PubMed Health⌕ Search

Biomedical subjects

M Asami

Publications and source records attributed to M Asami.

At least 37 records · Page 2Linked to original sources

Inhibition of prostaglandin production in the inflammatory tissue by loxoprofen-Na, an anti-inflammatory prodrug.

The effect of loxoprofen-Na, a novel non-steroidal anti-inflammatory drug with a prodrug property, on prostaglandin (PG) levels in the inflammatory tissue was investigated with a carrageenin-induced pleurisy model in rats. The intrapleural injection of carrageenin caused a marked increase in the levels of PGE2 and 6-keto-PGF1 alpha in the pleural exudate up to 3 hr after the injection. When [14C]PGE2 was injected into the cavity 2 hr after the carrageenin injection, the PG rapidly disappeared from the cavity (T 1/2 = 5 min). Thus, the PG level determined in the inflammatory exudate represents PG produced in the inflammatory tissue. Loxoprofen-Na, administered orally 2 hr after the carrageenin injection, dose-dependently inhibited the increase in the levels of PGs in the exudate 1 hr after administration (ID50 = 0.07 mg/kg for PGE2 and 0.10 mg/kg for 6-keto-PGF1 alpha). Indomethacin also inhibited PG production, but was less effective (ID50 = 0.24 mg/kg for PGE2 and 0.47 mg/kg for 6-keto-PGF1 alpha). Similar results were obtained 3 hr after the administration of these drugs (ID50 of PGE2 production = 0.14 mg/kg for loxoprofen-Na and 0.28 mg/kg for indomethacin). The time-course analysis of the effect of loxoprofen-Na showed that this drug had more immediate and stronger inhibitory activity than indomethacin. The relative potencies of suppression of protein leakage and leukocyte infiltration correlated well with the inhibition of PG production, but higher doses were needed for an obvious anti-inflammatory effect. The active metabolite (SRS trans-OH) of loxoprofen-Na determined in the inflammatory exudate 1 hr after oral administration of 0.2 and 2 mg/kg of loxoprofen-Na was 0.05 and 0.25 micrograms/mL, respectively. The concentration was sufficient to suppress PG production in the exudate, because the IC50 of the SRS trans-OH for PG production in vitro with leukocytes was 0.02 microgram/mL (0.01 microM). The potency of the SRS trans-OH metabolite to inhibit PGE2 production in leukocytes was about 20 times stronger than that of the parent compound and 3 times stronger than that of indomethacin.

6-Ketoprostaglandin F1 alpha↗

Susceptibility of multipotent haemopoietic stem cell deficient W/Wv mice to Plasmodium berghei-infection.

The susceptibility of haemopoietic stem cell deficient W/Wv mice to infection with Plasmodium berghei was examined. The mean survival time of W/Wv mice after the infection was shorter than that of the +/+ mice. Splenomegaly, a characteristic pathological change of the host after infection with malaria parasites was not observed in W/Wv mice. When haemopoietic activity of the infected mice was examined, a substantial increase in number of multipotent haemopoietic stem cells (CFU-S) and the committed stem cells for granulocytes and macrophages (CFU-GM) or for erythrocytes (CFU-E) was observed in the bone marrow and spleen of +/+ but not of W/Wv mice. CFU-S were not detected in W/Wv mice before or after infection. The number of CFU-GM and CFU-E in bone marrow and spleen of W/Wv mice decreased after infection. Bone marrow grafting from +/+ to W/Wv mice 8 weeks before infection prolonged the mean survival time of the mice and effectively restored the number of CFU-S in the spleen of W/Wv mice. These results indicate that multi-potent haemopoietic stem cells play an important role in the host's defence mechanisms against P. berghei-infection.

Anemia, Macrocytic↗

[Management of cesarean section under replacement therapy with factor VIII concentrates in a pregnant case with congenital combined deficiency of factor V and factor VIII].

The congenital combined deficiency of Factor V and Factor VIII, a rare bleeding disorder, was identified in a 25-year-old woman. She was admitted to our hospital with a complaint of genital bleeding. Her prothrombin time and activated partial thromboplastin time were prolonged. She had low levels of Factor V coagulant activity (F. V:C) 14%, and Factor VIII coagulant activity (F. VIII:C), 12%, and normal levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (Rcof) and Protein C antigen. Her Protein C inhibitor level was slightly low. Her Rcof, vWF:Ag and F. VIII:C were elevated following administration of 1-deamino-8-D-arginine-vasopressin (DDAVP), but her F. V:C remained unchanged. Four years later, her F. VIII:C rose to 70% during the course of her pregnancy, but her F. V:C value remained low. It was expected that the vaginal delivery would be possible at the termination of pregnancy. Premature rupture of the membranes and an anomaly of rotation appeared in the course of delivery, however, and cesarean section was accomplished without excess bleeding under replacement therapy with Factor VIII concentrates. These findings suggested that DDAVP and Factor VIII concentrates were useful for management of her delivery. However the mechanisms of the rise of plasma F. VIII:C during pregnancy in a case with congenital combined deficiency of Factor V and Factor VIII are unclear.

Adult↗

Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara canis-infected mice.

Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the livers of Toxocara canis-infected mice. At the peak of the response (day-13 after infection), the majority of hepatic hemopoietic foci were of the eosinophil lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day 13 contained large numbers of hemopoietic stem cells, more than half of which were cycling. When W/Wv mice, which are genetically deficient in multipotent hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci were rare throughout the course of infection. This impaired response of W/Wv mice was restored by bone marrow grafting from normal +/+ littermates. These results indicate that, in response to the increased demand, eosinophils are generated in the liver by the differentiation from multipotent stem cells, not only from the committed precursors.

Animals↗

Extramedullary eosinophilopoiesis in the liver of Schistosoma japonicum-infected mice, with reference to hemopoietic stem cells.

Extramedullary hemopoiesis recognized as hemopoietic foci increased in the liver of Schistosoma japonicum-infected mice in parallel with kinetic changes in periovular granuloma formation. At the peak of the response, about 65% of the hepatic hemopoietic foci were of eosinophil lineage. When S. japonicum-infected mice were irradiated, hepatic hemopoietic foci rapidly disappeared within 3 days, whereas inflammatory cells in the periovular granulomas slowly reduced in number. When the number of hemopoietic stem cells in the liver were examined by spleen-colony assay, kinetic changes in the number of hemopoietic stem cells in hepatic nonparenchymal cells paralleled those of hepatic hemopoietic foci. Hemopoietic stem cells were rare in the granuloma cells. These results indicate that in response to the increased demand for eosinophils and other inflammatory cells, the liver acts as an extramedullary hemopoietic organ in which inflammatory cells are generated from hemopoietic stem cells.

Animals↗

[Analysis of the denture dynamics in R.P.D.'s. 2. Influence of retainers on the dynamics of free-end-saddle].

The ordinary denture movement during function is defined as the "Denture dynamics" in R.P.D.'s. by K. H. Körber (1975). The Author has already reported the evaluating method of the denture dynamics objectively by two ways: The displacement sensors of magnetoresistors detected the vertical and horizontal movements of denture saddle in free end situation. Tiny accerelometer also detected the accerelation during the movements. In this present study, the correlations among the retainers used, the extent of the denture dynamics in displacement and accerelation, the occluding force and the abutment tooth mobility induced by the denture support were correlatively evaluated in two patients with class I free end R.P.D.'s. with interchangeable retainers by above methods. All the data were collected simultaneously by the electronic measuring and recording apparatus. Following results were obtained: 1. The denture dynamics depended on the selection of retainers examined. The extent of the dynamics reduced from the denture with the wrought wire clasps, the denture with the cast clasps, then to the denture with cone crown telescopes in sequence. 2. The occluding force increased just as the changes in sequence of the denture dynamics. 3. The abutment tooth moved to the distal in each case. The highest value of the mobility was found in the denture with the cast clasps, then in the denture with the wrought wire clasps. The least value of the tooth mobility was found in the denture with the cone crown telescopes. These results will strongly support the concept of the free end saddle R.P.D.'s anchored and supported rigidly by the abutments and the residual ridges in clinics.

Dental Abutments↗

[Localization of glycylproline dipeptidyl aminopeptidase in the liver tissue and possible mechanism of its release into blood flow].

We examined the localization of glycylproline dipeptidyl aminopeptidase (GPDAP) in the liver tissue and the mechanism of its release into blood flow. An immunohistochemical study using rabbit polyclonal antibody against the purified GPDAP from human liver obtained at autopsy was performed in liver biopsy samples with the peroxidase-antiperoxidase stain technique. GPDAP staining was detected on the liver cell membrane around bile canaliculi. After treatment with deoxycholic acid (DOC) or Triton X-100, this enzyme disappeared. GPDAP was solubilized rapidly from microsome of human liver by treatment with either DOC or Triton X-100. DOC or Triton X-100 solubilized GPDAP coincided with the isozyme that was the specific isozyme in sera of patients with acute hepatitis or obstructive jaundice. These results suggest that GPDAP localizes on the liver cell membrane around bile canaliculi and that this enzyme is released by the detergent action of bile acids.

Aminopeptidases↗

[A neuron-specific enolase (NSE) positive leiomyosarcoma].

A 40-year-old woman with multiple skin tumors was admitted to our hospital on September 5, 1989. Extensive studies by means of light and electron-microscopic examination and immunohistochemical analysis revealed a neuron-specific enolase (NSE) positive leiomyosarcoma. The level of her elevated serum NSE decreased after receiving her initial chemotherapy, but after the fourth session of chemotherapy, the NSE began to elevate again and she died on December 25, 1989. NSE appears to be a useful marker for determining if the neuronal and neuroendocrine cells are normal. This rare case, however, seems to demonstrate that abnormal, nonneuronal cells like a sarcoma also open metabolic pathways to synthesize NSE.

Adult↗

[B-chronic lymphocytic leukemia/prolymphocytic leukemia (CLL/PL)--a case report].

A 48-year-old male was admitted to our hospital on April 20, 1989 because of general fatigue and abdominal fullness. Physical examination showed hepatomegaly, massive splenomegaly, and systemic lymphadenopathy. Hematological findings revealed WBC 73,000/microliters, RBC 289 x 10(4)/microliters, Hb 8.0g/dl, and platelet 9.1 x 10(4)/microliters. WBC differential count demonstrated a mixture of 63% matured small lymphocytes and 32% prolymphocytoid cells. Bone marrow aspiration was unsuccessful with a dry tap. Surface marker analysis of peripheral blood lymphoid cells disclosed that they were positive for anti-HLA-DR, CD 5, CD 19, CD 20, CD 21, CD 25, Sm-IgM, Sm-IgD, and Sm-K. He was diagnosed as B-CLL/PL, and treated with VEPA with partial remission. CLL/PL which was advocated by Melo in 1986 is regarded as a distinct clinical entity intermediate between CLL and PLL in clinical and laboratory features. Our case is interesting with regard to good response to combination chemotherapy, though most cases of CLL/PL have a resistance to standard chemotherapy.

Antigens, CD↗

Lack of correlation between lysosomal enzyme activity and ascorbic acid content in brain of lead-treated animals.

The administration of lead acetate increased acid phosphatase activities in the rat brain and four regions (cerebral cortex, diencephalon plus mesencephalon, pons plus medulla, and cerebellum) of the guinea pig brain, whereas ascorbic acid content in the brain of these animals remained unchanged following lead administration. Acid phosphatase activity also showed an increase in scorbutic guinea pig brain. Lipid peroxidation facilitated by ascorbic acid in the cerebral lysosome fraction of rat was not affected by lead. These results suggest that ascorbic acid is not directly concerned with the alteration in acid phosphatase activity induced by lead treatment.

Acetylglucosaminidase↗

Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism.

Isotope ratio (IR) mass spectrometry was evaluated for the study of drug metabolism and balance using 13C, 15N2-labelled antipyrine (AP) as a test drug. Rats were given 40 mg kg-1 (13C,15N2)AP intraperitoneally. Breath, urine, faeces and blood were collected. Except for breath, samples were combusted in sealed quartz tubes. The resulting CO2 and N2 were analysed for excess 13C and 15N, relative to pre-dose samples, by IR mass spectrometry. In addition, blood levels of AP and cumulative excretion of urinary AP metabolites were determined by gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) and high-performance liquid chromatography (HPLC) respectively. Excess 13C and 15N levels in blood were comparable with observed levels of AP, and urinary recoveries of 13C (42%) were in good agreement with those calculated from HPLC data (45%). N-Demethylation, one of the important pathways of AP metabolism, was most rapidly determined by excess 13CO2 excretion in breath (8%). The IR mass spectral analysis complemented gas chromatographic/mass spectrum and HPLC analyses, and was less complex.

Animals↗

Some factors affecting enzyme release from cerebral lysosomes: inhibitory effects of lead.

The mode of the inhibitory effect of lead ion on the release of enzymes from cerebral lysosomes isolated from young Wistar rats was examined. The incubation of cerebral lysosomes in a low pH medium or with adenosine triphosphate (1 mM) at neutral pH resulted in the decrease of the release of acid phosphatase (EC 3.1.3.2) and beta-N-acetylglucosaminidase (EC 3.2.1.30) activities. Multivalent cations such as Mn2+, Co2+ and La3+ inhibited the enzyme release, while Ca2+ facilitated the release. On the other hand, lead ion suppressed the Ca2+-induced enzyme release, but this suppressive effect of lead ion was eliminated by the treatment of lysosomes with phospholipase C and phospholipase A2. These results suggest that lead ion may alter the ionic permeability of cerebral lysosomal membrane by reacting with membraneous phospholipids, and thus may prevent the release of lysosomal enzymes in vitro.

Adenine Nucleotides↗