Search PubMed⌕ Search

Biomedical subjects

T Seki

Publications and source records attributed to T Seki.

At least 343 records · Page 19Linked to original sources
PubMed1994

Column-switching liquid chromatographic method for the simultaneous determination of iothalamic acid and creatinine in biological fluids.

A column-switching liquid chromatographic method for simultaneous determination of iothalamate and creatinine in human serum and urine was developed. Iothalamate and creatinine were separated on a weakly acidic ion-exchange column (C1) by ion-exclusion chromatography and iothalamate excluded from the column was purified by gel chromatography on a hydrophilic gel column (C2) and then by ion-exchange chromatography on a weakly basic ion-exchange column (C3). Creatinine that was eluted from C1 after iothalamate was transferred to a hydrophilic gel column (C4) and then to a strongly acidic ion-exchange column (C5). The mobile phase for C1-C4 was a pH 3.8 propionate buffer (propionic acid-NaOH = 0.35 + 0.035 mol/kg in water) and a pH 5.6 propionate buffer (propionic acid-NaOH = 0.04 + 0.035 mol/kg in water) was used for C5. Diluted serum and urine samples could be injected directly on to C1, as the matrix of C1 is hydrophilic and C1 is backflushed after the transfer of the creatinine fraction from C1 to C4. Iothalamate and creatinine in the eluates were determined by measuring their ultraviolet absorption at 245 and 234 nm, respectively. The precision (R.S.D.) of the chromatographic method was 1.6% (n = 7) and 0.36% (n = 6) for diluted serum and urine with iothalamate concentrations of 1.0 and 10.0 mumol/l, respectively, and 0.85% (n = 7) and 0.55% (n = 7) for diluted serum and urine with creatinine concentrations of 5.77 and 272 mumol/l, respectively.

Chromatography, Gel↗
PubMed1994

The effect of different routes of administration on the metabolism of morphine: the disposition of morphine and its metabolites after topical application.

The disposition of morphine (MOR) and its metabolites in the rabbit was measured after topical administration of its hydrochloride salt (MOR.HCl), and their time course was compared with those after intravenous and oral administration. The area under the plasma concentration-time curve (AUC) ratio of metabolites/MOR after the topical application of MOR.HCl was similar to that after intravenous injection, but differed from that after oral administration. Pharmacokinetic parameters of the disposition of MOR and its metabolites were obtained by a general curve fitting of the time course of plasma concentrations of these compounds after intravenous injection of MOR.HCl and its metabolites, respectively. On the other hand, the time courses of plasma concentrations of the metabolites after intravenous, oral, and topical administration of MOR.HCl were simulated using a simple compartment model without consideration of enterohepatic circulation and the pharmacokinetic parameters obtained as above. The resulting curves of the metabolites agreed well with the observed values except for those after oral administration. These results suggest that no first-pass metabolism of MOR.HCl occurs after percutaneous administration, and that topical administration of this salt is more advantageous than oral administration in terms of bioavailability.

Administration, Oral↗
PubMed1994

Complete nucleotide sequence of the Streptomyces nigrifaciens plasmid, pSN22: genetic organization and correlation with genetic properties.

The complete nucleotide sequence of the multicopy, self-transmissible, broad-host-range Streptomyces plasmid pSN22, originating from Streptomyces nigrifaciens, was determined. pSN22 is a circular DNA molecule, 10,922 bp with 71.76% G + C. Computer-assisted analysis identified 10 open reading frames (ORFs); 8 of them--traA (155 amino acids [aa], traB (651 aa), traR (246 aa), spdB1 (107 aa), spdB2 (251 aa), spdB3 (70 aa), spdB4 (128 aa) and spdA (154 aa)--are involved in plasmid transfer and pock-formation. One ORF, rep (451 aa), probably encodes a replication protein similar to known replication proteins of rolling circle replicons. The four spdB genes have hydrophobic amino termini that might attach to the cytoplasmic membrane. The deduced rep proteins of pSN22 and pIJ101 are very similar, suggesting that both are derived from a recent common ancestor. The transfer regions of the two plasmids are, however, very different. The only detectable similarities between presumably analogous proteins are DNA- and NTP-binding motifs and hydrophobic regions. This suggests that two transfer regions are of separate origins.

Amino Acid Sequence↗
PubMed1994

Replication of the Streptomyces plasmid pSN22 through single-stranded intermediates.

The replication of the 11 kb conjugative multicopy Streptomyces plasmid pSN22 was analyzed. Mutation and complementation analyses indicated that the minimal region essential for plasmid replication was located on a 1.9 kb fragment of pSN22, containing a transacting element encoding a replication protein and a cis-acting sequence acting as a replication origin. Southern hybridization showed that minimal replicon plasmids accumulated much more single-stranded plasmid molecules than did wild-type pSN22. Only one strand was accumulated. A 500 bp fragment from the pSN22 transfer region was identified which reduced the relative amount of single-stranded DNA, when added in the native orientation to minimal replicon plasmids. This 500 bp DNA sequence may be an origin for second-strand synthesis. It had no effect on the efficiency of co-transformation, plasmid incompatibility, or stability. The results indicate that pSN22 replicates via single-stranded intermediates by a rolling circle mechanism.

DNA Replication↗
PubMed1994

Prophylactic chemotherapy with anthracyclines (adriamycin, epirubicin, and pirarubicin) for primary superficial bladder cancer. The Hokkaido University Bladder Cancer Collaborative Group.

A multicentric randomized trial was conducted to evaluate the efficacy of intravesical chemoprophylaxis for primary superficial bladder cancer. The 299 eligible patients with primary superficial bladder cancer were randomized into four groups (A, B, C, and D) after pathological confirmation. Intravesical instillation of drugs, which were dissolved in 20 ml physiological saline (PS; group A, 20 mg Adriamycin; group B, 20 mg epirubicin; group C, 20 mg pirarubicin; group D (control), PS alone], was performed once a week for 2 weeks after trasurethral resection and then once every 2 weeks for 14 weeks, once monthly for 8 months, and once every 3 months for 1 year. No significant difference in the patients' characteristics was found among the four groups. The follow-up period ranged from 3 to 31 months (mean, 14 months). The nonrecurrence rates were estimated by the method of Kaplan and Meier. The relative effects of five variables (the tumor status, size, grade, and stage and the treatment) on the efficacy of the chemoprophylaxis regimens were evaluated using a multiple regression model. Although the nonrecurrence rates determined for groups A and B were significantly higher than that found for group D (P < 0.05), no significant difference in the nonrecurrence rate was detected among groups A, B, and C. The multiple regression model indicated that the most important factors in preventing tumor recurrence at 12 or 24 months were the intravesical instillation of an anthracycline and the tumor status (solitary). These results demonstrate that intravesical instillation of the tested anthracyclines is effective for at least 2 years as prophylactic chemotherapy for primary superficial bladder cancer.

Administration, Intravesical↗
PubMed1994

Demographics of anti-asialoglycoprotein receptor autoantibodies in autoimmune hepatitis.

BACKGROUND/AIMS: The asialoglycoprotein receptor (ASGPR) is an established, liver-specific autoantigen. This multicenter study investigated the specificity of anti-ASGPR autoantibodies for autoimmune hepatitis (AIH) in different ethnic groups. METHODS: Nine hundred fourteen sera from European, Japanese, and North American (U.S.) patients with chronic inflammatory liver disorders were tested. An enzyme-immunoassay using human ASGPR and a radioimmunoassay against rabbit ASGPR, performed independently on coded sera, were compared. RESULTS: The highest frequency (76%) of anti-human ASGPR was found in AIH patients (11/24 U.S.; 21/25 European; 28/30 Japanese), particularly in those with active disease before treatment (53/62, 85%), and decreased in titer with response to immunosuppressive therapy. These antibodies were found at low titers in 43 (11%) of 385 patients with viral hepatitis and in 25 (7.6%) of 328 patients with other chronic inflammatory liver disorders (P < 0.0005 compared with all AIH patients). Twenty of 37 sera tested by enzyme-immunoassay and radioimmunoassay were positive, and nine were negative for anti-ASGPR by both assays (78% concordance); six sera were exclusively positive on human substrate. CONCLUSIONS: Circulating anti-ASGPR autoantibodies are closely associated with autoimmune hepatitis independent of geographic or ethnic criteria. Two anti-ASGPR assays currently in use show high reliability.

Asialoglycoprotein Receptor↗
PubMed1994

Genetic disorders of keratin: are scarring alopecias a sub-set?

Recent advances have challenged the prevailing view that keratins are merely passive bystanders of keratinocyte biology. With the exciting discovery that three autosomal dominant genetic skin disorders, epidermolysis bullosa simplex (EBS), epidermolytic hyperkeratosis (EHK) and palmoplantar keratoderma (PPK), are in fact disorders of keratins comes the realization that the integrity of the keratin filament network is crucial to the structural integrity of the skin. Since it has been recently established that mutations in keratins K5/K14, K1/K10 and K9 are causative for these keratinocyte disorders, it is very likely that mutations in K6 or in its obligate partner, K16 will result in disease. In order to test this we have produced transgenic mice that express a mutant K6 gene. These mice develop a progressive scarring alopecia at about 6 months of age. Later, the denuded areas developed a keratosis which was prone to infection. Ultrastructural analysis suggests that hair loss is due to the destruction of the outer root sheath. We believe that these mice are models of another keratin disorder.

Alopecia↗
PubMed1994

Expression of CD44 variant isoforms in normal and neoplastic cells of the lung.

CD44 is a cell surface receptor that has been implicated in lymphocyte homing, hematopoiesis, cell migration and possibly also tumor metastasis. In the present study, expression of CD44 variant (CD44v) isoforms was analyzed in 23 lung cancer specimens together with corresponding normal lung tissues by Southern blot analysis coupled with reverse transcription-polymerase chain reaction amplification. We found that CD44v isoforms were expressed in all lung cancer specimens, suggesting a possible role in the establishment of metastases by these highly malignant tumors, but normal tissues were also positive. This is in marked contrast to the previous reports of essentially negligible expression of CD44v isoforms in normal colon and breast, and suggests a physiological function in the lung.

Base Sequence↗
PubMed1994

A Ro/SS-A auto-antibody positive mother's infant revealed congenital complete atrioventricular block, followed by insulin dependent diabetes mellitus and multiple organ failure.

We experienced a congenital complete atrioventricular block infant who was born from a Ro/SS-A antibody positive mother. Ro/SS-A antibody was also found in this baby which was presumed to be mediated by the maternal placenta. Temporary cardiac pacing was required at birth and pacemaker implantation was performed at 9 months. At 11 months of age, the baby fell into shock and experienced multiple organ failure because of diabetes mellitus-induced coma. The association between congenital complete heart block and the Ro/SS-A antibody is well known. However, the accompaniment of insulin-dependent diabetes mellitus has not been reported previously. As the Ro/SS-A antigen appears in the cytoplasm of many tissues, the possibility of an association between Ro/SS-A antibody and diabetes mellitus is difficult to deny. We report this rare case to draw attention to the possibility that babies who are born from an Ro/SS-A antibody positive mother may develop diabetes mellitus as well as congenital complete heart block.

Adult↗
PubMed1994

In vivo effect of a selective endothelin receptor antagonist, BQ-123, on renal function in cyclosporin A-treated rats.

To investigate the possible involvement of endogenous endothelin (ET) in cyclosporin A (CsA) nephrotoxicity, we examined the renal effects of the selective [125I]ET-1 binding to porcine aortic membrane (ETA) receptor antagonist, BQ-123 (BQ), on CsA-treated rats. An osmotic minipump filled with BQ or its vehicle (saline), was subcutaneously implanted and animals were treated with CsA (50 mg/kg/d, i.p.) for 4 d. In both BQ- and its vehicle-treated rats, the 24-hour urine volume, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, urinary Ca/creatinine (Cr) and urinary NAG/Cr ratios were significantly increased compared with those before administration of CsA. In contrast, after administration of CsA, urinary Cr excretion was significantly decreased in both rat groups. Although urinary NAG excretion and the NAG/Cr ratio in the rats treated with BQ were significantly increased compared with those treated with saline, the serum Cr levels in BQ-treated rats were significantly lower than those in saline-treated rats. Urinary immunoreactive ET-1 (irET-1) excretion in all animals was significantly increased after administration of CsA. There were no significant differences in urinary irET-1 excretion in both BQ-treated and saline-treated rats with and without CsA. Expression of irET-1 was seen in the cytoplasm of renal tubules, but the degree of expression was similar in the BQ-treated and saline-treated rats on CsA. In the BQ-treated rats, small round areas with high grain densities over the glomeruli in the cortex and vesa recta bundles in the outer medulla were masked by the antagonist action of BQ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regulation of the transfer genes of Streptomyces plasmid pSN22: in vivo and in vitro study of the interaction of TraR with promoter regions.

Expression of the tra operon, essential for conjugative transfer of the 11-kb Streptomyces nigrifaciens plasmid pSN22, is negatively regulated by traR, which is located upstream of the tra operon and transcribed in the opposite orientation. The transcriptional start points for the tra and traR mRNAs were determined by primer extension; they are 72 bp apart and have identical -10 promoter sequences. The TraR protein was overexpressed in Escherichia coli and used for gel retardation and DNase I protection experiments. It bound specifically to the bidirectional tra-traR promoter region and protected four DNA regions, each of which contains a similar 12-bp sequence. The binding was strongest to the region downstream of the tra promoter, probably ensuring that expression of the potentially lethal traB gene is turned off before traR. The efficiency of intramycelial plasmid transfer was decreased by the mutation at the downstream region.

Bacterial Outer Membrane Proteins↗
PubMed1994

Nasal absorption of zidovudine and its transport to cerebrospinal fluid in rats.

The nasal absorption of zidovudine (AZT) and its subsequent transport to cerebrospinal fluid (CSF) was examined in rats. Both rapid absorption and a high CSF concentration were observed after the nasal application. Plasma and CSF concentrations of AZT increased when probenecid was coadministered with AZT. Thus, this nasal coadministration of AZT and probenecid could be useful for the treatment of AIDS patients with neuropathies.

Administration, Intranasal↗
PubMed1994

Studies on agents with vasodilator and beta-blocking activities. I.

A series of hydrazinopyridazine derivatives combined with a beta-blocking side chain were synthesized. When they were given intravenously to anesthetized rats, some of them exhibited both hypotensive and beta-blocking activities. Their structure-activity relationships for hypotensive and beta-blocking activities are discussed. Compound 11c had the best profile and was selected for further study.

Adrenergic beta-Antagonists↗
PubMed1994

[Estimation of localization of the accessory pathway in WPW syndrome with a standard 12 lead electrocardiogram. Development of new criteria for children].

In 128 children with WPW syndrome, localization estimation was based on the accessory pathway (ACP) localization criteria of the standard 12 lead electrocardiogram for adults proposed by Gallagher et al., Iwa et al., Lindsay et al., and Reddy et al. The rate of consistency of each set of criteria with body surface mapping (BSM) (based on the criteria of Kamakura et al.) was examined along with evaluation of reliability. Among the localization criteria, the most reliable set for children was that developed by Iwa et al. The addition of the precordial lead QRS transitional zone to the criteria established by Iwa et al. was proposed as a means of making the criteria were appropriate for children with WPW syndrome. The consistency rate of localization with this new criterion was added with the results of BSM reached 93% including interpolations. Thus this new localization criterion was considered effective for the estimation of ACP localization in children with WPW syndrome.

Adolescent↗
PubMed1994

[Dobutamine stress body surface mapping in Kawasaki disease].

The dobutamine (DOB) stress body surface mapping tests were carried out to detect myocardial ischemia in 23 patients who had Kawasaki disease previously. Eight of 23 patients (group A) had coronary stenosis of 75% or more diameter reduction in major coronary arteries without sufficient collateral flow, as shown by the coronary angiography, but without myocardial infarction. Nine patients (group B) showed no ischemic change exercised 201Tl myocardial scintigram. Six patients (group C) had myocardial infarction due to Kawasaki disease. ST segment potential mapping (0.04 sec after the J point in QRS) and ST-T Isointegral mapping were performed using CVM-3000 system (87 leads), and the following calculations were made: number of leads with horizontal or down-sloping ST depression of 0.10 mV or more, lasting 0.08 sec (nST); row number of the minimum lead in the Isointegral map (Imin); number of positive leads on the seventh row in Isointegral mapping (I-7); number of positive leads on the first row in Isointegral mapping (I-1) and I-7/I-1 ratio. Based on these calculations the criteria for detecting myocardial ischemia (nST < or = 2, Imin < or = 2, I-7/I-1 > or = 1) were created and their usefulness was tested using findings of coronary angiography and exercised 201Tl myocardial scintigram as the golden standard. For the diagnosis of ischemic lesion, the DOB stress body surface mapping test in group A had higher specificity (nST: 100%, Imin: 89%, I-7/I-1: 100% vs. 78%) and higher sensitivity (75%, 50%, 63% vs. 38%), than those by the Treadmill test, while ischemic changes were not detected in group C by this test. From these results it is concluded that it is useful in evaluating ischemic heart disease in children who can not perform Treadmill exercised test adequately.

Adolescent↗