Successful treatment with methotrexate of a child with atlantoaxial subluxation from enthesitis-related arthritis.
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Antirheumatic Agents↗
Biomedical subjects
K Koike
Publications and source records attributed to K Koike.
Irreversible blockade of the kappa-receptor by a newly synthesized dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group.
The interactions of the dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group (dynorphin derivative) with kappa-receptors were studied. The dynorphin derivative inhibited, in a concentration-dependent manner, the twitch response to electrical stimulation of the longitudinal muscle of the guinea-pig ileum which contains both mu- and kappa-receptors. It also inhibited the twitch response to electrical stimulation of the rabbit vas deferens, reported to contain only kappa-receptors; its pD2 value was 11.57 +/- 0.09, suggesting that the agonistic activity of the dynorphin derivative is mainly mediated through kappa-receptors. The KD and Bmax values of [3H]U-69593 were calculated from a Scatchard plot of the specific binding. After a 30 min treatment with 10(-5) M of this dynorphin derivative, the KD value did not alter but the Bmax value decreased. However, this decrease recovered after treatment with 2 x 10(-3) M of dithiothreitol. These results suggest that the dynorphin derivative binds to kappa-receptors through the disulfide bound. The dissociation constant of nalorphine-7,8-oxide (nalorphine-epoxide) was determined according to the method of Furchgott, by irreversibly binding a fraction of the kappa-receptors with the dynorphin derivative. The negative logarithms of the dissociation constants (pKA values) for nalorphine-epoxide did not differ in the guinea-pig ileum and rabbit vas deferens, suggesting that the kappa-receptors in the two preparations are identical. However, the pD2 value and efficacy for nalorphine-epoxide in the guinea-pig ileum were significantly greater than those in the rabbit vas deferens. These results indicate that the kappa-receptor reserve in the longitudinal muscle of the guinea-pig ileum is greater than in the rabbit vas deferens. It is thought that the dynorphin derivative, containing a 3-nitro-2-pyridinesulfenyl group, is useful to clarify the kappa-receptor mechanisms.
Amino Acid Sequence↗
Interactions of R(+) and S(-) isomers of befunolol, a partial agonist with high and low affinity sites of beta-adrenoceptors in guinea-pig taenia caecum.
The beta-adrenomimetic and beta-adrenolytic activities of R(+) and S(-) isomers of befunolol, a beta-adrenergic partial agonist, were studied in the guinea-pig taenia caecum. The pA2 value (9.38) of the S(-) isomer against S(-) isoprenaline was significantly different from that (7.94) of the R(+) isomer, while the pD2 values and intrinsic activities of R(+) and S(-) isomers were not significantly different from each other. The competitive inhibition curves of the specific binding of [3H]befunolol (50 nM) to the microsomal fraction from the guinea-pig taenia caecum by S(-) and R(+) isomers were biphasic, suggesting two different affinity binding sites. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site was 0.081 while the affinities of R(+) and S(-) isomers to the low affinity site were not significantly different from each other. The affinity ratio of the R(+) isomer against the S(-) isomer to the high affinity site resembled their potency ratio in beta-adrenergic blocking action. These findings suggest that beta-adrenoceptors contain two different affinity binding sites and that the high affinity binding site for isoprenaline is more stereoselective than the low affinity binding site.
Adrenergic beta-Antagonists↗
A regional difference in alpha 1-adrenoceptors in canine arteries.
Noradrenaline sensitivity (pD2-value) and agonist dissociation constant (pKA-value) were determined in the following 4 canine arteries: thoracic and abdominal aorta, mesenteric and renal. The experiments were done in the presence of beta- and alpha 2-adrenoceptor blockers, and inhibitors of neuronal and non-neuronal uptake of catecholamine. A positive correlation was found in the pD2- and pKA-values for noradrenaline (r = 0.976, P less than 0.05). The slope (0.92) was not significantly different from 1. The pD2- and pKp (negative log of dissociation constant of partial agonist)-values of clonidine, an alpha 1-adrenergic partial agonist, were also determined. There was a positive correlation between the pD2- and pKp-values (r = 0.974, P less than 0.05). Again, the slope (1.39) was not significantly different from 1. These results indicate that the regional difference in the pD2-values for noradrenaline and clonidine in canine arteries is due to the affinities to alpha 1-adrenoceptors and that there is a qualitative difference between alpha 1-adrenoceptor mechanisms in the arteries and veins. However, no positive correlation between the pD2-values for noradrenaline and clonidine was observed (r = 0.182, P greater than 0.05). Thus, it may be suggested that either the recognition sites for noradrenaline, clonidine and prazosin are different or else their mode of attachment to the same recognition site is not identical.
Animals↗
Comparison of beta-adrenoceptors in single smooth muscle cells and in isolated smooth muscle preparations from the guinea-pig taenia caecum.
Single smooth muscle cells were prepared from guinea-pig taenia caecum. To study the beta-adrenoceptors in the single cells, we observed mechanical responses of the single cells to beta-adrenergic drugs and also tested the binding of a [3H]-labelled drug to the single cells. The single cells showed a graded relaxing response to isoprenaline. The concentration-response curve was shifted in a parallel fashion by propranolol, indicating a competitive antagonism. The pA2 value of propranolol was in agreement with that estimated using the intact tissue. The dissociation constant of [3H]-dihydroalprenolol was similar to the value estimated in the microsomal fractions. The apparent dissociation constants of isoprenaline and propranolol estimated from inhibition of the specific binding of [3H]-dihydroalprenolol to the single cells were also in agreement with the values in the microsomal fractions. The results suggest that there is no change in the beta-adrenoceptor mechanism in single smooth muscle cells by isolating the cells.
Animals↗
Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine.
Some pharmacological properties of a newly synthesized morphine derivative, (-)-6 beta-acetylthiomorphine (AcS-morphine) were studied. AcS-morphine was about twice as potent as morphine in the inhibitory action of the twitch response of the guinea-pig ileal preparation to electrical stimulation. AcS-morphine, however, was 5 times as potent as morphine in the analgesic action in the rats. Both the effects of AcS-morphine were inhibited by naloxone, suggesting that the site of action of AcS-morphine is mu-receptors. It is interesting that 6 beta-isomer of AcS-morphine is 5 times as potent as 6 alpha-OH isomer of morphine in the analgesic action, because 6 alpha-OH isomer of morphine is much more potent than that of 6 beta-OH isomer. The effects of AcS-morphine on the specific binding of [3H]-naloxone, [3H]-ethylketocyclazocine and [3H]-D-Ala2-D-Leu5-enkephalin to the membrane fractions from the rat brain were tested. AcS-morphine was about 5 times as potent as morphine in its interactions with opioid receptors, as determined by the binding assay. AcS-morphine, as well as morphine, had a selectively high affinity to mu-receptors. The "sodium effect" and the "GTP effect" of AcS-morphine were almost the same as those of morphine. The dependence liability of AcS-morphine was preliminary tested in the guinea-pig ileal preparations treated with a high concentration of AcS-morphine for 24 hr. Results suggested that AcS-morphine is weaker than morphine in its dependence liability, though it seems almost certain that AcS-morphine does have this liability.
Analgesics↗
[Transcatheter closure of atrial septal defect with a prototype clamshell septal umbrella: one year follow-up].
Transcatheter closure of a secundum atrial septal defect was attempted using a prototype clamshell septal umbrella closure system in 11 patients (six males, five females, aged 4.4-15.0 years and weighing 16-51 kg). The balloon stretched atrial septal defects were 10.3 to 20 mm in diameter, and 23 to 40 mm diameter umbrellas were used. All patients improved clinically after the procedure. Fixed splitting of the second heart sound disappeared after closure in 10 patients, systolic murmur disappeared in nine, diastolic rumble in nine, and paradoxical ventricular septal motion in seven. Doppler color flow imaging immediately after implantation showed significant residual shunt in all patients; however, no shunt flow was observed in seven patients and minimal residual shunt was present in four one year after the procedure. Nine of 11 umbrellas demonstrated fracture of the stainless steel arm confirmed by chest radiography and cinefluorography. Arm fracture occurred between 1 week and 12 months after implantation. None of the devices were dislodged and no other complications were noted despite the fractures. Transcatheter closure of atrial septal defect is a feasible and useful procedure but the present device needs further modification.
Cardiac Catheterization↗
[Pediatric matrix biplane transesophageal echo probe: evaluation of probe selection in patients].
We have developed four different probes for the wide use of transesophageal echocardiography in children. The adult matrix biplane probe (M-BP) can generate transverse and longitudinal plane images simultaneously from a single transducer, and facilitates easier and faster understanding of the three-dimensional anatomy of the heart. This probe can be used in patients weighing more than 15 kg. The pediatric matrix biplane probe (PM-BP) has the same function as the M-BP in a smaller probe head and shaft, and can be used in patients weighing more than 5 kg. The conventional pediatric biplane probe (P-BP) with two transducers has a smaller probe head profile than the PM-BP, and can be used in a baby as small as 2.7 kg. The newborn single plane probe (N-SP) has the smallest profile with a 4 mm diameter shaft, and can be used like a nasogastric tube. We choose probes according to the size of the patient and purpose of the study. As a rule, smaller probes are less invasive and reduce the risk of the study. However, larger probes have better image quality and penetration. Proper selection of the probe is the key to the safe and effective use of this new methodology.
Child, Preschool↗
Some pharmacological properties of a newly synthesized 3-acetoxy-6 beta-acetylthio-10-oxo-N-cyclopropylmethyl-dihydronormorphine (KT-95).
The pharmacological properties of a newly synthesized 3-acetoxy-6 beta-acetylthio-10-oxo-N-cyclopropylmethyl-dihydronormorphine (KT-95) were examined. This compound, as well as (-)-3-acetyl-6 beta-acetylthio-N-cyclopropylmethylnormorphine (KT-90) and morphine, inhibited the twitch response to electrical stimulation of the guinea-pig ileal preparation that contains mu- and kappa-receptors. The inhibitory effect of KT-95 was about 17 times more potent than morphine, and about 4 times more potent than KT-90. In the guinea-pig ileal preparation, KT-95 behaved as a mu-antagonist against morphine in the presence of norbinaltorphimine (3 x 10(-8) M). In the rabbit vas deferens, containing kappa-opioid receptors, KT-95 inhibited the twitch response to electrical stimulation in a concentration-dependent manner. Norbinaltorphimine concentration-dependently caused parallel rightward shifts of the concentration-response curves to KT-95 in the guinea-pig ileum and in the rabbit vas deferens after electrical stimulation, suggesting that KT-95 behaved as an agonist for the kappa-opioid receptor. In the mouse vas deferens, that contains delta-receptors. KT-95 behaved also as a delta-antagonist against Leu-enkephalin in the presence of norbinaltorphimine. KT-95, KT-90 and morphine were examined for their potencies in displacing the specific binding of [3H]naloxone (mu-selective ligand), [3H]U69593 (kappa-selective ligand), and [3H]D-Ala2-D-Leu5-enkephalin (delta-selective ligand) to synaptosomal fractions from rat brain. Although KT-95 had a higher nonselective affinity to mu-receptors than KT-90 and morphine, the affinity of KT-95 to kappa-receptors was about 18 times higher than that of morphine, and about 5 times higher than that of KT-90. In the acetic acid-induced writhing test, subcutaneously injected KT-95 was more potent than morphine. Furthermore, the analgesic effect, induced by KT-95 (0.062 mumol/kg, s.c.), was abolished by simultaneous administration of norbinaltorphimine (0.020 mumol/mouse, s.c.), suggesting that the analgesic action of KT-95 is mediated through the kappa-opioid receptor. In the pressure test, KT-95 was 20.17 times more potent than morphine. The analgesic action, induced by KT-95 (2.05 mumol/kg, s.c.), was also in this test abolished by simultaneous administration of norbinaltorphimine (0.14 mumol/rat, s.c.), suggesting that this action of KT-95 is mediated through the kappa-opioid receptor. These results indicate that KT-95 behaves as a kappa-agonist with mu- and delta-antagonistic activities, and suggest that analgesia, induced by KT-95, is mainly mediated through kappa-receptors.
Analgesia↗
Effects of prolactin and estrogen on cell proliferation of the mouse liver induced by partial hepatectomy.
Estrogen or prolactin suppresses mouse hepatocellular tumorigenesis induced by carcinogens through inhibition of the growth of preneoplastic hepatocytes. In the present study, we investigated whether estrogen or prolactin inhibits proliferation of normal hepatocytes as well as preneoplastic hepatocytes in mice. The proliferation of mouse hepatocytes was induced by partial hepatectomy, and DNA synthesis of the liver was evaluated by measurement of 5-[125I]iododeoxyuridine ([125I]IdUrd) uptake/mg liver DNA after an injection of [125I]IdUrd into mice. For acute treatment with estrogen or prolactin, estradiol-17 beta (E2) (1 micrograms) or ovine prolactin (140 micrograms) was injected into ovariectomized mice twice a day from the day of partial hepatectomy. For chronic treatment with estrogen, ovariectomized mice received implants of E2 pellets containing 100 micrograms E2 40 days before partial hepatectomy, and for chronic treatment with prolactin, hyperprolactinemia was induced by pituitary graft under the renal capsule of ovariectomized mice 40 days before partial hepatectomy or by daily injections of perphenazine (150 micrograms/day) beginning 40 days before partial hepatectomy. The acute treatment with either estrogen or prolactin did not affect the hepatocyte proliferation induced by partial hepatectomy. Chronic hyperprolactinemia induced by the pituitary graft or by injections of perphenazine, and the chronic treatment with E2 pellets did not suppress either basal or partial hepatectomy-induced proliferation of hepatocytes. The present results show that acute and chronic treatments with estrogen or prolactin do not inhibit proliferation of mouse normal hepatocytes, and suggest that the effects of estrogen and prolactin on proliferation of mouse hepatocytes are different from those on proliferation of preneoplastic hepatocytes.
Animals↗