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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 181 records · Page 10Linked to original sources

Involvement of pituitary hormone in the sex-related regulation of hepatic epoxide hydrolase activity in mice.

The involvement of the pituitary gland in the expression of sex-related differences in the activities of epoxide hydrolase (EH) in liver was examined in hypophysectomized and neonatally monosodium L-glutamate (MSG)-treated male and female mice. In hypophysectomized mice, the hepatic microsomal EH activity of males and females increased considerably above those of the respective sham-operated controls, and the female activity exceeded that of the sham-operated males. The hypophysectomy caused a decrease in soluble EH activity in males, while the operation led to an elevation of the activity in females. Neonatal treatment with MSG resulted in marked increases of microsomal EH activity in males and females at adulthood and the activity was about 2 times that of the male control mice. Treatment of hypophysectomized males and females with growth hormone (GH) resulted in a significant decrease in microsomal EH activity below those of the corresponding hypophysectomized controls, while the hormone treatment had no effect on the soluble enzyme activities. These results suggest that murine hepatic microsomal EH activity is principally under the suppressive control of the pituitary and GH is a causal hormone involved in the expression of sexual dimorphism in the enzyme activity.

Animals↗

Magnetic resonance angiography of cerebral arteriovenous malformations.

Magnetic resonance (MR) angiography as a method for the long-term follow-up of cerebral arteriovenous malformations (AVMs) was assessed in 14 patients with cerebral AVMs. These patients were either untreated or treated with transarterial embolization and/or stereotactic radiosurgery (gamma knife). Two-dimensional- and three-dimensional (3D)-time-of-flight (TOF) techniques were useful for following AVMs with a small nidus and few feeders and drainers which were either untreated or had been treated only a few months previously. 3D-TOF MR angiography with a contrast agent was more useful for visualizing the vascular structure, including the residual nidus, during long-term follow-up of treated AVMs.

Adult↗

Determination of urinary glucuronide conjugates by high-performance liquid chromatography with pre-column fluorescence derivatization.

A simple and highly sensitive high-performance liquid chromatographic method for the direct determination of urinary glucuronide conjugates is described. The method is based on the direct derivatization of the glucuronic acid moiety in glucuronide conjugates with 6,7-dimethoxy-1-methyl-2 (1 H)-quinoxalinone-3-propionylcarboxylic acid hydrazide. The derivatization reaction proceeds in aqueous solution in the presence of pyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide at 0-37 degrees C. The resulting fluorescent derivatives are separated on a C18 column using methanol-acetonitrile-0.5% triethylamine in water (1:1:2, v/v) as mobile phase, and are detected spectrofluorimetrically at 445 nm with excitation at 367 nm. The detection limits (signal-to-noise ratio = 3) for the glucuronides are 13-48 fmol for an injection volume of 10 microliters (130-480 fmol per 5 microliters of human urine). The method was applied to the measurement of etiocholanorone-3-glucuronide and androsterone-3-glucuronide in human urine. The method is simple and rapid without conventional liquid-liquid extraction of the glucuronides from urine.

Adult↗

Design and synthesis of amphipathic 3(10)-helical peptides and their interactions with phospholipid bilayers and ion channel formation.

It has been reported that a peptide corresponding to the S4 segment in sodium channel protein is able to form voltage-dependent cation-selective ion channels (Tosteson, M. T., Auld, D. S., and Tosteson, D. C. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 707-710). However, biological and other physical properties remain unexamined. In the present study, three peptides, H-(Ala-Arg-Leu)8-OH (ARL8), H-(Val-Arg-Leu)8-OH (VRL8), and H-(Leu-Arg-Leu)8-OH (LRL8) which were designed on the basis of the S4 segment and expected to form 3(10)-helix, were synthesized and examined with regard to conformational change by the interaction with membranes, membrane perturbation ability, ion channel formation, and antimicrobial activity. According to CD spectra, these peptides were found to form a 3(10)-helical structure in the presence of dipalmitoyl-DL-alpha-phosphatidylcholine/dipalmitoyl-DL-alpha- phosphatidylglycerol (3:1) liposomes. The experiment of the peptide-induced leakage of carboxyfluorescein from liposomes showed that all the peptides had a strong ability to perturb membranes. The peptides were able to form cation-selective ion channels in planar asolectin lipid bilayers. The conductances of the ion channels were small (approximately 2 picosiemens for VRL8 and LRL8 and approximately 23 picosiemens for ARL8), suggesting that the peptides produce narrow pores or wider pores with certain permeable barriers that are a portion of the whole channels. The differences in their conductances depend possibly on the sizes of the side chains of Ala, Val, and Leu residues. However, non of the peptides showed antimicrobial activity (minimum inhibitory concentrations, > 50 micrograms/ml). Here, we present the first evidence that the peptides can form 3(10)-helical structures with long chain lengths in a lipid bilayer environment.

Amino Acid Sequence↗

The inhibitory effect caused by suramin on the paracrine growth of human cancer cells and fibroblasts.

The growth interactions between human cancer cells and primary cultured human fibroblasts, and the effects of suramin on them, were investigated using a double-chamber technique combined with a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. Human fibroblasts obtained from various organs resected surgically were cultured in a monolayer and used after the third or fourth passage. In the double-chamber assay, the growth of cancer cells in the top chamber was significantly stimulated by some types of fibroblasts in the bottom chamber in a fibroblast density-dependent manner. Interestingly, the growth of cancer cells was stimulated at 140%-147% by fibroblasts obtained from an organ where cancer cells had developed, the MCF-7 versus mammary fibroblasts, and in LS-180 versus colonic fibroblasts, but not by their fibroblast-conditioned medium. Suramin completely inhibited the growth-enhancing interaction between MCF-7 and mammary fibroblasts, and between SH-101 and lung fibroblasts at a clinical concentration of from 50 micrograms/ml to 300 micrograms/ml. It also reduced the growth of LS-180 co-cultured with colon-fibroblasts, but the inhibitory effect was incomplete. These results suggest that mutual growth reliance exists between human cancer cells and primary cultured fibroblasts by diffusible factors secreted by both cells, and that these enhancing effects are related in part to the growth and metastasis of cancer cells in vivo. Suramin was found to have an inhibitory effect on their interaction at a clinically achievable concentration in vitro.

Cell Division↗

Trochlear nerve neurinoma associated with a giant thrombosed dissecting aneurysm of the contralateral vertebral artery.

The authors encountered the unusual case of a 57-year-old man with a right trochlear nerve neurinoma associated with a giant thrombosed dissecting aneurysm of the left vertebral artery. The right trochlear nerve neurinoma was subtotally removed via the right subtemporal transtentorial route. The trochlear nerve entered the tumor directly posterolaterally. The left vertebral artery was clipped just proximal to the thrombosed dissecting aneurysm via the left lateral suboccipital approach. The patient was discharged without neurologic deficits except for the right trochlear nerve palsy. To our knowledge, this seems to be the first reported case of such an occurrence.

Aortic Dissection↗

Effect of trimebutine maleate on the contractile response of the isolated ileum from diabetic rats.

1. Tension of the isolated ileum from diabetic rats induced by streptozotocin was measured isometrically to study the mode of action of trimebutine maleate (TMB). 2. The hyperreactivity of contractile response to KCl was observed in the isolated ileum from diabetic rats. TMB inhibited the contraction induced by KCl and acetylcholine (ACh) in normal solution. 3. In Ca2+ free solution, the hyperreactivity of contractile response to KCl was attenuated, and TMB did not inhibit the contraction induced by KCl. In contrast, TMB inhibited the contraction induced by ACh even in Ca2+ free solution. 4. These results suggest that the hyperreactivity of contractile response to KCl in the ileum from diabetic rats is due to the enhancement of Ca2+ influx through voltage-dependent Ca2+ channel and that TMB inhibits the hyperreactivity of contractile response through the inhibition of Ca2+ movement by the cell.

Animals↗

Comparative effects of loperamide hydrochloride on prostaglandin E1-induced contraction in isolated fundus and ileum of guinea pigs.

The tension of isolated preparations of the fundus and the ileum of guinea pigs was measured isometrically to study the specific effect of loperamide hydrochloride on prostaglandin E1-induced contraction. Prostaglandin E1 caused concentration-dependent contraction in both the fundus and the ileum, and there was no significant difference between the fundus and the ileum. Loperamide hydrochloride inhibited prostaglandin E1-induced contraction in the fundus and the ileum. From the pD'2 value, loperamide hydrochloride caused greater inhibition of the contraction in the ileum than in the fundus. In a Ca(2+)-free solution containing 0.1 mM EGTA, prostaglandin E1-induced contraction in the ileum was almost eliminated, whereas 58% of the contraction in the fundus still remained. In Ca(2+)-free solution, loperamide hydrochloride and verapamil hydrochloride had no influence on prostaglandin E1-induced contraction, but markedly inhibited Ca(2+)-induced contraction. These results suggest that loperamide hydrochloride shows regional differences between gastrointestinal smooth muscles contracted by prostaglandin E1, and this may reflect one of the mechanisms in its antidiarrheal action through the suppression of peristalsis.

Alprostadil↗

A case of central diabetes insipidus with spontaneous remission after 8 years of the disease.

A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A water deprivation study revealed a defect in the urine concentrating function, which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not increased by smoking. His condition was well controlled by deamino-D-arginine vasopressin. However, since February 1992 he has become completely free from the need for medication to control his urine volume. Re-evaluation studies with water deprivation and smoking revealed dramatic improvements in the urine concentrating function and ADH response. A patient with idiopathic diabetes insipidus with spontaneous remission after 8 years is reported.

Diabetes Insipidus↗

Augmentation of baroreceptor reflex function by oral calcium supplementation in essential hypertension.

1. We studied the effect of oral calcium supplementation (1.0 g/day) for 1 week on baroreceptor reflex function and the lability of blood pressure in association with the changes in autonomic nervous activity in 14 hospitalized patients with mild to moderate essential hypertension (nine males and five females, mean age of 56 +/- 11.2 (s.d.) years). 2. Baroreceptor reflex sensitivity (BRS) was determined by the change in R-R intervals in response to the pressor response induced by phenylephrine injection. We measured coefficient of variation of R-R interval (CVR-R) and urinary excretion of catecholamines to evaluate the mechanism of change in BRS. We also used coefficient of variation of blood pressure (CVBP) and error of single cosinor analysis as parameters for lability of 24-h blood pressure. 3. The means of 24-h systolic and diastolic blood pressures showed no significant changes after calcium supplementation for 1 week. BRS and CVR-R were significantly increased by calcium supplementation. Daily excretions of norepinephrine and epinephrine corrected by creatinine were unchanged. Both CVBP and error of 24-h systolic blood pressure showed a significant decrease after calcium treatment. 4. These results indicate that oral calcium supplementation augments baroreceptor reflex function, in part through an enhancement of parasympathetic nervous activity, resulting in reduction of the lability of blood pressure in patients with mild to moderate essential hypertension.

Administration, Oral↗

Long-term follow-up study of 10 adolescent patients with sleep-wake schedule disorders.

Therapeutic trials for sleep-wake schedule disorders have been described, but a long-term follow-up of adolescents with such disorders have not previously been reported. We investigated 10 adolescents with sleep-wake schedule disorders who had formerly received intensive treatment. The investigation was carried out with detailed questionnaires about current sleep conditions and social state. The follow-ups were obtained from 1.2 to 11.2 years after the initial treatment. Three cases have remitted, and six have improved in illness severity. All patients showed improvement in social adaptation. Improvement in the social adaptation level was greater than improvement in the illness severity level. More cases should be studied to learn what factors influence the prognosis of these disorders.

Adolescent↗

Four new metabolites of Aspergillus terreus.

Four new metabolites (1-4) were isolated from mycelium of Aspergillus terreus IFO 6123 producing asterriquinone (ARQ). The structures of 1 and 2 were shown to be 3,6-bis[1-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-furo[3,2-b]furan- 2,5-dione (asterridinone) and 2,5-bis[1-(1,1-dimethyl-2-propenyl)-1H-indol-3- yl]-3-acetoxy-6-hydroxy-2,5-cyclohexadiene-1,4-dione (ARQ monoacetate), respectively, by the chemical and spectral data. Compounds 3 and 4 were identified with known asterriquinone isomers, 2-[1-(1,1-dimethyl-2-propenyl)-1H-indol-3-yl]-5-[2-(3-methyl-2-butenyl)- 1H-indol-3-yl]-3,6-dihydroxy-2,5-cyclohexadiene-1,4-dione (isoARQ) and 2,5-bis[2-(3-methyl-2-butenyl)-1H-indol-3-yl]-3,6-dihydroxy- 2,5-cyclohexadiene-1,4-dione (neoARQ), respectively.

Animals↗