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Biomedical subjects

T Kawata

Publications and source records attributed to T Kawata.

At least 127 records · Page 7Linked to original sources

cAMP-dependent protein kinase is required for the expression of a gene specifically expressed in Dictyostelium prestalk cells.

In the Dictyostelium slug there are two types of prestalk cells, pstA cells and pstO cells, that differ in their ability to utilize the distal and proximal parts of the promoter of ecmA, a gene that is specifically expressed in prestalk cells. When Rm, a dominant inhibitory form of the regulatory subunit of cAMP-dependent protein kinase (PKA), is expressed under the control of the complete promoter of the ecmA gene (in a construct termed ecmAO:Rm) development proceeds to the slug stage. Although able to form small but outwardly normal slugs, ecmAO:Rm cells are defective in prestalk cell differentiation. In ecmAO:Rm cells, the induction of pstA- and pstO-specific gene expression by the stalk cell inducer DIF is greatly inhibited. Paradoxically, a very large fraction of the cells in an ecmAO:Rm slug show evidence of once having expressed the ecmA and ecmO prestalk markers. However, we present evidence that this is due to abortive prestalk cell differentiation that terminates when sufficient Rm protein has accumulated to block PKA activity. This results in regulative transdifferentiation of prespore cells to form prestalk cells. During their transitory period as prestalk cells the ecmAO:Rm cells coexpress both the ecmA and ecmO markers, indicating a possible link between PKA activity and divergence of the two prestalk cell subtypes. Finally, we show that the level of the DNA binding activity believed to lie at the end of the DIF signal transduction pathway is reduced in ecmAO:Rm slugs.

Animals↗

Evidence that a combined activator-repressor protein regulates Dictyostelium stalk cell differentiation.

The ecmA gene is expressed in Dictyostelium prestalk cells and is inducible by differentiation-inducing factor (DIF), a low-molecular-weight lipophilic substance. The ecmB gene is expressed in stalk cells and is under negative control by two repressor elements. Each repressor element contains two copies of the sequence TTGA in an inverted relative orientation. There are activator elements in the ecmA promoter that also contain two TTGA sequences, but in the same relative orientation. Gel retardation assays suggest that the same protein binds to the ecmB repressor and the ecmA activator. We propose that DIF induces prestalk cell differentiation by activating this protein and that the protein also binds to the promoters of stalk-specific genes, acting as a repressor that holds cells in the prestalk state until culmination is triggered.

Animals↗

RNGB: a Dictyostelium RING finger protein that is specifically located in maturing spore cells.

The RING finger is a form of zinc finger motif found in proteins of widely varying biological function. The Dictyostelium RNGB protein contains a RING finger and also a K-box, a sequence motif found in several plant homeotic proteins. The rngB mRNA is present at low concentration in growing cells and gradually increases in abundance throughout development. However, the RNGB protein is not detected until culmination and we present evidence that suggests it is translationally regulated. The protein is specifically localised in maturing spore cells and is cytoplasmic, suggesting that the RING finger does not function as a DNA binding domain.

Amino Acid Sequence↗

Annuloplasty for severe mitral regurgitation due to dilated cardiomyopathy.

We present a 74-year-old woman who underwent corrective annuloplasty for severe mitral regurgitation due to dilated cardiomyopathy. Postoperatively, congestive heart failure improved, with her New York Heart Association status changing from IV to II, although her cardiac functional improvement was minimal. Severe mitral regurgitation may be the indication for annuloplasty in symptomatic patients with dilated cardiomyopathy when cardiac transplantation is not indicated.

Aged↗

Echocardiographic characteristics of the cryopreserved allograft aortic valve replacement assessed by intraoperative transoesophageal echocardiography.

Improvements in cryopreservation techniques have made possible excellent long-term results using aortic valve allografts. Few studies, however, have examined the echocardiographic characteristics of allograft aortic valves and postoperative valve function. Aortic allograft function was evaluated in 16 patients by intraoperative transoesophageal echocardiography, postoperative catheterization, and angiography. The mean(s.d.) coaptation zone length of the allograft leaflet was significantly greater (7.3(1.4) mm) than that of the normal aortic valve (3.2(0.8) mm) (P < 0.01). No regurgitation was noted in any patients with coaptation zone length of 7-11 mm (P < 0.01). The increment of the leaflet coaptation zone length did not produce a significant pressure gradient during exercise and appeared to be one of the important mechanisms for the prevention of postoperative aortic regurgitation, because commissural orientations may be distorted in the new aortic position. This finding is consistent with the report that allografts with the largest diameter implantable in the recipient annulus should be selected for use.

Adult↗

Fluoridation of hydroxyapatite powder by ammonium hexafluorosilicate.

Diamine silver fluoride [AgF: (NH3)2AgF] is a unique fluoride solution used clinically in Japan for primary teeth. AgF has been shown to reduce dental caries and dentine hypersensitivity. However, AgF also stains teeth black due to sulfide precipitation and thus is unacceptable for permanent teeth. In the present study, the potential value of ammonium hexafluorosilicate [SiF: (NH4)2SiF6], which has a formula similar to that of AgF but contains no Ag, was studied with respect to its ability to fluoridate apatite. Hydroxyapatite [HAP: Ca10(PO4)6(OH)2] powder was treated with several topical fluoride solutions, i.e. neutral sodium fluoride, acidulated phosphate fluoride (APF) along with AgF and SiF. Following treatment, the HAP powders were analyzed for their fluorine content, crystallinity changes, and solubility in acidic solution. The highest level of fluoridated HAP [FAP: Ca10(PO4)6(OH)xF2-x] was observed in HAP powder treated with SiF, even though more total fluorine in the form of FAP and CaF2 was observed in HAP powder samples treated with APF. Presumably as a consequence of this higher level of FAP formation after SiF treatment, the highest level of crystallinity along with the lowest solubility in acidic solution were observed in HAP powder treated with SiF solution. We concluded, therefore, that SiF may have potential value for use as a topical fluoride solution.

Acidulated Phosphate Fluoride↗

Protective effect of B464, a lipid A analog, on endotoxin-induced cellular responses and acute lung injury.

B464 is a novel synthetic analog of lipid A, a toxic component of endotoxin (LPS; lipopolysaccharide). We investigated the effects of B464 on both LPS-induced cellular responses in vitro and acute lung injury in vivo. In the in vitro study, B464 inhibited tumor necrosis factor-alpha (TNF-alpha) production from human monocytes, priming and stiffening of neutrophils, and expression of adhesion molecules on endothelial cells induced by LPS. We then studied the effects of B464 pretreatment on acute lung injury elicited by intravenous LPS administration in vivo. Guinea pigs were divided into saline control, B464 alone, LPS alone, and LPS + B464 groups. Animals were observed for 4 h after LPS administration, and lung injury was evaluated by extravascular lung water, 125I-albumin leakage in lung tissue, and lung neutrophil accumulation. In the LPS alone group, rapid and sustained peripheral neutropenia (p < 0.001 versus saline at 15 min and at 1, 2, and 4 h), an increased plasma TNF-alpha concentration (p < 0.005 at 1 h), and increases in lung injury parameters (p < 0.05) were observed. In the LPS + B464 group, no changes were observed in either plasma TNF-alpha or lung injury parameters. Transient peripheral neutropenia and subsequent rapid recovery (p > 0.05, p < 0.001, p < 0.01, and p > 0.05 at 15 min and 1, 2, and 4 h, respectively) were observed in the LPS + B464 group. These in vivo data, together with in vitro evidence of suppressed cellular responses, suggest that B464 (1) inhibits neutrophil accumulation in lung tissue, and (2) attenuates the development of acute lung injury by blocking the activation of neutrophils and mononuclear cells as well as the interaction between neutrophils and endothelial cells.

Animals↗

The angiotensin receptor antagonist 2-ethoxy-1-[[2'-(1H- tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV11974) attenuates the tubuloglomerular feedback response during NO synthase blockade in rats.

Nitric oxide (NO) produced in the juxtaglomerular apparatus may regulate the tubuloglomerular feedback (TGF) response. The inhibition of intrinsic NO results in significant renal hemodynamic changes, a phenomenon similar to that observed after angiotensin II (A-II) administration. We measured stop-flow pressure (Psf) during loop perfusion with artificial tubular fluid in Sprague-Dawley rats to establish whether alterations in TGF responsiveness during NO inhibition depend on the action of endogenous A-II. The NO synthase blocker N omega-nitro-L-arginine-methyl-ester (L-NAME: 10 mg/kg i.v.) significant increased TGF responsiveness, defined as the change in Psf on increasing loop flow from 0 to 40 nl/min compared with control (delta Psf: -21.3 +/- 2.6 vs. -9.7 +/- 0.6 mm Hg, P < .001). After concomitant treatment with the nonpeptide A-II type 1 receptor antagonist 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxic acid (CV11974: 1 mg/kg i.v.) and L-NAME, the TGF response was attenuated significantly (delta Psf: -7.6 +/- 1.9 mm Hg, P < .001). On the other hand, Psf in the absence of loop perfusion was increased similarly by L-NAME treatment in the presence (53.7 +/- 2.2 mm Hg) or absence of CV11974 (Psf 50.7 +/- 3.2 mm Hg). These results suggest that augmentation of the TGF response by endogenous NO inhibition depends, at least in part, on the intrinsic A-II activity.

Angiotensin II↗

[Ten-year survival and cardiac event-free rates in Japanese patients with the left anterior descending artery revascularized with internal thoracic artery or saphenous vein graft: a comparative study].

To evaluate the long-term results of surgical patients with coronary artery bypass grafting (CABG), we comparatively analyzed the 10-year survival and cardiac event-free rates between 713 patients group with at least one internal thoracic artery to the left anterior descending artery (LAD), (ITA-CABG) and 241 patients group revascularized with vein grafts alone (SVG-CABG). ITA-CABG patients had more progressed diseases with a higher incidence of risk factors than SVG-CABG patients: number of vessel diseased 2.5 +/- 0.7 vs 2.3 +/- 0.7, LMTD 20.2% vs 14.1%, diabetes mellitus 37.3% vs 27.0% and hyperlipidemia 38.0% vs 30.7%. The 10-year cumulative LAD graft patency and severe disease-free rate was 90.3 and 67.0% for ITAs and vein grafts in this series. The 10-year overall actuarial survival, cardiac death-free and cardiac event-free rates for ITA and SVG groups were 88.8 vs 79.5%, 97.4 vs 92.6% and 84.1 vs 73.1%, all with a statistical significance (generalized Wilcoxon or logrank method). For the patients with reduced ventricular systolic function (EF < or = 0.4), ITA-CABG offered a significantly better 10-year cardiac death free rate. Also, for the diabetic patients, ITA-LAD offered a significantly better 10-year cardiac event-free rate. In conclusion, the use of ITA graft can reduce postoperative cardiac events and enhance the long-term survival in Japanese patients. The ITA should be utilized at least for LAD in all CABG patients whenever feasible.

Coronary Artery Bypass↗

[Radiation-induced coronary ostial stenosis, a case of redo coronary bypass for the restenosis following patch angioplasty].

The patient was a 45-year-old woman who had had a tumor resection for thymic carcinoid and subsequent mediastinal irradiation (50 Gy) 3 years before the onset of angina pectoris during exercise. Coronary angiography (CAG) revealed an isolated ostial stenosis of the left main coronary trunk (LMT). Angiography also showed an occluded right internal thoracic artery (ITA) at its origin. The patient underwent patch angioplasty of the LMT orifice using a piece of the saphenous vein graft (SVG). One month after the operation, CAG revealed a success of operation with an enlarged LMT orifice and she was discharged. However, 3 months after the operation, angina pectoris recurred and a repeated CAG showed a 90% stenosis of the LMT at the place 1 cm distal to the orifice. Emergency CABG (the left ITA to the LAD and the SVG to the LCX) was accomplished with disappearance of angina. Post-CABG angiography revealed patent left ITA and SVG in association with complete obstruction of the LMT. One year after the second operation, she was free from symptoms. This case as well as other reports concerning radiation-induced coronary stenosis suggest that patch angioplasty for this specific lesions may have a high incidence of stenosis recurrence. Coronary bypass grafting that can be performed at the place away from the active proliferative lesion may be a better selection.

Angioplasty↗

[Surgery for WPW syndrome with concomitant CABG: a case report].

A 58-year-old man underwent simultaneous surgery for WPW syndrome complicated by frequent attacks of atrial tachyarrhythmia combined with angina pectoris persisting after anterior myocardial infarction. Repeated PTCA of 3 times failed and restenosis occurred with recurrent angina particularly when atrial tachyarrhythmia took place. The preoperative ECG suggested the presence of a left free wall accessory pathway confirmed by an electro-physiolosical study. Coronary bypass grafting (LITA-LAD, SVG-4 PD) and division with cryoalation of the accessory pathway were performed using a transseptal left atrial approach. The patient is doing well now and free from both angina and tachycardia.

Angina Pectoris↗

[A case report of aortic root replacement with fresh aortic homograft for valve detachment due infective endocarditis].

A 28-year-old male received a redo aortic valve replacement (AVR) with a 19 mm St. Jude Medical mechanical valve 3 months after the initial AVR because of recurrent valve detachment. We re-operated on this patient by aortic root replacement using a fresh aortic homograft. The donor of the homograft was a 59-year-old female who died of a traffic accident. The aortic root and valve was harvested aseptically and stored in a nutrient medium including antibiotics at 4 degrees C for 4 days. At the 3rd operation, aortico-ventricular discontinuity and an annular-abcess-like cavity were found. After debridement, the cavity was closed with a homograft aortic wall and then aortic root replacement was performed using a fresh aortic homograft. At first, prosthetic valve detachment seemed to be caused by infective endocarditis on the basis of his clinical history. However, causative organisms had never been recovered from the blood or the specimens obtained at the time of operation and reoperation. Post-operative HLA examination revealed No. 51 on HLA-B locus and thus we suspected that valve detachment might have been due to inflammation of the aortic wall caused by a subtype of Behçet disease. The early post-operative course was uneventful with a low dose of predonine. Post-operative aortography showed no aortic regurgitation and normal coronary anastomosis. Unfortunately however, he died suddenly 8 months after the operation. Autopsy demonstrated the presence of aortic wall necrosis with massive infiltration of macrophages and leucocytes resulting in dehiscence of the coronary anastomotic site. The cause of homograft detachment could not be determined for sure but might be recurrent infective endocarditis, although causative organisms were never identified, or infective endocarditis in combination with Behçet vasculopathy.

Adult↗

Secretion and processing mechanisms of procathepsin L in bone resorption.

Secretion of procathepsin L into the culture medium from a bone cell mixture was markedly enhanced by addition of parathyroid hormone (PTH), 1 alpha,25-(OH)2D3 or tumor necrosis factor alpha (TNF alpha). These stimulators of secretion of procathepsin L enhanced bone pit formation, which was inhibited by E-64, but not by CA-074, a specific inhibitor of cathepsin B. Procathepsin L may thus participate in the process of bone collagenolysis during bone resorption. Procathepsin L partially purified from rat long bones under cold conditions was rapidly converted to the mature form under acidic conditions at room temperature. This conversion was inhibited by E-64, suggesting that the procathepsin L secreted into lacunae is catalytically converted to the mature enzyme by cysteine proteinase(s).

Animals↗

Extracellular calcium causes the release of calcium from intracellular stores in chick osteocytes.

We have recently demonstrated that a rise in the extracellular divalent cation concentration induces a rapid elevation of cytosolic calcium in chick osteocytes. Here, we demonstrate that cytosolic calcium elevation that occurs in osteocytes on exposure to elevated extracellular calcium is independent of membrane voltage and is insensitive to modulation by organic calcium channel modulators, namely, BAY K 8644, nicardipine, and nifedipine. However, the calcium elevation was sensitive to modulation by an intracellular calcium antagonist, TMB-8, suggesting that the cytosolic calcium elevation was due to mobilization of this cation from an intracellular store.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Usefulness of interlocking detachable coil for embolization of the major aorto-pulmonary collateral artery: a case report.

A 5-yr-old male had undergone a right-modified Blalock-Taussig shunt operation at the age of 1 mo for stenotic patient ductus arteriosus and pulmonary atresia with ventricular septal defect. Before a corrective operation, the angiogram revealed one large major aorto-pulmonary collateral artery from the descending aorta to the right upper lung. Embolization of the major aorto-pulmonary collateral artery was successfully performed using interlocking detachable coils. This is the first reported case of embolization of the major aorto-pulmonary collateral artery using this device.

Angiography↗

Left atrial plication combined with mitral valve surgery in patients with a giant left atrium.

The benefits of performing left atrial plication during mitral valve surgery for patients with a giant left atrium were evaluated by analyzing the short- and long-term surgical results and changes in the left atrial dimension (LAD) and respiratory function of 30 patients. Of the 30 patients, 2 (7%) died of multiple organ failure on postoperative days 26 and 117, but no other deaths occurred during the mean follow-up of 5.9 +/- 2.1 years. Valve thrombosis was observed in one patient and cerebral complications with no residual deficit were observed in two patients, with a 9-year event-free rate of 87 +/- 7%. The LAD decreased significantly from 69.0 +/- 8.5 mm to 53.7 +/- 9.1 mm (P < 0.01) shortly after surgery, and this decreased was maintained even 5 years after surgery (53.3 +/- 11.4 mm). The cardiothoracic ratio decreased from 74.8 +/- 8.3% to 62.8 +/- 9.0% (P < 0.01) and the vital capacity of the lungs increased from 71.1 +/- 18.0% to 82.9 +/- 22.2% (P < 0.01). Thus, we conclude that performing left atrial plication during mitral valve surgery is safe and effective for patients with giant left atrium.

Adult↗

Systolic and diastolic function after patch reconstruction of left ventricular aneurysms.

Left ventricular function after patch reconstruction for postinfarction left ventricular aneurysms is largely unknown. In this study, 16 patients with an anteroseptal-lateral left ventricular aneurysm were treated by reconstruction of the left ventricle using a Dacron patch. Coronary artery bypass grafting was performed concomitantly in 9 patients. The size of the patch used was 57% +/- 19% of the resected myocardial scar area, including the sewing cuff area to be sutured. In these patients, the ejection fraction increased significantly from 0.28 +/- 0.12 to 0.39 +/- 0.12 (p = 0.007) at rest and from 0.32 +/- 0.14 to 0.41 +/- 0.10 (p = 0.008) during exercise. The left ventricular end-diastolic pressure and left ventricular end-diastolic volume index were reduced significantly from 14 +/- 7.0 to 8 +/- 3.2 mm Hg (p = 0.032), and from 178 +/- 116 to 92 +/- 21 mL/m2 (p = 0.016). The peak filling rate was improved significantly from 1.2 +/- 0.47 to 1.8 +/- 0.6/s (p = 0.048) postoperatively. The ratio of the peak flow velocity during the atrial kick phase to the peak flow velocity in the rapid filling phase, at the level of the mitral valve, improved (p = 0.016) after operation and remained improved up to 16 to 24 months after operation. Patch reconstruction of the left ventricle resulted in the recovery of systolic and diastolic function soon after operation, which has persisted into the late postoperative period.

Blood Pressure↗