Biomedical subjects

Hirokazu Kubota

Publications and source records attributed to Hirokazu Kubota.

13 recordsLinked to original sources

PubMed2006

Peripartum changes in plasma estrone sulfate and estradiol-17beta profiles associated with and without the retention of fetal membranes in holstein-friesian cattle.

The aim of this study was to evaluate the changes in plasma concentrations of estrone sulfate (E(1)S) and estradiol-17beta (E(2)beta) during the peripartum period (from day 10 prepartum to day 1 postpartum) associated with and without retention of fetal membranes (RFM) in Holstein-Friesian cattle (n=42). Plasma samples were analyzed for E(1)S and E(2)beta by ELISA. All parturitions were spontaneous and normal. Of 38 cattle delivering singletons, 29 had no RFM (singleton-normal group) and nine had RFM for more than 12 h (singleton-RFM group). Four cows gave birth to twins, and each twin had its own fetal membrane (FM). Two twinning cows expelled both FMs normally within 12 h (twin-normal group). In the remaining 2 twinning cows (twin-RFM group), the FM was expelled normally for one twin (first), while the FM of the other (second) was retained. There were no significant differences in the E(1)S concentrations or their increments from the concentrations on the preceding day between the normal and RFM groups of singleton cows on any peripartum day. The mean plasma E(2)beta concentrations on each day from day 10 to day 3 prepartum were significantly lower (P<0.05) in the singleton-RFM group compared with the singleton-normal group; however, on days 2 and 1 prepartum, the increments in the E(2)beta concentrations from the concentrations on the preceding days were significantly higher (P<0.05) in the singleton-RFM group than in the singleton-normal group. Thus, the plasma E(1)S concentrations just before parturition may not be associated with RFM. In the cows with RFM, the lower plasma E(2)beta concentrations that were found prior to day 2 prepartum may have been associated with immature placentomes, and the rapid rise in plasma E(2) beta within 1 to 2 days prior to calving may have produced asynchrony of placental and/or fetal maturation in relation to calving, thus resulting in RFM.

Animals↗

PubMed2006

Novel potent and selective calcium-release-activated calcium (CRAC) channel inhibitors. Part 2: Synthesis and inhibitory activity of aryl-3-trifluoromethylpyrazoles.

To identify potent and selective calcium-release-activated calcium (CRAC) channel inhibitors, we examined the structure-activity relationships of the pyrazole and thiophene moieties in compound 4. Compound 25b was found to exhibit highly potent and selective inhibitory activity for CRAC channels and further modifications of the pyrazole and benzoyl moieties of compound 25b produced compound 29. These compounds were potent inhibitors of IL-2 production in vitro and also acted as inhibitors in pharmacological models of diseases resulting from T-lymphocyte activation, after oral administration.

Animals↗

PubMed2006

Novel potent and selective calcium-release-activated calcium (CRAC) channel inhibitors. Part 1: synthesis and inhibitory activity of 5-(1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamides.

We synthesized and evaluated a series of 5-(1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamides to identify potent inhibitors of calcium-release-activated calcium (CRAC) channels with greater selectivity than voltage-operated calcium (VOC) channels. These efforts resulted in identification of compounds 22 and 24. The former exhibits highly potent and selective CRAC channel inhibitory activity, and the latter inhibited phytohemagglutinin-induced interleukin-2 production by Jurkat T lymphocytes and concanavalin A-induced hepatitis in mice.

Amides↗

PubMed2006

A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and cytokine production by facilitating transient receptor potential melastatin 4 channel activity.

3,5-Bis(trifluoromethyl)pyrazole derivative (BTP2) or N-[4-3, 5-bis(trifluromethyl)pyrazol-1-yl]-4-methyl-1,2,3-thiadiazole-5-carboxamide (YM-58483) is an immunosuppressive compound that potently inhibits both Ca2+ influx and interleukin-2 (IL-2) production in lymphocytes. We report here that BTP2 dosedependently enhances transient receptor potential melastatin 4 (TRPM4), a Ca2+-activated nonselective (CAN) cation channel that decreases Ca2+ influx by depolarizing lymphocytes. The effect of BTP2 on TRPM4 occurs at low nanomolar concentrations and is highly specific, because other ion channels in T lymphocytes are not significantly affected, and the major Ca2+ influx pathway in lymphocytes, ICRAC, is blocked only at 100-fold higher concentrations. The efficacy of BTP2 in blocking IL-2 production is reduced approximately 100-fold when preventing TRPM4-mediated membrane depolarization, suggesting that the BTP2-mediated facilitation of TRPM4 channels represents the major mechanism for its immunosuppressive effect. Our results demonstrate that TRPM4 channels represent a previously unrecognized key element in lymphocyte Ca2+ signaling and that their facilitation by BTP2 supports cell membrane depolarization, which reduces the driving force for Ca2+ entry and ultimately causes the potent suppression of cytokine release.

Anilides↗

PubMed2006

A novel dual antagonist of thromboxane A2 and leukotriene D4 receptors: synthesis and structure-activity relationships of chloroquinolylvinyl derivatives.

To discover an orally active thromboxane A(2) (TXA(2)) and leukotriene D(4) (LTD(4)) dual antagonist, we designed and synthesized chloroquinolylvinyl derivatives based on the structures of the TXA(2) antagonist daltroban and the LTD(4) antagonist montelukast. Among these derivatives, 4-{[(2-(4-chlorophenylsulfonylamino)-1-{3-[(E)-2-(7-chloro-2-quinolyl)vinyl]phenyl}ethyl)thio]methyl}benzoic acid (18d) showed potent inhibitory activity against U46619-induced aggregation of guinea pig platelets and LTD(4)-induced contraction in the guinea pig ileum, with IC(50) values of 340 nm and 0.40 nm, respectively. Oral administration of 18 d also inhibited both the LTD(4)-induced acceleration of plasma leakage to skin in guinea pig and the U46619-induced increase in airway resistance in guinea pig with ED(50) values of 0.47 mg/kg and 3.3 mg/kg, respectively.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2005

Onset and duration of luteal activity postpartum and their effect on first insemination conception rate in lactating dairy cows.

The incidence of different types of luteal activity postpartum and their effect on reproductive performance were studied in 21 postpartum dairy cows. Progesterone concentrations in defatted milk collected 3 times a week were determined by EIA. Reproductive tract examination was undertaken every other week postpartum. Body weight and body condition score (BCS) were measured before and after calving and the average 100-day milk yield was calculated. Nine (42.9%) cows had normal ovarian activity (first luteal activity < or = 50 days postpartum followed by regular cycles), 5 (23.8%) had prolonged luteal phase (PLP; ovarian cycle with luteal activity > or = 20 days pre-service) and in 7 (33.3%) cows the first luteal activity was shown later than 50 days postpartum (DOV). When compared with normal cows, both PLP and DOV had longer interval to first insemination (63.1 +/- 22.0 days versus 77.6 +/- 21.6 and 93.0 +/- 22.3 days, P<0.05 and P<0.01, respectively), lower first insemination conception rate (88.9% versus 0.0% and 57.1%, P<0.01 and P<0.05, respectively) and greater BCS loss (0.81 +/- 0.2 versus 1.05 +/- 0.21 and 1.04 +/- 0.10, respectively, P<0.01). Cows with PLP showed longer interval to uterine involution than normal and DOV groups (54.0 +/- 8.3 days versus 42.4 +/- 5.5 and 43.3 +/- 8.3 days, respectively, P<0.01) and higher 100-day milk yield (38.8 +/- 2.7 kg versus 33.6 +/- 4.7 and 29.9 +/- 6.1 kg, respectively, P<0.01). In conclusion, more than half of the cows had abnormal luteal activity postpartum, which adversely affected reproductive performance.

Analysis of Variance↗

PubMed2005

Preference for glucose in Zn-deficient rats selecting from glucose and fructose diets.

Glucose and fructose selection patters of rats were analyzed for 28 d by a 2-choice selection in either Zn-adequate or Zn-deficient status. In this paper, we describe the following serial studies: (1) For the first 24 h, rats fed a Zn-deficient diet preferred a fructose-diet compared with a glucose-diet. On and after the third day, rats fed both Zn-adequate and Zn-deficient diets preferred the glucose-diet. (2) Throughout the experimental period, many of the rats fed a Zn-adequate and Zn-deficient diet continuously selected one diet. (3) Some of the rats fed a Zn-adequate and Zn-deficient diet suddenly changed preference for the glucose-diet or the fructose-diet. (4) The sum of daily glucose- and fructose-diet intake in rats fed a Zn-deficient diet showed a characteristic variation with the cyclic period of 3.9 +/- 0.4 d.

Animals↗

PubMed2004

Atresia ani with diphallus and separate scrota in a calf: a case report.

Atresia ani, a common genetic defect in animals, is often accompanied by urogenital defects in calves. This paper reports a case of atresia ani with diphallus and separate scrota in a calf. The calf was born with atresia ani; surgery (to open the anus) was performed 3 days after birth. No urogenital abnormalities were noticed until 4 months after birth. At that time, two separate scrota (each containing a testis) and a sac-like structure in the middle of two scrota, were visible. The gait was abnormal, with abduction of the hind limbs while walking. Additionally, the hind legs appeared wider than usual at the hip joints. Two weeks later, two peni (diphallia) was observed, each in a separate preputial sheath. The calf had a normal karyotype on cytogenetic examination. Plasma concentrations of testosterone at 5.5, 6, and 7 months of age were 3.5, 1.9, and 1.7 ng/ml, respectively. At necropsy (7 months of age), the prepuce was thick and the glans of the right penis was adhered to the prepuce. The left penis did not have a urethra or retractor penis muscles. The sac-like structure in the middle of the two scrota contained the urinary bladder and a loop of small intestine. The pubic bone had failed to fuse at the pelvic symphysis. In conclusion, this is the first reported case of atresia ani with diphallus, separate scrota, and pubic bone separation in a calf.

Animals↗

PubMed2004

Luteal function and conception in lactating cows and some factors influencing luteal function after first insemination.

The objective of this study was to investigate the types and incidence of luteal sub-function in lactating cows after artificial insemination (AI) and their relationship with pregnancy, and to clarify the relationship between luteal function and parity, body condition score (BCS), milk yield, and dietary intake. In 19 cows, milk samples were collected daily from AI to confirmation of pregnancy. Milk progesterone concentrations were determined by EIA. Based on peak progesterone concentration and the day of onset of luteal phase, 15 of 30 progesterone profiles (50%) were normal, with progesterone concentration reaching 1.0 ng/ml within 5 days after insemination and > or =2.0 ng/ml thereafter. In addition, 6 (20%) were insufficient, (progesterone concentration remained < 2.0 ng/ml), 5 (17%) were delayed (progesterone reached 1.0 ng/ml after 5 days), 2 (7%) were both delayed and insufficient, one (3%) was short (progesterone >1.0 ng/ml for only 7 days), and one (3%) remained basal. Cows with a normal profile had a higher (P < 0.05) pregnancy rate than those with an abnormal profile (87% versus 33%, respectively). The amount of progesterone secreted in milk after first AI, as indicated by progesterone area under curve (AUC), was negatively correlated with milk yield (r = -0.83, P < 0.01), dry matter intake (r = -0.81, P < 0.05), total digestible nutrients (r = -0.82, P< 0.05), and digestible crude protein (r = -0.79, P <0.05). Cows that produced more milk and consumed more dry matter had less progesterone during the luteal phase. In conclusion, abnormal luteal function was associated with reduced pregnancy rates and high milk production and increased dietary intake during breeding were associated with reduced progesterone concentrations.

Animals↗

PubMed2003

A pyrazole derivative, YM-58483, potently inhibits store-operated sustained Ca2+ influx and IL-2 production in T lymphocytes.

In nonexcitable cells, Ca(2+) entry is mediated predominantly through the store depletion-dependent Ca(2+) channels called store-operated Ca(2+) (SOC) or Ca(2+) release-activated Ca(2+) channels. YM-58483, a pyrazole derivative, inhibited an anti-CD3 mAb-induced sustained Ca(2+) influx in acute T cell leukemia, Jurkat cells. But it did not affect an anti-CD3 mAb-induced transient intracellular Ca(2+) increase in Ca(2+)-free medium, nor anti-CD3 mAb-induced phosphorylation of phospholipase Cgamma1. It was suggested that YM-58483 inhibited Ca(2+) influx through SOC channels without affecting the TCR signal transduction cascade. Furthermore, YM-58483 inhibited thapsigargin-induced sustained Ca(2+) influx with an IC(50) value of 100 nM without affecting membrane potential. YM-58483 inhibited by 30-fold the Ca(2+) influx through SOC channels compared with voltage-operated Ca(2+) channels, while econazole inhibited both SOC channels and voltage-operated Ca(2+) channels with an equivalent range of IC(50) values. YM-58483 potently inhibited IL-2 production and NF-AT-driven promoter activity, but not AP-1-driven promoter activity in Jurkat cells. Moreover, this compound inhibited delayed-type hypersensitivity in mice with an ED(50) of 1.1 mg/kg. Therefore, we concluded that YM-58483 was a novel store-operated Ca(2+) entry blocker and a potent immunomodulator, and could be useful for the treatment of autoimmune diseases and chronic inflammation. Furthermore, YM-58483 would be a candidate for the study of capacitative Ca(2+) entry mechanisms through SOC/CRAC channels and for identification of putative Ca(2+) channel genes.

Anilides↗

PubMed2003

Plasma concentration of estrone sulfate during pregnancy in different breeds of Japanese beef cattle.

Plasma concentrations of estrone sulfate in different breeds of Japanese beef cattle and the relationship between those concentrations and feto-placental growth were examined in order to assess the possibility of monitoring abnormal growth of the fetus. Blood samples were obtained from cows from day 90 of gestation to parturition. The plasma concentration of estrone sulfate was measured by direct enzyme immunoassay. From day 180 of gestation, the mean concentration of estrone sulfate increased gradually and it was drastically elevated after day 240 of gestation with the maximum at day 285. Plasma concentrations of estrone sulfate on day 240 of gestation was significantly increased in F(1) cows (Holstein Friesian and Japanese Black) compared with those in other breeds of cow. From day 270 to 278 of gestation, estrone sulfate concentrations of Holstein Friesian cows inseminated by Holstein Friesian differed from those inseminated by Japanese Black. In the cow with retained placenta, the plasma concentration of estrone sulfate reached plateau at day 240 of gestation and did not increase thereafter. There was no significant relationship between estrone sulfate concentration and duration of gestation, calf birth weight, weight of placenta or viability of newborn calves. These results indicate that changes of plasma estrone sulfate concentration in Japanese beef cattle are very similar to those in Holstein dairy cattle. They also suggest that the plasma concentration of estrone sulfate is associated with the breed of pregnant cow and that its concentration is also affected by calf birth weight depending on the breed of bull. It seems possible to predict the incidence of retained placenta but not the calf birth weight and viability of newborn calves in Japanese beef cattle.

Animals↗

PubMed2003

The influence of various carbohydrates on the feeding pattern of rats fed zinc-deficient diets.

When dextrin, maltose, sucrose, glucose, and fructose were used as a source of carbohydrate in a diet, the food intake of rats fed either a Zn-adequate or Zn-deficient diet was evaluated daily over 28 d. The average food intake of all groups of rats fed the Zn-deficient diet was significantly lower than that of the corresponding groups of Zn-adequate control rats. The food intake of the dextrin group was the highest under both Zn-deficient and Zn-adequate diets, and that of the fructose group was the lowest. All rats of the dextrin, maltose, sucrose, glucose, and fructose groups with the Zn-deficient status showed a characteristic cyclic variation in food intake and fitted well to a Cosinor curve. The values of the mesor, amplitude, and period of the food intake cycles showed significant differences among the groups. The higher intake of the glucose diet than the fructose diet of rats fed a Zn-deficient diet may be related to the different metabolisms of the carbohydrates used, from the comparison of the quantities consumed in the corresponding carbohydrates of Zn-adequate diets.

Animals↗

PubMed2000

Recent progress in soliton transmission technology.

Recent progress on time-division multiplexed (TDM) and wavelength-division multiplexed (WDM) soliton transmission is described, in which dispersion management plays an important role in increasing the power margin and the dispersion tolerance. The characteristics of the dispersion-managed soliton are compared with those of return to zero and nonreturn to zero pulses. With a small dispersion swing, the system can still be described as an average soliton using the nonlinear Schrodinger equation, while with a large dispersion swing, the solitonlike steady-state pulse becomes a chirped Gaussian pulse, in which the governing equation is closer to a linear Schrodinger equation with a parabolic potential well. We describe an in-line modulation scheme for up to 80 Gbit/s per channel and its two channel WDM transmission over 10 000 km. Finally, we describe 640 Gbit/s (40 Gbit/sx16 channels) WDM soliton transmission over 1000 km with a dispersion-managed single-mode fiber. (c) 2000 American Institute of Physics.

Journal Article↗