Biomedical subjects

A Ikegawa

Publications and source records attributed to A Ikegawa.

9 recordsLinked to original sources

PubMed1998

Structure-activity of novel rhodacyanine dyes as antitumor agents.

We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favorable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubility in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothi azolidin-2 -ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.

Animals↗

PubMed1997

Synthesis and evaluation of novel rhodacyanine dyes that exhibit antitumor activity.

Rhodacyanine dyes and several analogous delocalized lipophilic cations (DLCs) were synthesized and evaluated as novel antitumor agents. Rhodacyanine dye consists of two heteroaromatic rings such as thiazoles at both termini of the conjugate systems and 4-oxothiazolidine (rhodanine) in the middle of it. Compounds with such a unique double-conjugate structure were found to inhibit the growth of several tumor cell lines, such as colon carcinoma CX-1, and to exhibit relatively low toxicity against normal kidney cell line CV-1 (e.g., IC50(CX-1) = 50 nM, IC50(CV-1) = 17.3 microM; selectivity index = 346 for compound 5). These compounds were also found to be efficacious in the tumor-bearing nude mice model (e.g., against human melanoma LOX; T/C (%) = 168 for compound 5). Structural modifications on rhodacyanine, including deletion of a heteroaromatic ring involved in the merocyanine conjugate system and replacement of rhodanine with a structurally related moiety such as 4-oxoimidazolidine or 4-oxo-1,3-dithiolane, resulted in a loss of the selectivity and/or the activity. Our current structure-activity studies imply that the double-conjugate system with a rhodanine moiety is essential for the selective activity of rhodacyanine dyes, and we find this class of compounds as unique antitumor agents candidates.

Animals↗

PubMed1997

First-trimester detection of amniotic sac in relation to miscarriage.

OBJECTIVES: The purposes of this study were to make clear the amniotic sac detection rate, and to determine whether the detection of an amniotic sac can effectively predict miscarriage in the first trimester. STUDY DESIGN: This study included 169 normal pregnancy cases and 169 miscarriage cases. Both groups consisted of cases with a crown-rump length (CRL) of less than 40 mm. RESULTS: In normal pregnancies, the amniotic sac was detectable at a CRL of 7 mm, or longer, and its detection rate varied proportionately with the length of the crown rump. In the miscarriage cases, the detection of an amniotic sac was possible at a CRL of less than 7 mm, and it was independent of the length of the crown rump. At a CRL of less than 7 mm, the amniotic sac was detected in 6 miscarriage cases, and the amniotic sac size increased after embryonic death in 19 miscarriage cases. The amniotic sac detection rate was 38% (65 cases) in all miscarriage cases. CONCLUSION: Detection of an amniotic sac might be one of the useful signs indicating miscarriage when the CRL is less than 7 mm, at which point detection in normal cases is not yet possible.

Abortion, Spontaneous↗

PubMed1995

Prediction of first-trimester miscarriage from embryonic bradycardia and embryonic growth delay.

OBJECTIVE: The purpose of this study was to determine whether subsequent and simultaneous measurements of embryonic heart rate (EHR) and crown-rump length (CRL) are useful in predicting miscarriage. STUDY DESIGN: A prospective cross-sectional study was performed on miscarriages with detectable embryonic heart rate (n = 33). Chromosomal tests were carried out in 9 of 33 cases. RESULT: In cases with embryonic bradycardia and/or embryonic growth delay, the mean CRL was 6.6 mm (n = 16), and embryonic death occurred at CRL values under 20 mm. In cases where neither bradycardia nor growth delay was detected, the CRL was 23.9 mm (n = 17) at embryonic death. Chromosomal abnormalities were present as triploidy (n = 5) and trisomy-16 (n = 2) in both and embryonic-growth-delay cases. CONCLUSION: Subsequent and simultaneous measurements of EHR and CRL are useful in predicting miscarriage in the first trimester, especially when the CRL is under 20 mm.

Abortion, Spontaneous↗

PubMed1986

[Dynamics of steroid levels in normal pregnant and parturient woman].

An extract of a relatively small volume of plasma sample was subjected to high performance liquid chromatography (HPLC) to separate unconjugated steroids, which were subsequently assayed by specific radioimmunoassay (RIA) methods. An aliquot of the sample was hydrolysed and the conjugated steroids were also determined in a similar way. These procedures were proved to be accurate, sensitive and specific to each steroid assayed, and were applied to measure steroids in the peripheral blood of pregnant and parturient women, and in the umbilical cord blood at delivery. Steroids assayed were as follows: Estrone (E1), estradiol (E2), estriol (E3), dehydroepiandrosterone (DHA), androstenedione (A), testosterone (T), 16 alpha-hydroxydehydroepiandrosterone (16 alpha-OH-DHA), 16 alpha-hydroxyandrostenedione (16 alpha-OH-A), 16 alpha-hydroxyestrone (16 alpha-OH-E1), DHA-sulfate (DHA-S), and 16 alpha-OH-DHA-sulfate (16 alpha-OH-DHA-S). Two trends were observed in blood concentrations of unconjugated steroids during the course of pregnancy. One group of steroids, E1, E2, E3 and 16 alpha-OH-E1, continued to increase toward the onset of labor. Another group of steroid, A, T, DHA, 16 alpha-OH-DHA and 16 alpha-OH-A, on the other hand, reached a peak concentration at 36 weeks of gestation, and decreased thereafter. During active labor, unconjugated steroids tended to increase except E1. However, concentrations of T decreased during delivery as compared to those near term. Levels of DHA-S tended to fall as gestational weeks advanced, while those of 16 alpha-OH-DHA-S remained significantly high. It was indicated that a simultaneous determination of various steroids in the same blood sample obtained during pregnancy and at delivery was very useful in elucidating the role of steroids in the initiation of labor.

Androgens↗

PubMed1985

[Studies on 16 alpha-hydroxyandrost-4-ene-3, 17-dione in human pregnancy measured by high performance liquid chromatography and radioimmunoassay].

16 alpha-hydroxyandrost-4-ene-3,17-dione (16 alpha OH-A) was measured in pregnant women by radioimmunoassay (RIA) with specific antiserum. After extraction of the serum the 16 alpha OH-A fraction was separated by the use of Sephadex LH-20 mini column. Lately, high performance liquid chromatograph (HPLC) was combined with RIA (HPLC-RIA) for the measurement of various kinds of steroids from an extract of a serum or urine sample. The purpose of this study was to establish the HPLC-RIA method for the measurement of 16 alpha OH-A in pregnant women. Pooled serum was extracted twice with 5 volumes of ethylether, and the combined extract was separated either by LH-20 mini column with the solvent system n-hexane:benzene:methanol = 8:1:1 or by HPLC ODS column with MeOH:CH3CN:H2O = 60:10:30. The 16 alpha OH-A fraction was collected and an aliquot was measured by RIA. The coefficients of variance for intra and inter-assay (n = 10) were computed to be 8.6 and 12.1% with LH-20, and 7.2 and 11.7% with HPLC, respectively. Recovery rate was 95.7 +/- 7.4% with LH-20 and 92.5 +/- 8.7% with HPLC. The values of 16 alpha OH-A as measured following two kinds of chromatographies were closely related to each other. The mean serum hormone concentrations +/- standard errors were as follows. In maternal peripheral blood up to 11 weeks 1.04 +/- 0.19 (LH-20) and 0.55 +/- 0.10 (HPLC), 12 to 23 weeks 1.22 +/- 0.23 (LH-20) and 0.67 +/- 0.77 (HPLC), 24 to 36 weeks 2.24 +/- 0.42 (LH-20) and 2.27 +/- 0.28 (HPLC), above 37 weeks 1.64 +/- 0.52 (LH-20) and 1.85 +/- 0.34 (HPLC), second stage of labor 5.07 +/- 1.28 (LH-20) and 4.73 +/- 0.54 (HPLC) ng/ml of steroid, respectively, were measured. Steroid concentration in umbilical arterial and venous blood were 7.87 +/- 1.41 (LH-20), 3.75 +/- 0.83 (HPLC) and 8.69 +/- 1.66 (LH-20), 5.38 +/- 0.87 (HPLC) ng/ml, respectively. The values of 16 alpha OH-A levels tended to increase as gestation proceeded. These data suggest production of 16 alpha OH-A by the feto-placental unit. An elevated level of 16 alpha OH-A is found in the umbilical venous blood as compared to the arterial samples. This indicates an extensive conversion. After onset of labor, the 16 alpha OH-A levels were significantly increased because of precursor steroid 16 alpha-hydroxydehydroepiandrosterone-sulfate is mobilized by the stress of labor.(ABSTRACT TRUNCATED AT 400 WORDS)

Androstenedione↗

PubMed1985

A new radioimmunoassay for serum 16 alpha-hydroxyandrost-4-ene-3,17-dione with specific antiserum.

A radioimmunoassay system for serum 16 alpha-hydroxyandrost-4-ene-3,17-dione was developed with the use of rabbit antiserum against 16 alpha-hydroxyandrost-4-ene-3,17-dione-3-(O-carboxymethyl)oxime which was conjugated with bovine serum albumin. The antiserum was highly specific for 16 alpha-hydroxyandrost-4-ene-3,17-dione, with cross reactions to other steroids being less than 0.8% except for androst-4-ene-3,17-dione(3.4% cross reaction). Use of LH-20 column chromatography, however, clearly separated these two steroids. Pregnancy sera were measured with this assay system after an addition of labelled internal standard, extraction and separation by column chromatography. The lower limit of detection for 16 alpha-hydroxyandrost-4-ene-3,17-dione was 2 pg/tube. The mean recovery rate of the added standard was 98.3 +/- 8.8% (mean +/- SE). Intra- and inter-assay coefficients of variation were 8.6% (n = 6) and 12.1% (n = 7), respectively.

Amniotic Fluid↗

PubMed1984

[Clinical studies on sulbactam/cefoperazone in the field of obstetrics and gynecology].

Sulbactam/cefoperazone (SBT/CPZ) was administered to 8 cases with gynecologic infections including pelvic peritonitis (2 cases), pyometra (2 cases), acute adnexitis, Bartholin abscess, endometritis and infected lymphocyst. The clinical efficacy was assessed as effective in 7 cases and poor in 1 case. The effective rate was 87.5%. No adverse reactions including clinical signs were observed. But slight elevation of GOT was observed in 1 case.

Adult↗

PubMed1982

[Studies on the safe limit of variable decelerations during labor].

Ninety neonates who presented variable decelerations during labor were divided into two groups, according to the one-minute Apgar scores of greater than or equal to 8 and 7 less than or equal to. Only neonates of singleton pregnancies and cephalic presentations of 34 weeks gestation or more were included in the study. Several parameters of this fetal heart rate (FHR) pattern and the presence or absence of meconium staining were compared. Followings were found to be statistically significant. 1) The duration of the variable deceleration (less than 2 hours). 2) The FHR deceleration/uterine contraction ratio (less than 80%). 3) The absence of meconium staining. An effort was made to establish safe limits of variable decelerations. These are shown in parentheses. Based on both these data and findings of others, a multifactorial scoring system named a variable deceleration score was proposed for the proper management of this FHR pattern. Five variables were selected for the system. These were: The duration of variable decelerations, the FHR deceleration/uterine contraction ratio, the duration and amplitude of dips, and the presence or absence of meconium staining. The system scores from 0 to 2 for each of five factors, and was designed to be able to predict depressed neonates with the numerical increase of the score.

Female↗