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Biomedical subjects

Y Shibutani

Publications and source records attributed to Y Shibutani.

At least 55 records · Page 3Linked to original sources

Role of urinary trypsin inhibitor in the maintenance of pregnancy in mice.

OBJECTIVE: To investigate the mechanisms whereby urinary trypsin inhibitor prevents lipopolysaccharide-induced preterm delivery in mice. METHODS: On day 15 of pregnancy, C3H/HeNCrg female mice impregnated by Crg:B6D2F1 male mice were treated intraperitoneally with lipopolysaccharide (50 micrograms/kg, twice at a 3-hour interval) to induce preterm delivery. Urinary trypsin inhibitor (2.5 x 10(4), 7.5 x 10(4), or 25 x 10(4) units/kg, ten times at 1-hour intervals) or saline solution was administered intraperitoneally to the animals. RESULTS: The incidence of preterm delivery was significantly decreased on a dose-related basis by urinary trypsin inhibitor treatment. Urinary trypsin inhibitor prevented the morphologic and functional changes in fetal membranes and cervical ripening preceding the onset of preterm delivery. Urinary trypsin inhibitor also suppressed the increase in plasma and amniotic fluid concentrations of interleukin-1 alpha, interleukin-6, and tumor necrosis factor-alpha after the lipopolysaccharide dosing in this animal model for preterm delivery. CONCLUSION: Urinary trypsin inhibitor prevents the pathogenicity of preterm delivery through the suppression of cytokine production.

Animals↗

Repeated administration of low-dose lipopolysaccharide induces preterm delivery in mice: a model for human preterm parturition and for assessment of the therapeutic ability of drugs against preterm delivery.

OBJECTIVE: Our purpose was to establish a new animal model for human preterm delivery for assessment of the protective effect of drugs against preterm delivery. STUDY DESIGN: C3H/HeN, C3H/HeN, and BALB/c female mice impregnated by C3H/HeN, B6D2F1, and B6D2F1 male mice, respectively, were treated intraperitoneally with Escherichia coli lipopolysaccharide (0 to 100 microgram/kg, single dose or repeated doses at 1- to 6-hour intervals) on days 12 through 17 of pregnancy. On day 15 of pregnancy, the C3H/HeN females that had been impregnated by B6D2F1 males and administered lipopolysaccharide were treated intraperitoneally with indomethacin (1000 microgram/kg), ritodrine hydrochloride (1000 microgram/kg), urinary trypsin inhibitor (25 x 10(4) units/kg), or gabexate mesylate (100 mg/kg); preterm or term delivery was recorded for these mice. RESULTS: C3H/HeN females impregnated by B6D2F1 males revealed the highest (100%) incidence of preterm delivery when the females were treated with 50 microgram/kg lipopolysaccharide twice at a 3-hour interval on day 15 or 17 of pregnancy. Indomethacin and urinary trypsin inhibitor used separately significantly decreased the incidence of preterm delivery, but only urinary trypsin inhibitor, and not any of the other drugs, significantly increased the incidence of term delivery in the mice. CONCLUSION: A new animal model for investigation of preterm delivery was established, and its usefulness for assessment of the protective effect of drugs against preterm delivery was demonstrated.

Animals↗

Usefulness of a new tactile sensor for measurement of uterine cervical ripening in mice in a quantitative and noninvasive manner.

OBJECTIVE: The purpose of this study was to establish a method with a new tactile sensor for determining in a quantitative and noninvasive manner the extent of uterine cervical ripening. STUDY DESIGN: We used a newly designed tactile sensor to measure the softness of the cervix in untreated nonpregnant, pregnant, parturient, and nursing mice and then on day 15 of gestation in pregnant mice treated with dehydroepiandrosterone sulfate or Escherichia coli lipopolysaccharide. Additionally, to elucidate the correlation between the extent of cervical softness and its morphologic changes, we observed microscopically the uterine cervices. RESULTS: The hardness of the murine cervix decreased with the progression of pregnancy and became minimal at delivery. We demonstrated for the first time with a tactile sensor for measuring hardness that dehydroepiandrosterone sulfate and lipopolysaccharide significantly decreased the stiffness of the murine cervix. These findings were supported by the morphologic observations on the cervices. CONCLUSIONS: These results show that the tactile sensor for measuring hardness makes it possible to determine the extent of cervical ripening quantitatively rather than qualitatively. We consider that cervical ripening determined objectively in this manner is a good parameter to predict the onset of preterm delivery.

Animals↗

Thyroid hemiagenesis with subacute thyroiditis.

A 58-year-old woman with thyroid hemiagenesis associated with subacute thyroiditis is described. Physical examinations revealed a firm nodule with spontaneous pain and tenderness in the left thyroid lobe. A serum thyroid hormone levels were elevated and thyroid scintiscan with 99mTc pertechnetate showed an extremely low uptake, we made a diagnosis of subacute thyroiditis. A 201Tl thyroid scan demonstrated an enlarged left lobe and absence of the right lobe. Ultrasonography of the thyroid gland revealed an enlarged left lobe occupied mostly with a hypoechoic region. An incidental finding was absence of the right lobe. Two months later thyroid function returned to normal. A follow-up thyroid scintiscan revealed a normal left lobe but absent right lobe. The diagnosis of hemiagenesis was confirmed by CT scan. This appears to be the first case report of thyroid hemiagenesis associated with subacute thyroiditis.

Blood Cell Count↗

Simultaneous high-performance liquid chromatographic determination of 6 beta-hydroxycortisol and cortisol in urine with fluorescence detection and its application for estimating hepatic drug-metabolizing enzyme induction.

A simple and sensitive high-performance liquid chromatographic method is described for the simultaneous determination of 6 beta-hydroxycortisol (6 beta-OHF) and cortisol (F) in urine. Urine (1 ml) containing fludrocortisone as the internal standard is extracted with ethyl acetate. The extract is washed successively with sodium hydroxide solution and water, and subsequently dried under a stream of nitrogen. The residue is redissolved in methanol. The 6 beta-OHF, F and fludrocortisone in the methanol solution are oxidized by cupric acetate and the resulting glyoxal compounds are converted into fluorescent derivatives with 1,2-diamino-4,5-methylenedioxybenzene (DMB). The DMB derivatives of the corticosteroids are separated within 70 min on a reversed-phase column, L-Column ODS, using stepwise elution with methanol-acetonitrile-0.5 M ammonium acetate and detected fluorimetrically at 350 nm (excitation) and 390 nm (emission). The lower limits of detection for 6 beta-OHF and F are 1.8 pmol (680 pg) and 2.4 pmol (950 pg)/ml urine (0.6 pmol and 0.8 pmol/100 microliters injection volume), respectively, at a signal-to-noise ratio of 3. This method can be applied to the determination of urinary 6 beta-OHF, and the ratio of 6 beta-OHF to F in humans and in rhesus monkeys treated orally with phenobarbital as a hepatic drug-metabolizing enzyme inducer.

Administration, Oral↗

[A case report of primary triple cancers in the thyroid, stomach and rectum with evidence of variable oncoprotein expressions].

A case with primary triple cancers including thyroid cancer is reported. A 57-year old woman complaining of laryngeal discomfort was found to have an firm elastic lump on the right anterior neck. On 123I scan, the nodule in the right thyroid lobe accumulated considerable amounts of radioiodine as a warm nodule, while the remainder of the gland showed decreased uptake. Thyroid hormone levels remained within normal ranges. Cytological findings obtained by fine-needle aspiration biopsy showed papillary carcinoma. Right lobectomy was performed. The histological examinations revealed papillary carcinoma embedded within adenomatous thyroid tissue. It is probable that the surrounding adenomatous tissue accumulated radioiodine, since the warm nodule on 123I scan was larger than the size of the carcinoma. Examinations of the gastrointestinal tract revealed the presence of poorly differentiated adenocarcinoma in the stomach and well differentiated adenocarcinoma (carcinoma in adenoma) in the rectum. Expressions of ras p21 and p53 were examined immunohistochemically in these carcinoma tissues. The ras p21 product was clearly detected in not only the thyroid carcinoma but in a part of the surrounding adenomatous regions as well. Both ras p21 and p53 proteins were observed in the rectal cancer tissue. In contrast, these oncoproteins were not found in the gastric cancer tissue. In this case ras oncogene activation may be an early event in the tumorigenic process of the thyroid and rectum. However, different genetic alterations seem to occur during the development of these three carcinomas.

Adenocarcinoma↗

Follow-up of benign hypoechoic peripheral zone lesions of the prostate gland: US characteristics and cancer prevalence.

PURPOSE: To evaluate the role of biopsy-proved benign peripheral zone hypoechoic lesions of the prostate gland, ultrasonographic (US) characteristics at follow-up, prostate-specific antigen (PSA) levels, and digital rectal examination (DRE) in prediction of cancer risk. MATERIALS AND METHODS: Retrospective analysis was performed for 105 consecutive patients with 148 benign hypoechoic lesions discovered at transrectal US (TRUS) and diagnosed with US-guided needle biopsy. At least one repeat TRUS study was performed in each patient. RESULTS: Among the benign lesions, 72% changed at follow-up TRUS, either disappearing or becoming smaller, less hypoechoic, and more vague. Cancer developed in 13% of patients. In 93% of patients in whom cancer developed, the appearance changed in the peripheral zone at follow-up TRUS. In this patient population, the positive predictive value for development of cancer was 16% with a changing TRUS appearance, 19% with an abnormal DRE result, and 27% with an elevated level of PSA; only the latter was statistically significant. CONCLUSION: The PSA value, alone or in combination with a changing TRUS appearance, is the best indicator for development of cancer.

Adult↗

[Metastatic carcinoma of the sigmoid colon to the thyroid gland].

A case of metastatic thyroid cancer from sigmoid colon cancer is presented. A 52-year-old woman had a sigmoidectomy due to adenocarcinoma of the sigmoid colon in April 1988. Serum carcinoembryonic antigen (CEA) levels gradually rose from July 1990 along with multiple metastatic lesions which appeared in the lung. They were resected in January 1991. Two months later the subject noticed a painless and firm lump on the left anterior neck. She was found to have a solitary mass in the left thyroid lobe. Thyroid function remained within normal range. Cytological findings obtained by fine-needle aspiration biopsy showed tall columnar carcinoma cells with an acinar pattern. Subtotal thyroidectomy was performed, and histological examination revealed metastatic adenocarcinoma from colon cancer. Immunohistochemical staining by anti-CEA was positive but anti-thyroglobulin was negative.

Adenocarcinoma↗

A case of acetohexamide-induced hypoglycemia: the influence of hypothyroidism on the metabolism of acetohexamide.

Prolonged hypoglycemia induced by acetohexamide (AH) in a patient with noninsulin dependent diabetes mellitus accompanied by primary hypothyroidism was presented. A 74-year-old man who had been treated with AH (500mg, daily) for diabetes mellitus since 1973 was admitted to our hospital in Oct. 1988 because of hypoglycemic coma. On admission, the level of blood glucose was 20mg/dl. Continuous intravenous administration of 10 per cent glucose solution led to improvement in the mental state on the second day. However, the level of blood glucose remained between 30 to 45mg/dl for four days after admission. On the fifth day, a fasting blood glucose level finally reached 75mg/dl. In a thyroid function test, the serum levels of thyroid hormone showed the following decreases: T3 68ng/dl, T4 2.8 micrograms/dl, free T4 0.3ng/dl, while basal TSH levels increased to 50.3 microU/ml. Since anti-thyroid microsomal antibody was positive and thyroid 99mTc-pertechnetate uptake was slightly elevated, the hypothyroidism in this patient was considered to be caused by chronic thyroiditis. Urinalysis was positive for protein. In a renal function test, the blood urea nitrogen was 26.7mg/dl and creatinine 1.7mg/dl, and creatinine clearance decreased to 22ml/min. After thyroid function returned to euthyroid, creatinine clearance improved (41 ml/min). To clarify the relationship between hypothyroidism and the metabolism of AH, the serum levels of AH and its metabolite hydroxyhexamide (HH) following oral administration of AH (500mg) were evaluated before and after thyroxine replacement therapy. The blood glucose level before therapy was lower than that after therapy, and hypoglycemic symptoms were observed early in the second and third morning after AH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetohexamide↗

Relation of serum and erythrocyte magnesium levels to blood pressure and a family history of hypertension. A follow-up study in Japanese children, 12-14 years old.

Serum and erythrocyte magnesium concentrations (S-Mg, E-Mg) were measured in 122 junior high school students followed up for two years from 12 to 14 years of age, and the relationship to blood pressure and a family history of hypertension were investigated. The subjects who had high S-Mg and E-Mg levels at the first examination two years prior tended to show high levels after this follow-up. There were significant positive correlations between two intraindividual values of S-Mg and E-Mg. A similar tendency was found for blood pressure. Tracking phenomena were observed with these measures. The subjects who had high E-Mg levels at the first examination showed no blood pressure elevation during the two-year period. The subjects with a family history of hypertension [FH(+)] showed a higher degree of blood pressure rise during two years than those with no family history [FH(-)], with a significant difference in systolic blood pressure at the age of 14. E-Mg tended to be lower in the FH(+) group than in the FH(-) group with a significant difference in 14-year-old girls. These results suggest that a hereditary predisposition to hypertension is related to magnesium metabolism and that intracellular magnesium deficiency may influence blood pressure elevation in the FH(+) children.

Adolescent↗

[General pharmacological studies on 5,8,11,14,17-eicosapentaenoic acid ethyl ester (EPA-E)].

EPA-E, even at 3,000 mg/kg, p.o., did not affect the general behaviors, spontaneous locomotor activities, pentobarbital hypnosis and body temperature; and it did not elicit anticonvulsant, analgesic and muscle relaxant actions. It had no influence on spontaneous EEG activities, even at 3,000 mg/kg, i.d. EPA-E at concentrations up to 10(-4) M, did not affect the tonus or agonist-induced contraction of the isolated ileum, trachea, fundus and vas deferens. EPA-E had no influence on the spontaneous movement of isolated ileum or uterus. EPA-E did not affect the nictitating membrane contraction and intestinal propulsive motility, and it did not damage gastric mucosa nor elicit antiulcer action. EPA-E at 1,000 mg/kg were without effect on gastric secretory volume (SV), total acidity (TA) and pepsin activities (PA). However, EPA-E at 3,000 mg/kg significantly decreased SV and TA without significantly decreasing PA. EPA-E caused no changes in the respiration, blood pressure, heart rate and ECG at the doses up to 3,000 mg/kg; and it did not affect the heart rate and contractile force on the isolated atria at concentrations up to 10(-4) M. The intracutaneous injection of 2.0% EPA-E produced neither anesthetic nor irritative action. EPA-E did not elicit hemolytic action at 10(-4) M. EPA-E, even at 3,000 mg/kg, did not affect the neuro-muscular transmission, urine volume, urinary excretion of electrolytes and carrageenin edema. These results suggested that EPA-E has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and so on.

Animals↗

Prolactin dynamics in a patient with isolated ACTH deficiency accompanied by hyperprolactinemia.

Case of isolated ACTH deficiency accompanied by hyperprolactinemia was reported. Prolactin (PRL) secretory dynamics were evaluated by several stimulation (thyrotropin-releasing hormone [TRH], sulpiride) and suppression (L-dopa) tests. Before glucocorticoid replacement therapy, both TRH and sulpiride administration resulted in PRL hyper-responsiveness. The sulpiride-induced PRL increase was higher than that induced by TRH. L-dopa administration resulted in normal PRL suppression. Following glucocorticoid replacement therapy, the elevated basal PRL level returned to normal, and PRL hyper-responsiveness to TRH or sulpiride also returned to normal. These data suggest that the elevation of basal PRL level and PRL hyper-responsiveness observed in this patient is caused by glucocorticoid deficiency.

Adrenocorticotropic Hormone↗

An epidemiological study of plasma renin activity in schoolchildren in Japan: distribution and its relation with family history of hypertension.

Plasma renin activity (PRA) was determined in a group of 610 Japanese schoolchildren aged 10-14 years in order to investigate the relationship between PRA distribution and a family history of hypertension. Plasma renin activity was higher in the subjects with a family history of hypertension (FH+) than in those without a family history of hypertension (FH-). Systolic blood pressure (SBP) was also higher in the FH+ group than in the FH- group. The FH- group showed a significant negative correlation between PRA and SBP (boys, r = -0.254, P less than 0.01; girls, r = -0.225, P less than 0.01), whereas the FH+ group showed no correlation between PRA and blood pressure. These results suggested that schoolchildren with a family history of hypertension might have an enhanced renin-aldosterone (R-A) system, resulting in elevation of blood pressure.

Adolescent↗

Serum and erythrocyte magnesium levels in junior high school students: relation to blood pressure and a family history of hypertension.

Serum and erythrocyte magnesium concentrations (S-Mg, E-Mg) were measured in 380 Japanese junior high school students, and the relationship to blood pressure and a family history of hypertension were studied. Systolic blood pressure was higher in the subjects with a positive family history of hypertension [FH(+)] than in those with a negative family history [FH(-)], whereas E-Mg was lower in the FH(+) group than in the FH(-) group with a significant different in boys. Furthermore, in the FH(+) group, systolic blood pressure was significantly higher in the subjects with lower S-Mg and E-Mg than in those with higher S-Mg and E-Mg. In the FH(-) group, however, no difference was observed in blood pressure levels between the two subgroups. These findings suggest that magnesium deficiency is partially responsible for a rise of blood pressure in the FH(+) children, and that a genetic predisposition of hypertension may be closely related to magnesium metabolism.

Adolescent↗

[Pharmacological properties of MO-8282, a novel antidepressant].

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.

Aggression↗

Antisickling effect of tellurite: a potent membrane-acting agent in vitro.

Potassium tellurite (K2TeO3) was found to be a potent antisickling agent that inhibited red cell sickling at concentrations less than 10 mumol/L. The inhibitory effect depended on the incubation time, with the effect increasing with longer incubation periods. Because tellurite causes swelling of red cells, and because the antisickling effect of tellurite correlated with the degree of red cell swelling, the antisickling effect of tellurite is assumed to be due to the decreased mean cell hemoglobin concentration. Swelling of red cells by tellurite was accelerated by the addition of reduced glutathione. Tellurite appears to be a new type of antisickling agent that interacts with the red cell membrane.

Antisickling Agents↗

[Anti-inflammatory actions of proteases, bromelain, trypsin and their mixed preparation (author's transl)].

Anti-inflammatory actions of proteases, bromelain (BR), trypsin (TR) and their mixed preparation (KT) were studied mainly in rabbits using various experimental test methods. Inhibitory action of edema formation induced by carrageenin was observed to be dose dependent with oral administrations of KT. This inhibitory action of KT was more remarkable than actions of BR and TR, suggesting a possible synergism between the latter two. Such action was also observed with non-steroidal anti-rheumatic drugs, phenylbutazone (PB), indomethacin and acetylsalicylic acid. Oral administration of KT exerted definite inhibition or a tendency toward inhibition against paw edema induced by dextran, histamine or egg albumin or skin edema induced by anti-rabbit serum and thermal stimulation. Furthermore, inhibition of vascular permeability increase induced by histamine and bradykinin as well as a tendency toward inhibition against protein exudation in CMC-pouch method were observed. On the other hand, contrary to PB, potent inhibitory action was not manifested in the persistent proliferative inflammation models, the granuloma formation induced formalin soaked filter paper and cotton pellet and the mustard edema. Therefore, it can be deduced that the inhibitory action of KT against edema formation may be dependent mainly on the inhibitory action of vascular permeability increase and the anti-inflammatory action may be specific for acute exudative inflammation.

Animals↗