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Biomedical subjects

K Kashiwai

Publications and source records attributed to K Kashiwai.

At least 19 recordsLinked to original sources

3,3'-Diiodothyronine sulfate excretion in maternal urine reflects fetal thyroid function in sheep.

We have shown that there is significant fetal-to-maternal transfer of sulfated metabolites of thyroid hormone after fetal infusion of a pharmacologic amount of 3,3',5-triiodothyronine (T(3)) or sulfated T(3) in late pregnancy in sheep (Am J Physiol 277:E915, 1999). The transferred iodothyronine sulfoconjugate, i.e. 3,3'-diiodothyronine sulfate (T(2)S), of fetal origin appears in maternal sheep urine. The present study was carried out to assess the contribution of T(2)S of fetal origin to the urinary pool in ewes. Eighteen date-bred ewes (mean gestational age of 115 d) and their twin fetuses were divided into four groups. In group I (control, n = 5), both ewes (M) and their fetuses (F) were sham operated for thyroidectomy (Tx). In group II, the ewes (MTx, n = 4) and, in group III, the fetuses (FTx, n = 4) were subjected to Tx. In group IV (MTx.FTx, n = 5), both the ewe and fetus had Tx. After 10-12 d, fetal and/or maternal hypothyroidism were confirmed by serum thyroxine (<15 nmol/L) measurements. In addition, we infused radioactive T(3) without disturbing the T(3) pool in three singleton near-term fetuses and assessed the amount of radioactive iodothyronine that appeared in maternal urine (MU). After infusing [(125)I-3'],3,5-T(3) via fetal vein to the near-term normal fetuses, radioactive T(2)S was identified as the major metabolite in MU by HPLC and T(2)S-specific antibody. MU T(2)S excretion (pmol/mmol creatinine) was significantly reduced by FTx and MTx.FTx but not by MTx. In addition, positive correlations (p < 0.01) were found between MU T(2)S excretion and fetal serum thyroxine and T(3) concentrations but not with maternal serum thyroxine or T(3) levels. T(2)S of fetal origin contributes significantly to the MU pool.

Animals↗

[Screening for prostatic diseases in one-day total health check-up by using prostate specific antigen, international prostate symptom score and QOL index].

We preliminarily studied screening for prostatic diseases in one-day total health check-up by employing prostate specific antigen (PSA), international prostate symptom score (IPSS) and quality of life (QOL) index. From January 6 to March 31, 1998, a total of 390 men were included in this study, whose age ranged from 50 to 78 years with the mean of 57.5 years. The questionnaires, IPSS and QOL index, were mailed to the participants in advance. PSA (IMx: Dainapack) was measured at the end of the health check-up and the results of tests were explained on the same day. Participants who showed more than 8 points in IPSS, more than 4 points in QOL index and/or more than 4.1 ng/ml in PSA were given a referral to urologists of corresponding hospitals for further examination. A total of 116 men (29.7%) were judged to need thorough examination. Among 106 men who were referred to urologists, only 34 (32.1%) had visited the urologists by the end of July 1998. Two men (0.51% in all participants) were diagnosed with prostate cancer, 10 received some pharmacotherapy, and 2 underwent transurethral resection of prostate. The results indicate that screening for prostatic diseases in total health check-up is useful, even in an institute without staff urologists, in close association with urologists.

Aged↗

Placental norepinephrine transporter development in the ovine fetus.

The placenta has been shown to be a site of expression of several of the monoamine membrane uptake transporters. However, the development and relative contribution of transport-dependent mechanisms to placental catecholamine clearance in vivo have not been demonstrated. These studies were designed to determine the development of the placental norepinephrine transporter (NET) and the relative contribution of transport dependent mechanisms to whole body and placental catecholamine clearance. Norepinephrine clearance and production rate were determined in 122 +/- 1 day gestation chronically catheterized fetal sheep. Placental clearance was shown to account for over 40 per cent of total intrauterine clearance and, of the clearance in the placenta, nearly 50 per cent was uptake, transport-dependent as shown by specific pharmacologic blockade. NET transport expression was examined by measurement nisoxetine binding in placenta and compared with binding in the frontal cortex of fetal, newborn and adult animals. Nisoxetine is a selective ligand for the norepinephrine transporter. Nisoxetine binding was 20-fold greater in placenta than in frontal cortex. Placental transporter binding decreased modestly in between 99 days gestation and term (145 days) but did not change in frontal cortex. These results suggest that expression of the norepinephrine transporter in the placenta is associated with a significant capacity for neurotransmitter re-uptake in utero. Given the high fetal norepinephrine production rate, this capacity is important for fetal homeostasis. This site of transporter expression may be important in the pathogenesis of derangements in catecholamine production in the fetus and in the adverse effects on the fetus of drugs, such as cocaine, which block catecholamine re-uptake.

Animals↗

The contribution of transporter-dependent uptake to fetal catecholamine clearance.

These studies were designed to determine the contribution of cocaine-sensitive, transporter-dependent, reuptake mechanisms to the intrauterine norepinephrine clearance rate in chronically catheterized fetal sheep. Baseline norepinephrine clearance and appearance rates were 125 +/- 20 ml/kg/min and 85 +/- 11 ng/kg/min, respectively. Transporter-dependent clearance represented 40% of the intrauterine clearance rate. The effects of chronic cocaine administration on fetal catecholamine clearance and appearance rate were then determined in animals treated with daily infusion of saline or cocaine. The total intrauterine clearance rate and the transport-dependent component of intrauterine clearance decreased significantly following the week of drug or placebo treatment, p < 0.05. This was associated with a threefold increase in circulating catecholamine concentrations in both groups of animals, p < 0.05. These results demonstrate that intrauterine catecholamine clearance is highly dependent on transporter-dependent mechanisms. Chronic intrauterine stress, manifested by increased circulating norepinephrine, is associated with a significant decrease in norepinephrine clearance and may be important in the pathogenesis of the adverse effects of stress on the fetus and of drugs like cocaine, which block catecholamine reuptake.

Animals↗

Placental norepinephrine clearance: in vivo measurement and physiological role.

The intrauterine clearance rate of catecholamines is higher than in newborn animals or in adults. The separate contributions of the fetus and placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transporter in vivo, we studied fetal sheep at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the kinetics of placental and fetal NE appearance and clearance rates. Umbilical flow was determined by [3H]NE infusion. Placental and total (fetal-placental) NE clearance rates were determined by measurement of [3H]NE from simultaneously drawn UV and AO samples. Total clearance was 99 +/- 8 ml.kg-1.min-1. Placental fractional [3H]NE extraction was 21% and accounted for 48% of total clearance. Fetal plasma NE production rate was 85 +/- 20 ng.kg-1.min-1. We conclude that placental catecholamine clearance is an important metabolic function of the placenta. This mechanism for clearance of the high fetal production rate of catecholamines is vital for fetal homeostasis. We speculate that derangements in placental catecholamine clearance may explain the exaggerated adverse effects on the fetus of drugs like cocaine, which block catecholamine transport.

Animals↗

Binding of [3H]triamcinolone acetonide to glucocorticoid receptors in brain cytosol fractions of rats with intact adrenals.

Binding of [3H]triamcinolone acetonide (TA) increased with prolongation of incubation periods of up to 5 h after the onset of incubation at 2 degrees C, with a plateau thereafter persisting for at least up to 48 h in brain cytosol fractions of rats with intact adrenals. Elevation of incubation temperature to 30 degrees C resulted in a marked reduction of the binding at equilibrium which persisted for only 1 to 2 h with complete abolition thereafter. The addition of sodium molybdate was effective in doubling the maximal value at 30 degrees C without markedly affecting the binding at 2 degrees C. [3H]TA binding at equilibrium determined at 2 degrees C was a reversible, saturable and structure selective process with uneven distribution profiles in rat brain. Among a variety of steroid hormones tested, TA was the most potent displacer with progressively less potent displacement by dexamethasone, deoxycorticosterone, progesterone, prednisolone, hydrocortisone and corticosterone. Among discrete brain regions examined, the highest density was detected in the cerebellum followed by the hippocampus, cerebral cortex, midbrain, striatum, hypothalamus and medulla-pons in a rank order of decreasing density. In contrast, both the cerebellum and medulla-pons had significantly higher affinities for [3H]TA than the cerebral cortex. Moreover, the binding was markedly inhibited by Zn2+ ions at 10 microM due to a decrease in the affinity. These results suggest that [3H]TA labels a ligand recognition domain on the cytoplastic glucocorticoid receptor complex with different affinities in rat brain.

Adrenal Glands↗

Marked eosinophilia induced by nafamostat mesilate, an anticoagulant in a hemodialysis patient.

A 61-year-old Japanese female on hemodialysis developed marked eosinophilia induced by nafamostat mesilate as an anticoagulant for hemodialysis. This is the first case of hypereosinophilic syndrome induced by nafamostat mesilate in a hemodialysis patient. The elevated eosinophil counts (51,900/mm3) are the highest for hemodialysis-associated eosinophilia. This eosinophilia was eliminated after cessation of nafamostat mesilate. We confirmed that the cause of this eosinophilia was nafamostat mesilate by using the challenge test.

Anticoagulants↗

[Megaureters in adults].

Megaureters are common in children but are rarely found in adults, probably due to the scarcity of clinical symptoms. Reconstruction surgery in adults has been performed only exceptionally up to a few years ago. We encountered 7 adults with 7 megaureters in the recent 6 years. The underlying pathologic entities responsible for the megaureters were non-peristaltic lower segment, ectopic ureter and ureterovesical junction stenosis. Six adults with 6 megaureters were treated by complete surgical reconstruction and reimplantation of the ureter. The outcome of all the reported cases was excellent.

Adult↗