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Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 163 records · Page 9Linked to original sources
PubMed1994

Current topic: human placental Fc receptors.

Human immunoglobulin G (IgG) Fc receptors are important in the materno-fetal relationship. Three classes of IgG Fc receptors are recognized which generate multiple isoforms, most of which are expressed in different cellular components of human placenta at different times during pregnancy. Although the distinct biological functions of Fc gamma R phenotypes expressed in human placenta are still unknown, recent data provide evidence for an important association between the Fc gamma R phenotype and transcytosis of IgG in the placenta. Selective transfer of maternal IgG across the placenta provides passive immunity to the fetus during the period when its own immune system is gaining protective potential. Furthermore, placenta-specific macrophages may contribute through Fc gamma R-mediated phagocytosis to the protection of the fetus from either infection or maternal immune attack against paternally inherited fetal antigens. Ontogeny and expression of various isoforms of Fc gamma R subtypes may be the key to the elucidation of the transport mechanism of maternal IgG to the fetus, in addition to the determination of the mechanisms of placental protection of the fetus against the maternal immune system.

Female↗
PubMed1994

Enhanced delivery and antitumor activity of doxorubicin using long-circulating thermosensitive liposomes containing amphipathic polyethylene glycol in combination with local hyperthermia.

Enhanced delivery of doxorubicin (DXR) to a solid tumor subjected to local hyperthermia was achieved by using long-circulating, thermosensitive liposomes (TSL) composed of dipalmitoyl phosphatidylcholine (DPPC)/distearoyl phosphatidylcholine (DSPC) (9:1, m/m) and 3 mol% amphipathic polyethylene glycol (PEG) in colon 26-bearing mice. Inclusion of 3 mol% of distearoyl phosphatidylethanolamine derivatives of PEG (DSPE-PEG, amphipathic PEG) with a mean molecular weight of 1000 or 5000 in DPPC/DSPC liposomes resulted in decreased reticuloendothelial system (RES) uptake and a concomitant prolongation of circulation time, affording sustained increased blood levels of the liposomes. Concomitantly, DXR levels in blood were also kept high over a long period. The presence of amphipathic PEG did not interfere with the encapsulation of DXR by the pH gradient method (> 90% trapping efficiency) or with the temperature-dependent drug release from the liposomes. The optimal size of these liposomes was 180-200 nm in mean diameter for thermosensitive drug release and prolonged circulation time. The DXR levels in the tumor after injection of long-circulating TSL (DXR-PEG1000TSL or DXR-PEG5000TSL, at a dose of 5 mg DXR/kg) with local hyperthermia were much higher than after treatment with DXR-TSL lacking PEG or with free DXR, reaching 7.0-8.5 DXR micrograms/g tumor (approximately 2 times or 6 times higher than that of DXR-TSL or free DXR, respectively). Furthermore, the combination of DXR-PEGTSL and hyperthermia effectively retarded tumor growth and increased survival time.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Detection of high-risk human papillomavirus in the cervix and semen of sex partners.

To investigate the possibility of sexual transmission of human papillomavirus (HPV), 53 married couples were examined for the presence of HPV-16 and -18 DNAs in the uterine cervix and semen using the polymerase chain reaction method. Twenty-three of the 53 women and 12 of the 53 male partners were positive for HPV-16 DNA. No HPV-18 DNA was detected in samples from any of the partners. In 27 pairs, both partners were negative for HPV DNA in cervix or semen; in the remaining 26 pairs, at least 1 of the partners was HPV-16-positive. In 9 (35%) of these 26 pairs, both partners were infected. Furthermore, 9 (75%) of the 12 women with HPV-positive partners were HPV-positive, while 9 (39%) of the 23 men with HPV-positive female partners were HPV-positive. These findings suggest an increased risk of HPV transmission via sexual intercourse, thereby underscoring the importance of preventive care against HPV infection during intercourse.

Adult↗
PubMed1994

Pyrazolopyridine derivative acts as a novel cyclooxygenase inhibitor: antiplatelet effect in aged patients with ischemic stroke.

OBJECTIVE: To examine the antiplatelet effect of a novel pyrazolopyridine derivative (KC-764) in geriatric patients with ischemic stroke. DESIGN: Randomized clinical trial of three graded dose levels. SETTING: A geriatric clinic attached to a nursing home. PATIENTS: Fifteen patients with a history of cerebral infarction with a mean age of 75 +/- 5 years (range, 65-83). Patients were divided into three groups and administered 10, 20, or 40 mg/day KC-764 for 8 weeks. MEASUREMENTS: Platelet aggregation induced by arachidonate, ADP, collagen and platelet-activating factor. Plasma or serum levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha. MAIN RESULTS: Platelet aggregation was inhibited by KC-764 administration and returned to the control level after discontinuation. Although plasma thromboxane B2 levels were markedly decreased, plasma 6-ketoprostaglandin F1 alpha was not affected. However, the dose of 10 mg/day was not sufficient to maintain an effective plasma level of KC-764. There were no side effects or changes in laboratory findings. CONCLUSIONS: We confirmed that KC-764 at a dose of 20 to 40 mg/day is an effective antiplatelet agent and a good candidate for a trial to see if it is feasible for long-term use for the prevention of ischemic stroke in high-risk patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Pharmacological characteristics of hyperambulation induced by the sigma ligand (+)-3-PPP in rats.

(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP), a sigma ligand, at doses above 3 mg/kg (s.c.) increased the ambulatory activity of rats, while the (-) isomer of 3-PPP with low affinity for sigma receptors, did not significantly modify the ambulatory activity at 10 and 30 mg/kg (s.c.). The ambulation-increasing effect of (+)-3-PPP was prevented by the sigma receptor antagonists BMY 14802 and rimcazole or the sigma/dopamine D2 antagonist haloperidol. The (+)-3-PPP effect was also attenuated by pretreatment with the monoamine depletor reserpine or the tyrosine hydroxylase inhibitor alpha-methyltyrosine, but was not affected by the tryptophan hydroxylase inhibitor p-chlorophenylalanine. Moreover, the (+)-3-PPP effect was antagonized by the dopamine D2 antagonist sulpiride, whereas pretreatment with the 5-HT1A agonist 8-OH-DPAT and the alpha-adrenoceptor antagonist phenoxybenzamine did not exert any significant effect. These results indicate that sigma receptors are involved in the neuronal mechanism(s) of hyperambulation induced by (+)-3-PPP, and the sigma system may exert both a presynaptic action and a dopamine D2 receptor-mediated action to increase the central dopaminergic function.

Adrenergic alpha-Antagonists↗
PubMed1994

[A correlative study of the aluminum content and aging changes of the brain in non-demented elderly subjects].

The interrelation of the aluminum content and aging change of the nerve cells was studied with special reference to the neurofibrillary tangle (NFT) and occurrence of senile plaque (SP), in 15 autopsied brains (cerebrum) of non-demented elderly subjects varying in age from 75 to 101 years old and 10 cases of non-demented non-elderly adult subjects. 1) In the brain of non-demented non-elderly adult subjects, the aluminum content of the hippocampus was 14.4 +/- 1.39 ppb and that of the cortex of the frontal lobe was 20.4 +/- 2.54 ppb. In the brain of the non-demented elderly subjects, the aluminum content of the hippocampus was 401.7 +/- 60.05 ppb and that of the cortex of the frontal lobe was 373.29 +/- 72.35 ppb. Comparison of the two groups showed obviously higher levels in the latter group, being 28 times in the hippocampus and 19 times in the cortex of the frontal lobe. 2) The histochemical demonstration of the aluminum localization by the Morin method disclosed the positive fluorescence reaction along the part of the disintegrating neurofibrillary tangle and amyloid core in the senile plaques of non-demented elderly subjects. In the normal brain tissue, positive fluorescence reaction was observed in the wall of the capillary vessels of the blood brain barrier, perivascular glial supporting tissues, the nuclei of the astrocytes and nuclei, nucleoli of the nerve cells partially. No fluorescence reaction was observed in the non-demented adult subjects. 3) Morphologically, the appearance of the neurofibrillary tangle was noted in some cases of non-demented elderly group with higher aluminum levels. Classical and diffuse type senile plaques were dispersed in the 1st to 4th zone of the cortex of the frontal lobe. However, diffuse type senile plaques in the hippocampus appeared to a lesser extent. Neurofibrillary tangles were slightly noted in the cortex of the frontal lobe, however marked increase was confirmed in the CA1 to CA3 zones of the hippocampus. Ultrastructurally, paired helical filaments (PHF) were noted in the neurofibrillary tangle constituent and the increase of amyloid fibrils in senile plaques was confirmed. In this study, high levels of the aluminum content of the brain were confirmed in the non-demented elderly subjects. Moreover, the histochemical demonstration of aluminum localization by the Morin method disclosed a positive fluorescence reaction along the sites of neurofibrillary tangles and amyloid core in the senile plaques of non-demented elderly subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

PF1018, a novel insecticidal compound produced by Humicola sp.

A new insecticidal compound PF1018 was isolated from the culture broth of Humicola sp. It exhibited insecticidal activity against a wide range of critical pest species. The structure of PF1018 was determined to be (7aS)-2-((2E)-1-hydroxy-3-((1S,3aR,4R,5R,7aR)-3a,4,5,7 a-tetrahydro-1,3,5,7- tetramethyl-5,1-((3S)-(Z)-2,3-dimethylpropeno)-1H-inden-4-yl )-2- propenylidene)pyrrolizidine-1,3-dione, by NMR spectral analyses coupled with X-ray crystallographic analysis and chemical degradation study.

Chromatography, High Pressure Liquid↗
PubMed1994

[The studies on the mechanism of platelet activation induced by exogenous arachidonic acid with special reference to intraplatelet Ca2+ mobilization].

It has been reported that the dose-response curves for exogenous arachidonic acid (AA)-induced human platelet aggregation and secretion are biphasic. Low concentration (0.5-10 microM) and high concentration (30 microM-50 microM) of AA increase both platelet aggregation and secretion. In contrast, middle concentration (10 microM-20 microM) of AA reduces the both phenomena. This mechanism, however, has not been elucidated in detail. Since calcium ion has been reported to act as an important second messenger for platelet activation, intracellular Ca2+ concentration ([Ca2+]cyt) using fura-2 and aequorin, the plasma membrane-bound Ca2+ using chlortetracycline(CTC), and Ca2+ flux across the plasma membrane using 45Ca2+, in human platelet suspensions were measured in the presence and/or in the absence of external Ca2+. Cyclic AMP, inhibitory substance of platelet activation, was also measured. The increase of [Ca2+]cyt induced by low concentration of AA was mainly derived from intracellular Ca2+ storage site via thromboxane A2-phospholipase C and the increase of [Ca2+]cyt induced by high concentration of AA was mainly derived from both membrane bound Ca2+ and influx of extracellular Ca2+. The membrane bound Ca2+ release was induced by the direct effect to the plasma membrane of AA in a dose dependent manner, and it was suggested that CTC molecules were not bound to the cytoplasmic organella membrane but only to the plasma membrane. [Ca2+]cyt measured using aequorin method was thought to reflect the change in the concentration of Ca2+ area directory under the plasma membrane. The time course of intracellular 45Ca2+ flux suggested that the plasma membrane Ca2+ pump might operate in AA-stimulated platelets. Inhibition of increase of [Ca2+]cyt, and the decrease of platelet aggregation observed in 10-20 microM AA stimulation were related to the increase of cyclic AMP level. These results support the clinical usefulness of drugs that increase the cyclic AMP level in platelet.

Arachidonic Acid↗
PubMed1994

[A simple method for measurement of cerebral blood flow using 123I-IMP SPECT with calibrated standard input function by one point blood sampling; validation of calibration by one point venous blood sampling as a substitute for arterial blood sampling].

In a simplified method for measurement of cerebral blood flow using one 123I-IMP SPECT scan and one point arterial blood sampling (Autoradiography method), input function is obtained by calibrating a standard input function by one point arterial blood sampling. A purpose of this study is validation of calibration by one point venous blood sampling as a substitute for one point arterial blood sampling. After intravenous infusion of 123I-IMP, frequent arterial and venous blood sampling were simultaneously performed on 12 patients of CNS disease without any heart and lung disease and 5 normal volunteers. The radioactivity ratio of venous whole blood which obtained from cutaneous cubital vein to arterial whole blood were 0.76 +/- 0.08, 0.80 +/- 0.05, 0.81 +/- 0.06, 0.83 +/- 0.11 at 10, 20, 30, 50 min after 123I-IMP infusion, respectively. The venous blood radioactivities were always 20% lower than those of arterial blood radioactivity during 50 min. However, the ratio which obtained from cutaneous dorsal hand vein to artery were 0.93 +/- 0.02, 0.94 +/- 0.05, 0.98 +/- 0.04, 0.98 +/- 0.03, at 10, 20, 30, 50 min after 123I-IMP infusion, respectively. The venous blood radioactivity was consistent with artery. These indicate that arterio-venous difference of radioactivity in a peripheral cutaneous vein like a dorsal hand vein is minimal due to arteriovenous shunt in palm. Therefore, a substitution by blood sampling from cutaneous dorsal hand vein for artery will be possible. Optimized time for venous blood sampling evaluated by error analysis was 20 min after 123I-IMP infusion, which is 10 min later than that of arterial blood sampling.

Amphetamines↗
PubMed1994

[Evaluation of the entrance examination for baccalaureate nursing program].

The purpose of this study was to examine the relationship among the variables of the entrance examination for baccalaureate nursing program, records from senior high school, and records of the courses during nursing program. The variables of the entrance examination were the scores obtained by subjects on their entrance examination which included Japanese, English, Chemistry, short essay examination, and interview. Senior high school records included grade-point-average, Japanese, Social Studies, Mathematics, Science, Health Science, Arts, English and Home Economics. The variables of records during nursing program were achievement scores of the essential courses which taken by all subjects. The data were attained from records of 551 baccalaureate program graduates (graduates from 1982 to 1991, 61 students with recommendation entrance included) from one of the urban colleges of nursing in Japan. Peason product moment correlations and stepwise multiple regression analyses were used to identify the relationship between variables. As results, there were no relationship between entrance examination records and senior high school records except English (r = .47, p < .001). There was moderate relationship between entrance examination English and English during nursing program. Between senior high school record and nursing program records, there was a weak relationship between English & Foreign languages, Health Sciences & Physical Exercise, Science & Natural Science. Among those courses during nursing education, there was a tendency for English scores correlated significantly high with another courses than any other subjects. These findings indicate that educators could identify students early in their college education who would have difficulty in nursing courses and assist them in their learning.

Education, Nursing, Baccalaureate↗
PubMed1993

Mobility and molecular orientation of vitamin E in liposomal membranes as determined by 19F NMR and fluorescence polarization techniques.

To elucidate the molecular orientation and mobility of alpha-tocopherol (vitamin E) in membranes, 19F nuclear magnetic resonance (NMR) was applied. In bilayer phosphatidylcholine (PC) liposomes, 19F NMR spin-spin relaxation times (T2) of 19F-labeled methyl groups on either the chromanol moiety or the isoprenoid side chain of alpha-tocopherol were significantly decreased compared to those for alpha-tocopherol in solution (CDCl3), suggesting that the vitamin E molecule exists in the lipid core of membranes and that its motional freedom is significantly restricted. The difference in T2 values between the solution state and PC liposomes was greatest for the 5a-CF3 on the chromanol moiety compared with other methyl groups on the isoprenoid side chain. Hence, it is thought that the chromanol moiety of alpha-tocopherol may fit tightly near the surface of the membrane because of its hydrophilicity. When Pr3+ was added to the liposomal suspension, the intensity of the NMR signal for 5a-CF3 changed faster than those of the other methyl groups. When the surface of the liposomal membranes was positively charged using stearyl amine, the mobility of the 5a-methyl group, expressed as the correlation time (tau c), was quite similar to that in negatively charged membranes. These results indicate that the chromanol moiety of alpha-tocopherol may orient near the membrane surface, and that the hydroxyl group may be hydrogen bonded to the ester carbonyl of PC. For further confirmation of this conclusion, time-dependent changes in the fluidity of liposomes caused by the addition of Pr3+ were measured at the surface and inner region of liposomal membranes using a fluorescence polarization technique. The fluidity increased in the surface region and decreased in the inner region of liposomes containing alpha-tocopherol. These results show that when praseodymium ions may pass through the liposomal membrane, the hydrogen bonds between alpha-tocopherol and the ester carbonyl of PC may be broken, leading to the formation of an alpha-tocopherol-Pr3+ complex, thus causing the fluidity to increase. Based on the findings obtained, mobility and molecular orientation of vitamin E in membranes are proposed.

Fluorescence Polarization↗
PubMed1993

Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA.

Previously we showed that motility-related protein (MRP-1) is an antigen recognized by monoclonal antibody (mAb) M31-15 inhibiting cell motility and that the sequence of MRP-1 coincides with that of CD9. In the present study, plasmid was constructed in which human MRP-1/CD9 cDNA is expressed under the control of the Abelson murine leukemia virus promoter sequence. The expression plasmid for MRP-1/CD9 was introduced into Chinese hamster ovary cells, human lung adenocarcinoma cell line MAC10 (MRP-1 positive), and human myeloma cell line ARH77 (MRP-1 negative). All of the MRP-1/CD9 (over)expressing clones obtained from these transfected cells showed suppressed cell motility (penetration and phagokinetic track assays) depending on the degree of expression of MRP-1/CD9. Overexpression of MRP-1/CD9 by MAC10 cells resulted in the suppression of cell motility (maximally 73%) associated with considerable inhibition of the cell growth (maximally 48%). However, the inhibition of the growth of MAC10 cells by mAb M31-15 was < 17% at an antibody concentration of 1-5 micrograms/ml, which inhibits cell motility by > 90%. These results suggest that MRP-1/CD9 directly regulates cell motility and may also affect cell growth. Effects on metastasis by the expression of MRP-1 CD9 were investigated with mouse melanoma BL6 cells-BALB/c nu/nu mouse system. Metastatic potential of all transformants expressing MRP-1/CD9 was lower than that of parent BL6 cells.

Animals↗
PubMed1993

Inhibition of multidrug resistance by a new staurosporine derivative, NA-382, in vitro and in vivo.

The effects of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine (NA-382), on multidrug resistance in tumor cells were investigated. Protein kinase-inhibitory activity of NA-382 was lower but more selective to Ca2+/phospholipid-dependent protein kinase than that of staurosporine. NA-382 at noncytotoxic concentrations effectively reversed in vitro multidrug resistance of Adriamycin-resistant P388 (P388/ADR) cells, without influencing the drug sensitivity of sensitive P388 cells. NA-382 inhibited extrusion of vinblastine (VBL) and increased intracellular accumulation of VBL, more in P388/ADR cells than in sensitive P388 cells, with higher potency than staurosporine. This compound also reduced VBL resistance of other multidrug-resistant cell lines, AH66 and K562/ADR, by inhibiting VBL efflux and promoting VBL accumulation. NA-382 also dose dependently potentiated the effects of VBL and Adriamycin in P388/ADR-bearing mice. The toxicity of staurosporine was too high to use the combination with VBL in vitro and in vivo. NA-382 accumulated VBL in P388/ADR cells even after desensitization of Ca2+/phospholipid-dependent protein kinase by treatment with 12-O-tetradecanoylphorbol-13-acetate and 18 h, while being suppressed by 12-O-tetradecanoylphorbol-13-acetate added simultaneously or shortly before NA-382. Both staurosporine and NA-382 inhibited the photolabeling of [3H]azidopine on M(r) 140,000 P-glycoprotein in the plasma membrane from P388/ADR cells. These results indicate that this new staurosporine analogue, NA-382, reverses multidrug resistance by directly inhibiting the drug binding to P-glycoprotein, but not by Ca2+/phospholipid-dependent protein kinase inhibitory action.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Cytosolic free magnesium concentration in human platelets.

Although the magnesium ion (Mg2+) is considered to play an important role in cell activation, information is limited by the lack of suitable methods for measuring cytosolic free Mg2+ concentration ([Mg2+]i). We measured [Mg2+]i in resting and activated human platelets using a new fluorescent Mg(2+)-indicator, mag-fura-2. [Mg2+]i was 0.54 +/- 0.14 mM in resting platelets from 15 healthy volunteers. [Mg2+]i was elevated to 1.33 +/- 0.44 mM and 0.92 +/- 0.37 mM in platelets stimulated with thrombin and collagen, respectively. Increased Mg2+ was considered to be derived chiefly from intracellular Mg2+ mobilization. These results suggest that platelet activation is associated with the increase in [Mg2+]i. The estimation of [Mg2+]i using this method is useful for the investigation of mechanism for various cell activation.

Blood Platelets↗
PubMed1993

Membrane-spanning Fc gamma receptor III isoform expressed on human placental trophoblasts.

PROBLEM: Fc receptor for immunoglobulin (Fc gamma R) is an important mediator of immunological functions in the feto-maternal relationship. We have demonstrated by immunohistochemical means that three distinct classes of Fc gamma Rs are expressed in the different cell components of the human placenta. METHOD: In this study, Fc gamma RIII isoform expressed on placental trophoblasts (PTs) was investigated by indirect immunofluorescence and cDNA cloning. PTs, isolated from human term placenta by digestion with proteolytic enzyme, were reacted with monoclonal antibodies (MAb) against the Fc gamma Rs and other surface markers of leukocytes and subjected to flow cytometric analysis. RESULTS: PTs were positively stained with 3G8 and Leu1 1b against Fc gamma RIII, partially stained with MAb against MHC class I, but not with 32.2 (Fc gamma RI), IV3 (Fc gamma RII), or MAbs against CD4, CD19, or CD56, indicating that only low affinity receptor, Fc gamma RIII, is expressed on PTs. The DNA sequence of cloned Fc gamma RIII CDNA from PTs by PCR was identical to that of natural killer (NK) cell isoform, including the position of the stop codon that differs from the granulocyte isoform by several nucleotide substitutions. We further analyzed the susceptibility of PTs against phosphatidylinositol specific phospholipase C (PI-PLC) to determine the structural topology of PT isoform. While the reactivity with 3G8 on PTs was not influenced by treatment with PI-PLC, that on granulocytes was significantly diminished with PI-PLC. CONCLUSIONS: This result confirmed that Fc gamma RIII on PTs is a membrane-spanning molecule, and that it is distinctive from PI anchoring Fc gamma RIII on granulocytes.

Antibodies, Monoclonal↗