Search PubMed⌕ Search

Biomedical subjects

K Shiota

Publications and source records attributed to K Shiota.

At least 199 records · Page 11Linked to original sources
PubMed1985

Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice.

Di(2-ethylhexyl)phthalate (DEHP) and mono-(2-ethylhexyl)phthalate (MEHP) were administered PO or IP to pregnant ICR mice at varying doses on days 7, 8, and 9 of gestation. In groups given DEHP orally, resorptions and malformed fetuses increased significantly at 1,000 mg/kg. Fetal weights were also significantly suppressed. Anterior neural tube defects (anencephaly and exencephaly) were the malformations most commonly produced. No teratogenic effects were revealed by IP doses of DEHP and PO or IP doses of MEHP, although high doses were abortifacient and lethal to pregnant females. Thus DEHP is highly embryotoxic and teratogenic in mice when given PO but not IP. The difference in metabolism, disposition, or excretion by the route of administration may be responsible for the difference in DEHP teratogenicity. Although MEHP is a principal metabolite of DEHP and is several times more toxic than DEHP to adult mice, it seems that MEHP and its metabolites are not teratogenic in ICR mice.

Abnormalities, Drug-Induced↗
PubMed1985

Acute effect of triiodothyronine on the dynamics of thyrotropin release from superfused anterior pituitary cells.

The effects of triiodothyronine (T3) on the dynamics of thyrotropin (TSH) release induced by TSH-releasing hormone (TRH) were examined in the presence or absence of a protein synthesis inhibitor, cycloheximide (CX), in a superfusion system using primarily cultured cells of the rat anterior pituitary gland on microcarrier beads. When the cells were continuously stimulated with TRH (10 nM, 180 min), TSH release occurred in a biphasic manner and the profile of TSH release was characterized by an initial sharp peak (phase I), followed by a lower plateau form phase (phase II). Both phase-I and phase-II releases were significantly suppressed in the presence of T3 (1 ng/ml), which was added to the superfusion medium 1 h before initiation of TRH stimulation. The biphasic nature of the release profile was maintained in the presence of T3, suggesting that the site of the T3 action may be common between phase-I and phase-II release. We have already suggested that phase-I release is protein synthesis-independent and phase-II release protein synthesis-dependent using CX in TRH-stimulated cells. In the presence of CX, phase-I release was not suppressed by T3, while phase-II release was still suppressed by T3. The inability of CX to reverse the T3-induced suppression of phase-II release may be masked by the direct CX effect on phase-II release of TSH. The present study indicates that each component (phase I and phase II) of the biphasic release of TSH induced by TRH stimulation was acutely suppressed by T3 and suggests that the T3 action is mediated through protein synthesis.

Animals↗
PubMed1984

Maternal reproductive loss and cleft lip with or without cleft palate in human embryos.

Recognized spontaneous abortions in previous pregnancies were significantly more frequent in mothers of 87 Japanese embryos with cleft lip with or without cleft palate (CL(P] than in mothers of normal embryos. The number of prior pregnancies was found to be smaller in mothers of CL(P) embryos with additional defects, suggesting that unrecognized abortions might also occur more frequently in these women. The higher incidence of abortions was associated with more severe forms of CL(P), ie, CL(P) with associated anomalies rather than isolated CL(P), and bilateral rather than unilateral CL. These results are compatible with the "multifactorial two-threshold" model with a lower threshold beyond which the malformation occurs and a higher one beyond which the embryo dies. The present results are in contrast with the reduced spontaneous abortion rates in families of CL(P) probands reported previously. The reduced rates may be due to selection of those families in which CL(P) embryos escaped spontaneous abortion and survived to birth, although the effects of compensatory reproduction or maternal recall bias in postnatal data cannot be ruled out completely.

Abortion, Spontaneous↗
PubMed1984

Biphasic release of thyrotropin in response to thyrotropin-releasing hormone (TRH) from rat anterior pituitary cells in vitro: possible dependence on protein synthesis.

Mechanisms related to the biphasic release of TSH were studied using primary cultured cells of the rat anterior pituitary gland on micro-carrier beads in a superfusion system. Release of TSH in response to continuous exposure to TRH exhibited a biphasic pattern; the first phase was characterized by a rapid, transient and high-rate release (phase I) and the second phase by a chronic and low-rate release (phase II). The shift of the release from phase I to phase II occurred by treatment with TRH at concentrations from submaximal to maximal. When the Ca2+ concentration in the medium was decreased, the phase I release was partially inhibited, while the phase II release was completely inhibited, suggesting a difference between the mechanisms in phase I and phase II release. The phase I release was not suppressed by cycloheximide. This protein synthesis-independent release of phase I seemed to be linked to the intracellular releasable pool of TSH. The phase II release was suppressed by the presence of a protein synthesis inhibitor. After the phase II release was suppressed by cycloheximide, the magnitude of phase I release in response to re-exposure to TRH markedly decreased. The decreased phase I release in response to TRH was observed with the cells which were previously stimulated by high K+ instead of TRH, suggesting that the decrease in the response of phase I reflects the depletion of a releasable pool of TSH rather than homologous desensitization of thyrotrophs with TRH. These results suggest that the phase I release of TSH depends on a portion of the previously prepared-releasable pool while phase II release depends on previously prepared plus newly prepared pools of TSH. Replenishment of the releasable TSH pool was considered to involve protein synthesis.

Animals↗
PubMed1984

In vitro thyrotrophin release with thyrotropin-releasing hormone and an analogue, DN-1417.

Using dispersed and primarily cultured cells of rat pituitary glands, thyrotrophin (TSH) release by TSH-releasing hormone (TRH) and an analogue, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L- prolinamide (DN-1417) which is more potent than TRH on central nervous system behavioural paradigms, was examined under conditions of static incubation and superfusion. Static incubations of the cells with different concentrations of DN-1417 (10(-7)-10(-4) M) and TRH (10(-10)-10(-6) M) resulted in a dose-related increase of TSH release and the response to both peptides, in logarithmic doses, was in parallel. The potency of DN-1417 related to TSH release was 0.14-0.26% that of TRH. Maximal TSH release induced by DN-1417 (10(-5) M) was slightly but significantly greater than that by TRH (10(-7) M). In the presence of 3-isobutyl-1-methylxanthine, the TSH response to either of the peptides was augmented, and the difference in the maximal TSH release by either peptide became insignificant, suggesting that TRH as well as DN-1417 act through the same mechanism of mediation by the cyclic nucleotides. In the superfusion study, a biphasic profile of TSH release was observed during a continuous exposure (100 min) to maximal doses of either the analogue or TRH. The biphasic release of TSH was thought to be specific to TRH action because high K+ produced a different profile of the release. These results indicate that the potency of DN-1417 in TSH release is considerably lower than that of TRH, and also suggest that the direct action of DN-1417 on TSH release is qualitatively similar to that of TRH.

Animals↗
PubMed1983

Isolation and characterization of a 4-O-methylglucuronic acid-containing glycosphingolipid from spermatozoa of a fresh water bivalve, Hyriopsis schlegelii.

A novel glycosphingolipid, provisionally named Lipid IV (Hori, T., Sugita, M., Ando, S., Kuwahara, M., Kumauchi, K., Sugie, E., and Itasaka, O. (1981) J. Biol. Chem. 256, 10979-10985), was obtained from spermatozoa of the fresh water bivalve, Hyriopsis schlegelii. The yield of the glycolipid was 2.2 mg/g of dried spermatozoa. The structure of the glycolipid was elucidated by partial hydrolysis, permethylation analysis, and proton nuclear magnetic resonance. The following structure is proposed: GlcA4Me beta 1-4(GalNAc3Me alpha 1-3)Fuc alpha 1-4GlcNAc beta 1-2Man alpha 1-3(Xyl beta 1-2)Man beta 1-4Glc beta 1-Cer. The acidic glycolipid is unique in containing 4-O-methylglucuronic acid as well as an internally located fucose. Palmitic acid, stearic acid, and C18-sphingosine are the major aliphatic components. This composition is similar to those of other neutral spermatozoan glycolipids, Lipid I (Hori, T., Sugita, M., Kanbayashi, J., and Itasaka, O. (1977) J. Biochem. (Tokyo) 81, 107-114) and Lipid II (Hori, T., Takeda, H., Sugita, M., and Itasaka, O. (1977) J. Biochem. (Tokyo) 82, 1281-1285), suggesting a possible metabolic relationship among them.

Acidic Glycosphingolipids↗
PubMed1983

Kinetic study on disappearance of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) from plasma using a radioimmunoassay for DN-1417 isobutylamide.

Kinetic study of disappearance of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) from human plasma has been performed by a sensitive and specific radioimmunoassay (RIA) using antiserum against DN-1417 isobutylamide. Antibody against N-[2-hydroxy-4-(isobutylcarbamoyl)butyryl]-L-histidyl-L-prolinamide (DN-isobutylamide) did not cross-react with any other TRH-related peptides tested. DN-isobutylamide was radioiodinated with 125I by the chloramine T method and the product had a specific activity of about 160 microCi/microgram. The sensitivity of the RIA was 50 pg per tube, and the intra- and inter-assay coefficients of variation at concentrations of 1-10 ng/ml were 7.0-11.6%. DN-1417 in the plasma was converted to a stable form, DN-isobutylamide, by incubation with isopropanol-isobutylamine at room temperature for 2 h. DN-Isobutylamide was separated from 2-hydroxy-4-carboxybutyryl-L-histidyl-L-prolinamide (DN-COOH) using a SEP-PAKTM C18 cartridge before RIa. The recovery of DN-isobutylamide from plasma was 86.2-98.2%. The half-life, volume of distribution and plasma clearance rate of DN-1417 examined in 6 normal male volunteers by intravenous injection of 500 micrograms DN-1417 citrate were 11.5 +/- 5.6 min in the first phase and 89.5 +/- 33.5 min in the second phase, 25.3 +/- 10.0 liters and 745.8 +/- 278.6 1/d, respectively. These results indicate that RIA of DN-isobutylamide is useful for analysing DN-1417 metabolism in humans.

Adolescent↗
PubMed1983

Bioactivation of thalidomide by a monkey liver fraction in a rat limb culture system.

The effect of thalidomide on a rat limb bud system has been studied in vitro. Thalidomide and adult monkey liver supernatants activated with cofactors for the mixed function monooxygenase system inhibited growth. Similar preparations from the rat did not inhibit growth. Planimetric measures of the surface area of limb buds were found to correlate closely with their protein contents. The ability to compare metabolizing systems from different mammals may be useful in extrapolating teratologic data between different species.

Animals↗
PubMed1983

[Coenzyme Q10 in cancer chemotherapy--experimental studies on augmentation of the effects of masked compounds, especially in the combined chemotherapy with immunopotentiators].

Immunopotentiators may mitigate the depression of immunological function caused by the cancer itself or by chemotherapeutics. However, it has been found that these immunopotentiators reduce the metabolic activity of the host against drugs, including "masked" chemotherapeutics, which might be activated by metabolization in the body. Reported here is the result of serial experiments carried out on the activation of cyclophosphamide (CPM) in tumor-bearing animals, pretreated with phenobarbital, a drug-metabolizing enzyme inducer, and coenzyme Q10, a physiological activator of the electron transfer system in mitochondrias, in combination with immunopotentiators. Female Donryu rats (120 g body weight) implanted with Yoshida Sarcoma cells (YS) (2.5 X 10(6) i.p.) were treated with CPM (160 mg/kg X 1 i.p.), 84 hrs after implantation; the levels of the normustard-like substances (active metabolites of CPM) were serially measured. Some of the animals were also treated with PSK (125 mg/kg X 5 i.p.), a proteinpolysaccharide immunopotentiator obtained from mycelia of the Coriolus vesicolor, or with OK-432 (10 KE/kg X 5 i.m.), a streptococcal immunopotentiator. The results obtained were as follows: The blood levels of the normustard-like substances were lowered, i.e. the CPM activation was depressed in the YS-bearing rats and the depression was markedly intensified by PSK or OK-432 administration. Phenobarbital (40 mg/kg X 3 i.p.) or coenzyme Q10 (5 mg/rat X 5 i.p.) administration could mitigate the depression of the blood levels caused by the immunopotentiators, and the combination of phenobarbital with coenzyme Q10 could recover the blood levels up to those of the YS-bearing control rats, or even higher. YS-implanted (i.p.) rats treated with CPM+ immunopotentiators+coenzyme Q10 survived longer than those treated with CPM+immunopotentiators. These findings suggest the usefulness of coenzyme Q10 for the enhancement of cancer immunochemotherapy using masked compounds combined with immunopotentiators; all the more so, because coenzyme Q10 has also an immuno-stimulating effect, moreover, it presents almost no side effects in clinical application.

Animals↗
PubMed1982

Vaginal spermicides and miscarriage seen primarily in the emergency room.

Among 813 women who had obtained a vaginal spermicide within 48 weeks of the estimated date of fertilization (EDF), 47 (5.8%) had an early miscarriage. Among women who had obtained oral contraceptives, 35/1,127 (3.1%) miscarried, and among women who obtained neither, 140/4,231 (3.3%) miscarried. The risk ratio estimate comparing spermicide users with nonusers was 1.8 (90% confidence interval 1.4, 2.3). The association was strongest among women who had obtained a spermicide within 12 weeks of the EDF. Examination of abortus material revealed that the association with spermicides was strongest among those where an abnormal fetus was present.

Abnormalities, Drug-Induced↗
PubMed1982

Neural tube defects and maternal hyperthermia in early pregnancy: epidemiology in a human embryo population.

A causal relationship between neural tube defects and maternal febrile illness in early pregnancy was investigated retrospectively using human embryo data from Japan. The frequency of febrile illness was compared with corresponding data from normal controls, and holoprosencephalic and polydactylous embryos. Within the group of neural tube defects, the prevalence of maternal hyperthermia was significantly higher than in normal control and holoprosencephaly mothers. The association was constant and highly significant specifically for exencephaly, which is an embryonic forerunner of anencephaly. The correlation with myeloschisis (without exencephaly) was not significant. In eight out of the ten cases in which the timing of the fever was known, it occurred during the clinically determined critical period of neural tube closure in human embryos. These results support the hypothesis that maternal hyperthermia in early pregnancy can cause neural tube defects in man, especially anencephaly.

Anencephaly↗
PubMed1982

Radioimmunoassay for an analog of thyrotrophin-releasing hormone, gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417).

A heterologous radioimmunoassay method was established to determine plasma levels of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417). As this compound is unstable in the incubation buffer, we introduced a conversion step. DN-1417 in the plasma was extracted with a solution of isopropanol-isobutylamine (4 : 1) and incubation was performed at room temperature for 2 h for the conversion of DN-1417 into N-[2-hydroxy-4-(isobutylcarbamoyl)butyryl]-L-histidyl-L-prolinamide (DN-isobutylamide). 125I-labeled 2-hydroxy-4-carboxybutyryl-L-histidyl-L-prolinamide and antisera, which was raised in the rabbit using an esterified derivative of DN-1417 conjugated with BSA as an antigen, were used for a sensitive radioimmunoassay of DN-isobutylamide. In this system, 0.2 ng DN-isobutylamide/ml plasma, equivalent to 0.16 ng DN-1417/ml, was detected and there was no apparent interference from its metabolites. The within-assay coefficients of variation were 7.6% at 7.73 ng/tube and 13.7% at 1.32 ng/tube. The between-assay coefficients of variation were 16.1% at 6.43 ng/tube and 12.2% at 1.20 ng/tube. The mean recovery rate of the assay system was 76.0 +/- 3.2% (S.E.M.).

Animals↗
PubMed1982

Multivariate analysis using a linear discriminant function for predicting the prognosis of congestive heart failure.

Some of cases of congestive heart failure (CHF) are intractable or refractory and respond poorly to conventional treatment. We have examined factors which may influence the clinical course and prognosis. The subjects were 114 hospitalized patients with CHF. Of these, 77 had a good response to treatment and were classified as the curative group (Group C) while the remaining 37 who were difficult to treat, including those with poor prognosis, were designated the refractory group (Group R). Of the various clinical background factors including the findings of laboratory and other examinations, the following 8 variables made a significant contribution to differentiation between the 2 groups: 1) heart rate (X1), 2) hemoglobin content (X2), 3) serum K (X3), 4) serum total protein (X4), 5) A/G (X5), 6) BUN (X6), 7) grade of hepatomegaly (X7), and 8) number of previous CHF episodes (X8). The linear discriminant function represented by the following equation using these 8 variables showed an excellent result in differentiating the 2 groups. Y = - 9.64 - 0.0686X1 + 0.345X2 + 1.351X3 + 1.513X4 + + 1.988X5 - 0.0876X6 - 0.792X7 - 0.737X8. When Y value is over 0, Group C is judged. When Y value is under 0, group R is judged. We concluded that the discriminant equation covering these 8 factors is a useful means of predicting the prognosis in CHF and the response to treatment.

Adult↗