-related protein (PTH-rP) but negligible amounts of immunoreactive PTH. Thus, the PTH-like activity for stimulating cAMP generation in the bone and kidney was attributed to PTH-rP. Chromatographic analyses on reverse phase high performance liquid chromatography (HPLC) separated the PTH-rP activity from that of TGF-alpha and the bone resorbing activity in vitro was found only in the fractions of PTH-rP. It was concluded that this breast cancer produced PTH-rP as well as TGF-alpha, and the former was thought to have a major role to play in the humoral hypercalcemia of malignancy observed in this patient.

Adult↗
PubMed1988

Reduction of epidermal growth factor binding in human breast cancer cell lines by an alkyl-lysophospholipid.

The effects of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH3), an alkyl lysophospholipid derivative, on the binding of epidermal growth factor (EGF) to human breast cancer cell lines (MCF-7, ZR-75-1, and BT-20), the human epidermoid cancer cell line (A431), and the rat fibroblast cell line (NIH3T3) were investigated. The addition of 10 micrograms/ml ET-18-OCH3 to the growth medium reduced the binding of EGF to hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) and A431 but did not change that to the hormone-independent breast cancer cell line (BT-20). ET-18-OCH3 suppressed the EGF-binding prior to the onset of its inhibitory action on cell growth in MCF-7 and ZR-75-1. Scatchard plot analysis demonstrated that ET-18-OCH3 reduced the number of EGF receptor sites without affecting the affinity of EGF receptors in MCF-7 and ZR-75-1. Both EGF-binding and cell growth in NIH3T3 were not changed by treatment with 10 micrograms/ml ET-18-OCH3. These results suggest that ET-18-OCH3 inhibits the growth of hormone-dependent breast cancer cell lines (MCF-7 and ZR-75-1) by reducing the binding capacity of EGF receptors and consequently by disturbing the transfer of a variety of growth-promoting signals.

Antineoplastic Agents↗
PubMed1988

Identification of neutrophil alkaline phosphatase-inducing factor in cystic fluid of a human squamous cell carcinoma as granulocyte colony-stimulating factor.

We have previously shown that a factor termed neutrophil alkaline phosphatase-inducing factor (NAP-IF) has the capacity to induce neutrophil alkaline phosphatase (NAP) in postmitotic granulocytes (PMGs). This factor has characteristics similar to those of granulocyte colony-stimulating factor (G-CSF), suggesting that the two factors assayed by different methods may be attributable to an identical macromolecule. In a preliminary experiment, we showed that purified natural G-CSF (nG-CSF) could induce NAP in vitro in the presence of 10% (v/v) fetal calf serum (FCS). In this study, purified human nG-CSF and recombinant G-CSF (rG-CSF) induced NAP in granulocytes from both normal individuals and patients with chronic myelogenous leukemia in a dose-dependent fashion in serum-free and serum-containing culture conditions. The induction of NAP by G-CSF was detectable at 0.4 ng/ml and became maximal between 10 and 20 ng/ml. Anti-G-CSF serum incubated with either NAP-IF or rG-CSF inhibited induction of NAP. Morphological examinations revealed that granulocytes cultured with G-CSF were more mature than those cultured without G-CSF, indicating that G-CSF promoted maturation of granulocytes in parallel with NAP induction. These results indicate that NAP-IF in the cystic fluid of a human squamous cell carcinoma is identical to G-CSF and that induction of NAP by G-CSF is really a reflection of cell maturation promoted by G-CSF.

Alkaline Phosphatase↗
PubMed1988

On the activities of parathyroid hormone-like factor and transforming growth factors in extract of pancreatic cancer associated with humoral hypercalcemia of malignancy.

Extract of exocrine pancreatic cancer associated with humoral hypercalcemia of malignancy was examined for biological activities of PTH-like factor and transforming growth factor (TGFA and TGFB), both of which are possible causes of hypercalcemia. The crude extract had both PTH-like and TGF activities. On Bio Gel P-60 column chromatography, PTH-like and TGFA activities were eluted at around 10 kD, whereas TGFB activity was eluted at around void fractions, 10 kD and 6 kD. Liver extract, used as a control material, exhibited only TGFB activity at around 6 kD. CM-cellulose column chromatography of 10 kD fractions resulted in a subtle distinction between PTH-like activity and TGF activities. Further fractionation of the peak with PTH-like activity on reverse-phase high performance liquid chromatography separated PTH-like activity distinctly from TGFB activity. TGFA activity was lost through the procedure. It was concluded that the exocrine pancreatic cancer associated with hypercalcemia produced not only PTH-like activity but also TGFA and TGFB activities. Several chromatographic analyses suggested that PTH-like activity and at least TGFB activity stem from distinct molecules and that the PTH-like factor has no significant TGFB activity intrinsically.

Cell Line↗
PubMed1987

An increase in basophils in a case of acute myelomonocytic leukaemia associated with marrow eosinophilia and inversion of chromosome 16.

A patient with acute myelomonocytic leukaemia (M4 subtype) with pericentric inversion of chromosome 16, inv(16)(p13q22), and a marked basophilia is described. Results from transmission electron microscopy suggested that the basophils were immature. Clinically, although leukaemic cells had a tendency to infiltrate a number of tissues and organs, such as skin, gingiva, liver and lung, the patient was successfully treated with chemotherapy. The increase in basophils accompanied by marrow eosinophilia may be the result of abnormal differentiation of leukaemic cells that have the capacity to differentiate into both the eosinophilic and basophilic pathways.

Adult↗