Wave propagation through disordered media and universal conductance fluctuations.
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Journal Article↗
Biomedical subjects
S Iida
Publications and source records attributed to S Iida.
Site-specific DNA recombination system Min of plasmid p15B: a cluster of overlapping invertible DNA segments.
Plasmid p15B of Escherichia coli 15T- carries a 3.5-kilobase segment that undergoes frequent DNA inversion mediated by the DNA inversion enzyme Min, a member of the Din family of site-specific recombinases. While the previously described Din inversion systems invert a DNA segment between two crossover sites in inverted orientation, the Min system produces more complex DNA rearrangements. These have been physically characterized by electron microscopy and by restriction cleavage analysis. The results can best be explained by a model that involves six crossover sites (called mix) and predicts 240 isomeric forms of the invertible region. The model was confirmed by sequencing the six mix sites in plasmids that contain the invertible DNA segments in a frozen configuration. All mix sites fit the dix consensus sequence, and they are all good substrates for DNA inversion when carried in inverted orientation. Recombination between two mix sites in direct orientation was rare, in line with the notion that Din inversion systems are topologically biased to the inversion reaction. Another recently described multiple inversion system, the shufflon of the E. coli plasmid R64, is neither functionally nor structurally related to the Min system of p15B.
Chromosome Deletion↗
An enzyme-linked immunosorbent assay (ELISA) for adenosine 3',5'-cyclic monophosphate (cAMP) in human plasma and urine using monoclonal antibody.
A reliable and sensitive ELISA for cAMP in human plasma and urine is described, using a monoclonal antibody and a 96 well microtiter plate. Succinyl cAMP is conjugated to human serum albumin and adsorbed to the ELISA plate, giving an immobilized antigen approach which simplifies subsequent assay procedures. As low as 1.56 fmol/well of both plasma and urinary cAMP is measurable. Recoveries of added cAMP in plasma and urine were from 99% to 109%. Intra-assay coefficients of variation were less than 6.1% for plasma and 7.0% for urine samples. Inter-assay coefficients of variation for plasma and urine samples were less than 8.9% and 9.5%, respectively. There was a good correlation between the values obtained by ELISA and radioimmunoassay (RIA) (plasma: r = 0.94, n = 66; urine: r = 0.98, n = 64; nephrogenous cAMP: r = 0.96, n = 51).
Antibodies, Monoclonal↗
Structural change of troponin C molecule and its domains upon Ca2+ binding in the presence of Mg2+ ions measured by a solution X-ray scattering technique.
A small-angle X-ray scattering study on troponin C showed that two domains of the molecule move closer to each other and the molecule shrinks along its long axis upon Ca2+ binding in the absence of Mg2+ ions (Fujisawa, T., Ueki, T., & Iida S. (1988) J. Biochem. 105, 377-383). When Mg2+ ions bind to troponin-C, the radius of gyration changes from 27.8 to 24.3 A and the average radius of gyration of the two domains is estimated to be 15.1 A. These radii indicate that the distance between the centers of the two domains is 38.1 A. Such a change is analogous to the previous result for troponin C with two Ca2+ ions bound at the high-affinity sites. Thus, the structural behavior of troponin C molecule is essentially the same when Ca2+/Mg2+ ions bind to its high-affinity sites. On the other hand, the effect of Ca2+ binding to the low-affinity sites in the presence of Mg2+ ions is quite different from the previous result. The binding of Ca2+ ions causes a dimerization of troponin C molecules with an apparent constant of 511 M-1. Such a characteristic behavior, implying the occurrence of a surface property change, may be related to the physiological role of troponin C molecule in the muscle. The scattering experiments on the tryptic fragments of troponin C also had interesting and important results: the C-domain shrinks, with the radius of gyration changing from 17.0 to 14.9 A while the N-domain swells from 13.9 to 15.0 A upon Ca2+ binding. Such an opposite change is consistent with the results of circular dichroism and spectroscopic studies of the domains.
Binding Sites↗
The Min DNA inversion enzyme of plasmid p15B of Escherichia coli 15T-: a new member of the Din family of site-specific recombinases.
Plasmid p15B is a bacteriophage P1-related resident of Escherichia coli 15T-. Both genomes contain a segment in which DNA inversion occurs, although this part of their genomes is not identical. This DNA segment of p15B was cloned in a multicopy vector plasmid. Like its parent, the resulting plasmid, pAW800, undergoes complex multiple DNA inversions: this DNA inversion system is therefore called Min. The min gene, which codes for the p15B Min DNA invertase, can complement the P1 cin recombinase gene. The Min inversion system is thus a new member of the Din family of site-specific recombinases to which Cin belongs. The DNA sequence of the min gene revealed that Min is most closely related to the Pin recombinase of the e14 defective viral element on the E. coli K12 chromosome. Like other members of the Din family, the min gene contains a recombinational enhancer element which stimulates site-specific DNA inversion 300-fold.
Amino Acid Sequence↗
Anti-human immunodeficiency virus type 1 activities and pharmacokinetics of novel 6-substituted acyclouridine derivatives.
The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell systems, including peripheral blood lymphocytes. They are not inhibitory to the replication of HIV-2. HEPT-S emerged as the most active congener, with a 50% inhibitory concentration of 1.6 microM for HIV-1 (human T-cell lymphotropic virus type IIIB) in MT-4 cells. We also examined the pharmacokinetics of the compounds following oral administration to rats. The pharmacokinetic profile varied considerably from one compound to another. The highest concentration in plasma (7.4 micrograms/ml, or 22.8 microM) was achieved by HEPT-S within 30 min after administration of an oral dose of 20 mg/kg of body weight. HEPT-S can be considered a promising candidate for the treatment of HIV-1 infections.
Animals↗
Inhibitory effect of somatomedin C/insulin-like growth factor I on adrenocorticotropin- or forskolin-induced steroidogenesis in isolated rat adrenocortical cells.
The effects of recombinant human somatomedin C/insulin-like growth factor (IGF-I) on the steroidogenic response of isolated rat adrenocortical cells to ACTH, forskolin, and (Bu)2cAMP were examined during short term incubations. The effect of IGF-I on cAMP production by cells stimulated with ACTH or forskolin was also examined. IGF-I inhibited ACTH-, forskolin-, and (Bu)2cAMP-induced corticosterone production in a concentration-dependent manner. IGF-I (30 ng/ml) also significantly inhibited ACTH-induced cAMP production. However, the peptide had no significant effect on forskolin-induced cAMP production. IGF-I suppressed ACTH-induced cAMP production both in the presence and absence of 3-isobutyl-1-methylxanthine, suggesting that IGF-I acts to inhibit the formation of cAMP rather than the stimulation of cAMP degradation. The observation that IGF-I inhibited steroidogenesis induced by (Bu)2cAMP strongly suggests that one site of inhibition is at some step(s) distal to cAMP formation. However, the inhibition of cAMP production after stimulation with ACTH also suggests a plasma membrane site of action for IGF-I in adrenocortical cells.
Adrenal Cortex↗
A patient with hypocortisolism and Cushing's syndrome-like manifestations: cortisol hyperreactive syndrome.
One patient is reported who has the manifestations of Cushing's syndrome in spite of persistent hypocortisolemia. His serum levels of cortisol and free cortisol were below normal, and 24-h urinary excretion of 17-hydroxycorticosteroids and cortisol were decreased. There was a rapid and substantial increase in serum cortisol in response to synthetic ACTH-(1-24). Plasma levels of ACTH were marginally increased by successive administration of CRH and vasopressin, which were followed by substantial increases in serum cortisol. Glucocorticoid activity of the patient's serum, as measured by a RRA was low. There were no responses of urinary 17-hydroxycorticosteroids after metyrapone treatment. These laboratory examinations ruled out any known clinical conditions resulting in hypocortisolemia. The clinical condition could also be explained by cortisol hyperreactivity of the patient's cells. In vitro hyperreactivity to glucocorticoids was demonstrated in cultured skin fibroblasts whose aromatase activity was increased 1.5- to 1.8-fold above that of normal cells, and [3H]thymidine incorporation was inhibited more effectively by the addition of cortisol or dexamethasone. The mechanism by which the patient is hyperreactive to glucocorticoids remains unexplained.
Adrenocorticotropic Hormone↗
[A follow-up survey for hearing aids evaluation using speech maps].
A new method for assessing the selected hearing aids was developed and applied 53 patients with hearing impairment. Our previous paper showed that the average confusion distance which was introduced in this method was useful for estimating the hearing aids. We carried out a follow-up survey in order to measure the usefulness of this method after 3 or 4 years practical hearing aid use. There were 34 patients out of 53 from whom we could obtain adequate information about their hearing aids. They were asked to rate their satisfaction with the recommended instrument in five degrees. Fifteen of the 34 patients who had purchased the recommended hearing aid rated it very satisfactory; four rated the aid satisfactory; eight rated the aid helpful; six rated the aid sometimes helpful; and one rated the aid unsatisfactory. The Spearman's rank correlation coefficient between the change in the speech discrimination score with and without a hearing aid and the user's evaluation was 0.34. The Spearman's rank correlation coefficient between the change in the average confusion distance and user's evaluation was 0.41. The value 0.34 is not significant, but the value 0.41 is significant at the 1% level of significance. Therefore, we think that the average confusion distance should be taken into consideration as well as the speech discrimination score at least for predicting successful hearing aid use. Finally we feel that there is need for the inclusive system which is able to estimate both the speech mediated communication ability and user's satisfaction.
Evaluation Studies as Topic↗
[Pure white cell aplasia (PWCA) with an inhibitor against colony-forming unit of granulocyte-macrophage (CFU-GM)].
We reported here a case of pure white cell aplasia (PWCA). A 23-year-old man was admitted to our hospital in September 1989 because of agranulocytosis, fever, and anal pain. He had no history of toxic-drug exposure or blood transfusion. Laboratory studies were all within the normal range except white blood cell count of 2,300/microliters with no neutrophils and low serum IgA level (28 mg/dl). Bone marrow examination showed hypocellular with erythroid predominance and no granulocyte maturation beyond the myelocyte. Complement-dependent suppression of autologous and heterologous granulocyte-macrophage colony-forming units by the patient's serum could be demonstrated. Though corticosteroid administration was ineffective, neutropenia improved by plasmapheresis. Furthermore, recombinant granulocyte colony stimulating factor (rG-CSF) could release him from persistent bacterial infection of anal fistula by transient improvement of neutropenia. These findings suggest a humoral autoimmune mechanism for the pathogenesis of PWCA and the effectiveness of rG-CSF for the patient with severe infections.
Adult↗
Factor VII deficiency first observed at preoperative routine clotting test.
Factor VII deficiency was first observed in a 24-year-old female in the routine clotting test for tooth extraction. Her factor VII was 22%, mildly below normal limits. Factor IX complex was not administered as replacement therapy when her impacted tooth was extracted. There was no sign of abnormal postoperative bleeding. As this disease was a rare disorder, the minimum safe level of factor VII for tooth extraction was unknown. We had a opportunity to study a patient with this disorder observed in the preoperative routine clotting test for tooth extractions.
Adult↗
Disseminated intravascular coagulation after hepatic resection.
Disseminated intravascular coagulation (DIC) after hepatic resection is a serious complication that leads to a fatal outcome unless prompt treatment is instituted. Between April 1973 and June 1988, DIC occurred postoperatively in 18 of 192 patients who underwent hepatic resection because of a variety of diseases of the liver and biliary tract. The diagnosis was made on the basis of changes in platelet count, fibrinogen level, serum level of fibrin degradation product (FDP), and protamine sulfate test. Heparin was used in an earlier series but has been discontinued because of difficulty in determining the optimal dose in patients undergoing liver resection. Instead, we now use gabexate mesilate, which blocks the coagulation cascade without the aid of antithrombin III and works as an anticoagulant. Fifteen patients had uneventful recoveries, but three died. Two died of aggravation of DIC, which was a result of reoperation performed under the diagnosis of surgical bleeding. The other patient died of liver failure after fever of unknown cause persisted for 4 months. The rationale for the diagnosis and treatment of DIC after liver resection is documented, and the problems involved are discussed.
Anticoagulants↗
Hepatic resection for hepatocellular carcinoma.
Between July 1973 and September 1988, 119 patients with hepatocellular carcinoma underwent hepatic resection at Keio University Hospital, Tokyo. Hepatic resection was performed not only for patients with liver cirrhosis and obstructive jaundice but also for patients with advanced disease. Eighty (67.2%) of the 119 patients had liver cirrhosis and four patients had obstructive jaundice. Two or more segments of the liver were resected in 56 (47.0%) patients, 29 of whom had liver cirrhosis. Eleven patients died within 30 days after surgery, an operative mortality rate of 9.2%. Seven additional patients could not be discharged from the hospital, resulting in a hospital death rate of 5.9%. Seventeen of these 18 patients had cirrhosis. Selection of patients with sufficient reserve function of the remaining liver portion, caused a great reduction of the incidence of postoperative death. The 5-year actuarial survival rate for the 101 patients who were discharged from the hospital was 39%, and 13 patients lived longer than 5 years, the longest survival period being 13 years 10 months. Hepatocellular carcinoma is amenable to hepatic resection if patients with sufficient reserve function of the liver are selected.
Adolescent↗
[Three cases of malignant lymphoma of the cervix uteri].
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Biomarkers, Tumor↗
[The mechanism of cytotoxicity of monoclonal antibodies to gynecological cancer cell-lines].
The cytotoxicity including complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of two kinds of monoclonal antibodies (Mo-Ab), namely, MSN-1 which was obtained by means of an immunization procedure with intact SNG-II cells from human endometrial adenocarcinoma and HMST-1 obtained from hybridoma fused lymphocytes from lymph node with murine myeloma cells were studied by the 51Cr liberation test in vitro. 1) Against SNG-II, MSN-1 and HMST-1 showed significant CDC activity at 38.4 +/- 4.2% and 41.9 +/- 4.8% respectively, when a guinea pig complement was used. However, no significant CDC, action on SKG-IIIb was induced by MSN-1 or HMST-1. 2) Mo-Ab:MSN-1 and HMST-1 showed no significant liberation of 51Cr in relation to SKG-IIIb and SNG-II when using peripheral blood lymphocyte (PBL) separated by centrifugation gradient as the effector cells, and then the cytotoxicity of PBL alone against K-562 cell, SNG-II and SKG-IIIb was 40%, 9% and 2% respectively. This suggested that neither Mo-Ab had any ADCC activity and that SKG-IIIb and SNG-II cells were NK resistant cell-lines.
Adenocarcinoma↗
Pharmacokinetics of 4-acetylaminophenylacetic acid. 1st communication: absorption, distribution, metabolism and excretion in mice, rats, dogs and monkeys after single administration of 14C-labeled compound.
Absorption, distribution, metabolism and excretion of 4-acetylaminophenylacetic acid (MS-932) were studied in mice, rats, dogs and monkeys after intravenous or oral administration of 5 or 10 mg/kg of 14C-MS-932. After the intravenous injection of 14C-MS-932, the radioactivity concentrations in the plasma decreased biexponentially. The half-lives of the elimination phase (t1/2, beta) were 2.58 h for mice, 2.35 h for rats, 1.88 h for dogs and 1.24 h for monkeys. After the oral administration of 14C-MS-932, the radioactivity concentrations in the plasma reached maximums between 0.4 and 1.3 h, thereafter decreasing with half-lives similar to those found for the intravenous injection. The systemic availability of this drug was 72-100% in all the species tested. No clear sex-related difference in radioactivity concentrations was found in rat plasma. After both intravenous and oral administrations, in all the species tested, almost all the radioactivity administered was excreted in the urine. Biliary excretion of radioactivity in bile duct-cannulated rats was only 1.42% of the intravenous dose over a 24-h period. Lymphatic absorption of radioactivity was negligible (0.2% of the dose over a 6-h period). After oral administration of 14C-MS-932, the radioactivity concentrations in the rat tissues tested reached maximums within 1 h, decreasing rapidly thereafter similar to the decrease in the concentration in the plasma. Much higher concentrations were present in the kidney and gastro-intestinal tract than in the plasma, whereas the concentrations in the other tissues were lower. Results obtained by whole-body autoradiography were consistent with those obtained for the radioactivity in excised tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Pharmacokinetics of 4-acetylaminophenylacetic acid. 2nd communication: tissue accumulation and enzyme induction in rats after repeated administration, and placental and milk transfer after single dosing.
The absorption, distribution, metabolism and excretion of 14C-labeled 4-acetylaminophenylacetic acid (MS-932) were studied in male rats after administration of an oral dose of 10 mg/kg once a day for 21 days. Comparison with the single dosing showed no marked alterations in absorption, distribution, metabolism and excretion. There were no significant differences in the activities of hepatic aniline hydroxylase and aminopyrine N-demethylase between the MS-932 treated group (10 mg/kg for 8 days) and the 0.5% aqueous sodium carboxymethyl cellulose control group (p greater than 0.05). Placental transfer of radioactivity was studied after single oral administration of 10 mg/kg of 14C-MS-932 to pregnant rats on the 12-13th and 19-20th days of gestation. Radioactivity concentrations were highest in the maternal plasma and lowest in the amniotic fluid and fetus for both middle and late pregnancies. The concentrations in the amniotic fluid and fetus decreased more slowly than did the concentration in the maternal plasma. Excretion of radioactivity to milk was studied after single oral administration of 10 mg/kg of 14C-MS-932 to lactating rats on the 10th day after parturition. Radioactivity concentrations in the rat milk were maximal at 1 h after dosing and were lower than in the maternal plasma at all the sampling times.
Aminopyrine N-Demethylase↗
Carcinoma of the main hepatic duct junction: indications, operative morbidity and mortality, and long-term survival.
Carcinoma of the main hepatic duct junction tends to spread extensively along the hepatic ducts into the liver parenchyma. Therefore extensive resection of the bile ducts combined with hepatic resection is the procedure of choice. Between January 1973 and April 1989, 25 of 50 patients with this type of carcinoma underwent resection, a resectability rate of 50%. One patient died of staphylococcal sepsis on the postoperative day 42 after right trisegmentectomy and resection of the bile ducts, a hospital death rate of 4%. Twenty-four patients were discharged from the hospital. The 5-year actuarial survival rate calculated by the Kaplan-Meier method was 19%. Four patients lived longer than 5 years after surgery; the longest survival was 9 years after right trisegmentectomy and resection of the bile ducts. These four patients had clear margins at the resected bile ducts. This article was designed to clarify the point at issue by presenting our results in terms of indications, operative morbidity and mortality, and long-term survival.
Adult↗