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T Yamagata

Publications and source records attributed to T Yamagata.

At least 127 records · Page 7Linked to original sources
PubMed1997

Existence of a muscle spindle on the posterior cricoarytenoid muscle of the guinea pig.

We examined a muscle spindle in the posterior cricoarytenoid muscle of the adult guinea pig. The spindle capsule contained three intrafusal muscle fibres. At the equatorial region, three intrafusal fibres did not form a typical aggregation of nuclei such as bags and chains observed in common mammalian muscle spindles. Two intrafusal fibres of the three were innervated by sensory endings which branched and arranged irregularly. These sensory endings lay on the surface of intrafusal fibres in shallow grooves or deeply penetrated into the fibre. The third intrafusal fibre, lacking sensory innervation, showed a similar fine structure to extrafusal fibres. These findings suggest that the muscle spindle in the posterior cricoarytenoid muscle of the guinea pig is strikingly different in the structure of intrafusal fibres and in the arrangement of sensory endings from that in common mammalian skeletal muscles. The occurrence and role of these different structures were discussed.

Animals↗
PubMed1997

Occurrence of capillaries with fenestrae in the intrinsic laryngeal muscles of the guinea pig after unilateral denervation.

Capillaries in the posterior cricoarytenoid and the arytenoid muscles of the guinea pig were examined by electron microscopy 3 days after transection of unilateral recurrent laryngeal nerve. The denervated posterior cricoarytenoid muscle had neuromuscular junctions (NMJs) lacking terminal axons, while in the unpaired arytenoid muscle, normal and denervated NMJs coexisted among muscle fibres being seemingly normal. Capillaries in both muscles were almost of the continuous type. However, approximately 10% of capillaries around the denervated NMJs and among some muscle fibres in both muscles, often had a small number (< 10) of fenestrae bridged by a single-layered diaphragm. The untreated normal muscles contained only continuous capillaries. These findings suggest that denervation may induce the fenestrated changes of intramuscular capillaries.

Animals↗
PubMed1997

Precise switching of DNA replication timing in the GC content transition area in the human major histocompatibility complex.

The human genome is composed of long-range G+C% (GC%) mosaic structures thought to be related to chromosome bands. We previously reported a boundary of megabase-sized GC% mosaic domains at the junction area between major histocompatibility complex (MHC) classes II and III, proposing it as a possible chromosome band boundary. DNA replication timing during the S phase is known to be correlated cytogenetically with chromosome band zones, and thus the band boundaries have been predicted to contain a switch point for DNA replication timing. In this study, to identify to the nucleotide sequence level the replication switch point during the S phase, we determined the precise DNA replication timing for MHC classes II and III, focusing on the junction area. To do this, we used PCR-based quantitation of nascent DNA obtained from synchronized human myeloid leukemia HL60 cells. The replication timing changed precisely in the boundary region with a 2-h difference between the two sides, supporting the prediction that this region may be a chromosome band boundary. We supposed that replication fork movement terminates (pauses) or significantly slows in the switch region, which contains dense Alu clusters; polypurine/polypyrimidine tracts; di-, tri-, or tetranucleotide repeats; and medium-reiteration-frequency sequences. Because the nascent DNA in the switch region was recovered at low efficiency, we investigated whether this region is associated with the nuclear scaffold and found three scaffold-associated regions in and around the switch region.

Base Sequence↗
PubMed1997

Triple synergism of human T-lymphotropic virus type 1-encoded tax, GATA-binding protein, and AP-1 is required for constitutive expression of the interleukin-5 gene in adult T-cell leukemia cells.

Accumulated evidence demonstrates that adult T-cell leukemia (ATL) is frequently associated with eosinophilia, and human T-lymphotropic virus type 1 (HTLV-1)-infected cells frequently express interleukin-5 (IL-5). However, the molecular mechanism of constitutive IL-5 expression in HTLV-1-infected cells remains unclear. To clarify the mechanism of aberrant IL-5 expression in HTLV-1-infected cells, we investigated the response of the human IL-5 promoter to the HTLV-1-encoded protein Tax. Cotransfection experiments using Jurkat cells revealed that Tax is incapable of activating the IL-5 promoter by itself but that it synergistically transactivates the promoter with GATA-binding protein (GATA-4) and 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation. By introducing a series of mutations within the IL-5 promoter, we found that conserved lymphokine element 0 (CLE0) is responsible for mediating the signal induced by Tax-TPA. A deletion construct of the promoter indicated that the -75 GATA element and CLE0 are sufficient to mediate synergistic activation of the IL-5 promoter. Electrophoretic mobility shift assays using Jurkat cell nuclear extracts demonstrated that TPA induces a transcription factor to bind CLE0, and an experiment using JPX-9 cell nuclear extracts showed that Tax enhances this binding activity. An antibody supershift experiment revealed that this band consists of c-Jun and JunD. However, among the Jun family members, only c-Jun is able to cooperate with Tax and GATA-4 to activate the IL-5 promoter. We have determined the minimum factors required for IL-5 gene activation by reconstituting the IL-5 promoter activity in F9 cells. This is the first report to demonstrate the functional involvement of Tax protein in IL-5 gene regulation and to suggest the functional triple synergism among Tax, GATA-4, and AP-1, which disrupts regulated control of the gene and leads to constitutive expression of the IL-5 gene.

Calcimycin↗
PubMed1997

Bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo: effect of inhibition of nitric oxide synthesis.

OBJECTIVE: To clarify whether endothelium derived nitric oxide contributes to exogenous bradykinin induced dilatation of human epicardial and resistance coronary arteries in vivo. DESIGN: Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), on bradykinin induced dilatation of the epicardial and resistance coronary arteries. SETTING: Hiroshima University Hospital. PATIENTS: 20 patients (16 men and four women, mean (SD) age 56 (9) years) with angiographically normal smooth epicardial coronary arteries. INTERVENTIONS: Serial infusions of bradykinin (0.5, 1.5, and 2.5 micrograms/min) were given into the left coronary ostium before and after L-NMMA infusion (60 mumol/min). MAIN OUTCOME MEASURES: Epicardial coronary diameter, coronary blood flow, and coronary vascular resistance. RESULTS: Bradykinin-induced epicardial coronary vasodilatation after L-NMMA (dilatation by 2.5 micrograms/min, 3.8(1.4)% in the proximal and 5.9(1.8)% in the distal segments, mean (SEM)) was less (p < 0.001, respectively) than before L-NMMA (11.7(2.5)% and 15.1(2.0)%, respectively). In contrast, L-NMMA did not affect the bradykinin induced increase in coronary blood flow and decrease in coronary vascular resistance. CONCLUSIONS: Endothelium derived nitric oxide contributes to bradykinin induced dilatation of epicardial coronary arteries, but may be less important in coronary resistance vasodilatation.

Adult↗
PubMed1997

Blink induced centrotemporal spikes in benign childhood epilepsy with centrotemporal spikes.

A 10 year old girl with benign childhood epilepsy with centrotemporal spikes showed centrotemporal spikes induced by blinking even in a dark room. Spikes could not be induced by photic stimulation, eye closure, eye movement, eye deviation, or passive blinks. There have been no previous reports of spikes induced by blinks in benign childhood epilepsy with centrotemporal spikes.

Blinking↗
PubMed1997

Effects of volume loading on pulmonary venous flow and its relation to left atrial functions.

Although pulmonary venous (PV) flow is closely related to left atrial (LA) pressure dynamics, few investigators have discussed it in relation to LA functions, i.e., reservoir, conduit, and booster pump functions. We examined changes in PV flow rate, LA dimension, and left ventricular filling volume in 11 dogs, and assessed the effects of multistaged volume loading on PV flow and LA functions. Systolic PV flow rate (S) increased significantly and reached a plateau, reflecting a limited LA reservoir function. Diastolic PV flow rate (D) increased significantly with an increase in LA pressure. S/D ratio increased non-significantly from 0.87 +/- 0.07 before volume loading to 0.96 +/- 0.08 until S reached a plateau and then decreased to 0.76 +/- 0.08 (p < 0.05) because of a significant increase in D without an increase in S at the higher stages of volume loading. During atrial contraction, increases in LA active shortening and left ventricular filling volume were limited, indicating a limited LA forward ejection. The difference between PV flow rate just before and at the end of atrial contraction increased and correlated positively with left ventricular end-diastolic pressure (r = 0.57, p < 0.01). PV flow varies according to the degree of volume loading and reflects LA functions, which exhibit limited increases in response to volume loading.

Animals↗
PubMed1997

[Morphological development of the intrinsic laryngeal muscles in rat--a scanning electron microscopic and histochemical study].

The postnatal development of the subneural apparatus (SNA) and differentiation of muscle fibers of the intrinsic laryngeal muscles (ILMs) in the rat were investigated on the 1st, 5th, 15th, 30th and 90th days after birth. The cricothyroid (CT), thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles in the ILMs were examined. Furthermore, we compared the development of these muscles with that of the skeletal muscles of the hindlimb, the extensor digitorum longus (EDL) and soleus (SOL) muscles. The SNA was observed with a scanning electron microscope. The SNA was quantitatively analyzed by use of two parameters: the ratio of the length of the secondary synaptic cleft to its maximal width (L/W ratio) and the ratio of the area of the secondary synaptic clefts to that of the primary synaptic cleft(s) (ASC/APC ratio). The muscle fiber types were classified according to the density of each muscle fiber by the ATPase stain. On the 15th postnatal day, the SNAs of the CT and TA muscles had a tendency to show more advanced development than those of the PCA muscle. The SNAs of the ILMs appeared to develop earlier than those of the EDL and SOL muscles. The L/W and ASC/APC ratios of the ILMs inclined to be higher than those of the hindlimb muscles. On the 30th day, the SNAs of the PCA muscle were still immature, while those of the CT and TA muscles had become nearly mature. The EDL muscle showed completely mature development and outstripped the ILMs. In contrast, the SNA of the SOL muscle was the least mature of all muscles. The L/W ratios of the ILMs were not significantly different from each other, while the ASC/APC ratio of the PCA muscle was significantly lower than those of both the CT and TA muscles. The L/W and ASC/APC ratios of the EDL muscle were the highest of all muscles examined and those of the SOL muscle were the lowest. The muscle fiber types were not significantly different in the ILMs throughout the course. On the 30th day, the EDL muscle had reached the mature adult proportion of the muscle fiber types, while the ILMs and SOL muscle needed further development. Phylogenetically, the TA muscle appeared as a sphincter of the lower airway and then the PCA muscle, as a dilator, appeared. The CT muscle arose after separation of the thyroid and cricoid cartilages. These findings infer that the lag in development of the PCA to the TA muscle in early postnatal life was due to the importance of the protective function of the lower airway and the phylogenetical difference. Moreover, these results suggest that the ILMs, which are indispensable for sucking, develop early in life, followed by rapid development of the EDL muscle to start quadruped walking after the 15th day. Thus, different muscles need to develop as an animal grows because distinct functions of muscles are necessary for normal living. In conclusion, the ILMs may have a specific mode of postnatal development in contrast with those of the hindlimb muscles.

Animals↗
PubMed1997

[CT-guided localization for thoracoscopic pulmonary wedge resection].

Recently the identification of small-sized peripheral lung lesions has rapidly increased due to advancements in roentgenology. But for smaller lesions, definitive diagnoses by means of transbronchial or percutaneous biopsy have become more difficult. So we must resort to thoractomic or thoracoscopic biopsy. However, for thoracoscopic surgery palpation is inadequate, so the identification of deep or small lesions is difficult. Thoracotomy seems to be too invasive when used only for examination and not for therapy. Therefore, we tried CT-guided localization for thoracoscopic pulmonary wedge resection. Thus far we have performed CT-guided localization in 24 cases. Immediately prior to thoracoscopic surgery we placed marking devices in or beside the lesions after percutaneous puncture. As marking devices we used Kopans spring hook wire or a Naruke point marker. Pathological diagnoses of these lesions indicated 13 primary lung cancers (11 adenocarcinomas, 1 carcinoid, 1 squamous cell carcinoma), 4 focal fibroses, 2 metastases of renal cell carcinoma, 1 hamartoma, 1 tuberculoma, 1 cryptococcosis, 1 interstitial pneumonia, and 1 subpleural lymph node. The tumor diameters at their greatest dimension ranged from 3 to 33 mm (9.0 +/- 6.6 mm). The distance from the viceral pleura to the tumor surface ranged from 0 to 24 mm (10.9 +/- 6.7 mm). In one case pneumothorax occurred due to the shallow position of the tumor and the loss of the marking device. If these problems (pneumothorax, bleeding, loss of marking devices and others) are prevented, CT-guided localization should be performed as soon as possible before surgery. The identification of small peripheral lesions can almost be determined by CT now, so such identification may be the most reliable technique to employ during surgery.

Endoscopy↗
PubMed1997

Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins.

Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.

Base Sequence↗
PubMed1996

Elastic fiber degeneration in Costello syndrome.

Clinical and pathological observations of a 6-month-old-boy with Costello syndrome are reported. The main clinical findings were loose skin of the neck, hands, and feet, deep palmar and plantar creases, typical "coarse" face with thick lips and macroglossia, relative macrocephaly, mental retardation, short stature, arrhythmia, large size for gestational age, and poor feeding. At age 6 months he died of rhabdomyolysis. The major pathological findings were fine, disrupted, and loosely-constructed elastic fibers in the skin, tongue, pharynx, larynx, and upper esophagus, but not in the bronchi, alveoli, aorta, or coronary arteries. Hyperplasia of collagen fibers in the skin, hyperplasia of the mucous glands in the bronchus, narrowing of the pulmonary artery, degeneration of the atrial conduction system, calcification and ballooning of skeletal muscle fibers with infiltration of macrophages, and myoglobin depositions in the collecting ducts in the kidney were also observed. The degeneration of elastic fibers was confirmed in the skin of a second Costello syndrome patient. Expression of elastin mRNA in the patient's fibroblasts was normal in size and amount. Given that elastic fiber degeneration was observed in the tissues with clinical symptoms, we speculate that a defect of elastic fibers, possibly relating to alternative splicing in the elastin gene or to defects in elastin microfibrils, might be involved in the pathogenesis of Costello syndrome.

Abnormalities, Multiple↗
PubMed1996

The Epstein-Barr virus (EBV) alters the B cell glycolipid which is recognized by the human monoclonal antibody to i-blood group antigen.

To analyze the differentiation-related glycolipids, we have recently developed human monoclonal anti-i antibodies (mAbs) using a combination of EBV-transformation and bovine i-active glycolipid (NeuAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer)-containing liposome immune lysis assay (LILA). Using complement cytolysis with these mAbs, we found the occurrence of a surface antigen (Ag) in the EBV-negative but not in the EBV-positive cell lines. The fresh EBV infection reveals that the suppressed expression of the antigen was a result of the EBV infection. The Ag recognized with these mAbs appeared to have a very low density on the B cell lines. Unexpectedly, thin layer chromatogram (TLC)-immunostaining using the mAbs revealed that the major immunoreactive substance in the EBV-negative B cell lines was an extremely minor glycolipid that was distinct from the i-active glycolipid however, this was not the case in the EBV-positive B cell lines.

Antibodies, Monoclonal↗
PubMed1996

Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis.

OBJECTIVES: This study sought to investigate the role of nitric oxide, an endothelium-derived relaxing factor, in flow-mediated vasodilation in human epicardial coronary arteries. BACKGROUND: Endothelium-derived relaxing factors may be released from the coronary artery endothelium in response to increases in blood flow. METHODS: We studied the effect of the nitric oxide synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler flow velocity measurements. Adenosine at 100 micrograms/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood flow. Acetylcholine at 3 and 30 micrograms/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetylcholine were infused before and after the intracoronary infusion of L-NMMA (25 mumol/min for 5 min). RESULTS: Infusion of L-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 +/- 0.14 to 2.74 +/- 0.13 mm [mean +/- SEM], p < 0.01). Adenosine increased coronary blood flow before and after L-NMMA (+399.5 +/- 27.5% and +511.9 +/- 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and after L-NMMA (+9.2 +/- 1.5%, p < 0.01 and +8.6 +/- 2.1%, p < 0.01, respectively). A dose of 3 micrograms/min of acetylcholine significantly dilated the proximal left anterior descending artery before L-NMMA (+7.6 +/- 1.0%, p < 0.01), but acetylcholine-induced vasodilation was attenuated after L-NMMA (-1.8 +/- 1.0%). CONCLUSIONS: Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries.

Acetylcholine↗
PubMed1996

Nitric oxide production by coronary conductance and resistance vessels in hypercholesterolemia patients.

NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide (NO) synthesis, was used to investigate the effects of inhibition of NO synthesis on the coronary conductance and resistance vessels in hypercholesterolemic patients. Acetylcholine (3 and 30 micrograms/min) was administered to 10 hypercholesterolemic and 10 control patients before and after L-NMMA (25 micromol/min) infusion. Epicardial coronary diameter was measured by quantitative angiography, and coronary blood flow (CBF) was derived from Doppler flow-velocity and coronary diameter measurements. In hypercholesterolemic patients, acetylcholine-induced dilation of epicardial arteries was attenuated, and the percentage increase in CBF caused by acetylcholine was smaller than that in control patients. L-NMMA attenuated acetylcholine-induced dilation of epicardial arteries in control patients. L-NMMA had no effect on CBF responses to acetylcholine in both patient groups. L-NMMA significantly decreased the baseline coronary diameter and CBF in both groups. These results indicated that hypercholesterolemia impaired the acetylcholine-induced dilation of the conductance and resistance coronary vessels. This impairment in the conductance vessels was dependent on NO production; that of resistance vessels was not. The basal release of NO in conductance and resistance vessels was preserved in hypercholesterolemic patients.

Acetylcholine↗
PubMed1996

Elevated platelet count features the variant type of BCR/ABL junction in chronic myelogenous leukaemia.

A variant form of BCR/ABL junction was identified in a patient with chronic myelogenous leukaemia (CML). The BCR/ABL fusion mRNA of this patient showed in-frame junction between BCR exon c3 and ABL exon 2. Although the diagnosis of CML was made, the patient showed clinical features of essential thrombocythaemia (ET) rather than that of typical CML. Treatment with interferon-alpha showed no cytogenetic response. The c3-a2 type of BCR/ABL junction seems to be associated with elevated platelet count and thus could form a novel clinical entity different from typical CML.

Adolescent↗
PubMed1996

Interaction of ganglioside with specific peptide sequences as a mechanism for the modulation of calmodulin-dependent enzymes.

We examined the interaction between gangliosides and synthetic peptides of calmodulin (CaM)-dependent enzymes to confirm the hypothesis that interaction between gangliosides and the CaM-like site (CLS) of the enzyme is a mechanism for the modulation of the enzyme activity by gangliosides. Gangliosides, GD1b, GT1b, and GD1a, inhibited the activity of CaM-independently activated cAMP-phosphodiesterase and their inhibition was cancelled by a peptide consisting of 17 amino acid residues of a plasma membrane Ca(2+)-pump CLS, suggesting the involvement of the interaction between the peptide and the gangliosides. The peptide of an assumed CLS of phosphodiesterase also cancelled the inhibition. On the other hand, the gangliosides interacted with synthetic CaM-binding site (CBS) peptides of phosphodiesterase, calcineurin, Ca(2+)-pump, and Ca2+/calmodulin-dependent protein kinase II. Moreover, gangliosides GM3 and LM1, that activate but do not inhibit phosphodiesterase, interacted with the CBS peptides, whereas they did not bind to CLS peptides. On the basis of these new findings, we propose a revised model for the ganglioside-mediated modulation of CaM-dependent enzymes, i.e. without CaM, gangliosides bind to CBS and thus stimulate the enzyme activity, acting like CaM. At higher concentrations, they bind to CLS of the enzymes as well and inhibit the activity, acting like the CBS of the enzyme.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Electrophysiologic effects of a class I antiarrhythmic agent, cibenzoline, on the refractoriness and conduction of the human atrium in vivo.

We investigated the effects of a class I antiarrhythmic drug, cibenzoline, on human atrial muscle in vivo. Electrophysiologic measurements were performed in 44 patients (mean age 49 +/- 15 years), before and after an intravenous infusion of cibenzoline 1.4 mg/kg in 5 min. Extrastimuli at a basic cycle length (BCL) of 500 ms were delivered from the right atrial appendage. The effective refractory period of the right atrium (ERP-A), the conduction time from the high right atrium to the coronary sinus, maximum conduction delay (Max. CD), repetitive atrial firing zone (RAFZ), fragmented atrial activity zone (FAAZ), and conduction delay zone (CDZ) were measured. Patients were divided into two groups according to whether repetitive atrial firing (RAF) was induced (group A, n = 18) or not (group B, n = 26). Cibenzoline increased ERP-A from 198 +/- 25 to 214 +/- 26 ms (p < 0.05) and decreased Max. CD from 55 +/- 23 to 43 +/- 19 ms (p < 0.05). There were significant decreases in the RAFZ (10 +/- 17 to 4 +/- 10 ms, p < 0.05), the FAAZ (20 +/- 25 to 12 +/- 18, ms p < 0.05), and the CDZ (41 +/- 21 to 32 +/- 19 ms, p < 0.05). Cibenzoline significantly increased ERP.A (186 +/- 25 to 212 +/- 26 ms, p < 0.05) in group A, but not in group B. There were significant decreases in the RAFZ [25 +/- 19 to 9 +/- 15 ms (p < 0.05) and FAAZ 22 +/- 29 to 11 +/- 21 ms, (p < 0.05)] in group A, but not in group B. The results suggest that cibenzoline can suppress paroxysmal atrial fibrillation by prolongation of ERP-A and may also have preferential effects on the substrate of atrial fibrillation and RAF.

Anti-Arrhythmia Agents↗