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Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 19 recordsLinked to original sources
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↗
PubMed1991

Differential mRNA expression of three distinct classes of Fc gamma receptor at the feto-maternal interface.

Heterogeneous expression of three classes of Fc gamma receptor (Fc gamma RI, IIa, IIb, and III) in the human placenta and decidua was examined by Northern blot hybridization and cDNA amplification analysis by polymerase chain reaction. Messenger RNA of Fc gamma RI, IIa and III genes were consistently expressed in the human placenta in all trimesters of gestation. The transcripts of the Fc gamma RIIb gene, on the other hand, dramatically increased in placentae at the second and third trimesters. This characteristic expression of Fc gamma RIIb after 20 gestational weeks was confirmed by sequential cDNA amplification analysis. Fc gamma RI, IIa and III mRNAs, but not Fc gamma RIIb, were also detected in the human decidua. Interestingly, while Fc gamma R mRNA could be induced in uterine endometrium by pseudopregnancy therapy using estrogen and progesterone, there was no detectable mRNA in hormone-unprimed normal endometrium. These findings suggest that Fc gamma Rs expressed at the feto-maternal interface can be transcriptionally regulated by sex steroid hormones as multifunctional molecules. In addition, the Fc gamma RIIb molecule is predominantly produced by placental tissues after the mid-trimester of gestation and possibly plays an important role in the transport of IgG molecules from mother to fetus.

Antigens, CD↗
PubMed1991

Probabilistic assessment of the HLA sharing of recurrent spontaneous abortion couples in the Japanese population.

In spite of a number of investigations, the concept of human leukocyte antigen (HLA) sharing in recurrent spontaneous abortion (RSA) couples remains controversial. We introduced the basal antigen sharing rate (BSR) by the original mathematical approach using the gene frequency of all HLA specificities derived from our regional control population and applied this parameter for the comparison with RSA couples. RSA couples were classified into three subgroups; primary (3 or more consecutive abortions), secondary (3 or more consecutive abortions after 1 live birth), and potential (2 consecutive abortions) aborters. No significant differences between the HLA class I sharing rates (one or more antigens shared on a single locus) of the all RSA subgroups and the calculated BSRs were observed. In the HLA-DR and DQ loci, on the other hand, the antigen sharing rates of primary aborters were significantly higher than BSRs (p less than 0.01/DR, p less than 0.05/DQ). While potential aborters showed a result similar to that of the primary aborters, no significant antigen sharing of HLA class II was observed in secondary aborters. Our data suggest that BSR is a useful parameter for detection of significant HLA sharing in regional populations and the consecutive abortions that occurred primarily are certainly relevant to HLA class II sharing.

Abortion, Spontaneous↗
PubMed1991

Urate oxidase activity and copper content in the liver of macular mutant mouse, a model animal for human congenital copper deficiency, Menkes' kinky hair disease.

The macular mouse is an X-linked recessive inherited mutant and is considered to be a model for human congenital copper deficiency, Menkes' kinky hair disease. The activity of urate oxidase, which has been believed to be a copper enzyme, and copper content in the liver of the mutant mouse were determined. The oxidase activity was maintained at normal level even though there was very low level of copper present in the liver through days 7 to 14. Copper administration increased the copper content in the liver to the normal level, but did not affect the oxidase activity.

Animals↗
PubMed1991

Pyrrolomycin group antibiotics inhibit substance P-induced release of myeloperoxidase from human polymorphonuclear leukocytes.

In order to search for microbial modulators of the activity of neuropeptide, we established a screen based on substance P (SP)-induced myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). SP induced MPO release in a dose-dependent manner at concentrations ranging from 1 approximately 10 x 10(-4) M. In comparison at 1 x 10(-4) M, induction was also observed with SP derivatives but not with other neuropeptides such as neurokinin and enkephalin. Based on this, we searched for microbial inhibitors against SP-induced MPO release. An actinomycete metabolite designated HS3, which turned out to be identical with dioxapyrrolomycin or A1-R2081, and structurally related pyrrolomycins were found to inhibit SP-induced MPO release. In addition, these compounds inhibited the f-Met-Leu-Phe (FMLP)-induced MPO release from PMN. Pyrrolomycin derivatives with an N-methylated pyrrole ring showed, however, a selective inhibition of the SP-induced MPO release. This was in contrast to results with aseanostatin P5 which selectively inhibited FMLP-induced MPO release.

Actinomycetales↗
PubMed1991

[Intracellular Ca2+ mobilization and its regulation in platelet activation].

It has been generally accepted that platelets play etiological roles for the development of atherosclerosis and arterial thrombosis. Platelet activation may be dependent upon the cytosolic free Ca2+ concentration ([Ca2+]i), and regulated by PGI2 and endothelium-derived relaxing factor (EDRF) released by vascular endothelium. We have studied here the effect of endothelial cells (EC) on platelet activation and intracellular Ca2+ mobilization. Effluent of non-stimulated EC column inhibited thrombin-induced platelet aggregation and intracellular Ca2+ mobilization. An addition of this effluent to platelet suspension leaded to increase in intraplatelet cyclic AMP (cAMP) which was inhibited by the treatment of indomethacin to EC, suggesting that this effect was involved in PGI2 released by EC. On the other hand, effluent of thimerosal-stimulated EC column inhibited platelet aggregation and increase in [Ca2+]i stimulated with thrombin, and leaded to increase in intraplatelet cyclic GMP (cGMP). But the treatment of indomethacin to EC had no effect of this inhibition. The effect of thimerosal-stimulated EC was inhibited by the addition of 1-NG-monomethylarginine (NMA), EDRF/NO inhibitor, suggesting that EDRF released by thimerosal-stimulated EC produced an increase in cGMP and inhibited platelet activation. Although forskolin-induced in cAMP caused a marked prevention of inositol 1, 4, 5-trisphosphate (IP3) production stimulated with thrombin, 8-bromo cGMP and EDRF-induced increase in cGMP had no effect of IP3 production. An increase in cAMP and cGMP was considered to inhibit intracellular Ca2+ mobilization by different mechanisms in platelets.

Blood Platelets↗
PubMed1990

[MR imaging of mucocutaneous malignant melanoma in the head and neck].

MR imaging was performed in three patients with mucocutaneous malignant melanoma of the head and neck, and surgical specimens were investigated in MR-pathological correlation. Two of 3 cases were revealed to be melanotic melanoma; one arose in the maxillary sinus, and another in the bulbar conjunctiva. The remaining case was amelanotic melanoma originating in the nasal cavity. Two cases of melanotic melanoma showed different intensity on T1WI according to the melanin concentration; the more the melanin-producing process existed, the higher intensity in the tumor was shown. On T2WI there were also some differences in signal intensity; the case having more concentration of melanin changed lower partially in the areas where very high intensity was noted on T1WI, while another case remained unchanged. These findings are based on the inherent paramagnetic effect mostly compatible with the previous reports. On the other hand, the amelanotic melanoma was demonstrated as an intermediate intensity both on T1- and T2WI. Because of the higher incidence of hemorrhage in/around the tumor, it is an important diagnostic clue to this tumor, as in our case of amelanotic type. On reviewing the three cases, we consider that MR imaging offers a useful adjunct in the diagnosis of malignant melanoma.

Aged↗