[Clinical significance of endothelin with obstructive jaundice: preliminary report].
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Animals↗
Biomedical subjects
M Kodama
Publications and source records attributed to M Kodama.
High-performance liquid chromatographic determination of N-nitroso-N-alkylureas by pre-column fluorescence derivatization and application to blood analysis.
A method for the derivatization and separation of N-nitroso-N-alkylureas [alkyl = methyl (NMU), ethyl (NEU), and n-butyl (NBU)] has been developed. Fluorescent derivatives were formed with sodium sulphide, taurine and o-phthalaldehyde and separated by reversed-phase high-performance liquid chromatography. The limits of detection of standard NMU, NEU and NBU were 0.25, 0.8 and 1.5 pmol/200 microliters, respectively. The method was applied to the determination of NMU in blood after extraction with acetonitrile in the presence of calcium chloride. NBU was used as the internal standard. The recovery of NMU from blood was ca. 95%, and the limit of detection was 10 pmol/400 microliters blood. NMU levels in rabbit blood following a single oral administration were also measured.
Acetonitriles↗
Calorimetric investigations of phase transitions of sonicated vesicles of dimyristoylphosphatidylcholine.
The process of conversion of large multilamellar vesicles (MLVs) of dimyristoylphosphatidylcholine (DMPC) into the final state of small unilamellar vesicles (SUVs) with an increase in time length of ultrasonic irradiation was investigated by calorimetry and negative-stain electron microscopy. The process was found out to be composed of two stages depending on the primary (near 24 degrees C) and secondary (near 19 degrees C) peaks due to the gel-to-liquid crystal phase (Tm) transition, respectively; a new transition peak for the secondary Tm appears after a maximum broadening of the primary Tm peak is attained. Sonicated vesicles characterized by the primary peak of the broadest shape were observed to be about 200 nm in mean diameter and mostly four or so lamellae, and have an internal aqueous space, in contrast to sonicated SUVs (approx. 40 nm in diameter) characterized by the limiting secondary Tm peak. Thermal data associated with the Tm transition for these two sonicated vesicles were compared with that of the MLV. The enthalpy and entropy changes and cooperative units increased in the order sonicated SUV < sonicated large vesicle < MLV. Furthermore, the enthalpy changes were revealed to fairly differ between the sonicated large vesicle and SUV. Based on the effect of the annealing treatment at -5 degrees C on these vesicles the present result suggested a large contribution of the aggregation state of DMPC molecules to the enthalpy possessed by the vesicles of a gel phase temperature, which is related to the mode of the Tm transitions, primary and secondary.
Calorimetry, Differential Scanning↗
Characterization of T cells infiltrating the heart in rats with experimental autoimmune myocarditis. Their similarity to extrathymic T cells in mice and the site of proliferation.
A model of experimental autoimmune myocarditis, which resembles fatal giant cell myocarditis in humans, was previously established in rats immunized by s.c. injection of human cardiac myosin. We characterized herein the surface phenotype of lymphocytes infiltrating the heart and pericardial cavity as well as of mononuclear cells in various organs by using mAb in conjunction with immunofluorescence tests. Since profound thymic atrophy always accompanied the diseased states, attention was focused on characterization of T cells with properties similar to those of extrathymic T cells. In mice, extrathymic T cells were activated in association with thymic atrophy, expressed high levels of LFA-1 and IL-2R beta-chains, and contained a significant proportion of double negative CD4-CD8- T cells. In diseased rats, a large proportion of activated T cells that expressed high levels of LFA-1 and IL-2R was demonstrated in the pericardial effusion and heart tissue. Such T cells were rare in the other organs. Light scatter and microscopic observation revealed that activated lymphoblasts were most abundant in the pericardial effusion. Moreover, one-fourth of such T cells in the pericardial effusion displayed double negative phenotype. These cells in rats might correspond to the extrathymic T cells in mice. However, only a limited population of such activated T cells infiltrated the heart tissue. Concerning the location of such T cells mainly in the outer layer of the heart, it raised the possibility that extrathymic T cell differentiation in these autoimmune rats might occur in the pericardial cavity, and the differentiated cells then migrated to the sites of the cardiac lesion.
Animals↗
Crystalline cylindrical structures of Na(+)-bound dimyristoylphosphatidylglycerol as revealed by microcalorimetry and electron microscopy.
Multilamellar vesicles of dimyristoylphosphatidylglycerol (DMPG) in an aqueous medium of 1 M NaCl at pH 7.0 converted to defined cylindrical structures of crystalline phase, on annealing of 5 degrees C of a gel phase temperature. The new crystalline phase transformed into the liquid crystal phase at a transition point (44.2 degrees C) nearly the same as that of the protonated DMPG, but with a transition enthalpy (19.2 kcal/mol) larger than that of the Ca(2+)-bound DMPG of much higher transition temperature. Electron microscopic observations revealed that a set of outer membranes (8-10 lamellae) separated from the MLV grows into helical structures and, finally, into the crystalline cylindrical structures with an increase in annealing time.
Calorimetry↗
Cardiac contractile proteins and autoimmune myocarditis.
Concerning cardiac contractile proteins, antigenicity and myocardiotogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocarditis. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the alpha-helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxicity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.
Actins↗
10(6) Depletion of WBC with CF-2, a new leukocyte removal filter.
A new leukocyte removal filter, Nipro CF-2, was evaluated. A non-woven polyester filter, gravity flow device that does not require priming and rinsing after use was developed to remove white blood cells from 400 ml of whole blood or concentrates of 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low WBC counts. To evaluate the efficiency of this filter, leukocyte counts were measured by flow cytometry using a Coulter EPIC-C cytometer. After filtration through a CF-2 filter, more than 99.9999% of WBCs were depleted from 6 of 17 samples. The mean value of WBC depletion was 99.9994%. The CF-2 filter achieved nearly a million-fold depletion of WBCs from whole blood concentrates.
Cell Separation↗
FK506 therapy of experimental autoimmune myocarditis after onset of the disease.
Preventive effects of FK506 on autoimmune myocarditis have been demonstrated, but the therapeutic efficacy of the agent in established myocarditis yet remains to be assessed. In this study, effects of FK506 on experimental autoimmune myocarditis were investigated by the use of the agent after the onset of the disease. Lewis rats were immunized with either cardiac myosin or bovine serum albumin (BSA) in complete Freund's adjuvant. The onset of the disease was ascertained by examining randomly chosen cardiac myosin-immunized rats. Animals were divided into four groups: the BSA-immunized saline-treated group (group A, n = 6); the BSA-immunized FK506-treated group (group B, n = 6); the myosin-immunized saline-treated group (group C, n = 6); and the myosin-immunized FK506-treated group (group D, n = 11). Saline or 1.0 mg/kg/day of FK506 were intramuscularly injected from day 16 to day 27. All the rats were put to death on day 28. Rats of group C became severely ill by the third week, while in contrast, rats of group D remained active, as did rats of groups A and B. The heart weight/body weight ratio was significantly lower in group D than in group C rats. Group mean values were 3.48 +/- 0.10 gm/kg for group A, 3.48 +/- 0.16 gm/kg for group B, 4.94 +/- 0.66 gm/kg for group C, and 3.88 +/- 0.43 gm/kg for group D. Rats of group C showed severe myocarditis with mononuclear cell infiltration, myocardial necrosis, and interstitial edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Study of blood compatible polymers. III. Copolymers of N-benzyl, N-(2-hydroxyethyl) acrylamide and 2-hydroxyethyl methacrylate.
Copolymerization of 2-hydroxyethyl methacrylate (HEMA) and N-benzyl, N-(2-hydroxyethyl) acrylamide (BENAAm) was carried out at different mole ratios of the monomers to obtain copolymers of varying composition. BENAAm content of the copolymers varies between 13 and 70%. Investigation of the interaction of rabbit platelets with these polymer surfaces showed that copolymers with higher BENAAm content inhibit the platelet deformation. Human umbilical cord fibroblast cells proliferated very well on the copolymer surfaces. The cell growth rate on polyHEMA was relatively low. Maximum cell growth was observed on the copolymer having 87% HEMA.
Acrylic Resins↗
Lithocholic acid-sensitive mutant cells isolated from Chinese hamster ovary cells are cross-sensitive to cytoskeleton-disturbing agents.
The lithocholic acid-sensitive mutant cells were isolated from CHO-9 cells mutagenized with ethylmethane sulfonate, through clonal selection on 96-well dishes. The isolated mutant cells (LSJ-11) were 3-fold more sensitive than controls in the survival to lithocholic acid and were also sensitive to other bile acids such as deoxycholic acid and cholic acid. As a preliminary characterization, it was found that the mutant cells were also sensitive to cytoskeleton-disturbing agents such as colchicine, colcemide, taxol and cytochalasin B. This is the first observation that a bile acid-sensitive mutant was isolated and was partially characterized.
Animals↗
Effects of cyclosporine, prednisolone and aspirin on rat autoimmune giant cell myocarditis.
OBJECTIVES: Preventive effects of cyclosporine, prednisolone and aspirin on autoimmune giant cell myocarditis in rats were investigated. BACKGROUND: The therapeutic efficacy of immunosuppressants for human myocarditis is controversial. Although harmful effects of immunosuppressive therapy on experimental viral myocarditis have been reported, the effects on autoimmune myocarditis have not been investigated. Recently, a novel experimental autoimmune myocarditis model characterized by congestive heart failure and multinucleated giant cell has been established. Using this model, the preventive effects of cyclosporine, prednisolone and aspirin on autoimmune myocarditis were investigated. METHODS: Lewis rats were immunized with cardiac myosin in complete Freund's adjuvant on days 0 and 7. In experiment 1, four groups of seven rats each were established. Rats in each group received for 21 days intraperitoneal injections of either 1) phosphate-buffered saline solution, 1 ml/day (control); 2) cyclosporine, 20 mg/kg body weight per day (cyclosporine 20); 3) prednisolone, 4 mg/kg per day; or 4) aspirin, 15 mg/kg per day. In experiment 2, two additional groups (five rats each) received for 21 days an injection of cyclosporine, 1 or 5 mg/kg per day (cyclosporine 1 and cyclosporine 5, respectively). All rats were killed on day 21, when histopathologic studies were performed and the titers of antimyosin antibodies were measured. RESULTS: The rats in the control, prednisolone and aspirin groups became ill and immobile in week 3. In comparison, rats in the cyclosporine 5 and 20 groups were still active until death was induced. Heart weight/body weight, lung weight/body weight and liver weight/body weight ratios in the rats in the cyclosporine 5 and cyclosporine 20 groups were significantly lower than those in the control group, and no differences were detectable among rats in the control, prednisolone and aspirin groups. The rats in the latter three groups and the cyclosporine 1 groups showed severe myocarditis with multinucleated giant cells. However, myocarditis was effectively prevented in the rats in the cyclosporine 5 and 20 groups. The histologic scores in each group were 2.91 in the control group, 2.14 in the prednisolone group, 2.91 in the aspirin group and 0.02, 2.58 and 0.07, respectively, in the cyclosporine 20, 1 and 5 groups. Production of antimyosin antibodies was remarkably suppressed in rats in the cyclosporine 5 and 20 groups in comparison with values in all other groups. CONCLUSIONS: Autoimmune myocarditis is preventable by cyclosporine but not by prednisolone or aspirin in usual dosages.
Animals↗
Biological effects of diesel exhaust particles. I. In vitro production of superoxide and in vivo toxicity in mouse.
The problem of whether or not active oxygen species are involved in pulmonary injury by diesel exhaust particles (DEP) was investigated. We found that DEP could produce superoxide O2.- and hydroxyl radical (.OH) in vitro without any biological activating systems. In this reaction system, O2.- and .OH productions were inhibited by addition of superoxide dismutase (SOD) and dimethylsulfoxide, respectively. DEP which were washed with methanol could no longer produce O2.- and .OH, indicating that active components were extractable with organic solvents. These oxygen radicals were also identified by electron spin resonance (ESR) measurement. Furthermore, DEP instilled intratracheally to mouse caused high mortality at low dose, although methanol-washed DEP did not kill any mouse. The cause of death seemed to be pulmonary edema mediated by endothelial cell damage. The instilled DEP markedly decreased the activities of SOD, glutathione peroxidase, and glutathione S-transferase in mouse lungs. On the other hand, the death rate and lung injury were markedly prevented by polyethylene glycol conjugated SOD (PEG-SOD) pretreatment prior to DEP administration. The mortality and lung injury by DEP were also suppressed by butylated hydroxytoluene (BHT) pretreatment. From these results, it was suggested that most parts of DEP toxicity in lungs are due to active oxygen radicals such as O2.- and .OH, and that the cause of death is due to pulmonary edema mediated by endothelial cell damage.
Animals↗
Expression of sialyl-Tn antigen is correlated with survival time of patients with gastric carcinomas.
Expression of sialyl-Tn antigen (STN) was examined by an immunohistochemical method in 85 primary gastric carcinomas. The STN expression occurred in 53 (62.4%) cancers, and the positive staining was correlated with degree of gastric wall and lymph vessel invasion, lymph node metastasis, and stage of tumour. Five-year survival rates of patients with STN-positive cancers (47.2%) were significantly lower than those with STN-negative cancers (84.4%) (P < 0.01), and patients with STN-positive cancers at stage III and stage IV had a worse prognosis. In the cancers with serosal invasion, patients with STN-positive cancer disclosed a significantly poorer prognosis than those with STN-negative cancers (P < 0.01). Therefore, it is suggested that a careful follow-up study and intensive postoperative therapy are needed for patients with advanced gastric cancers with positive STN expression.
Antigens, Tumor-Associated, Carbohydrate↗
Theories of breast carcinogenesis.
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Animals↗
Isodunnianin: a new sesquiterpene enhancing neurite outgrowth in primary culture of fetal rat cerebral hemisphere from Illicium tashiroi.
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Animals↗
Effects of point mutation in a flexible loop on the stability and enzymatic function of Escherichia coli dihydrofolate reductase.
To elucidate the role of a flexible loop in the stability and function of Escherichia coli dihydrofolate reductase, glycine-121 in the flexible loop (117-131) was substituted to valine and leucine by site-directed mutagenesis. Despite the increased hydrophobicity of the side chains, the free energy changes of unfolding of the two mutants (G121V and G121L) determined by urea denaturation at 15 degrees C were decreased by 1.22 and 0.38 kcal/mol, respectively, compared with that of the wild-type. Thermal denaturation temperature, as monitored by differential scanning calorimetry, was decreased by 2.4 and 5.2 degrees C for G121V and G121L, respectively, accompanying the decrease in enthalpy change of denaturation. These findings indicate that the structure of DHFR is destabilized by the mutations, predominantly due to the large decrease in enthalpy change of denaturation relative to entropy change of denaturation. The steady-state kinetic parameter in the enzyme reaction, Km, was not influenced but kcat was greatly decreased by these mutations, resulting in 240- and 52-fold decreases in kcat/Km for G121V and G121L, respectively. The main effect of the mutations appeared to be modification of the flexibility of the loop due to overcrowding of the bulky side chains, overcoming the enhancement of hydrophobic interaction.
Base Sequence↗
Treatment of septic shock with a protease inhibitor in a canine model: a prospective, randomized, controlled trial.
OBJECTIVES: To evaluate the efficacy and mechanism of action of a protease inhibitor (ulinastatin) in septic shock. DESIGN: Prospective, randomized, controlled trial. SETTING: A university laboratory. SUBJECTS: Twelve mongrel dogs. INTERVENTIONS: One of the protease inhibitors, ulinastatin, a glycoprotein (molecular weight 67,000 daltons) detected in human urine was estimated. We used Escherichia coli to obtain a model of septic shock in dogs in vivo study. Human neutrophils were used as an activating target in vitro. MEASUREMENTS AND MAIN RESULTS: The final concentration of E. coli was 1.9 x 10(6) colony-forming units/mL. There was no significant difference in E. coli concentration between ulinastatin-treated and control groups. Human neutrophils treated with 100 U/mL of ulinastatin showed 70.5% to 78.7% of the superoxide production or untreated neutrophils. Phagocytic activity was enhanced in a dose-dependently manner by ulinastatin. At a ulinastatin concentration of 100 U/mL, an approximate two-fold increase in activation was found. In the ulinastatin-treated group, cardiac index, blood pressure, lactic acid, blood glucose, and blood base values significantly improved 60 mins after ulinastatin administration, and the bacterial count was significantly decreased, while the endotoxin concentration in the control group showed a continuous increase of endotoxin concentration. The improvement in the monitored factors observed 60 mins after initiation of treatment persisted after the end of treatment. The survival rate after 1 wk in the ulinastatin-treated group was 84% (five of six dogs survived), while it was 16% (one of six dogs survived) in the control group (p = .04). CONCLUSIONS: Ulinastatin does not have antimicrobial activity, and it does not sufficiently activate phagocytes. It is suggested that the efficacy of this agent in experimental septic shock is due to a mechanism that activates the reticuloendothelial system and septic reactions.
Adult↗
Identification of basic fibroblast growth factor in papillary carcinoma of the thyroid.
Basic fibroblast growth factor (bFGF) was identified in the papillary carcinoma of the human thyroid. Immunohistochemically, it was found that the reactivity for bFGF was localized in the cytoplasm of the neoplastic cells of the five papillary carcinomas. However the extract of the papillary carcinomas contained the mitogenic activity for endothelial cells. This bioactive molecule was determined as bFGF by using the heparin-Sepharose affinity chromatography and western blot analysis. The bFGF derived from human thyroid papillary carcinoma and the recombinant human bFGF stimulated the bromodeoxyuridine incorporation by the cultured human thyroid papillary carcinoma cells. These cells also showed positive staining for thyroglobulin and cytokeratin. These results indicate that bFGF, probably produced by the neoplastic cells, plays an important role in the development of papillary carcinoma of the thyroid with stimulation of angiogenesis as well as proliferation of the parenchymal cells.
Carcinoma, Papillary↗