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Biomedical subjects

H Sako

Publications and source records attributed to H Sako.

At least 37 records · Page 2Linked to original sources
PubMed1998

Overexpression of phospholamban alters inactivation kinetics of L-type Ca2+ channel currents in mouse atrial myocytes.

In mammalian ventricular myocytes, inactivation of L-type Ca2+ channels (CaCh) is controlled by voltage- and Ca2+-dependent mechanisms. The Ca2+-dependent component is regulated by the Ca2+ released from the sarcoplasmic reticulum (SR). However, little is known about the inactivation properties of CaCh in atrial myocytes, which lack spatial coupling between CaCh and SR Ca2+ release channels. The cardiac SR Ca2+ load is determined by the activity of SR Ca2+-ATPase, which is inversely regulated by the levels of phospholamban (PLB). To investigate the role of SR Ca2+ in atrial myocytes, Ca2+ currents (I Ca) were recorded in mouse atrial myocytes recorded from wild-type (WT) mice and the characteristics were compared to those obtained from atrial myocytes from the transgenic mice overexpressing PLB (PLB-OEX). ICa from WT exhibited fast and slow components of inactivation and the rate of inactivation was slowed when SR Ca2+ was depleted by caffeine, suggesting that the inactivation of atrial ICa is modulated by SR Ca2+ load. The current density and voltage-dependence of ICa were similar between the two groups. However, the fast component of inactivation was significantly reduced in PLB-OEX. When Ca2+ was replaced by Ba2+ or in the presence of caffeine, inactivation was slowed and the decay of the current was not significantly different between WT and PLB-OEX. These results suggest that the inactivation of ICa in mouse atrial myocytes involves Ca2+-dependent and voltage-dependent components. The decrease in the faster component of inactivation in PLB-OEX is consistent with the idea that CaCh and SR Ca2+ release channels are functionally coupled and Ca2+ released from the SR contributes the Ca2+-dependent inactivation component.

Animals↗
PubMed1998

Ca2+ entry through cardiac L-type Ca2+ channels modulates beta-adrenergic stimulation in mouse ventricular myocytes.

beta-adrenergic receptor (beta-AR) stimulation increases cardiac L-type Ca2+ channel (CaCh) currents via cAMP-dependent phosphorylation. We report here that the affinity and maximum response of CaCh to isoproterenol (Iso), in mouse ventricular myocytes were significantly higher when Ba2+ was used as the charge carrier (IBa) instead of Ca2+ (ICa). The EC50 and maximum increase of peak currents were 43.7 +/- 7.9 nM and 1.8 +/- 0.1-fold for ICa and 23.3 +/- 4.7 nM and 2.4 +/- 0.1-fold for IBa. When cells were dialyzed with the faster Ca2+ chelator, BAPTA, both sensitivity and maximum response of ICa to Iso were significantly augmented compared to cells with EGTA (EC50 of 23.1 +/- 5.2 nM and maximal increase of 2.2 +/- 0.1-fold). Response of ICa to forskolin was also significantly increased when cells were dialyzed with BAPTA or when currents were measured in Ba2+. In contrast, depletion of the sarcoplasmic reticulum (SR) Ca2+ stores by ryanodine did not alter sensitivity of ICa to Iso or forskolin. These results suggest that the Ca2+ entering through CaCh regulates cAMP-dependent phosphorylation, and such negative feedback may play a significant role in cellular Ca2+ homeostasis and contraction in cardiac cells during beta-AR stimulation.

Adrenergic beta-Agonists↗
PubMed1998

Azathioprine-induced megaloblastic anemia with pancytopenia 22 years after living-related renal transplantation.

Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in renal transplant recipients treated with azathioprine (Az). However, severe anemia is a rare side effect of Az. We recently observed a case of severe megaloblastic anemia with pancytopenia in a renal transplant recipient who had been receiving Az therapy for 22 years. The patient was a 46-year-old woman who had been administered Az and prednisolone at a dose of approximately 1.7 mg/kg and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She did not have vitamin B12 or folate deficiency. Therefore, FK506 (tacrolimus), a macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells and is known to have less myelosuppression than Az, was substituted for Az. Although the leukopenia improved, the anemia and thrombocytopenia did not improve in the short term. She developed dyspnea and severe subcutaneous bleeding of the right lower extremity due to knee contusions. Hemodialysis was started to treat her uremic state. Although it was impossible to evaluate the long-term effects of FK506 therapy for the pancytopenia in our case, the conversion from Az to a less myelosuppressive drug, such as FK506, should be considered in renal transplant recipients with severe myelosuppression caused by long-term Az treatment.

Anemia, Megaloblastic↗
PubMed1998

Experimental study of seita-fitting.

The purpose of this study was to verify the difference between carrying a load on the sacrum (LOS) and on the lumbar vertebrae (LOL) in oxygen uptake, muscle activities, heart rate, cadence, and subjective response. Nine males (26.7 +/- 3.1 years old), each carrying a 7.5 kg carrier frame and a 40 kg load, walked on a treadmill at a speed of 50 m/min. EMGs were recorded from the trapezius, rectus abdominis, erector spinae, vastus lateralis, rectus femoris, vastus medialis, biceps femoris long head, tibial anterior, soleus, medial head of gastrocnemius, and the lateral head of gastrocnemius. For each subject the integrated EMG (IEMG) was normalized by dividing the IEMG in the LOL and LOS by the IEMG in a no-load condition (NL) for each investigated muscle. The following was significantly higher in LOL than in LOS: oxygen uptake; IEMG of the tibial anterior, soleus, and medial head of gastrocnemius; cadence; and rated perceived exertion. However, IEMG of the erector spinae was significantly lower in LOL than in LOS. These results suggest that seita-fitting in LOS causes a decrease of leg muscle activities, which causes oxygen uptake to decrease beyond the increase of the erector spinae activity.

Adult↗
PubMed1997

Benign cervical teratoma in an adult: report of a case.

Cervical teratomas are rarely encountered in adults. We report herein the case of a 21-year-old woman who was admitted to our hospital for surgical treatment of a neck tumor, 7.5 x 4.5 x 2.7 cm in size, located in the left lower pole of the thyroid. Ultrasonography (US) and computed tomography (CT) revealed a multicystic tumor. The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma-related antigen (SCC) in the cystic fluid were extremely elevated in contrast to the normal levels found in the serum. The tumor was completely excised and histological examination revealed it to be composed of elements derived from the three germ layers, confirming a diagnosis of benign cystic teratoma.

Adult↗
PubMed1997

cAMP-dependent regulation of cardiac L-type Ca2+ channels requires membrane targeting of PKA and phosphorylation of channel subunits.

The cardiac L-type Ca2+ channel is a textbook example of an ion channel regulated by protein phosphorylation; however, the molecular events that underlie its regulation remain unknown. Here, we report that in transiently transfected HEK293 cells expressing L-type channels, elevations in cAMP resulted in phosphorylation of the alpha1C and beta2a channel subunits and increases in channel activity. Channel phosphorylation and regulation were facilitated by submembrane targeting of protein kinase A (PKA), through association with an A-kinase anchoring protein called AKAP79. In transfected cells expressing a mutant AKAP79 that is unable to bind PKA, phosphorylation of the alpha1C subunit and regulation of channel activity were not observed. Furthermore, we have demonstrated that the association of an AKAP with PKA was required for beta-adrenergic receptor-mediated regulation of L-type channels in native cardiac myocytes, illustrating that the events observed in the heterologous expression system reflect those occurring in the native system. Mutation of Ser1928 to alanine in the C-terminus of the alpha1C subunit resulted in a complete loss of cAMP-mediated phosphorylation and a loss of channel regulation. Thus, the PKA-mediated regulation of L-type Ca2+ channels is critically dependent on a functional AKAP and phosphorylation of the alpha1C subunit at Ser1928.

Animals↗
PubMed1997

Modulation of cardiac Ca2+ channels by isoproterenol studied in transgenic mice with altered SR Ca2+ content.

Phospholamban (PLB) ablation is associated with enhanced sarcoplasmic reticulum (SR) Ca2+ uptake and attenuation of the cardiac contractile responses to beta-adrenergic agonists. In the present study, we compared the effects of isoproterenol (Iso) on the Ca2+ currents (ICa) of ventricular myocytes isolated from wild-type (WT) and PLB knockout (PLB-KO) mice. Current density and voltage dependence of ICa were similar between WT and PLB-KO cells. However, ICa recorded from PLB-KO myocytes had significantly faster decay kinetics. Iso increased ICa amplitude in both groups in a dose-dependent manner (50% effective concentration, 57.1 nM). Iso did not alter the rate of ICa inactivation in WT cells but significantly prolonged the rate of inactivation in PLB-KO cells. When Ba2+ was used as the charge carrier, Iso slowed the decay of the current in both WT and PLB-KO cells. Depletion of SR Ca2+ by ryanodine also slowed the rate of inactivation of ICa, and subsequent application of Iso further reduced the inactivation rate of both groups. These results suggest that enhanced Ca2+ release from the SR offsets the slowing effects of beta-adrenergic receptor stimulation on the rate of inactivation of ICa.

Adenosine Triphosphatases↗
PubMed1996

Repair of a ruptured aortic arch aneurysm complicated by postoperative paraplegia: report of a case.

We report herein the rare case of a 79-year-old man who suffered permanent paraplegia after undergoing an otherwise successful total arch replacement for a ruptured aortic arch aneurysm. During cardiopulmonary bypass, perfusion to the distal aorta was maintained from the femoral artery, and postoperative aortography showed intact tributaries from the aorta including the intercostal arteries. Postoperative paraplegia is an extremely rare complication of operations on the aortic arch; however, we speculate that the paraplegia in this patient could be attributed either to a steal phenomenon involving the radicular artery, or to the anatomical particularity of the spinal cord artery described by Cole and Gutelius as the "segmental system".

Aged↗
PubMed1996

A research to develop a predicting system of mammalian subacute toxicity. II. Single dose detailed toxicity studies.

"Single dose detailed toxicity study" in rats was conducted with 6 chemical substances to establish a predicting system of subacute toxicity of non-congeneric industrial chemicals. In the detailed examinations, new and previously reported biological parameters were developed and utilized for the establishment and confirmation of the correlations for both qualitative and quantitative prediction of target organs and effects in repeated dose toxicity studies of non-congeners; the new parameters were concerned with liver, kidneys and blood and the established relating equations for prediction had a correlation coefficient of 0.83 (liver), 0.49 (kidneys) and 0.94 (blood), while the old parameters effectively confirmed the previous correlations. The serial changes in the study gave a biological explanation to the established relationships between acute and subacute toxicities in terms of extrapolation.

Animals↗
PubMed1996

[A clinical study of recurrent breast cancer].

In a recent 14-year period from December 1978 to December 1993, 180 patients with breast cancer were treated at the hospital, and out of these 180 patients, 38 patients (21.1%) who had a recurrent breast cancer were clinically evaluated. The first recurrence occurred in the local skin in 13 patients, regional lymph node in 1, bone in 13, lung in 4, liver in 4 and in other areas in 3. Histologically, the incidence of scirrhous carcinoma recurrence was higher than that of papillotubular carcinomas. There was no recurrence in mucinous carcinomas. The frequency of recurrence became higher in accordance with TNM classification, namely, 6.7% in Stage I, 23.7% in Stage II, 37.5% in Stage IIIa, and 47.1% in Stage IIIb cancers. An increasing tendency in the recurrence rate was also noted with an increase of tumor diameter or lymph node metastasis. Otherwise, there was no difference in cumulative survival after recurrence between TNM classification. There were no correlations between the estrogen receptor and incidence of recurrence or 5-year survival rate. The disease free interval (DFI) was less than 2 years in about 60% of the recurrent cases. DFI of bone metastasis was longer than for the other sites of recurrence. The survival rate increased according to prolongation of DFI. After through evaluation of these results, one should pay close attention to follow-up after mastectomy.

Adult↗
PubMed1996

[A case of aortic dissection associated with congenital bicuspid aortic valve].

It is known that bicuspid aortic valve with dilatation of the ascending aorta is one of risk factors of the aortic dissection. A case of acute aortic dissection (DeBakey type-II) associated with bicuspid aortic valve who underwent successfully operation 8 hours after onset is reported. This patient went into cardiogenic shock because of cardiac tamponade and aortic valve regurgitation immediately after onset. Aortic valve and the ascending aorta were replaced using composite graft (#23 SJM prosthetic aortic valve and 26 mm woven Dacron vascular graft) combined with coronary artery reconstruction by Cabrol's technique. Aortic valve showed bicuspid and histological examination revealed cystic medionecrosis and loss of elastic fiber. Postoperative course was uneventful and this patients is doing well 3 years after the operation.

Acute Disease↗
PubMed1996

[Dynamic Gd-DTPA-enhanced MR imaging in evaluation of the function of transplanted kidneys].

The purpose of the study was to evaluate the potential of dynamic Gd-DTPA-enhanced MR imaging in assessing of the function of transplanted kidneys. Dynamic MR imaging was performed using the GRASS pulse sequence in 21 subjects (56 examinations), and in each examination 30 images were obtained after a bolus injection of Gd-DTPA. Imaging findings including signal increase and/or signal drop in cortex, signal drop in medulla, and signal drop in calyces were utilized for the evaluation of renal function. Renal function was also evaluated using the following parameters: Ta, time between the initial observation of signal increase in cortex and signal drop in medulla. Tb, time between the initial observation of signal drop in medulla and in calyces; Tc, Ta + Tb, and Max. C/M, maximum ratio of signal intensity between cortex and medulla among 30 images. In the group of patients with normal graft function (Ccr > or = 60ml/min), all imaging findings were observed. In the group of patients with mild graft dysfunction (30ml/min < or = Ccr < 60ml/min), all imaging findings but signal drop in cortex were observed. The time parameters of Ta, Tb, and Tc were significantly larger, and Max. C/M was significantly smaller than those observed in the group with normal graft function. In the group of patients with severe graft dysfunction (Ccr < 30ml/min), almost none of the findings were observed. The investigation in patients in the postoperative state revealed a close correlation of the imaging findings and the values of parameters with changes in graft function over time. The results indicated the usefulness of the method in semiquantitative evaluation of graft function, including that of patients in postoperative state. This study suggests that dynamic Gd-DTPA-enhanced MR imaging could be a valuable method for the management of transplanted kidneys.

Adolescent↗
PubMed1995

The effect of body position on a free-floating ball thrombus as observed by transesophageal echocardiography.

Two cases of free-floating left atrial ball thrombi (FLABT) in association with mitral stenosis were observed by transesophageal echocardiography (TEE). Our report describes the relation between body position and thrombi kinetics. Both cases demonstrated similar kinetics. In the supine and right lateral decubitus positions, the thrombi recoiled from and sometimes became entrapped within the mitral valve. In the sitting and left lateral decubitus positions, the thrombi appeared to be nearly fixed and did not contact with the mitral valve. Our results indicate that the latter two positions prevent thrombi disintegration and incarceration into the mitral valve. Finally, TEE is an extremely useful tool for assessing the safest position for individuals with FLABT.

Aged↗
PubMed1995

Relationship between apparent total body clearance of cyclosporin A and its erythrocyte-to-plasma distribution ratio in renal transplant patients.

To establish an optimal method for determining a cyclosporin A (CyA) regimen based on physiological changes that occur during immunosuppressive therapy, the relationship between apparent CyA body clearance (CL/f) and the CyA erythrocyte-to-plasma distribution ratio (CyA-EP) was examined using clinical time courses obtained during routine monitoring. The CyA-EP, which was calculated by a multiple regression formula using routine data, was increased during renal dysfunction involving the normal recovery phase after transplantation, during nephrotoxicity, during acute tubular necrosis, and during acute renal rejection. CyA total body clearance (CLt), calculated by multiplying CL/f and converted bioavailability, fc (which is equal to 0.009 x LD, where LD represents the CyA level in blood per dose ratio), showed hyperbolic decay with increasing CyA-EP (the mean CLt was defined as follows: CLt = 0.937/CyA-EP), whereas fc showed exponential decay with increasing CyA-EP (the mean fc was defined as follows: fc = 0.593 x exp(-0.155 x CyA-EP)). These findings suggest that total CyA body clearance and its bioavailability were suppressed during the renal dysfunction phase. Hence, the mean CL/f as a function of the CyA-EP was given by the following equation: CL/f = 1.390 x exp(0.204 x CyA-EP)/CyA-EP. Since the CyA-EP reflects a patient's disease state and alterations in the CyA pharmacokinetic profile, these model formulae should provide an adequate method for determining a CyA dosage regimen for several disease states after renal transplantation.

Adult↗
PubMed1995

Hemodynamic profiles during concurrent intraaortic balloon pumping and venoarterial bypass--a canine study comparing subclavian and femoral artery perfusion sites.

Concomitant use of venoarterial bypass (VAB) with centrifugal pump and intraaortic balloon pumping (IABP) is a common technique for cardiopulmonary resuscitation. This experimental study examines whether coronary perfusion and hemodynamics are affected by the site of the blood supply, comparing the subclavian artery and the femoral artery. VAB and IABP were performed in 11 mongrel dogs with cardiopulmonary failure induced by acute myocardial infarction and hypoventilation. Aortic root pressure (AP), left atrial pressure, central venous pressure and coronary sinus blood flow (CSF) were measured, and blood gas analysis was performed. Subclavian artery perfusion (SAP) and femoral artery perfusion (FAP) were compared at bypass ratios of 25, 50, 75, 85, 100%. At bypass ratios of 75% and 85% the mean systolic AP was higher with SAP than with FAP. The mean diastolic AP was higher with SAP than with FAP at a bypass ratio of 50% or higher. CSF was higher with SAP than with FAP at a bypass ratio of 50% or higher. The coronary arteriovenous O2 content difference was lower with SAP than with FAP at a bypass ratio of 85% or higher. In conclusion, at a high bypass ratio, SAP was more effective than FAP in achieving diastolic augmentation, thus enhancing myocardial oxygen balance, even though SAP had less of a systolic unloading effect. These data support the use of SAP over FAP in patients with severe cardiopulmonary dysfunction requiring high-flow bypass, and especially in patients with myocardial ischemia.

Animals↗
PubMed1995

[Factors affecting the occurrence of anastomotic leakage after graft replacement of type A aortic dissection].

Fifty-seven patients of type A aortic dissection were underwent operations from Jan. 1985 to Nov. 1994. The number of patients who underwent graft replacement of the aorta and received aortogram after the operation was twenty-nine. To investigate factors affecting the occurrence of anastomotic leakage after graft replacement of the aorta, the aortograms of the 29 patients were examined retrospectively. The aortograms revealed leakage at the distal anastomotic site on 11 of the 29 patients. Eight factors: the kind of graft, Marfan's syndrome, the use of felt at the anastomotic site, the clamping method, distal anastomotic site, acute or chronic, the state of the aortic wall at the anastomotic site and the blood pressure control after operation, were examined relating to the occurrence of anastomotic leakage. The results showed 3 factors; acute or chronic, the state of the aortic wall and the blood pressure control, affected the occurrence of anastomotic leakage. In short, the anastomotic leakage easily occurred in patients who underwent in the acute stage and whose blood pressure was uncontrolled after the operation. Therefore, strict control of the blood pressure after the operation is the most effective for preventing anastomotic leakage.

Anastomosis, Surgical↗