Treatment of warfarin-induced hair loss with ubidecarenone.
Explore the source record for details and available documents.
Alopecia↗
Biomedical subjects
T Nagao
Publications and source records attributed to T Nagao.
Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.
To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line); those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B*3502, B*3507, and B*3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B*3503 molecules. The CTL-resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Ca(2+)-independent fusion of secretory granules with phospholipase A2-treated plasma membranes in vitro.
The fusion of secretory granules with plasma membranes prepared from rat parotid gland was studied in vitro to clarify the mechanism of exocytosis. Fusion of the granules with plasma membranes was measured by a fluorescence-dequenching assay with octadecyl rhodamine B, and release of amylase was also measured to confirm the fusion as a final step of the secretory process. Plasma membranes that had been pretreated with porcine phospholipase A2 (PLA2) in the presence of 20 microM Ca2+ fused with the granules within 30 s, and induced amylase release by reacting with the membranes of granules, whereas without this pretreatment they had no significant effect. The fusion process accompanied by amylase release was induced in the presence of 10 mM EGTA, and therefore was apparently Ca(2+)-independent. On the other hand, the presence of EGTA or 100 microM quinacrine, an inhibitor of PLA2, during treatment of plasma membranes with PLA2 inhibited their fusogenic activity, suggesting the importance of activation of PLA2. Arachidonic acid and linoleic acid were released from the plasma membranes during the PLA2 treatment. The presence of albumin, an adsorbent of fatty acids, during the treatment also inhibited the activity. Pretreatment of the membranes with arachidonic acid or linoleic acid did not have any effect, but the presence of exogenously added arachidonic acid during PLA2 treatment enhanced the membrane-fusion-inducing effect of PLA2. Pretreatment of the membranes with lysophosphatidylcholine induced fusogenic activity. These findings suggest that the conformational change in the plasma-membrane phospholipids induced by PLA2 and the presence of arachidonic acid or linoleic acid produced by PLA2 are important in the process of fusion of secretory granules with the plasma membranes of rat parotid acinar cells and that the fusion process itself is independent of Ca2+.
5,8,11,14-Eicosatetraynoic Acid↗
Synchronous potentials and elevations in [K+]o in the adult rat entorhinal cortex maintained in vitro.
Extracellular field-potential recordings and measurements of the extracellular concentration of potassium ([K+]o) were made in layers II and III of the adult rat entorhinal cortex in a slice preparation. Two types of spontaneous, synchronous potentials were induced by the convulsant drug 4-aminopyridine (4AP, 50 microM). The first type was seen in all slices (n = 19) and consisted of a negative-going field potential that lasted 0.5-3.5 s and occurred at rates of 0.013-0.13 Hz. This event was accompanied by an elevation in [K+]o that attained peak values of 4.0-7.6 mM. The second type was reminiscent of ictal epileptiform discharges and was recorded in 6 of 19 slices; it lasted 21-190 s, recurred at 0.001-0.003 Hz and was associated with [K+]o increases that had peak values of 14-17 mM. Whenever such an ictal discharge occurred, it was closely preceded and thus appeared to be initiated by the first type of field potential. Perfusion with N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxy-piperazine-4-yl)propyl-1-phosphonate (CPP; 10 microM) abolished the ictal discharge (n = 4). This pharmacological procedure did not abolish the negative-going potentials that continued to occur during further application of the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM; n = 4). These glutamatergic-independent potentials were, however, blocked by the GABBAA-receptor antagonist bicuculline methiodide (10 microM, n= 3). Thus, as in hippocampus, 4AP can induce in the entorhinal cortex a synchronous GABA-mediated potential that is resistant to excitatory amino acid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
4-Aminopyridine↗
Effect of anti-ICAM-1 and anti-LFA-1 antibodies on rat liver transplantation.
The effect of the anti-cell adhesion molecule antibodies, anti-ICAM-1 (1A29) and anti-LFA-1 (WT1), on rat liver transplantation was investigated. Livers from ACI rats were transplanted into Lewis rats by Kamada's method and during the recipient operation 1A29 1 mg/kg, and WT1 1 mg/kg were administered intravenously to one group of rats (treated group). The survival time of the treated group was significantly longer than that of the untreated group, but permanent unresponsiveness could not be induced. Postmortem examination revealed little histological evidence of acute rejection in treated rats, in which the main cause of death was thought to be chronic rejection.
Animals↗
Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining.
We analyzed the p53 expression immunohistochemically in 50 specimens of hepatocellular carcinoma (HCC) using two monoclonal antibodies (DO7 and PAb1801) and one polyclonal antibody (CM1), which recognize both wild and mutant type p53 proteins and can be used for paraffin-embedded sections. Fifteen of the 50 HCC specimens (30%) showed p53 expression localized at tumor nuclei, and this expression was significantly more frequent in HCCs with histologically lower differentiation. Except for serum titers of alpha-fetoprotein, the p53 expression had no statistically significant correlation with clinicopathological parameters, including hepatitis virus infection, tumor size, and background liver diseases. Conversely, the cell proliferative activities of tumor cells as assessed by mitotic index and immunostaining for MIB-1 were well correlated with the grade of histological differentiation. Moreover, MIB-1 immunostaining was shown to be useful in distinguishing well differentiated HCC from hepatocytes in chronic liver diseases. It also was shown that p53 expression was strongly associated with cell proliferative activity. Our results indicate that p53 expression takes place in the late stage of tumor progression and is related to the high malignant potential of HCCs.
Antibodies, Monoclonal↗
Citalopram, a serotonin reuptake inhibitor, and brain ischemia in SHR.
The effects of citalopram, a serotonin (5-HT) reuptake inhibitor, on cerebral blood flow (CBF) and concentration of 5-HT and its metabolite were investigated in spontaneously hypertensives rats (SHR) subjected to forebrain ischemia. Cerebral ischemia was induced by bilateral carotid artery occlusion. The concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), increased during cerebral ischemia in most brain regions examined, while that of 5-HT increased only in the frontal cortex and the striatum. Citalopram restored the 5-HIAA concentrations to the preischemic normal levels. Citalopram had no effect on the cortical CBF, before and during ischemia. These results suggest that citalopram attenuates ischemia-induced hypermetabolism of 5-HT in the brain. The effects of citalopram are independent of hemodynamic factors including cerebral blood flow, and are likely to be mediated by a direct inhibition of the neuronal 5-HT reuptake system.
Animals↗
Inhibition of acetylcholinesterase modulates the autoregulation of cerebral blood flow and attenuates ischemic brain metabolism in hypertensive rats.
We designed the present study to examine whether or not the inhibition of acetylcholinesterase modulates cerebral microcirculation in hypotension and improves brain metabolism in ischemia induced by bilateral carotid artery occlusion in hypertensive rats. Blood flow to the parietal cortex was determined by the H2 clearance method. Lactate, pyruvate, and ATP were estimated by enzymatic methods. Acetylcholinesterase inhibitor (AChEI, ENA-713), at 0.05, 0.1, or 0.5 mg/kg, was intravenously injected 10 min before either hemorrhagic hypotension or cerebral ischemia. The levels of acetylcholine in the control were 29.3 +/- 8.1 (mean +/- SD) and 39.5 +/- 8.1 pmol/mg in the cortex and hippocampus, respectively, and they were significantly decreased by 15-19% after 60 min of ischemia in the vehicle-treated rats. AChEI preserved the levels to 93-98% of the control (p < 0.05 versus vehicle). The lower limit of autoregulation was 74 +/- 9% of the resting values. The administration of AChEI helped preserve blood flow and lowered the limit to 64 +/- 6% (p < 0.05 versus control). After 60 min of ischemia, lactate increased 6.5-fold and ATP decreased to 64% of the control value. The administration of AChEI dose-dependently reduced the lactate level 1.9- to 3.9-fold and well preserved the ATP level to 94-97% of the control. The inhibition of acetylcholinesterase activity may preserve cerebral autoregulation during hypotension and protect cerebral metabolism against ischemic insult.
Acetylcholine↗
Pure red cell aplasia caused by parvovirus B19 infection in a renal transplant recipient.
Explore the source record for details and available documents.
Humans↗
Platelet activation is not involved in acceleration of the coagulation system in acute cardioembolic stroke with nonvalvular atrial fibrillation.
BACKGROUND AND PURPOSE: It is generally accepted that the coagulation system is activated in ischemic stroke and that platelet activation is involved in the pathogenesis of this disease. However, little is known about how and to what extent platelet activity participates in coagulation system enhancement. We evaluated the hemostatic condition, especially with regard to platelet function and the coagulation system, within 3 days of onset of acute stroke. The study participants were limited to elderly patients with cardioembolic stroke due to nonvalvular atrial fibrillation. METHODS: Seventeen elderly patients with acute cardioembolic stroke due to nonvalvular atrial fibrillation were investigated. Within 3 days of stroke onset, beta-thromboglobulin (BTG), platelet factor 4 (PF4), thrombin-antithrombin III complex (TAT), and D-dimer from arterial blood were carefully evaluated in these patients. Blood samples from 19 healthy age- and sex-matched control subjects were also examined. RESULTS: The two studied markers of platelet activity did not change in the patients or the control subjects, and the between-group differences between the stroke and control groups were not statistically significant (BTG, 43.8 versus 31.9 ng/mL; PF4, 9.06 versus 5.78 ng/mL; respectively). In contrast, the two studied coagulation-system indicators were markedly elevated in the patients compared with the control subjects (TAT, 13.8 versus 3.5 ng/mL, P < .01; D-dimer, 366.3 versus 147.2 ng/mL, P < .01; respectively). CONCLUSIONS: Platelet function was not enhanced in the acute stage of cardioembolic stroke with nonvalvular atrial fibrillation. This result indicates that enhancement of the coagulation system in cardioembolic stroke is not the result of platelet hyperfunction, ie, "platelet-fibrin" thrombi, but rather of "stasis-related" thrombi formation.
Aged↗
Inhibitory effects of cucurbitane triterpenoids on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumor. II.
To search for possible anti-tumor-promoters, we carried out a primary screening of twenty-four 29-nor-cucurbitacin glucosides isolated from the roots of Cayaponia tayuya (Cucurbitaceae) using an in vitro synergistic assay system. Of these glucosides, cayaponosides B (5), B3 (7), D (8), D3b (22) and C2 (23) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 5 and 23 exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.
Animals↗
Differential effects of selective beta 1-agonist stimulation on epi- and endocardial oxygen tension in anesthetized dogs.
We investigated the effects of selective beta 1 adrenoceptor stimulation on oxygen tension (pO2) in the myocardium of anesthetized dogs. A beta 1-selective full agonist, T-0509 (0.01-0.05 microgram/kg, i.v.), caused positive inotropic and chronotropic effects, and increased left circumflex blood flow, although it did not change arterial blood pressure. These effects were inhibited by bisoprolol (10 micrograms/kg), but not by ICI 118551 (30 micrograms/kg). Under control conditions, subepicardial pO2 (pO2 epi) and subendocardial pO2 (pO2endo) were approximately 33 and 27 mmHg, respectively. T-0509 (0.05 microgram/kg) decreased pO2epi in all cases, with a mean decrease of 2.6 +/- 0.5 mmHg, and this was significantly inhibited by bisoprolol. T-0509 caused an increase (7 out of 10 dogs) or a slight decrease (3 out of 10) in the pO2endo; the mean increment was 2.0 +/- 1.3 mmHg (n = 10). Isoproterenol (0.01-0.05 microgram/kg, i.v.) exerted positive inotropic and chronotropic effects that were sensitive to bisoprolol, and a hypotensive effect that was sensitive to ICI 118551. Isoproterenol caused an increase in blood flow that was sensitive to ICI 118551. Isoproterenol (0.05 microgram/kg) decreased pO2epi in all cases, with a mean decrease of 2.7 +/- 0.5 mmHg, which was significantly inhibited by bisoprolol. Isoproterenol caused an increase (5 out of 10) or a slight decrease (5 out of 10) in the pO2endo; the mean increment was 1.1 +/- 1.2 mmHg (n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-1 Receptor Agonists↗
Effect of DP-1904, a thromboxane A2 synthase inhibitor, administered from the autologous phase on crescentic-type anti-GBM nephritis in rats.
The antinephritic effect of DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid hydrochloride], a thromboxane (TX) A2 synthase inhibitor, was compared with that of OKY-046 and azathioprine, using an experimental model of nephritis, crescentic-type anti-glomerular basement membrane (GBM) nephritis. Test drugs were given p.o. once daily from an autologous phase in which proteinuria was already fully developed. DP-1904 (15 and 45 mg/kg per day) and OKY-046 (20 mg/kg per day), another TXA2 synthase inhibitor, significantly inhibited the development of glomerular alteration as well as the elevation of proteinuria. On the other hand, azathioprine (20 mg/kg per day), an immunosuppressive agent, failed to suppress the proteinuria. A single administration of DP-1904 or OKY-046 inhibited glomerular TXB2 production and increased glomerular prostaglandin (PG) E2 and 6-keto PGF1 alpha production in nephritic rats. Both drugs apparently decreased the depositions of both rabbit immunoglobulin (Ig) G and rat IgG on GBM in nephritic rats, but azathioprine inhibited only the deposition of rat IgG. These results suggest that DP-1904 may be an effective agent for the treatment of proliferative glomerulonephritis and its antinephritic effect may be due to the amelioration of abnormal metabolism of arachidonic acid.
Animals↗
Barium and strontium can substitute for calcium in stimulating nitric oxide production in the endothelium of canine coronary arteries.
We investigated whether Ba2+ and Sr2+ can substitute for Ca2+ in stimulating the nitric oxide (NO) production and cause relaxation in vascular smooth muscle. Ba2+ and Sr2+, like Ca2+, relaxed K(+)-depolarized canine coronary arteries in the presence of diltiazem. The Ba(2+)- and Sr(2+)-induced relaxation was endothelium-dependent and was largely inhibited by NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine (L-NNA), but not by indomethacin. These cations increased cyclic GMP levels in the coronary artery to a similar extent, and the increment was completely abolished by L-NMMA. The relaxation induced by each cation was attenuated in the presence of a combination of propranolol, phentolamine and atropine, and L-NNA markedly inhibited any remaining relaxation. This indicates that these cations produce endothelium-dependent relaxation through NO production as well as the relaxation mediated by neurotransmitters. The present study suggests that Ba2+ and Sr2+ can substitute for Ca2+ in the activation of the NO synthase pathway in the endothelium of canine coronary arteries.
Animals↗
Purification and some properties of a protease from Streptomyces limosus.
Streptomyces limosus was selected because it secreted a novel protease that catalyzed the synthetic reaction forming Pro-Pro-Pro from Pro-Pro. The protease was purified to an electrophoretically homogeneous state and an activity of more than about 20,000-fold that of the culture broth. The molecular mass of the enzyme was estimated to be 50 kDa by SDS-polyacrylamide gel electrophoresis. The enzyme was most active in alkaline pH for the synthetic reaction producing Pro-Pro-Pro from Pro-Pro, although for the hydrolytic reaction forming proline it was most active in neutral pH. The enzyme was inhibited by 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) and diazoacetyl-DL-norleucine methyl ester (DAN). It can be considered that this enzyme belongs to the class of aspartic proteases. The substrate specificity indicates that this enzyme has a strong affinity for proline as a N-terminal amino acid of peptides.
Amino Acid Sequence↗
Annual screening for oral cancer and precancer by invitation to 60-year-old residents of a city in Japan.
Since 1986, annual screening for oral cancer and precancer by postal invitation has been undertaken among 60-year-old residents of Tokoname city, Japan. Clinical examination of the oral soft tissues is performed by groups of four different, specially trained general dental practitioners in the city health centre on one day each year. Following screening each subject receives an individual consultation with an oral medicine specialist. Individuals considered to need full diagnostic follow up or treatment are advised to attend a secondary care referral facility. Between 1986 and 1993, 802 out of 5187 eligible residents (15.5 per cent) were screened of whom 38 (4.7 per cent) were designated by the screeners as positive for oral cancer, erythroplakia, leukoplakia, lichen planus or chronic candidosis. Of these, 32 were referred and 25 attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Twenty subjects were confirmed as having a potentially malignant lesion. For these referred patients only, the proportion of correct decisions by the screeners out of all oral cancer/precancer screening decisions was 81 per cent. Positive and negative predictive values for those attending for follow up were 0.80 and 0.82 respectively. Ways of improving the effectiveness and adequacy of the programme are considered.
Biopsy↗
Pharmacokinetics of human activated protein C. 1st communication: plasma concentration and excretion of a lyophilized purified human activated protein C after intravenous administration in the mouse and the rabbit.
Pharmacokinetic studies of human activated protein C (CAS 42617-41-4, APC) were investigated in mice and rabbits with 125I-labeled compound. Plasma levels of APC were determined by three different assays: total radioactivity, APC antigenicity determined by sandwich enzyme-linked immunosorbent assay (ELISA), and the amidolytic activity which was performed by immunologically captured APC. APC concentration obtained from these assays were shown to be correlated well at early times post-dose. After intravenous administration, total radioactivity in the plasma declined tri-exponentially, but antigenicity and amidolytic activity in the plasma declined biexponentially. Plasma AUC increased proportionally with the dose, and the total body clearance and t1/2 did not change significantly. In addition, no significant difference was observed between the pharmacokinetics in male and female mice. In rabbit study, the profiles of times vs APC concentration in the plasma was similar to those in mice after single bolus injection. The plasma concentrations of APC during and after infusion in rabbits were also determined. APC concentration increased during infusion and reached almost steady state at the end of infusion. The profiles of the APC concentration in benzamidine citrate plasma corresponded to the simulated curves which were characterized by the parameters obtained from the single bolus experiment. Plasma disposition profiles of the protein were studied with high performance gel chromatography method. The radioactivity in the unchanged APC was observed at 15 min after administration. At 1 h, most of the radioactivity was observed in larger molecule fraction than the intact APC. These results corresponded to the decrease of amidolytic activity in the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Pharmacokinetics of human activated protein C. 2nd communication: tissue distribution study of a lyophilized purified human activated protein C after single or repeated intravenous administration in male mice and placental transfer and milk passage study after intravenous administration in pregnant and lactating mice.
Tissue distribution studies of human activated protein C (CAS 42617-41-4, APC) were performed in mice after single or repeated administration, and placental transfer and milk passage study were investigated. At 15 min after a single intravenous administration of 125I-APC, radioactivity was mainly distributed to the blood and blood rich organ, such as liver, and then rapidly eliminated. The radioactivity distributed to tissues was almost negligible at 24 h after administration except for the thyroid. The qualitative study of the distribution of radioactivity to tissues by whole body autoradiography demonstrated the correspondence to the result of the quantitative assay of distribution of radioactivity after single administration of 125I-APC. The influence of repeated administration of APC on its pharmacokinetic disposition was studied by administering 125I-APC once a day to mice for 14 days. Though plasma radioactivity at 15 min in mice during repeated administration of 125I-APC was almost similar to that at 15 min after a single administration, the radioactivity at 24 h after administration was 2 times higher than that after a single administration. The profile of plasma radioactivity during and after repeated administration corresponded to the simulation curve which was described with the pharmacokinetic parameters obtained previously after the single administration. Distribution profile after repeated administration at 15 min after the 4th, 7th, 10th and 14th administration was almost similar to that at 15 min after a single administration except for the thyroid and spleen. In the thyroid, the radioactivity was 500 times higher than that after a single administration, and HPLC analysis demonstrated that the radioactivity was attributed to thyroglobulin. As to the spleen, the radioactivity was about 52% of that after a single administration. During the repeated administration, the spleen became larger than that after a single administration and the final weight was 2 times heavier than that of the non-treated animal. The decrease in radioactivity of the spleen during repeated administration was attributed to the hypertrophy of the organ. Placental transfer of 125I-APC was studied with pregnant mice quantitatively and qualitatively. Radioactivity distributed in fetuses was low at every point examined, and the result corresponded to the autoradiography. During lactation, radioactivity transferred to milk and milk to plasma ratio reached 5.7 after intravenous administration of 125I-APC. HPLC analysis of the milk radioactivity demonstrated that most of the radioactivity was present in the macromolecules produced by the lactating mother.
Animals↗