[A case of midbrain infarction with ipsilateral hand tremor].
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Cerebral Infarction↗
Biomedical subjects
K Miyata
Publications and source records attributed to K Miyata.
[Two cases with SLE and MCTD developed after a long period of chronic arthritis that was initially diagnosed as JRA].
In order to discuss the diversity of clinical features and the difficulty in diagnosis of children with juvenile rheumatoid arthritis (JRA), we present two cases who have documented the development of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) after a long period of disease characterized only by arthritis that was initially diagnosed as JRA. The first case was a girl diagnosed for her arthritic joints as polyarticular JRA at 15 years of age. At onset, she had Raynaud phenomenon but autoantibodies such as anti-nuclear antibody (ANA), anti-DNA antibody, and rheumatoid factor were negative. Five years after onset, she became ANA positive and 3 years later she became pregnant. During her pregnancy, she became positive for anti-DNA antibody without any signs of nephritis. One month after the delivery, however, she developed butterfly rash, carditis, nephritis, and was diagnosed as SLE. No destructive changes were observed in her joints though arthritis continued for 8 years form onset to pregnancy. The second case was a 3 years old girl who was diagnosed as polyarticular JRA. Treatment by aspirin induced complate remission after one year from the onset. However, 10 years after that remission, she developed Raynaud phenomenon and arthralgia in her knees and hip joints. Her laboratory findings showed hypergammaglobulinemia, positive ANA, positive anti-DNA antibody, positive anti-RNP antibody. She was eventually diagnosed as MCTD when she was found to have polymyositis by EMG and serum CK. In the present paper, two cases imply the difficulty in diagnosing JRA and diversity of rheumatic diseases such as JRA, SLE and MCTD. Closer and longer period of observation is essential for the JRA patients with nondestructive arthritis.
Adolescent↗
Participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats.
The participation of a cholinergic mechanism in 5-hydroxytryptamine (5-HT)3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats was investigated. The selective 5-HT3 receptor antagonists ramosetron (YM060, 0.1-10 micrograms/kg i.v.) and ondansetron (1-100 micrograms/kg i.v.) dose-dependently enhanced the gastric emptying of glass beads in rats. The 5-HT4 receptor agonist 5-methoxytryptamine (5-MOT, 1 mg/kg s.c.) and substituted benzamides (5-HT4 receptor agonist/5-HT3 receptor antagonists) cisapride (1-10 mg/kg s.c.) and zacopride (1-1000 micrograms/kg s.c.) produced significant gastroprokinetic responses in rats. The substituted benzamide-induced gastroprokinetic responses were inhibited by a high dose of tropisetron (10 mg/kg s.c.), a 5-HT3 and 5-HT4 receptor antagonist, and partially inhibited by GR113808 ([1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidyl]methyl 1-methyl-1H-indole-3-carboxylate, 1 mg/kg s.c.), a selective 5-HT4 receptor antagonist. On the other hand, the 5-MOT-induced gastroprokinetic response was almost completely inhibited by GR113808. In contrast, tetrodotoxin (TTX, 0.1-10 micrograms/kg s.c.) and atropine (1-1000 micrograms/kg s.c.) dose-dependently inhibited gastric emptying. The enhancement of gastric emptying induced by selective 5-HT3 receptor antagonists, substituted benzamides and 5-MOT was inhibited by TTX (10 micrograms/kg s.c.) and by atropine (1 mg/kg s.c.). These results suggest that substituted benzamides stimulated gastric emptying partly due to their 5-HT4 receptor agonistic properties, and that both 5-HT3 receptor antagonism and 5-HT4 receptor agonism stimulated the gastric emptying in rats. It is also suggested that a cholinergic mechanism participates in the 5-HT3 and 5-HT4 receptor-mediated stimulation of gastric emptying in rats.
Animals↗
Investigation of 5-HT3 receptor-mediated contraction in guinea-pig distal colon.
We investigated the participation of cholinergic and tachykininergic mechanisms in 5-hydroxytryptamine (5-HT)-induced contraction via 5-HT3 receptors in longitudinal and circular muscle of guinea-pig isolated distal colon. 5-HT produced concentration-dependent contractile responses in longitudinal and circular muscle. The 5-HT3 receptor antagonists ramosetron (YM060) ((R)-5-[(1-methyl-3-indolyl) carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride), YM114 (KAE-393) ((R)-5-[(2,3-dihydro-1-indolyl)carbonyl]-4,5,6,7-tetrahydro-1 H-benzimidazole hydrochloride), ondansetron and granisetron produced a concentration-dependent shift to the right of the 5-HT concentration-response curves in both muscle. However, methysergide and GR113808 had no effect on 5-HT-induced contraction. In the longitudinal muscle, atropine concentration-dependently inhibited 5-HT-induced contraction, and tetrodotoxin abolished it. (+/-)-CP96,345 attenuated the contractile response to 5-HT, but (+/-)-SR48,968 had no effect on it. In the presence of atropine, (+/-)-CP96,345 completely blocked 5-HT-induced contraction. In the circular muscle, atropine had no effect on the contractile response to 5-HT, whereas tetrodotoxin completely suppressed it. The contractile response elicited by 5-HT in the circular muscle was not inhibited by either (+/-)-CP96,345, (+/-)-SR48,968, devazepide, L-365,260 or indomethacin. It is suggested that 5-HT acts via 5-HT3 receptors to release acetylcholine and substance P, which in turn are responsible for contraction of the longitudinal muscle. In the circular muscle, as in the longitudinal muscle, 5-HT-induced contraction is mediated by the 5-HT3 receptor. Unlike the case in longitudinal muscle, however, this contraction involves neither cholinergic nor tachykininergic transmission. It is also suggested that neither cholecystokinin (CCK) nor prostaglandins participate in 5-HT3 receptor-mediated contraction in circular muscle.
Animals↗
Hemodialysis effect on serum boron level in the patients with long term hemodialysis.
Serum and dialysate boron levels in 17 patients with long term hemodialysis (HD) were determined by inductively coupled plasma emission spectrometry (ICPES). Serum boron level was compared with the value of age matched 467 healthy controls and the relationship between serum and dialysate boron level was analyzed. The results showed that serum boron level was significantly higher at the beginning of HD, and lower at the completion of HD in comparison with controls. Although the dialysate was contaminated with trace boron, HD resulted in an excessive decrease of serum boron, rather than boron exposure from the dialysate. Boron hemodialyzability was almost proportional to the gradient of the boron level at the beginning of HD and it could be controlled by the adjustment of the gradient. In conclusion, the serum boron level was very much disturbed in long term HD patients. If boron excess in serum at the beginning of HD, or deficiency at the completion of HD may contribute to the complications of HD patients, fine adjustment and close surveillance of the gradient should be taken into account.
Acute Kidney Injury↗
Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice.
The role of 5-HT3 receptors in the control of intestinal propulsive activity was investigated in mice by a simple method in which the time taken for excretion of the head of an orally administered non-absorbable marker (whole gut transit time) was measured. Selective 5-HT3 receptor antagonists ramosetron (YM060) at 0.01-0.3 mg/kg s. c. and ondansetron at 0.1-1 mg/kg s.c. dose-dependently prolonged the whole gut transit time. Prokinetic benzamides, such as renzapride (0.3-10 mg/kg s.c.), zacopride (0.01-0.3 mg/kg s.c.) and cisapride (0.1-3 mg/kg s.c.), which have been reported to possess 5-HT3 receptor blocking properties, also dose-dependently prolonged it. These results indicate that activation of 5-HT3 receptors seems to be one factor that underlies the physiological control of intestinal propulsive activity in mice. In contrast to their beneficial therapeutic effects on gastroduodenal dysmotility, prokinetic benzamides, at least those which have 5-HT3 receptor antagonistic activity, may be unsuitable in the treatment of impaired lower intestinal propulsive activity.
Adrenergic alpha-Agonists↗
[Differential diagnosis of mitochondrial myopathy from dermatomyositis with various autoantibodies].
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Antibodies, Antinuclear↗
Mammalian mature osteoclasts as estrogen target cells.
The decrease in estrogen levels that follows the onset of menopause causes rapid bone loss, resulting in osteoporosis. However, the mechanism by which this occurs remains unclear, especially concerning the regulation of osteoclasts, i.e. the bone-resorbing cells. Using a pit assay involving isolated mature osteoclasts from rabbit long bones, we found that estrogen inhibited the bone-resorbing activity in a dose- and time-dependent manner. Furthermore, we clarified by Northern analysis that estrogen down-regulated the mRNA levels of cathepsin K/OC-2 and that putative estrogen receptor (ER) mRNA was expressed in these osteoclasts. Moreover, other sizes of mRNAs that hybridized with ER cDNA probe were found in these cells. Our results suggest that osteoclasts may be indeed target cells for estrogen and that estrogen might regulate a part of bone metabolism through osteoclasts.
Animals↗
Acceleration of influenza virus clearance by Th1 cells in the nasal site of mice immunized intranasally with adjuvant-combined recombinant nucleoprotein.
The protective roles of influenza viral nucleoprotein (NP), together with the cellular mechanism of the protection in the nasal site, were examined in BALB/c mice immunized intranasally with an adjuvant (cholera toxin B subunit containing 0.2% of the whole toxin)-combined A or B virus recombinant NP. The NP-immune mice, when challenged intranasally with a sublethal dose of the virus 3 wk after immunization, had accelerated virus clearance from the nasal site in both an influenza type-specific and a nonspecific manner, as shown by the protection from high morbidity from the second day after challenge. Both type-specific and nonspecific acceleration of recovery was confirmed by the increased survival rate after challenge with a lethal dose of virus in mice immunized and boosted with adjuvant-combined NP. The acceleration of nasal virus clearance was accompanied with acceleration of type-specific systemic delayed-type hypersensitivity (DTH) and with IFN-gamma production by nasal lymphocytes. The nasal lymphocytes from the immunized and challenged mice generated a significantly high level of DTH when transferred locally, but no class I MHC-restricted CTL response. Moreover, nasal CD4+ T cells, induced by NP immunization and increased in number by the subsequent challenge, were involved in the accelerated IFN-gamma production. These results suggest that nasal Th1 cells, capable of producing IFN-gamma and mediating DTH, are involved in the type-specific acceleration of recovery from influenza after challenge in mice immunized intranasally with adjuvant-combined NP, although the nonspecific mechanism of accelerated recovery remains to be solved.
Adjuvants, Immunologic↗
Comparison of [3H]YM060 binding to native and cloned rat 5-HT3 receptors.
We characterized [3H]YM060 ([methyl-3H]-(-)-(R)-5-[(methyl-1H- indol-3-yl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole monohydrochloride) binding in membrane homogenates prepared from three different rat tissues (cerebral cortex, ileum and colon), and compared the binding characteristics between the native and cloned rat 5-HT3 receptors. The dissociation constant (Kd) of [3H]YM060 was similar in all membranes. In competition studies, the affinity of 5-HT3 receptor agonists and antagonists was similar between the native and the cloned rat 5-HT3 receptors. In conclusion, intra-species difference of 5-HT3 receptor was not observed in rats and pharmacological properties of the cloned rat 5-HT3 receptor were nearly identical to that of the native rat 5-HT3 receptor.
Animals↗
Low shed L-selectin levels in Kawasaki disease with coronary artery lesions: comment on the article by Furukawa et al.
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Child, Preschool↗
Characterization of 5-hydroxytryptamine (5-HT) receptor subtypes influencing colonic motility in conscious dogs.
We examined the effects of exogenous 5-hydroxytryptamine (5-HT) and selective 5-HT receptor agonists and antagonists on proximal, middle and distal colonic motility in conscious fasted dogs with extraluminal force transducers implanted chronically. 5-HT (0.003-0.1 mg/kg i.v.) dose-dependently enhanced motility along the entire length of the colon. The 5-HT (0.03 mg/kg i.v.)-induced response was inhibited by 0.1-1.0 mg/kg i.v. methysergide, a 5-HT1/2 antagonist, at all recording sites and by 0.1-1.0 mg/kg i.v. ketanserin, a 5-HT2A antagonist, at the middle and distal sites only. At 1 mg/kg i.v., YM060, a 5-HT3 antagonist, reduced the amplitude of the initial transient high-amplitude contractions induced by 5-HT, but did not affect the tonic contraction induced by 5-HT. At doses up to 3 mg/kg i.v., 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino) ethyl ester (SDZ205-557), a 5-HT4 antagonist, and hexamethonium (up to 10 mg/kg i.v.) did not affect 5-HT-induced responses at any recording site. Renzapride, a 5-HT4 agonist, also stimulated motility along the entire length of the colon at 0.3 mg/kg i.v.. The renzapride-induced response was inhibited by 1 mg/kg i.v. SDZ205-557 or 3 mg/kg i.v. hexamethonium. m-Chlorophenylbiguanide (m-CPBG), a 5-HT3 agonist, (1 mg/kg i.v.) produced a transient high-amplitude contraction at all recording sites and this contraction was eliminated by pretreatment with 0.03 mg/kg i.v. YM060. The contraction produced by m-CPBG declined rapidly, so the increase in the motility index by m-CPBG was not significant at any recording site. Of the antagonists tested, 0.1-1 mg/kg i.v. methysergide produced a delayed and prolonged contractile response at the middle and distal sites. The onset of the response was delayed about 20 min after application and the response was maintained over the subsequent 60-min observation period. The methysergide (1 mg/kg i.v.)-induced response was inhibited by 3 mg/kg i.v. hexamethonium. The other antagonists, ketanserin, YM060 and SDZ205-557, had no contractile effect at any recording site. These results indicate that exogenous 5-HT stimulates motility along the entire length of the fasted canine colon and that 5-HT-induced responses in the proximal colon are mediated mainly by 5-HT1, whereas those in the middle and distal colon are mediated by both 5-HT1 and 5-HT2 receptors. Renzapride and methysergide also stimulate colonic motility via additional mechanisms. The activation of 5-HT4 receptors and the blockade of endogenous 5-HT inhibitory regulation via 5-HT1 receptors may be involved in the action of renzapride and methysergide respectively.
4-Aminobenzoic Acid↗
Hepatosplenic abscess caused by Curvularia boedijn in a patient with acute monocytic leukemia.
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Abscess↗
A case of Kabuki make-up syndrome with EBV+Burkitt's lymphoma.
Kabuki make-up syndrome was first reported in 1981 and is characterized by peculiar facies with post natal growth deficiency and mental retardation. Since the first report, approximately 100 cases have been reported, but there have been no reports of tumor development. A case is reported of a patient with Kabuki make-up syndrome who developed malignant lymphoma in his abdomen at the age of 3 years. The tumor was histologically diagnosed as Burkitt's lymphoma and Epstein-Barr virus was detected by in situ hybridization.
Abdominal Neoplasms↗
Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. II. Synthesis and structure-activity relationships of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.
A novel series of 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 4,5,6 and 7 was prepared and evaluated for activities as 5-hydroxytryptamine (5-HT3) receptor antagonists which may be useful for the treatment of irritable bowel syndrome (IBS) as well as nausea and vomiting associated with cancer chemotherapy. These compounds were designed by modifying the aromatic-carbonyl part of N-(2-methoxyphenyl)-4,5,6,7-tetrahydro-1H-5-benzimidazolylcarboxamide 3, leaving the imidazole moiety unchanged as the amine part. The indole derivatives 7d, g, h and indolizine derivatives 7k, l were found to be highly potent on the von Bezold-Jarisch (B.J.) reflex test with ID50 values of below 0.1 microgram/kg, and the indoline derivative 6c, indole derivatives 7a, d, g, benzofurane derivative 7j and indolizine derivative 7k were observed to be very potent on the colonic contraction with IC50 values of below 0.1 microM. In particular, 7l was the most potent on the B.J. reflex (ID50 = 0.018 microgram/kg), approximately 200 and 50 times more potent than ondansetron 1 and granisetron 2, and 7k was the most potent on the colonic contraction (IC50 = 0.011 microM), approximately 70 and 6 times more potent than 1 and 2, respectively.
Animals↗
Biological activity of analogues of YM022. Novel (3-amino substituted phenyl)urea derivatives of 1,4-benzodiazepin-2-one as gastrin/cholecystokinin-B receptor antagonists.
A series of (3-substituted phenyl)urea analogues of the potent gastrin/cholecystokinin (CCK)-B receptor antagonist YM022 has been prepared. Structure-activity relationship studies of this series suggested that a number of analogues retained good in vitro potency for gastrin/CCK-B receptor. In particular, the (3-amino substituted phenyl)urea derivatives (10-12) were more potent inhibitors of pentagastrin-induced gastric acid secretion in rats than YM022 on intraduodenal (i.d.) administration.
Animals↗
Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. III. Pharmacological evaluations and molecular modeling studies of optically active 4,5,6,7-tetrahydro-1H-benzimidazole derivatives.
The R- and S-enantiomers of the 4,5,6,7-tetrahydro-1H-benzimidazole derivatives 3-8 were prepared by optical resolution. Each R-isomer, except for 3, was almost two orders of magnitude more potent than its S-isomer as a 5-hydroxytrptamine (5-HT3) receptor antagonist, as judged from they effect on the von Bezold-Jarisch reflex (B. J. reflex) in rats, the contraction of isolated guinea-pig colon and the receptor-binding affinity. The (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] derivative 6R.HCl (ramosetron = YM060) and (--)-(R)-5-[(1-indolinyl)carbonyl] derivative 4R.HCl (YM114 = KAE-393) given p.o. were hundreds of times more potent than 1 (ondansetron) and 2 (granisetron) in their inhibitory effects on cisplatin-induced emesis in ferrets and restraint stress-induced increases in fecal pellet output in rats. Three-dimensional molecular modeling studies suggested that the 'chiral selection' of the enantiomers might be influenced by the steric repulsion between the aromatic ring part and the conformationally restricted 4,5,6,7-tetrahydro-1H-benzimidazole ring in "equatorial-twist" conformation. In our pharmacophore model for the 5-HT3 receptor antagonist, a basic center exists at the left side of the aromatic-carbonyl plane when viewing from the aromatic part with the carbonyl oxygen atom upwards, whereas the "handedness" is ambiguous in the previously proposed model.
Animals↗
Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. IV. Synthesis and pharmacological evaluation of the oxidation products of (-)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] -4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride (YM060: ramosetron).
In physicochemical and pharmacokinetic evaluations of (--)-(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl] -4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride 1 (YM060: ramosetron), which is a highly potent 5-hydroxytryptamine(-HT3) receptor antagonist, 4-hydroxy-6-[(1-methyl-1H-indol-3-yl) carbonyl]4,5,6,7-tetrahydro-1H-benzimidazole 2 was identified as a degradation product and metabolite of 1. The (--)-(4R,6S)-isomer 2 was synthesized from the diketone derivative 3, via the stereoselective reduction of 3 followed by the stereocontrolled epimerization of the (--)-(4S,6S)-isomer 10, the epimer of 2. The stereochemistry of 2 and 10 was determined by NMR and HPLC studies. Compounds 2 and 10 were found to be potent 5-HT3 receptor antagonists, like 1. Among the other oxidation products, the diketone derivatives 3 and 7 and the dihydroxylated derivative 4 retained antagonistic activity similar to that of ondansetron. This is of interest, because they do not possess the amine group which is known to be necessary for high affinity to the 5-HT3 receptor.
Animals↗