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Biomedical subjects

S Takagi

Publications and source records attributed to S Takagi.

At least 433 records · Page 24Linked to original sources

[A double-blind comparative study of S 6472 (a long-acting cefaclor) versus a conventional cefaclor preparation in complicated urinary tract infections].

For an objective evaluation of the clinical efficacy, safety and usefulness of S 6472 (a long acting cefaclor) in non-catheterized patients with complicated urinary tract infections, a double-blind comparative study was performed using conventional cefaclor preparation (hereafter, CCL) as the control drug. S 6472 was administered orally at a single dose of 750 mg twice daily, and CCL at a single dose of 500 mg 3 time daily. The duration of the treatment was 5 days for either drug. Clinical efficacies were evaluated according to the criteria for evaluation of drug efficacy by the Japanese UTI Committee (3rd edition), and the following results were obtained. 1. The initial distribution of the patients' background characteristics was not significantly different between the S 6472 and CCL groups. 2. The overall clinical efficacy rates were 76.2% in the S 6472 group and 75.5% in the CCL group, indicating no significant difference between the 2 groups. When clinical efficacies evaluated according to different types of infections (UTI groups), the differences between the 2 drug groups were not significant in any of disease groups 2, 3, 4, and 6. 3. Clinical efficacy rates as evaluated by attending physicians were not significantly different between the 2 groups, either. 4. Bacteriological responses were evaluated as eradicated in 81.2% in the S 6472 group and 78.3% in the CCL group, suggesting no statistically significant difference. 5. The incidences of side effects were 2.9% (4/139) in the S 6472 group and 0.7% (1/141) in the CCL group, thus no significant differences existed between the 2 groups. On laboratory examination, 4 and 5 abnormal test values, respectively, were detected in 3/94 patients in the S 6472 group and 5/100 patients in the CCL group, but the difference was not significant between the 2 groups, either. All of these side effect symptoms and abnormal laboratory test values were mild in severity and transient. The results of the overall safety rating which was based on the evaluations of the side effects and laboratory test values indicated no significant difference between the 2 groups. 6. According to judgement by the attending doctors, the clinical usefulness rates evaluated based on the results of the efficacy and safety ratings were not significantly different between the S 6472 and CCL groups. These findings suggest that S 6472 produces excellent therapeutic results in complicated UTI patients without indwelling catheters and its clinical efficacy, safety, and usefulness are equal to those of the conventional CCL.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Polyamine detection system for high-performance liquid chromatography involving enzymatic and chemiluminescent reactions.

We have developed a new specific detection system for polyamines, separated by high-performance liquid chromatography, to replace the usual o-phthalaldehyde (OPA) postlabeling method. This system utilizes a chemiluminescent reaction to determine the amount of hydrogen peroxide generated through the enzymatic oxidation of polyamines. With this method, as little as 5 pmol of putrescine could be accurately determined (S/N = 4), and linearity between the amount of this polyamine and the relative chemiluminescence intensity was observed up to 500 pmol. In the cases of cadaverine, spermidine, and spermine, the linearity continued to 1 nmol. The within-assay coefficients of variation for these four polyamines ranged between 0.97% and 2.03%. As compared with the OPA method, the new method is highly specific for polyamines due to the high specificity of the enzyme used. Another advantage of the new method is the direct determination of polyamines in urine samples that contain various compounds that interfere with the OPA method.

Chromatography, High Pressure Liquid↗

Effect of combination of 5-fluorouracil, epirubicin and mitomycin C (FEM) on advanced gastric carcinoma.

Fifteen patients with advanced gastric carcinoma were treated with the combination of 5-Fluorouracil (5-FU), Epirubicin (EPI) and Mitomycin C (MMC). Twelve of 15 patients were evaluable. Three patients showed partial response (25%) and 4 showed no change (33%) according to the criteria of Japan Society for Cancer Therapy. Mean survival time for responders, nonresponders and all evaluable patients were 14. 3, 3.6 and 6.3 months, respectively. Two patients with partial response lived over 18 months. Major toxicities included myelosuppression, nausea and vomiting, and alopecia. These were mild in general and reversible by discontinuance. No cardiotoxicity developed. It was concluded that this combination therapy is beneficial in patients with advanced gastric carcinoma because it showed measurable clinical effectiveness with less toxicity than FAM therapy (a combination of 5-FU, Doxorubicin and MMC).

Adult↗

Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2.

Tumor-infiltrating lymphocytes (TIL) were isolated from 40 of 51 consecutive human liver tumor samples (primary hepatocellular carcinoma, 16 of 18; metastatic, 23 of 29; benign, one of four). Functional and phenotypic characteristics of fresh and recombinant interleukin-2 (rIL-2)-expanded TIL were evaluated. The expansion of TIL from hepatic tumors in the presence of 1000 units/ml of rIL-2 was possible in 60% of cases. In comparison to TIL from metastatic liver tumors, TIL obtained from primary liver tumors expanded faster and better in rIL-2 cultures. Expanded TIL from primary tumors had significantly higher cytotoxicity against K562 targets, but not Raji targets, than those from metastatic tumors. Cytotoxicity against fresh autologous tumor targets was detected in seven of eight cultures tested. TIL from primary tumors retained antitumor reactivity significantly longer in culture. The optimal in vitro cytotoxicity was achieved between days 20 and 60 of culture in the presence of rIL-2. Antitumor activity was associated with the increase in these TIL cultures of a cell population expressing the Leu19 antigen with or without the CD3 antigen. The frequency of the CD3+Leu19+ population showed a bimodal distribution during culture: the first peak of CD3+Leu19+ cells occurred between days 30 and 60 and was associated with the increased antitumor activity; the second peak occurred after day 60 and was not associated with activity. These findings demonstrate that TIL from most human hepatic tumors can be successfully isolated, cultured in rIL-2, and enriched in Leu19+ effectors. In addition, these TIL upon IL-2 activation in vitro are capable of lysing fresh autologous and/or allogeneic tumor targets.

Antigens, Differentiation↗

Changes in liver and spleen volume in alcoholic liver fibrosis of man.

Alcoholic liver fibrosis is a relatively common form of alcoholic liver disease in Japan. It is regarded by some investigators as a prodromal stage of alcoholic liver cirrhosis, but little is known about the volumes of the liver and spleen in this disease state. Therefore, liver and spleen volumes were measured by computed tomography in 32 patients with alcoholic liver fibrosis in comparison with 10 healthy volunteers. Patients with alcoholic liver fibrosis were divided into three subgroups (13 of Grade 1, 9 of Grade 2 and 10 of Grade 3) according to the severity of fibrosis. The volume was calculated from the sum of the area measurements of successive transverse sections of the two organs. The liver volume (mean +/- S.D.) in Grade 2 alcoholic liver fibrosis (1,281 +/- 112 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (1,017 +/- 73 cm3) and in Grade 1 (1,090 +/- 157 cm3), and the liver volume in Grade 3 (1,490 +/- 132 cm3) was larger than in Grade 2 (p less than 0.01). The mean volume of hepatocytes estimated by a two-dimensional image analysis system was significantly (p less than 0.05) larger in Grade 3 than in Grade 2, and that in Grade 2 was larger than in Grade 1. The spleen volume in Grade 3 (151 +/- 40 cm3) was significantly (p less than 0.01) larger than in healthy volunteers (86 +/- 26 cm3), Grade 1 (89 +/- 38 cm3) and Grade 2 (68 +/- 19 cm3). The presumed reason for hepatic volume increase would be the ballooning of hepatocytes along with increased fibrotic component.

Humans↗

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

We have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Adult↗

Phenotypical and functional heterogeneity of the large granular lymphocytes increased after various treatments in a patient with combined immunodeficiency.

A boy with combined immunodeficiency having low natural killer (NK)-cell activity received thymopoietin pentapeptide (TP-5) treatment, transplanted with T cell-depleted HLA-haploidentical bone marrow (BMT) cells from his father and with thymus tissue from an infant at different times during the first year of life. He showed a marked increase in large granular lymphocytes (LGL) both during the treatment with TP-5 and after BMT. The LGL generated following TP-5 injection had a T3+Leu11- surface phenotype and low NK activity. In contrast, the LGL appearing after BMT showed T3-, Leu7+, and/or Leu11+ surface phenotypes, had high NK- and K-cell activities, and were lymphokine-activated killer (LAK)-cell precursors. These killer activities were assigned to the Leu7-Leu11+ subset and proved to be of recipient origin. LGL proliferation following BMT was accompanied by neutropenia, which was improved in association with a reduction in the number of LGL and the appearance of T cells of BMT donor origin following thymus transplantation. This suggested the inhibition of granulopoiesis by the LGL and an in vitro study revealed that the Leu7+Leu11- subset of LGL suppressed the growth of granulocyte/macrophage colony-forming units. These results indicated that phenotypically different LGL could be generated by different treatments and that the LGL showing NK activity were distinct from those regulating granulopoiesis. It was also suggested that the generation of LGL was controlled by T cells.

Adjuvants, Immunologic↗

The important role of left ventricular relaxation and left atrial pressure in the left ventricular filling velocity profile.

To evaluate the determinants of left ventricular filling, left ventricular filling velocity was measured by pulsed Doppler flowmetry during catheterization of the right and left sides of the heart in 37 patients with cardiac disease before and during leg elevation. During leg elevation, despite no significant change in the time constant of isovolumic relaxation (T), the peak rapid filling velocity (PVRF) increased in association with an increase in pulmonary wedge pressure (PWP), but the peak atrial filling velocity was unchanged. The PVRF correlated with the pulmonary wedge V wave - left ventricular minimum pressure difference (r = 0.68) and in multivariate regression with both T and mean PWP (R = 0.73). These results indicate that left ventricular filling is determined by both left ventricular relaxation and left atrial pressure and that an increase in left atrial pressure changes the left ventricular filling velocity profile in a manner that mimics the pattern with normal diastolic function.

Adult↗

An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen.

A monoclonal antibody A5 (MAb-A5), which was raised against Xenopus tadpole tectal cells, recognizes a cell surface-related protein molecule (A5 antigen) expressed on the visual centers of Xenopus tadpoles (S. Takagi, T. Tsuji, T. Amagai, T. Takamatsu, and H. Fujisawa, 1987, Dev. Biol. 122, 90-100). The present immunohistochemistry using MAb-A5 indicated that, in addition to the visual centers, A5 antigen was expressed on the general somatic sensory tract in the medulla and spinal cord of Xenopus tadpoles. As the general somatic sensory tract has been shown to be a pathway for ectopically transplanted retinal axons (M. Constantine-Paton and R. R. Capranica, 1976, J. Comp. Neurol. 170, 17-32; M. J. Katz and R. J. Lasek, 1979, J. Comp. Neurol. 183, 817-832), we examined whether retinal axons transplanted close to the spinal cord or medulla preferentially grow into the A5 antigen-positive general somatic sensory tract. We performed eye transplantation at embryonic stages and detected precise locations and trajectories of transplanted retinal axons within the medulla and spinal cord in tadpoles after filling retinal axons with horseradish peroxidase (HRP). HRP histochemistry in combination with MAb-A5 immunohistochemistry indicated that almost all HRP-filled transplanted retinal axons joined the A5 antigen-positive general somatic sensory tract. These findings suggest the involvement of A5 antigen in specific cell-cell recognition between retinal axons and their targets.

Animals↗

Dorsal light response and changes of its responses under varying acceleration conditions.

In order to improve our understanding about functions of the gravity sensors, we have conducted four experiments in goldfish: 1) To define the effect of visual information influx on the static labyrinthine response, the dorsal light response (DLR) which had been proposed by von Holst as a model for postural adjustment in fish was reexamined with a newly designed, rotatory illumination device. The fish responded to illumination from the upper half of the visual field and a narrow range around 180 degrees of the lower half visual field. The maximal tilting angle of normal fish was about 40 degrees under horizontal illumination. 2) Under the changes of the gravito-inertial force level produced by a linear sled, the threshold of the gravity sensors was determined from postural adjustment responses. 3) Under hypogravic conditions during the parabolic flight of an airplane, the light-dependent behavior was investigated in intact and labyrinthectomized goldfish. 4) As one of the most likely candidates of the neural centers for the DLR, the valvula cerebelli, which receives its visual information not through the optic tectum but through the pretectal areas, is confirmed by the brain lesion experiments.

Acceleration↗

Modification of essential carboxyl group in rabbit muscle phosphorylase by water-soluble carbodiimide.

Water-soluble carbodiimide (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) (EDC) and glycine ethyl ester (GEE) as a nucleophile were used to modify the essential carboxyl group of phosphorylases. The inactive b form of the muscle phosphorylase was modified faster than the active a form and potato phosphorylases. Use of N,N,N',N'-tetramethyl-ethylenediamine (TEMED)-HCl buffer system (pH 6.2) resulted in a remarkable difference from the previous results obtained with phosphate and beta-glycerophosphate buffer systems. That is, the substrate glucose 1-phosphate gave the best protection of the three phosphorylase activities. Glucose and glycogen were also effective to retard the inactivation of muscle phosphorylases, though glycogen was not effective for the potato enzyme. The EDC-GEE-modified phosphorylase b retained the affinity for AMP-Sepharose, though partially modified enzyme completely lost the homotropic cooperativity. Phosphorylase b was subjected to differential labeling with [14C]GEE. A labeled peptide was obtained after CNBr cleavage and peptic digestions, and corresponded to the catalytic site sequence surrounding the GEE-substituted Asp 661 and Glu 664. Either or both of these EDC-modified carboxyl residues may have an important role in the catalytic reaction.

Amino Acids↗

Ethanol patch test--a simple and sensitive method for identifying ALDH phenotype.

The ethanol patch test, which is considered to be a cutaneous model of flushing, was performed on 311 healthy Japanese (237 adults and 74 children). By comparing the results with aldehyde dehydrogenase (ALDH) phenotype determined by isoelectric focusing from hair roots samples, it was demonstrated that the ethanol patch test is a good indicator of the ALDH phenotype. The usefulness of this test in future studies was discussed.

Adult↗

Thioredoxin and glutaredoxin enhance the binding of L-triiodothyronine to its hepatic nuclear receptors.

The influence of thioredoxin and glutaredoxin on binding of L-triiodothyronine (T3) to the rat hepatic nuclear T3 receptor was compared with that of the exogenous activator dithiothreitol. Specific [125I]T3 binding, the affinity constant, Ka, and the maximal binding capacity, MBC, were measured using whole nuclei, solubilized preparations of receptor, and chromatographed nuclear receptor. Both the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH) and the glutaredoxin system (glutaredoxin, glutathione reductase, glutathione, and NADPH) increased specific binding of T3 to nuclei, solubilized receptor, and chromatographed receptor significantly. Compared with the values obtained in the absence of added thiol (Ka = 1.6 +/- 0.1 x 10(9) M-1, MBC = 1.7 +/- 0.06 pM), the thioredoxin and glutaredoxin systems increased Ka by 147 and 112%, respectively, while decreasing MBC by 51 and 45%, respectively, when chromatographed receptor was used. The same tendency was observed with solubilized receptor. However, dithiothreitol increased Ka without affecting MBC when solubilized receptor was used. These results, the first demonstration of endogenous disulphide reductant systems enhancing binding of T3 to its receptor, suggest that the thioredoxin and (or) glutaredoxin systems may modulate the physiological effects of thyroid hormone.

Animals↗

A quasi-constant composition method for studying the formation of artificial caries-like lesions.

Caries-like lesions were formed in human tooth enamel in a quasi-constant composition titration system without the use of surface dissolution inhibitors or weak acids. The titration system maintained the composition of the demineralizing solution constant to within 6% on the average. Thus, the rate of lesion formation may be quantitatively assessed from the rate of titration. The system has sufficient sensitivity for measuring the rate of lesion formation in a small area, e.g., 15 mm2, of a single human enamel specimen.

Chemical Phenomena↗

Monoclonal antibodies against species-specific antigens in the chick central nervous system: putative application as transplantation markers in the chick-quail chimera.

With the recent progress in transplantation of neuronal tissues, cellular markers are needed to distinguish the grafted cells from the host. To generate monoclonal antibodies (MAb) recognizing species-specific antigens in the chick nervous system, we immunized mice with chick optic nerves and obtained 2 MAb which bind to chick but not to quail neural tissues. MAb-39B11 recognizes the cell surface antigen on the nerve fibers. MAb-37F5 recognizes the cytoplasmic components in several cell types, including ependymal cells and some large neurons. The utility of these MAb as markers for chick cells in the chick-quail chimeric brain and their advantages over conventional markers are discussed.

Animals↗