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Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 181 records · Page 10Linked to original sources
PubMed1993

Effect of staurosporine derivatives on protein kinase activity and vinblastine accumulation in mouse leukaemia P388/ADR cells.

Inhibition by staurosporine derivatives of cyclic AMP-dependent protein kinase (A-kinase) and protein kinase C (C-kinase), and drug resistance has been investigated. The substitution of an acetyl or an ethoxycarbonyl group for the amine N-ethoxycarbonyl-7-oxostaurosporine moiety on the tetrahydropyran ring of staurosporine decreased inhibition of both protein kinases, but increased selectivity for C-kinase by further modification of the lactam moiety to the imide (NA-382). The activities of SF-2370 on protein kinases were decreased by decarboxylation and hydroxyalkylation. These staurosporine derivatives enhanced accumulation of vinblastine in adriamycin-resistant P388 (P388/ADR) cells in a dose-dependent manner. The potency for the drug accumulation of these compounds was correlated with their inhibitory activity on the drug efflux, but was not correlated with their activity on protein kinases. Staurosporine and NA-382, with high potency for vinblastine accumulation, inhibited the photolabelling of [3H]azidopine on 140 kDa P-glycoprotein in the plasma membrane. The tetrahydrofuran compounds and NA-357, which had low potency for the drug accumulation, hardly interacted with azidopine on P-glycoprotein. Most of these compounds were highly cytotoxic by themselves, and only NA-382 was less cytotoxic among them and completely reversed the vinblastine-resistance of P388/ADR cells at a non-cytotoxic concentration. These results suggest that staurosporine derivatives can enhance drug accumulation and inhibit drug resistance through their direct action on the P-glycoprotein.

Affinity Labels↗
PubMed1993

[An adult case of secundum atrial septal defect with severe postoperative pulmonary hypertensive crisis].

We reported an adult case of secundum atrial septal defect with severe postoperative pulmonary hypertensive crisis. A 52 year-old female with secundum atrial septal defect and pulmonary hypertension underwent ASD patch closure. After the operation she experienced severe postoperative pulmonary hypertensive crisis. Only administration of PGE1 through the pulmonary artery was effective of hemodynamic improvement and reduction of pulmonary hypertension. Histological diagnosis of lung biopsy showed thromboembolism of small pulmonary artery. Pulmonary hypertension has not been evident during the 3 months since the cardiac catheterization was performed.

Alprostadil↗
PubMed1993

[Bilateral coronary-pulmonary artery fistulas with a large saccular aneurysm: a case of cardiac tamponade following rupture of the coronary artery aneurysm].

A case of bilateral coronary-pulmonary artery fistulas with a large saccular aneurysm is reported as follows. The patient was a 72-year-old woman who was referred to our hospital with a complaint of abnormal shadow on chest X-ray and had the past history of cardiac tamponade. The fistula was ligated and the aneurysm was resected with the extracorporeal circulation. Her Postoperative course was uneventful. Coronary arteriography showed that bilateral coronary-pulmonary artery fistulas had completely disappeared.

Aged↗
PubMed1993

[A new design of annulus sizer].

Reconstruction of the right ventricular outflow tract at the time of total correction of tetralogy of Fallot, the pulmonary valve annulus has been sized with fingers and Hegar dilators at our institute. But it has not always been sized correctly. To preclude such a problem, we designed new annulus sizers which have two cylindrical parts and a flexible handle (100 mm). The cylindrical parts are 40 mm in length, 8 to 30 mm in diameter, and have three lines marked every 10 mm from the end. Adjustment of the line to the valve annulus allows for correct measurement of the size. Moreover, we consider these sizers to be beneficial for annuloplasty of the atrioventricular valve, measurement of the mitral valve area after commissurotomy and the inner diameter of arteries.

Cardiac Surgical Procedures↗
PubMed1993

[Antitumor activity of a new antiestrogenic drug, toremifene (NK622) against human breast cancer xenografts in nude mice].

NK622, a novel tamoxifen(TAM) analog with nonsteroidal structure is an antiestrogenic drug with less toxicity compared with that of TAM. We studied the in vivo antitumor activity against human breast cancer xenografts in nude mice. NK 622 significantly inhibited the growth of estrogen-dependent Br-10 breast cancer but not inhibited the growth of estrogen-independent MC-2-JCK and MC-5-JCK when orally administered once daily for 14 days at the maximum tolerated dose (200mg/kg/day). The dose of NK622 in animal studies was calculated by measuring plasma level in patients receiving 40 mg/body/day oral treatment and clinically equivalent dose (CED) was determined. At the calculated CED, NK622 significantly inhibited the growth of Br-10. These results indicate that NK622 is a promising drug comparable to TAM because of the growth inhibition of estrogen-dependent breast cancers.

Animals↗
PubMed1992

[MR imaging of bone metastasis].

One hundred and three patients with known malignancy and suspected bone metastasis underwent magnetic resonance imaging. In 93%, the metastatic lesions, detected both on plain films and radionuclide bone scans, showed decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. All lesions, except one lesion showing much blastic change on plain films, showed contrast enhancement with Gd-DTPA administration. Although further investigation is needed, a correlation between the type of primary malignancy and the signal intensity of the metastatic lesion is suggested. Among 312 metastatic lesions detected by MR imaging, 272 lesions (87%) and 134 lesions (40%) were also detected by radionuclide bone scans and plain films, respectively. In five cases, MR imaging clearly revealed the lesion compressing the spinal cord, which helped us formulate a therapeutic plan. We conclude that MR imaging is the most sensitive examination for detecting bone metastasis and is necessary for planning treatment.

Bone Neoplasms↗
PubMed1992

Purification of rabbit, rat and mouse protein C with the use of monoclonal antibody to human protein C, PC01.

Ca(++)-dependent monoclonal antibody specific to gamma-carboxyglutamic acid (Gla) domain of protein C was produced. It did not cross-react to the other vitamin K-dependent plasma proteins but to protein C of the other species. Using this monoclonal antibody, PC01, rabbit (170 micrograms), rat (60 micrograms) and mouse (40 micrograms) protein Cs were isolated from 100 ml of their plasma by affinity chromatography. All of these protein Cs were two chain form linked by disulfide bond as well as human protein C and activated by thrombin-thrombomodulin complex. Rat and mouse protein Cs showed similar characters to human protein C. On the other hand rabbit protein C had different M(r) of heavy and light chains and showed lower anticoagulant activity compared with human protein C.

Animals↗
PubMed1992

Reversal of vinblastine resistance by a new staurosporine derivative, NA-382, in P388/ADR cells.

Activities of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine (NA-382), on cyclic AMP-dependent protein kinase (A-kinase), Ca2+/phospholipid dependent protein kinase (C-kinase), and drug resistance were investigated and compared with those of staurosporine. Protein kinase-inhibitory activity of NA-382 was lower but more selective to C-kinase than that of staurosporine. NA-382 was less toxic to P388 cells and at a non-cytotoxic concentration completely reversed the vinblastine (VBL) resistance of Adriamycin-resistant P388 (P388/ADR) cells without influence on the effect of VBL on the parental P388/S cells. However, the cytotoxicity of staurosporine was too high to give the combination effect with VBL. NA-382 dose-dependently increased VBL-accumulation and inhibited VBL-efflux in P388/ADR with higher potency than staurosporine. Both compounds inhibited the photolabeling of [3H]azidopine on 140-kDa P-glycoprotein in the plasma membrane from the resistant cells. These results suggest that a staurosporine analog, NA-382, reverses multidrug resistance by inhibiting the drug-efflux system or P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Purification of sufficiently gamma-carboxylated recombinant protein C and its derivatives. Calcium-dependent affinity shift in immunoaffinity and ion-exchange chromatography.

Protein C, which is an important anti-thrombotic factor in the blood coagulation cascade, undergoes several post-translational modifications. gamma-Carboxylation on nine glutamic acid residues at the N-terminal region of the light chain [gamma-carboxylated glutamic acid (Gla) domain] is considered to be critical for full anti-clotting activity. It is also known that when recombinant protein C is expressed in animal cells this particular modification is often lost. We were successful in preparing a monoclonal antibody (PC01) which distinguishes the sufficiently gamma-carboxylated protein from the rest by its specific affinity for the Ca(2+)-induced conformational change of the former, and thereby developed a simple process of purifying sufficiently gamma-carboxylated protein C. Culture supernatant of Chinese hamster ovary cell transformants was first applied to Q-Sepharose and recombinant protein C was partially purified. It was then loaded onto a PC01 affinity column in the presence of 5 mM calcium chloride. Sufficiently gamma-carboxylated protein C was retained while insufficient-carboxylated protein C quickly passed through. The former was eluted with 5 mM EDTA efficiently and with high purity, contained eight Gla units per molecule, and had similar anti-clotting activity. The flow-through was relatively impure protein C which contained five Gla units per molecule and showed limited anti-clotting activity. We extended the application of the Ca(2+)-induced conformational change to conventional ion-exchange chromatography. The sufficiently gamma-carboxylated protein C was found to elute earlier in the salt gradient from an anion-exchange column in the presence of 5 mM calcium chloride being fully separated from the insufficiently carboxylated protein C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation.

Plasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP.

Biomarkers↗
PubMed1992

The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival.

OBJECTIVE: The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. STUDY DESIGN: Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. RESULTS: Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. CONCLUSION: The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus.

Female↗
PubMed1992

Human placenta constitutively produces interleukin-8 during pregnancy and enhances its production in intrauterine infection.

Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on neutrophils. To address the significance of IL-8 in the fetoplacental unit during pregnancy, we cultured human placental explants that had been obtained by vaginal delivery, Caesarean section, or artificial abortion and then measured the IL-8 titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4 ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6 ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced significantly higher amounts of IL-8. The presence or absence of labor did not affect the amount of placental IL-8 production. However, placentae with chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL-8 production than those without chorioamnionitis (p less than 0.0001). Northern blot analysis of IL-8 mRNA expression demonstrated a constant level during pregnancy with or without chorioamnionitis, indicating the possibility that the major site of regulation of IL-8 synthesis in the placenta is posttranscriptional. Immunohistochemical analysis of first and third trimester placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing cells to be trophoblasts and macrophage-like cells. IL-8 produced by the placental cells might contribute to potentiation of the immunocompetence of placental cells against bacteria invading the fetoplacental unit.

Blotting, Northern↗
PubMed1992

A case of malignant lymphoma accompanied by Klinefelter's syndrome.

A 66-year-old Japanese male with diffuse non-Hodgkin's lymphoma, of the pleomorphic type, complicated with Klinefelter's syndrome is reported. His phisique was characterized by a long arm span, disproportionately longer lower body dimensions and a small sized penis. He had no children. Chromosomal study revealed 47, XXY and hormonal quantification showed hypergonadtropic hypogonadism. Although chemotherapy was administered, his disease took a progressive course and he died. A discussion of chromosomal alteration and oncogenesis and review of the literature are included.

Aged↗
PubMed1992

Optical resolution of (+/-)-all-trans-3-hydroxyretinal by use of high-performance liquid chromatography.

Racemic all-trans-3-hydroxyretinal (3-OH-RAL) (1) was converted by a reaction with (-)-camphanic acid chloride (CpCl) into a diastereomixture of camphanates (2a) and (2b) which was separated by preparative high-performance liquid chromatography (HPLC) to give two esters (2a) and (2b) in pure state, respectively. Saponification of (2a) and (2b) independently afforded optically active (3S)- and (3R)-3-OH-RALs (3a) and (3b), respectively, whose absolute structures were determined by circular dichroism (CD) spectra. Racemic 3-OH-RAL was separated to two peaks by HPLC using chiral column (ChiraSpher, Merck). Cochromatography with authentic specimens (3a) and (3b) showed that the peak with a short retention time corresponded to (3R)-isomer and the other to (3S).

Chromatography, High Pressure Liquid↗
PubMed1992

A new anthelmintic cyclodepsipeptide, PF1022A.

The novel anthelmintic cyclodepsipeptide PF1022A was isolated from cultured mycelia of Mycelia Sterilia PF1022 (FERM BP-2671). It showed strong anthelmintic activities against Ascaridia galli in chickens. The structure of PF1022A was determined to be cyclo(D-lactyl-L-N-methylleucyl-D-3-phenyllactyl-L-N-meth ylleucyl-D-lactyl-L-N- methylleucyl-D-3-phenyllactyl-L-N-methylleucyl) by spectroscopic analyses and chemical studies.

Animals↗
PubMed1991

Identification of the motility-related protein (MRP-1), recognized by monoclonal antibody M31-15, which inhibits cell motility.

A murine monoclonal antibody (M31-15) was identified using the penetration-inhibiting assay of a human lung adenocarcinoma cell line (MAC10) and remarkably inhibited the phagokinetic tract motility of various cancer cell lines. The antigen, motility-related protein (MRP-1), recognized by M31-15, was 25- and 28-kD proteins, and M31-15 was used to isolate a cDNA clone from a human breast carcinoma cDNA library. Sequence analysis revealed that MRP-1 had strong similarity with a B cell surface antigen (CD37), a melanoma-associated antigen (ME491), the target of an antiproliferative antibody (TAPA-1), a human tumor-associated antigen (CO-029), and the Sm23 antigen of the trematode parasite Schistosoma mansoni.

Adenocarcinoma↗