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Biomedical subjects

S Yamauchi

Publications and source records attributed to S Yamauchi.

At least 19 recordsLinked to original sources

Intracoronary flecainide induces ST alternans and reentrant arrhythmia on intact canine heart: A role of 4-aminopyridine-sensitive current.

BACKGROUND: The electrical alternans shown on an ST segment, ST alternans, is known as one of the most important predictors of ventricular fibrillation (VF). It has also been reported that sodium channel inhibition changes action potential configuration, especially on the repolarization phase. Thus, the sodium channel blocker may produce ST alternans and trigger reentrant arrhythmia. METHODS AND RESULTS: A sodium channel blocker (disopyramide, lidocaine, or flecainide) was infused selectively into the left anterior descending coronary artery in anesthetized, open-chest dogs. Sixty unipolar electrograms were simultaneously recorded from the entire cardiac surface of the heart. The amplitude of ST alternans (STa) was determined as the difference in the ST-segment magnitude between 2 consecutive electrograms. We accepted the greatest STa among 60 leads for evaluation. High-dose flecainide (100 microg. kg-1. min-1) increased STa and evoked a spontaneous VF. The STa in high-dose flecainide loading (8.7+/-3.4 mV; mean+/-SEM) was significantly greater than that in disopyramide or lidocaine (0. 9+/-0.4 and 0.8+/-0.2 mV, P<0.05). Treatment of 4-aminopyridine (4-AP) suppressed the increase in STa and the occurrence of VF evoked by flecainide, while E4031 or verapamil did not inhibit those. CONCLUSIONS: Flecainide caused the ST alternans that was closely correlated to the occurrence of VF. Because the ST alternans was suppressed by 4-AP treatment, a 4-AP-sensitive current such as Ito or Isus may play an important role on this phenomenon.

4-Aminopyridine

Purification and characterization of chondroitin 4-sulfotransferase from the culture medium of a rat chondrosarcoma cell line.

Chondroitin 4-sulfotransferase, which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 4 of N-acetylgalactosamine in chondroitin, was purified 1900-fold to apparent homogeneity with 6.1% yield from the serum-free culture medium of rat chondrosarcoma cells by affinity chromatography on heparin-Sepharose CL-6B, Matrex gel red A-agarose, 3',5'-ADP-agarose, and the second heparin-Sepharose CL-6B. SDS-polyacrylamide gel electrophoresis of the purified enzyme showed two protein bands. Molecular masses of these protein were 60 and 64 kDa under reducing conditions and 50 and 54 kDa under nonreducing conditions. Both the protein bands coeluted with chondroitin 4-sulfotransferase activity from Toyopearl HW-55 around the position of 50 kDa, indicating that the active form of chondroitin 4-sulfotransferase is a monomer. Dithiothreitol activated the purified chondroitin 4-sulfotransferase. The purified enzyme transferred sulfate to chondroitin and desulfated dermatan sulfate. Chondroitin sulfate A and chondroitin sulfate C were poor acceptors. Chondroitin sulfate E from squid cartilage, dermatan sulfate, heparan sulfate, and completely desulfated N-resulfated heparin hardly served as acceptors of the sulfotransferase. The transfer of sulfate to the desulfated dermatan sulfate occurred preferentially at position 4 of the N-acetylgalactosamine residues flanked with glucuronic acid residues on both reducing and nonreducing sides.

Animals

Wavelength and conduction inhomogeneity in each atrium in patients with isolated mitral valve disease and atrial fibrillation.

INTRODUCTION: Patients with mitral valve disease frequently have atrial fibrillation (AF), and the left atrium is presumed to be the primary atrium that develops AF. However, it is still not clear whether the electrophysiologic abnormalities responsible for AF are confined to the left atrium in this subset of patients. METHODS AND RESULTS: To examine the AF vulnerability of each atrium, we measured the wavelength and inhomogeneity of the conduction at the lateral right atrium, lateral left atrium, and Bachmann's bundle after defibrillation of AF in seven patients undergoing the maze procedure and mitral valve surgery for AF and isolated mitral valve disease, respectively (AF group). The data were compared with five coronary surgery patients in sinus rhythm (SR group). The wavelength in the AF group was significantly shorter (P < 0.05) than in the SR group not only at the lateral left atrium (225 +/- 62 vs 285 +/- 36 mm) but also at the lateral right atrium (214 +/- 54 vs 254 +/- 34 mm). The variation coefficient of the local maximum activation phase difference in the AF group (1.9 +/- 0.8 at the right atrium, 2.1 +/- 0.8 at the lateral left atrium, and 2.0 +/- 0.6 at Bachmann's bundle) was significantly greater (P < 0.05) than in the SR group at all atrial regions. CONCLUSION: AF vulnerability was not confined to the left atrium immediately after defibrillation in AF patients with isolated mitral valve disease. Electrical remodeling resulting from perpetuation of AF, pathological changes extending to the right atrium, geometric changes caused by the atrial interactions occurring across the interatrial septum, or a combination of these may explain the results.

Atrial Fibrillation

"Hexatuple" coronary bypass with in situ arterial grafts.

A fifty-seven year old male patient with severe three-vessel coronary artery disease underwent successful coronary bypass surgery in six vessels utilizing the in situ left internal thoracic and right gastroepiploic arteries. Each arterial conduit was anastomosed sequentially to as many as three coronary vessels respectively. Surgical results were excellent and the patient continues to do very well. A postoperative angiogram showed well-working arterial conduits without any anastomotic problems. Multiple sequential anastomoses of the in situ arterial conduits, although rather technically demanding, can provide better long-term results in patients requiring multiple coronary revascularization. When sequential anastomoses of the right gastroepiploic artery are being considered, the length and caliber of the artery should be evaluated by an angiogram since it varies in size compared to the internal thoracic artery.

Anastomosis, Surgical

The clinical significance of performing preoperative angiography of the internal thoracic artery in coronary artery bypass surgery.

This study was designed to clarify the clinical significance of and indications for performing preoperative internal thoracic artery (ITA) angiography in patients undergoing coronary artery bypass surgery. A total of 300 possible candidates for coronary artery bypass grafting (CABG) underwent ITA angiography during diagnostic catheterization. Semi-selective angiography of bilateral ITAs were performed by injecting contrast medium manually with a 5-F right Judkins coronary catheter. The posteroanterior view of the arteriograms was recorded on a 35-mm cine film or a cut-film. Unusual angiographic findings of the ITAs were observed in nine patients (3%). These findings included: an atrophic ITA in three patients with ipsilateral subclavian artery occlusions; enlarged ITAs giving collaterals to the lower extremities in one patient with extensive aortoiliac occlusive disease; occluded ITAs in one patient with Takayasu's arteritis and two patients with a history of CABG; and a small but nonsclerotic ITA in one patient. Atherosclerotic occlusive ITAs were found in only one patient. Thus, we concluded that routine preoperative angiography of the ITA is not necessary because it is rarely affected by atherosclerosis. However, it should be performed for any of the following reasons: a cervical or supraclavicular bruit; an upper extremity blood pressure difference of greater than 20 mmHg; an extensive aortoiliac occlusion; and certain disorders such as Takayasu's arteritis or Kawasaki disease, or a history of open heart surgery.

Adult

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts.

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1alpha in the presence or absence of pirfenidone (range 0-1000 microM), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1alpha-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts.

Anti-Inflammatory Agents, Non-Steroidal

Varying types of circus movement re-entry with both normal and dissociated contralateral conduction causing different right and left atrial rhythms in canine atrial flutter.

The purpose of this study was to develop an animal model of atrial flutter (AFL) or fibrillation (AFB) and to determine precisely the pathway of atrial activation during arrhythmias induced by programmed stimulation. In 10 dogs, a shunt from the left subclavian artery to the left upper pulmonary vein was created to produce left atrial enlargement. Five months later, using programmed electrical stimulation, it was possible to induce 17 sustained atrial tachycardias in 9 of the 10 dogs, including 9 episodes of AFL caused by circus movement re-entry, 6 episodes of focal tachycardia, and 2 episodes of AFB. Short cycle length left atrial tachycardias caused by either circus movement or a focus did not propagate in a uniform 1:1 pattern to the right atrium (RA), resulting in RA dissociation. In these arrhythmias, complex wavefronts from both current and preceding left atrial cycles coexisted in the RA. Circus movement was associated with a spectrum of different re-entrant pathways with different path lengths. These differences in the path length were determined by various ways in which obstacles such as the superior vena cava and orifice of the right atrial appendage or pulmonary vein orifices were combined by contiguous areas of functional block.

Animals

Reduction of alkyl (2-oxocyclohexyl)acetates by baker's yeast.

Baker's yeast reduction of methyl and ethyl (2-oxocyclohexyl) acetates proceeded with enantio- and diastereo-selectivity, affording the corresponding (2S)-trans-alcohols (major), (2S)-cis-alcohols (minor), and the unaltered (1S)-ketones with high optical purity.

Acetates

Simultaneous subclavian artery reconstruction in coronary artery bypass grafting.

BACKGROUND: Subclavian artery occlusive lesion, although rare, is sufficiently important to consider before coronary artery bypass grafting because it can cause not only symptoms of the lesion per se, but also the postoperative coronary-subclavian steal phenomenon. METHODS: Four patients undergoing coronary artery bypass grafting received simultaneous reconstruction of the subclavian artery. During aortic cross-clamping, an 8-mm ring-reinforced polytetrafluoroethylene graft was attached to the aorta perpendicularly. The prosthetic graft was led to the proximal segment of the axillary artery through the second intercostal space and anastomosed to the inferior surface of the artery. RESULTS: Three patients received unilateral reconstruction of the subclavian artery, whereas another received bilateral reconstruction. There were no complications related to the subclavian reconstruction procedure. Post-operative angiograms revealed excellent patency of the prosthetic grafts. All of the patients have been asymptomatic with follow-up periods ranging from 9 to 50 months. CONCLUSIONS: To perform simultaneous subclavian artery reconstruction along with coronary artery bypass grafting, the aortoaxillary bypass procedure using an 8-mm polytetrafluoroethylene graft may be the method of choice because it has lower potential for complications and is less technically demanding.

Aged

Simultaneous surgical correction of a common atrium and impure flutter.

We performed surgical correction and treatment of a common atrium and chronic impure flutter using a computerized mapping system in a 49-year-old man. A reentrant circuit was observed to exist around the left atrial appendage. In contrast to the regular activation in the left atrium, the activation sequence of the right atrium was extremely chaotic. Cryolesions were applied to the area of the reentrant pathway. After the operation, sinus rhythm was restored.

Atrial Fibrillation

Continuous transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass in children.

The purpose of this study was to evaluate the effectiveness of transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass after intracardiac repair in children. The left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion were monitored continuously by transoesophageal echocardiography in controls weaned easily from cardiopulmonary bypass (group A, n = 25), and those weaned with difficulty from cardiopulmonary bypass after mechanically assisted circulation (group B, n = 16). In group A, left ventricular ejection fraction and left ventricle wall motion were within normal range, and did not change significantly during weaning after cardiopulmonary bypass when compared with pre-bypass data. In contrast, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion in group B during the first trial of weaning from bypass were significantly worsened. Hence, assisted circulation was performed until the data obtained via transoesophageal echocardiography improved with regard to maintenance of fluid balance, catecholamine dosage and assisted pump flow. All cases in group B were weaned safely from cardiopulmonary bypass despite their critical condition. In conclusion, continuous transoesophageal echocardiography monitoring may be a useful tool in children with severe heart failure for safe weaning from cardiopulmonary bypass after intracardiac repair.

Adolescent

Identification, partial characterization, and distribution of versican and link protein in bovine dental pulp.

The dynamics of changes in the cellularity and extracellular matrix composition of dental pulp varies considerably during tooth development and maturation. In this paper, we studied matrix proteoglycans where we hypothesized that they played important roles in structural, spatial, and transport aspects of pulpal development and maintenance. The pulpal tissue was collected from partially erupted bovine incisors, pulverized, and then extracted with 6 M guanidine-HCl. The extract was subjected to anion column chromatography (DEAE-8HR), and the fractions collected were screened by dot-blot immunoassay by means of monoclonal antibodies generated against 4- and 6-sulfated chondroitin sulfate isomers, and keratan sulfate, 2-B-6, 3-B-3, and 5-D-4, respectively. The chondroitin-6-sulfate was the major glycosaminoglycan species and occurred as a large-molecular-weight proteoglycan (> 500 kDa). After further purification, it was subjected to agarose/acrylamide composite gel electrophoresis, and it migrated as a single band stained with Stains-All. The band was immunopositive against antibody 3-B-3 by Western blot analysis. The partial amino acid sequence analyses of the core protein clearly indicated this molecule to be versican. The presence of link protein was also confirmed by Western blot analysis with an anti-link protein monoclonal antibody, 8-A-4. Furthermore, immunohistochemical study indicated that the distributions of versican and link protein coincide in the dental pulp and are enriched in the peripheral area of the tissue just beneath the odontoblast layer. Since the dental pulp contains hyaluronan, versican may bind to hyaluronan via its hyaluronan-binding domain, where this association is stabilized by link protein. This complex, then, could form large hydrated proteoglycan aggregates that fill the extracellular space, support odontoblasts, and/or facilitate the transport function of metabolites and nutrients within the tissue.

Amino Acid Sequence

Serum bone alkaline phosphatase isoenzyme levels in normal children and children with growth hormone (GH) deficiency: a potential marker for bone formation and response to GH therapy.

Serum bone alkaline phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.

Adolescent

Infective endocarditis. Considerations for the timing of surgical intervention and type of infecting microorganism.

To determine the appropriate timing for surgical intervention in infective endocarditis (IE), we evaluated 24 patients (17 males, 6 females, with one included twice) who underwent surgical intervention for IE of native valves (NVE, n = 21) and prosthetic valves (PVE, n = 3) between January 1989 and September 1994. The mean age was 41 +/- 13 years (range 6 to 64 years). The most common infective organisms were Staphylococcus (33% of NVE) and Streptococcus (19% of NVE), with five NVE patients (24%) negative for blood culture. The PVE patients showed a different pattern of infecting organisms, with Enterococcus in one and Pseudomonas in another. From the resected valve culture and pathological findings, 12 patients were in the active stage at operation. Two in-hospital deaths occurred for a mortality rate of 8.7% (2/23). Further, surgical interventions were performed earlier with Staphylococcal infections than with Streptococcal infections, because hemodynamic compromise presented more progressively in the former. Also resected valve cultures and the pathological findings showed that a persistent infectious process existed in many cases of Staphylococcal infection in spite of intensive antibiotic therapy. In conclusion, we suggest that internists make referrals for surgical intervention for patients with NVE or PVE as early as possible in the active stage of infection.

Adolescent

Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Animals

Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy.

Pirfenidone (PFD) is a new compound that prevents and even reverses the extracellular matrix accumulation in several organs as shown by experimental and clinical studies. In the present study, we examined the effect of PFD (500 mg/kg daily in the food) on the progression of chronic renal failure (CRF) in the 5/6 nephrectomy rat model. Proteinuria progressively increased in rats with renal ablation (C) at 12 weeks. Urinary protein excretion in PFD-treated rats (P) was numerically lower than C, but the difference did not reach statistical significance. In contrast, in the chronic phase, PFD improved renal function and reduced collagen accumulation detected by hydroxyproline content (OH-Pro) in the cortex of the remnant kidney. Although creatinine clearance decreased with time in C, the values in P were significantly better at 10 and 12 weeks. The OH-Pro in C at 12 weeks was significantly higher than that of no-ablation, sham-operated rats, whereas OH-Pro in CRF was lower in (P). Expression of mRNA for type IV and I collagen in the cortex also increased in C, but it was inhibited in (P). To study the role that TGF-beta plays in the regulatory process following CRF, we examined the expression of TGF-beta mRNA in this model. Levels of cortical TGF-beta mRNA in C were significantly elevated at 12 weeks. The increase was suppressed by PFD. These results demonstrate that PFD attenuates the development of CRF by preventing collagen accumulation in this model, and suggest that PFD can be clinically useful for treating CRF.

Animals