Comparison of effects of carvedilol versus metoprolol on cytokine levels in patients with idiopathic dilated cardiomyopathy.
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Adrenergic beta-Antagonists↗
Biomedical subjects
Yuji Hara
Publications and source records attributed to Yuji Hara.
Transient receptor potential 1 regulates capacitative Ca(2+) entry and Ca(2+) release from endoplasmic reticulum in B lymphocytes.
Capacitative Ca(2+) entry (CCE) activated by release/depletion of Ca(2+) from internal stores represents a major Ca(2+) influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca(2+) release-activated Ca(2+) currents and inositol 1,4,5-trisphosphate (IP(3))-mediated Ca(2+) release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor-mediated Ca(2+) oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP(3) receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca(2+) signaling in B lymphocytes.
Animals↗
Comparison of treatment effects of bevantolol and metoprolol on cardiac function and natriuretic peptides in patients with dilated cardiomyopathy.
This study was designed to compare the efficacy of bevantolol, a beta(1)-selective blocker with alpha-blockade and vasodilating activity, with that of metoprolol, a beta(1)-selective receptor blocker, for the treatment of idiopathic dilated cardiomyopathy (DCM). Forty-one patients with DCM were enrolled to receive either bevantolol or metoprolol in addition to the standard therapy for DCM. They were classified into two groups: 16 patients were treated with bevantolol and 25 were treated with metoprolol. Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured before treatment and after 6 months of treatment. Left ventricular dimension at end-diastole and end-systole was significantly lower and fractional shortening was significantly higher after treatment than before treatment in both groups. The plasma ANP and BNP levels were significantly decreased in both groups. Changes in all variables, except for systolic blood pressure, showed no significant differences between the two groups. In conclusion, bevantolol showed parallel beneficial effects to those of metoprolol on cardiac function and natriuretic peptides in patients with DCM.
Adrenergic beta-Antagonists↗
LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death.
Redox status changes exert critical impacts on necrotic/apoptotic and normal cellular processes. We report here a widely expressed Ca2+-permeable cation channel, LTRPC2, activated by micromolar levels of H2O2 and agents that produce reactive oxygen/nitrogen species. This sensitivity of LTRPC2 to redox state modifiers was attributable to an agonistic binding of nicotinamide adenine dinucleotide (beta-NAD+) to the MutT motif. Arachidonic acid and Ca2+ were important positive regulators for LTRPC2. Heterologous LTRPC2 expression conferred susceptibility to death on HEK cells. Antisense oligonucleotide experiments revealed physiological involvement of "native" LTRPC2 in H2O2- and TNFalpha-induced Ca2+ influx and cell death. Thus, LTRPC2 represents an important intrinsic mechanism that mediates Ca2+ and Na+ overload in response to disturbance of redox state in cell death.
Animals↗
Use of thallium-201 myocardial scintigraphy for the prediction of the response to beta-blocker therapy in patients with dilated cardiomyopathy.
This study was performed to evaluate whether thallium-201 myocardial scintigraphy (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predict the usefulness of beta-blocker therapy in patients with dilated cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before beta-blocker therapy. Patients were classified into group A, if their cardiac function improved, and group B, whose function remained unchanged. Two types of extent score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES-2) and mean-3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated, and according to ES and ES difference, DCM cases were classified into 3 groups: mild-defect type (mild-type), moderate-defect type (moderate-type) and severe-defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated, and the percent washout ratio of myocardial MIBG was obtained from these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type cases. A significant relation was observed between the defect type on Tl-201 and the response to beta-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and washout ratio were not significantly different in the 2 groups. Tl-201 may be useful for predicting the response to beta-blocker therapy in patients with DCM.
3-Iodobenzylguanidine↗
Attenuation of biventricular pressure gradients by cibenzo-line in an 18-year-old patient with hypertrophic obstructive cardiomyopathy.
An 18-year-old male patient with biventricular hypertrophic obstructive cardiomyopathy (HOCM) had successful reduction of the pressure gradients by cibenzoline. At 11 months after birth, he was first diagnosed with cardiac murmurs and by the age of 5 years, he was diagnosed with subpulmonic infundibular stenosis with a pressure gradient of 10 mmHg by cardiac catheterization. At the age of 14, re-catherterization revealed hypertrophic cardiomyopathy with isolated obstruction of the right ventricular outflow tract, with a pressure gradient of 70 mmHg, but no obstruction in the left ventricle. He began daily treatment with 30 mg propranolol. At the age of 18, he was admitted for cardiac evaluation. An echocardiogram revealed left mid-ventricular and subpulmonic obstructions associated with pressure gradients of 88 mmHg and 65 mmHg, respectively. A single oral dose of 200 mg of cibenzoline decreased the pressure gradients in the left and right ventricles (38 mmHg and 36 mmHg, respectively). He was then given 300 mg daily of cibenzoline, and both pressure gradients remained low without any complications 8 months later at the time of discharge.
Adolescent↗
[A case of central diabetes insipidus caused by metastatic small cell lung cancer].
A 58-year-old man was admitted to our hospital because of cough, polydipsia and polyuria. Chest CT films showed mediastinal lymphadenopathy, nodules in the lung fields, and pleural effusion. Histopathologic examination of transbronchial biopsy specimens showed oat cell carcinoma. MRI films revealed tumorous swelling of the pituitary stalk. Central diabetes insipidus caused by pituitary metastasis of small cell lung cancer was diagnosed. After treatment with whole-brain irradiation and chemotherapy, the size of the swollen pituitary stalk was reduced and his urine volume decreased. He died of respiratory insufficiency 15 months after the initial diagnosis. No recurrence of pituitary metastasis was apparent. This was a rare case of central diabetes insipidus caused by pituitary metastasis of small cell lung cancer successfully treated with radiotherapy and chemotherapy.
Carcinoma, Small Cell↗
TRP channels: molecular diversity and physiological function.
Calcium ions (Ca(2+)) are particularly important in cellular homeostasis and activity. To elicit physiologically relevant timing and spatial patterns of Ca(2+) signaling, ion channels in the surface of each cell precisely control Ca(2+) influx across the plasma membrane. A group of surface membrane ion channels called receptor-activated cation/Ca(2+) channels (RACCs) are activated by diverse cellular stimuli from the surrounding extracellular environment via receptors and other pathways such as heat, osmotic pressure, and mechanical and oxidative stress. An important clue to understanding the molecular mechanisms underlying the functional diversity of RACCs was first attained by molecular identification of the transient receptor potential (trp) protein (TRP), which mediates light-induced depolarization in Drosophila photoreceptor cells, and its homologues from various biological species. Recent studies have revealed that respective TRP channels are indeed activated by characteristic cellular stimuli. Furthermore, the involvement of TRP channels has been demonstrated in the signaling pathways essential for tissue-specific functions as well as ubiquitous biological responses, such as cell proliferation, differentiation, and death. These findings encourage the usage of TRP channels and their signalplexes as powerful tools for developing novel pharmaceutical targets.
Amino Acid Sequence↗