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K Miyata

Publications and source records attributed to K Miyata.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dynamic process of apoptosis in adult rat cardiomyocytes analyzed using 48-hour videomicroscopy and electron microscopy: beating and rate are associated with the apoptotic process.

Dynamic process of apoptosis has not been elucidated in adult rat cardiomyocytes. Soluble Fas ligand (0.1 microg/ml) in the presence of actinomycin D (0.05 microg/ml) induced apoptosis in cultured adult rat cardiomyocytes, as documented by activated caspase-3, DNA fragmentation, and apoptotic ultrastructure. In the present model, we observed 60 adult cardiomyocytes with a normal rod shape under a real-time videomicroscope continuously for 48 hours. Seventeen cells (28%) were unchanged and 7 cells (12%) showed oncosis (so-called necrosis) in which no beating was evident. In the remaining 36 cells (apoptosis, 60%), a slow beating (17 +/- 3/min) was initiated 16 +/- 1 hours later. Approximately 1 hour later, the rod cells showed long-axial shortening as bone- or club-like, or square-shaped, accompanied with faster beating rates (35 +/- 7/min). In 29 cells (type A1 and A2), marked shrinkage occurred; the cellular shape became almost completely round with a smooth surface and the beating ceased 3.0 +/- 0.4 hours later. Then, smooth budding appeared 0.6 +/- 0.2 hours later. Apoptotic bodies were found in 8 cells 10 +/- 4 hours later (type A1, 13%) but not in 21 cells (type A2, 35%). In the other 7 cells (type A3, 12%), the cell surface became rough 8 +/- 3 hours later and the beating ceased. Maximal beating rate was greatest in type A1 (72 +/- 26/min) and greater in type A2 (29 +/- 5/min) than in type A3 (10 +/- 2/min). Electron microscopy confirmed apoptotic ultrastructure even in the cardiomyocytes with bone-, club-like, or square shapes, suggesting that type A3 as well as A1 and A2 is also under apoptotic process. A caspase inhibitor, zVAD.fmk, blocked beating, apoptotic morphology, and DNA fragmentation, indicating these depended on caspase activation. In the caspase-dependent apoptotic process of cultured adult cardiomyocytes, beating and the following deformity of the cellular edges were the initial signs and the rate of beating was related with the subsequent three different processes of apoptosis.

Animals↗
PubMed2001

Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo.

OBJECTIVE: We recently demonstrated that Rho-kinase/ROK/ROCK is functionally upregulated at the arteriosclerotic coronary lesions and plays a key role for coronary vasospastic responses in our porcine model with interleukin (IL)-1beta. In the present study, we tested our hypothesis that Rho-kinase is involved in the pathogenesis of coronary arteriosclerosis per se in our porcine model. METHODS: Segments of the left porcine coronary artery were chronically treated from the adventitia with IL-1beta. Two weeks after the procedure, coronary stenotic lesions with constrictive remodeling and vasospastic response to serotonin were noted at the IL-1beta-treated site, as previously reported. Then, animals were randomly divided into two groups; one group was treated with fasudil for 8 weeks followed by 1 or 4 weeks of washout period and another group served as a control. After oral absorption, fasudil is metabolized to hydroxyfasudil that is a specific inhibitor of Rho-kinase. RESULTS: In the fasudil group, coronary stenosis and vasospastic response were progressively reduced in vivo, while the coronary hyperreactivity was abolished both in vivo and in vitro. Furthermore, Western blot analysis showed that in the fasudil group, the Rho-kinase activity (as evaluated by the extent of phosphorylation of myosin binding subunit of myosin phosphatase, one of the major substrates of Rho-kinase) was significantly reduced, while histological examination demonstrated a marked regression of the coronary constrictive remodeling. CONCLUSIONS: These results indicate that Rho-kinase is substantially involved in constrictive remodeling and vasospastic activity of the arteriosclerotic coronary artery, both of which could be reversed by long-term inhibition of the molecule in vivo. Thus, Rho-kinase may be regarded as a novel therapeutic target for arteriosclerotic vascular disease.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells.

Atorvastatin is a new HMG-CoA reductase inhibitor that strongly lowers plasma cholesterol and triglyceride (TG) levels in humans and animals. Since previous data indicated that atorvastatin has prolonged inhibition of hepatic cholesterol synthesis, we tested whether this longer duration of inhibitory effect on cholesterol synthesis decreased hepatic lipoprotein secretion in vitro. We used the HepG2 hepatoma cell line to: (1) determine the time required until levels of secreted apo B-100 and TG declined significantly, (2) examine the relation to the mass of cellular cholesteryl ester (CE) and (3) test microsomal triglyceride transfer protein (MTP) activity which leads to decreased apo B-100 production. Although atorvastatin significantly inhibited cholesterol synthesis in HepG2 cells regardless of treatment duration (1, 14 or 24 h), it did not inhibit TG synthesis. Apo B-100 and TG secretion were unchanged after 1-h atorvastatin treatment, but declined significantly after 24-h treatment. Atorvastatin treatment also reduced cellular CE mass, exhibiting both time- and dose-dependency. Mevalonolactone, a product of HMG-CoA reductase, attenuated the inhibitory effects of atorvastatin. Atorvastatin strongly reduced mRNA levels of MTP, whereas it did not inhibit MTP activity as measured by TG transfer assay between liposomes. Simvastatin also induced treatment- and time-dependent reductions in apo B-100, whereas the MTP inhibitor BMS-201038 exhibited no time dependency, instead inhibiting this variable even on 1-h treatment. These results indicate that reduced apo B-100 secretion caused by atorvastatin is a secondary result owing to decreased lipid availability, and that atorvastatin's efficacy depends on the duration of cholesterol synthesis inhibition in the liver.

Anticholesteremic Agents↗
PubMed2001

Mechanical detachment of the anterior hyaloid membrane from the posterior lens capsule.

OBJECTIVE: To investigate the incidence of spontaneous detachment of the anterior hyaloid membrane from the posterior lens capsule and to explore the possibility of surgical separation of the anterior hyaloid membrane. DESIGN: Prospective nonrandomized interventional comparative trial and comparative human tissue study. PARTICIPANTS: Thirty-eight eyes of 32 patients undergoing primary pars plana vitrectomy combined with cataract extraction and intraocular lens implantation and 3 eye bank eyes for histopathologic examination. METHODS: The anterior hyaloid membrane and posterior lens capsule were observed with a fiberoptic endoscope. Surgical separation of the anterior hyaloid membrane was attempted by either the hydrodissection method before cataract extraction (18 eyes) or the direct suction method after cataract extraction (20 eyes). In eye bank eyes, histopathologic examination was performed with (one eye) and without (two eyes) surgical separation of the anterior hyaloid membrane. MAIN OUTCOME MEASURES: Incidence of spontaneous detachment and success rate of surgical detachment of the anterior hyaloid membrane. RESULTS: No eye displayed spontaneous detachment of the anterior hyaloid membrane. Using the hydrodissection method, complete detachment of the anterior hyaloid membrane was achieved in 10 eyes (55.6%), partial detachment was attained in 2 eyes (11.1%), and detachment was not induced at all in 6 eyes (33.3%). With the direct suction method, the anterior hyaloid membrane was completely separated from the posterior lens capsule in 10 eyes (50%), partially detached in 10 eyes (50%), and not detached at all in any eye. The direct suction method had a significantly higher success rate than the hydrodissection method (P < 0.001, chi-square test). In eye bank eyes, the surgical manipulation induced complete separation of the anterior hyaloid membrane from the lens capsule. CONCLUSIONS: Spontaneous detachment of the anterior hyaloid membrane from the posterior lens capsule is very rare. Under endoscopic observation, surgical detachment of the anterior hyaloid membrane was possible in half of the patients.

Adult↗
PubMed2001

Corneal irregular astigmatism and contrast sensitivity after photorefractive keratectomy.

OBJECTIVE: To investigate the relation between contrast sensitivity and corneal irregular astigmatism in eyes after photorefractive keratectomy (PRK). DESIGN: Prospective observational case series. PARTICIPANTS AND CONTROLS: Seventy-nine eyes without corneal haze 6 months or more after PRK and 30 normal control eyes. METHODS: Videokeratography was taken with TMS-1 (Computed Anatomy Inc. New York, NY), and contrast sensitivity for day and night vision was measured using a Multivision Contrast Tester 8000 (Vistech Consultants, Inc., Dayton, OH). MAIN OUTCOME MEASURES: Regular and irregular astigmatism (asymmetry and higher order irregularity components) were computed using Fourier series harmonic analysis of the videokeratography data. Area under the log contrast sensitivity function (AULCSF) was calculated from the contrast sensitivity data taken at five spatial frequencies. RESULTS: After PRK, AULCSFs were significantly smaller for day vision (P = 0.007, unpaired t test) and night vision (P = 0.020) compared with normal controls. AULCSFs for day vision were significantly negatively correlated with asymmetry (Pearson's correlation coefficient, R = -0.23, P = 0.049) and higher order irregularity (R = -0.33, P = 0.004) components but not with the regular astigmatism component (P > 0.3). AULCSF for night vision correlated significantly with asymmetry (R = -0.31, P = 0.013) and higher order irregularity (R = -0.30, P = 0.016) components but not with the regular astigmatism component (P > 0.3). CONCLUSIONS: Corneal irregular astigmatism after PRK significantly influences contrast sensitivity.

Adult↗
PubMed2001

beta-amyloid deposits in transgenic mice expressing human beta-amyloid precursor protein have the same characteristics as those in Alzheimer's disease.

A transgenic mouse expressing the human beta-amyloid precursor protein with the "Swedish" mutation, Tg2576, was used to investigate the mechanism of amyloid-beta peptide (Abeta) deposition. We characterized Abeta deposits in the cerebral cortex biochemically and pathologically. A surface-enhanced laser desorption/ionization affinity mass spectrometric study using the 6E10 monoclonal antibody demonstrated that the major species of Abeta in a formic acid-extracted fraction of the cortex were Abeta(1-38), Abeta(1-40) and Abeta(1-42). Immunohistochemistry using antibodies to the carboxy-terminal epitopes of Abeta(1-40) and Abeta(1-42), as well as 6E10, showed that plaques containing Abeta(1-42) were more numerous than those containing Abeta(1-40) throughout the cortex. Laser confocal analysis of the immunoreactivities in the plaques demonstrated that Abeta(1-40) was preferentially located in the central part of the Abeta(1-42) positive plaques. Enzyme-linked immunosorbent assay measurements of Abeta(1-40) and Abeta(1-42) showed that Abeta(1-40) was several-fold more abundant than Abeta(1-42). From these data we suggest that Abeta(1-42) deposition may precede Abeta(1-40) deposition, while Abeta(1-40) begins to deposit in the central part of the plaques and accumulates there. Furthermore, localization of Abeta(1-40) corresponded almost exactly to congophilic structures, which were associated with aberrant swollen synapses detected with antibodies to synaptophysin and alpha-synuclein. Thus, Abeta deposits in Tg2576 mice have similar characteristics to those in Alzheimer's disease.

Alzheimer Disease↗
PubMed2001

Involvement of the brain-derived neurotrophic factor/TrkB pathway in neuroprotecive effect of cyclosporin A in forebrain ischemia.

Recent studies have shown that cyclosporin A, a specific antagonist of calcineurin, a phosphatase, ameliorates neuronal cell death in the CA1 sector of the hippocampus after forebrain ischemia in animal models. The mechanism of this neuroprotective effect, however, has not yet been established. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophins, is one of the potent survival and developmental factors whose expression is regulated by cyclic AMP-response element-binding protein (CREB). Activation of CREB is dependent on its phosphorylation at Ser(133), and calcineurin has been reported to dephosphorylate CREB via protein phosphatase 1. Based on these observations, we attempted to investigate how cyclosporin A treatment would affect the changes of phosphorylated CREB (pCREB), BDNF and its receptor tyrosine kinase B (TrkB) after forebrain ischemia in rats. Phosphorylation of CREB was kept augmented throughout the time course examined in cyclosporin A-treated animals, while it ceased without cyclosporin A. Reverse transcription-polymerase chain reaction revealed prolonged maintenance of BDNF mRNA expression in the CA1 sector of cyclosporin A-treated animals. The protein expression of BDNF and TrkB appeared to be up-regulated in cyclosporin A-treated animals, whereas it was transiently up-regulated but decreased to the marginal level of expression without cyclosporin A.From these results we suggest that cyclosporin A induces pCREB by an inhibition of calcineurin, resulting in the induction of BDNF. The mechanisms by which cyclosporin A protects the CA1 region from neuronal cell death in forebrain ischemia may involve the interaction of pCREB, BDNF and TrkB.

Animals↗
PubMed2001

Risk factors for persistence of pulmonary arterial branch stenosis in neonates and young infants.

BACKGROUND: Pulmonary arterial branch stenosis (PBS) in neonates is considered to be transient. However, PBS has been found not only in neonates, but also in young infants. Among these patients, we encountered several patients whose PBS was still present after the age of 1 year. METHODS: To clarify the natural history of PBS in neonates and young infants, we retrospectively reviewed the records of 103 patients diagnosed with PBS in the neonatal period and early infancy. RESULTS: The PBS findings were improved in all patients. Pulmonary arterial branch stenosis disappeared in 94 patients by the age of 1 year (group A), but persisted after I year of age in nine patients (group B). Group B patients had a significantly lower mean birth weight and greater deltavelocity (the difference in the peak flow velocity between the main pulmonary artery and stenotic branch) at diagnosis than group A patients. Incidences of low birth weight (< 2,500 g) and deltavelocity above 1.2 m/s were significantly higher in group B than group A patients. There was no significant difference in the frequency of premature infants (gestational age < 36 weeks) between the groups, suggesting that intrauterine growth retardation may be related to developmental abnormalities of the pulmonary arterial branch. CONCLUSIONS: All cases of PBS in neonates and young infants were improved. However, PBS persisted in some patients after the age of 1 year. Low birth weight and deltavelocity above 1.2 m/s are risk factors for persistent PBS. Pulmonary arterial branch stenosis was not present after the age of 1 year in 62 of 63 patients without either of these risk factors.

Age Factors↗
PubMed2001

Effect of YM-40461, a novel surfactant secretagogue, on chronic obstructive pulmonary diseases and similar symptoms in guinea pigs.

YM-40461 (1-(2-dimethylaminoethyl)-1-(3,4,5-trimethoxyphenyl)urea, CAS 142912-85-4), is a novel surfactant secretagogue. The effect of YM-40461 on symptoms, e.g. change of airway functions and hypoxemia, were examined using guinea pigs with induced subacute bronchitis. Bronchitic guinea pigs exhibited basal lung resistance (RL) was 0.152 +/- 0.005 cm H2O/ml/s (normal: 0.130 +/- 0.002 cm H2O/ml/s) and basal lung compliance (CL) of 0.455 +/- 0.011 ml/cm H2O (normal: 0.509 +/- 0.009 ml/cm H2O). Although YM-40461 slightly improved the lung resistance in these animals, it improved significantly and dose-dependently the lung compliance (0.468 +/- 0.008 ml/cm H2O for 1 mg/kg, 0.477 +/- 0.008 for 3 mg/kg, 0.490 +/- 0.011 for 10 mg/kg, p < 0.05 at 10 mg/kg) compared to nontreated bronchitic guinea pigs. YM-40461 improved airway functions in bronchitic guinea pigs just as wall as the beta 2-adrenoceptor agonist salbutamol. Additionally, YM-40461 significantly reduced airway hyperreactivity in response to intravenously infused acetylcholine (ACh). Basal PaO2 was 83.1 +/- 0.7 cm H2O in healthy guinea pigs and 71.2 +/- 1.7 cm H2O in bronchitic guinea pigs, indicating hypoxemia. A dose of 10 mg/kg of YM-40461 relieved hypoxemia in these animals with the values returning to 81.8 +/- 1.9 cm H2O (p < 0.05). These results suggest that YM-40461 ameliorates chronic obstructive pulmonary disease (COPD)-like symptoms in bronchitis models due to increased surfactant in the airway.

Acetylcholine↗
PubMed2001

Interleukin-11 induces osteoblast differentiation and acts synergistically with bone morphogenetic protein-2 in C3H10T1/2 cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of hematopoietic cell growth and is involved in bone resorption. We report here the involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased alkaline phosphatase (ALP) activity and upregulated expression levels of osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid-binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression of these genes except for MyoD. The expression patterns of ALP activity and osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be involved in early differentiation of osteoblasts at a step earlier than that which is affected by rHuBMP-2. In support of this hypothesis, combined treatment with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA expression of OC and type II collagen, rHuIL-11 also abrogated the increased levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic differentiation of progenitor cells and plays an important role in osteogenesis.

Alkaline Phosphatase↗
PubMed2001

Effect of donor age on morphologic variation of cultured human corneal endothelial cells.

PURPOSE: To examine the effect of donor age on the morphologic variation of cultured human corneal endothelial cells (HCEC). METHODS: HCEC were obtained from the remaining corneoscleral rims of seven human corneas used for penetrating keratoplasty. The donor age ranged from 2 to 75 years. Primary cultures were established from explants of the endothelial cell layer, including the Descemet's membrane, and were propagated on culture dishes coated with bovine corneal endothelial extracellular matrix. At the fourth passage, frequency distribution of cell area in the confluent monolayer was calculated and the effect of donor age on cell area was analyzed. RESULTS: The percentage of HCEC with cell area over 2000 microm2 significantly increased with donor age (r = 0.935, p = 0.0007). CONCLUSION: Cultured HCEC established from older donor tissue display greater heterogeneity. The use of HCEC from younger donors may be preferable to maximize the benefits of HCEC transplantation.

Adolescent↗
PubMed2001

Adenovirus-mediated transfer of dominant-negative rho-kinase induces a regression of coronary arteriosclerosis in pigs in vivo.

Small GTPase Rho and its target Rho-kinase/ROK/ROCK play an important role in various cellular functions, including smooth muscle contraction, actin cytoskeleton organization, and cell adhesion and migration, all of which may be involved in the pathogenesis of arteriosclerosis. Here, we show that adenovirus-mediated transfer of dominant-negative Rho-kinase (DNRhoK) induces a marked regression of coronary constrictive remodeling and abolishes coronary vasospastic activity in vivo. Porcine coronary segments were chronically treated with interleukin-1beta, which resulted in the development of constrictive remodeling and vasospastic responses to serotonin, as previously reported. Adenovirus-mediated transfer of DNRhoK, but not that of beta-galactosidase, into the interleukin-1beta-treated coronary segment caused a marked regression of the constrictive remodeling and abolished the vasospastic activity in 3 weeks. Western blot analysis showed that the phosphorylation of adducin and the ezrin/radixin/moesin family, the target proteins of Rho-kinase, were upregulated at the coronary lesions and were significantly suppressed by the transfer of DNRHOK: These results indicate that Rho-kinase is substantially involved in coronary constrictive remodeling and vasospastic responses, both of which can be reversed by the selective inhibition of the molecule in our porcine model in vivo.

Adenoviridae↗
PubMed2001

[Atorvastatin (Lipitor): a review of its pharmacological and clinical profile].

Hypercholesterolemia is a major risk factor for the development of coronary heart disease. HMG-CoA reductase inhibitors have been used as first-line drugs because of both their superior cholesterol lowering effect and reliable safety profile. Since there are many patients whose plasma cholesterol level does not reach the therapeutic target even if reductase inhibitors are available, more effective drugs have been strongly required for a long time. Atorvastatin, one of the most recently introduced statins, produces greater plasma LDL-cholesterol reductions than other statins. This pronounced effect of atorvastatin seems to be due to its long-lasting action, presumably a reflection of longer residence time of atorvastatin and its active metabolites in the liver. Clinical trials of atorvastatin have also demonstrated marked plasma triglyceride reductions. The triglyceride reduction with atorvastatin seems to stem from the following two indirect mechanisms, limiting VLDL secretion from the liver and increase in clearance of triglyceride-rich lipoprotein via induced LDL receptors from plasma. Eleven clinical trials of atorvastatin, which have been developed in Japan, clearly demonstrated its ability to reduce LDL-C levels more strongly and in significantly more patients to LDL-C treatment goals than other reductase inhibitors with similar safety profiles. Therefore, atorvastatin adds a new dimension to the effective management of hypercholesterolemia and combined hyperlipidemia.

Animals↗
PubMed2001

Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo.

We investigated the effects of YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate], a new orally active muscarinic M3-receptor antagonist, on bowel dysfunction in vivo using experimental models that reproduce the symptoms present in irritable bowel syndrome (IBS). YM905 potently inhibited restraint stress-induced fecal pellet output in fed rats (ED50: 4.0 mg/kg) and diarrhea in fasted rats (ED50: 1.7 mg/kg), with similar potencies to the inhibition of bethanechol-, neostigmine- and nicotine-induced fecal pellet output in rats (ED50: 3.3, 7.9 and 4.5 mg/kg, respectively). YM905 also inhibited 5-hydroxytryptamine (5-HT)-, prostaglandin E2- and castor oil-induced secretory diarrhea in mice (ED50: 5.5, 14 and 6.3 mg/kg, respectively), but showed no significant effect on cholera toxin-induced intestinal secretion in mice. In addition, YM905 (3, 10 mg/kg) reversed morphine-decreased postprandial defecation in ferrets, a model of spastic constipation, whereas remosetron, a 5-HT3-receptor antagonist, was not effective. The mode of YM905 action was similar to that of darifenacin, a selective M3-receptor antagonist, with equivalent potencies. By contrast, propantheline, an antimuscarinic drug that has been used for IBS, was much less potent. These results show that YM905 ameliorates a wide spectrum of bowel dysfunctions through the blockade of M3 receptors, suggesting its therapeutic potential for treating IBS.

Animals↗
PubMed2001

Pharmacological effect of tamsulosin in relation to dog plasma and tissue concentrations: prostatic and urethral retention possibly contributes to uroselectivity of tamsulosin.

In the present study the pharmacokinetics and pharmacodynamics of tamsulosin were investigated in anesthetized male dogs. Hypogastric nerve stimulation elevated the intraurethral pressure (IUP), which was inhibited dose dependently by intraduodenal administration of tamsulosin (3-30 microg/kg). The inhibition peaked about 90 min after dosing and lasted up to 240 min. The basal mean blood pressure did not change significantly during the observation period. The plasma, prostatic, and urethral concentrations of tamsulosin were determined by the liquid chromatography-mass spectrometry/mass spectrometry method. The plasma concentration reached the maximal level within 30 min after dosing and gradually declined thereafter. The maximal total plasma concentration of tamsulosin (C(max, t)) and its unbound concentration (C(max, u)) correlated with the maximal effect on IUP response [r(2) = 0.81 (p<0.01, n = 15) and r(2) = 0.84 (p<0.01, n = 15), respectively]. Each individual unbound plasma concentration did not correlate, however, with its associated inhibition of IUP response (r(2) = 0.04, n = 126). Although the plasma concentration of tamsulosin decreased nearly to the lower limit of quantitation 240 min after dosing, the prostatic and urethral concentrations remained high, i.e., 13 to 44 times greater than the plasma concentration. Our data demonstrate that the maximal inhibition by tamsulosin of IUP response is well correlated with the maximal plasma concentration in the early phase. The sustained effect of tamsulosin on IUP response that follows may be related to prostatic and urethral retention of tamsulosin.

Adrenergic alpha-Antagonists↗
PubMed2001

Antiasthmatic effect of YM976, a novel PDE4 inhibitor, in guinea pigs.

YM976 is a novel and specific phosphodiesterase 4 inhibitor. In our previous report, we indicated that YM976 has less emetogenicity, a major adverse effect of PDE4 inhibitors, than rolipram. In the present study, we examined the antiasthmatic effects of YM976 in guinea pigs. YM976 orally administered exhibited inhibition of antigen-induced bronchoconstriction, airway plasma leakage, airway eosinophil infiltration, and airway hyperreactivity (AHR), with ED(50) values of 7.3, 5.7, 1.0, and 0.52 mg/kg, respectively. Rolipram also dose dependently suppressed these responses. Prednisolone suppressed eosinophil infiltration and AHR, whereas it failed to inhibit bronchoconstriction and plasma leakage. Theophylline moderately suppressed bronchoconstriction and edema, but neither eosinophil infiltration nor AHR. YM976 suppressed the peroxidase activity in the bronchoalveolar lavage fluid, and elevated the intracellular peroxidase activity and cAMP contents of infiltrated cells, suggesting that YM976 inhibited not only the infiltration but also the activation of leukocytes. In vitro studies revealed that YM976 potently suppressed eosinophil activation (EC(30) = 83 nM), and exerted a little relaxation on LTD(4)-precontracted tracheal smooth muscle (EC(50) = 370 nM). Rolipram exhibited a potent tracheal relaxation activity (EC(50) = 50 nM). In vivo studies indicated that the inhibitory effect of YM976 on LTD(4)-induced bronchospasm was marginal even at 30 mg/kg p.o., although rolipram significantly inhibited the bronchospasm at the same dose. These results suggested that YM976, unlike rolipram, showed the inhibition of antigen-induced airway responses due to anti-inflammatory effects, but not to direct tracheal relaxation. In conclusion, YM976 may have potential therapeutic value in the treatment of asthma through its anti-inflammatory activities.

Animals↗
PubMed2001

Anti-alpha-fodrin antibodies in Sjögren's syndrome in children.

OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjögren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.

Adolescent↗