Biomedical subjects

T Isomura

Publications and source records attributed to T Isomura.

At least 91 records · Page 5Linked to original sources

PubMed1993

Tyrosine kinase activity of the ret proto-oncogene products in vitro.

We investigated tyrosine kinase activity of the ret proto-oncogene products (proto-Ret proteins), using a cell lysate of NB-39-nu neuroblastoma cells. The 150 kDa and 170 kDa proto-Ret proteins immunoprecipitated with antibodies against their carboxy-terminal 20 amino acids were shown to be phosphorylated predominantly on tyrosine residues in immunocomplex kinase assay. The level of tyrosine phosphorylation of the 150 kDa proto-Ret protein was approximately 10-fold higher than that of the 170 kDa proto-Ret protein, although both proteins were expressed at similar levels in neuroblastoma cells. This result was confirmed by using a lysate of SK-N-MC human primitive neuroectodermal tumor cells transfected with the ret proto-oncogene. The kinase activity of proto-Ret proteins was significantly inhibited by antibodies against their kinase domain, indicating that these antibodies recognize crucial epitopes for the enzymatic activity. On the other hand, the proto-Ret proteins were not phosphorylated in vivo in NB-39-nu cells and SK-N-MC transfectants.

Amino Acids↗

PubMed1993

Use of the right gastroepiploic artery as a pedicled arterial graft for coronary revascularization.

Between April 1988 and August 1991, the right gastroepiploic artery (RGEA) was used as a pedicled arterial graft for coronary arterial bypass grafting (CABG) in 44 patients. Their ages ranged from 8 to 72 years (mean: 58.7 years), and body size was small for 21 patients (body surface area < 1.6 m2). The mean number of distal anastomoses was 3.2 +/- 0.7 per patient. The RGEA was anastomosed to the right coronary system in 35 patients and to the left in 9 patients. Perioperative vasospasm of the RGEA occurred in 4 patients, but no vasospasm was seen after intraluminal injection of diluted papaverine hydrochloride was used in the last 9 patients. The size of the RGEA at the site of anastomosis was 1.9 +/- 0.4 mm in diameter. The RGEA was harvested in 48 patients; however, two of the RGEAs were smaller than 1.0 mm in diameter and two showed severe calcification with stenosis of more than 75%. Consequently, those conduits were not used. Indications for the use of the RGEA were: relatively young age for 17, matching size of the coronary artery and the RGEA for 11, poor quality of the internal thoracic artery (ITA) or saphenous vein graft (SVG) for 10, lower leg atherosclerosis in 3, a diseased ascending aorta in 2, and Kawasaki disease in 1. The patency rate of the RGEA for 36 patients was 94.4% and relief of angina 95.5%. An exercise tolerance test performed within 2 months after operation showed improved capacity (mean 7.2 metabolic units).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Left atrial plication and mitral valve replacement for giant left atrium accompanying mitral lesion.

Between January 1982 and November 1992, 38 patients received simultaneous mitral valve replacement (MVR) and left atrial plication (LAP) because of giant left atrium accompanying mitral lesion. Their ages ranged from 33 to 70 years, and the mitral lesion was caused by rheumatic heart disease in all patients. MVR was performed with a St. Jude Medical prosthesis for all patients and the left atrial wall was plicated with running 3-0 Nespolene to reduce the width to 3 to 5 cm. Respiration requiring mechanical ventilation more than 48 hours after operation occurred in four patients (10.5%) and postoperative low cardiac output requiring a high dose of dopamine HCl or intraaortic balloon pumping in nine patients (23.7%). The left atrial diameter measured by echocardiogram was a mean of 7.3 +/- 1.0 cm before operation and 5.8 +/- 1.0 cm postoperatively. The cardiothoracic ratio on the chest roentgenogram registered a preoperative mean of 73.3% +/- 9.8% and was 65.7% +/- 8.4% after operation. The pre- and postoperative values were significantly different (p < 0.01). The postoperative exercise level was a mean of 5.3 metabolic units for 24 patients and the postoperative New York Heart Association functional classification indicated Class I or II for 37 patients with no evidence of left atrial thrombus except in the case of one early death. LAP with MVR for patients with giant left atrium due to mitral lesion appeared to result in improvement in respiratory and circulatory functions.

Adult↗

PubMed1993

Beneficial effect of the addition of nitroglycerin to the cardioplegic solution on the cold-stored reperfused isolated rat heart.

We discuss here the effect of the addition of trinitroglycerin to the cardioplegic solution on the isolated rat heart after eight hours of storage. This effect was evaluated by measuring cardiac function as well as myocardial calcium and enzymes. Male Wistar rats were divided into three groups based on the concentration of trinitroglycerine in the cardioplegic solution. In the control group, the fluid used was a crystalloid cardioplegic solution (K+ 25 mEq/L) without trinitroglycerin and for groups I and II, trinitroglycerin was added at concentrations of 2 micrograms/ml and 5 micrograms/ml, respectively. All hearts were arrested with the cardioplegic solution at 4 degrees C and then immersed for eight hours in Euro-Collins' solution at 4 degrees C. The postperfusion coronary flow showed higher rates for groups I and II than for the control group (p < 0.05), while the difference between groups I and II was not significant. In group I, the total concentrations of creatine kinase-MB, lactate and malondialdehyde after reperfusion showed the lowest levels; this group also had the lowest content of myocardial calcium. These results indicate that the addition of nitroglycerin, especially at a concentration of 2 micrograms/ml, to the cardioplegic solution elicits better cardiac function for immersed rat heart.

Animals↗

PubMed1993

Clinical study of 47 patients with reoperation after open mitral commissurotomy.

Mitral lesion in 47 patients who received reoperation after an initial open mitral commissurotomy (OMC) for mitral stenosis (MS) was studied. The diagnosis before OMC consisted of pure MS in 38 patients, with mild mitral regurgitation (MR) in 8 and with moderate MR in 1. At OMC the diameter of the mitral orifice was a mean of 1.3 +/- 0.5 cm and a mobile cusp was found in 12 and a thickened cusp in 35 patients. Subvalvular fusion was seen in 15 patients, calcification of cusp or subvalvular region in 10 and left atrial thrombus in 6. After OMC, the diameter of the mitral orifice was opened to a mean of 3.2 +/- 0.3 cm. The interval between the initial operation and the time of reoperation was a mean of 124 months. The mitral lesion necessitating reoperation was MS in 18, moderate to severe MR in 10, and MSR in 19. At reoperation the mitral orifice ranged in diameter from 0.8 to 4.2 cm (mean, 2.3 +/- 0.8 cm). There was no correlation between the occurrence of MR or restenosis and the subvalvular division at initial OMC. Left atrial thrombus was identified in four and calcification in 17 patients. At reoperation 46 patients received mitral valve replacement, while only 1 received a second OMC. The removed valve showed no pathological findings of active rheumatic lesion but more severe calcification and hyalinization of the valve than those at initial operation. There were three early deaths (6.4%) after reoperation. The recurring mitral lesion seemed to consist of deteriorated pathological changes of the valve and MR and thus mitral valve replacement was recommended to provide a favorable operative result for non-flexible lesion after OMC.

Adult↗

PubMed1993

[The preventive effect of additional albumin in crystalloid cardioplegic solution on myocardial reperfusion injury].

The effect of additional albumin in crystalloid cardioplegic solution (CS) was investigated for infant with open heart surgery. Patients were divided into two groups; CS containing with or without 1% albumin. CS without albumin was administered for Group-I in 13 patients and CS with albumin for Group-II in 14 patients. The blood samples were collected from radial artery and coronary sinus at 5, 15 and 30 minutes after reperfusion and blood gas analysis, hemoglobin, lactate, creatine kinase-MB (CK-MB) and malondialdehyde (MDA) were measured. In percentage of CK-MB secretion, no significant differences were seen between two groups. However, in oxygen consumption, lactate and MDA secretion, significant differences between the groups were noted at five minutes after reperfusion. In conclusion, additional albumin in CS solution, especially in infant cases was effective for myocardial preservation immediately after reperfusion.

Albumins↗

PubMed1993

[The effect of additional albumin with optimal concentration on the reperfusion after preservation of isolated rat hearts].

We studied the effect of additional albumin in preservation solution on reperfusion after immersion of isolated rat hearts by measuring cardiac function, myocardial enzymes and calcium. Male Wistar rats weighing 300 gr to 450 gr were used. Isolated rat hearts were arrested by cardioplegic solution and washed out with preservation solution. Then, the hearts were immersed at 4 degrees C for six hours. The group was divided into four by the concentration of additional albumin in preservation solution which basically consisted of Euro-Collins solution. In control group, the cardiac function was immediately measured after the heart was isolated. Albumin was not added in group I (n = 16), 2% of albumin in group II (n = 18), 5% of albumin in group III (n = 17) and 7% of albumin in group IV (n = 18). There were no significant differences between groups II and III in cardiac function and myocardial enzymes. The levels of myocardial malondialdehyde (nmol/g dry weight) and calcium (mumol/g dry weight) at 15 minutes after reperfusion were 279.3 +/- 38.1, 5.9 +/- 5.3 in group I; 243.3 +/- 86.5, 4.1 +/- 2.0 in group II; 217.1 +/- 106.6, 4.1 +/- 1.3 in group III and 274.9 +/- 77.1, 4.9 +/- 1.2 in group IV, respectively. Although no statistical significances were seen among those results, those data might suggest the relationship between the recovery of cardiac output and myocardial ATP contents. Those results also suggested that additional albumin with optimal concentration might inhibit reperfusion injury.

Albumins↗

PubMed1993

[Post-transfusional syndrome like graft versus host disease].

We studied clinical and immunological changes of the post-transfusional syndrome like graft versus host disease (GVDH) in six patients after open heart surgery and in one patient after hepatectomy. In the patient with hepatocellular carcinoma, transcatheter arterial embolization had been previously done. All patients received homologous blood transfusion during and after surgery and erythroderma associated hyperthermia occurred approximately 10 days after operation. Patients receiving open heart surgery died on between postoperative 17th and 21st day. One patient with hepatectomy died on the 29th day after operation. Skin biopsies in all patients showed the findings of acute GVHD. The number of CD3+ and CD4+ T lymphocytes decreased at postoperative day 1, however, the number of CD3+ T lymphocyte increased in three patients after postoperative day 14. The postoperative value of interleukin-2 production was low in patients in whom the value was measured. The immunological status in host has not been clearly resolved. However, the postoperative changes of lymphocytes subsets were abnormal and IL-2 production in two patients showed low level. Therefore, it was considered that pre and postoperative measurement of cell-modiated immunity might predict the occurrence of the post-transfusional GVHD and might be one of useful examinations to prevent the disease.

Aged↗

PubMed1993

Characterization of the ret proto-oncogene products expressed in mouse L cells.

The ret proto-oncogene (proto-ret) encodes a receptor type tyrosine kinase with a cadherin-related sequence in the extracellular domain. To investigate whether the proto-Ret protein functions as a cell adhesion molecule like cadherins, we transfected the human proto-ret gene fused to the SV40 promoter or cytomegalovirus (CMV) promoter into mouse L cells in which cadherins are not expressed. Three transfectants with high levels of expression of the proto-Ret proteins were obtained. The proto-Ret proteins were expressed as 150 kDa and 170 kDa glycoproteins in transfectants as observed in human neuroblastoma cells. Cell fractionation experiments revealed that the 170 kDa protein but not the 150 kDa protein was detected predominantly in the plasma membrane fraction, indicating that the 170 kDa protein represents the mature glycosylated form of the proto-Ret protein present on the cell surface. Both 150 kDa and 170 kDa proto-Ret proteins showed tyrosine kinase activity in immunocomplex kinase assay. It is known that cadherins have Ca(2+)-dependent homophilic binding activity and are resistant to trypsinization in the presence of Ca2+. When L cells expressing the proto-Ret proteins were treated with trypsin in the presence of Ca2+, the 170 kDa protein was resistant to its digestion. On the other hand, it was completely digested in the presence of EGTA, suggesting the possibility that the proto-Ret protein interacts with Ca2+ like cadherins. However, the transfectants did not show clear adhesive properties in cell aggregation assays.

Animals↗

PubMed1993

[Direct implantation of the left coronary artery to the ascending aorta in Bland-White-Garland syndrome].

A seventeen-year-old male with Bland-White-Garland syndrome underwent direct implantation of the left coronary artery to the ascending aorta. Under cardiopulmonary bypass, the main pulmonary artery was completely transected and the left coronary artery (LCA) was excised with a cuff of the pulmonary artery wall. Then the proximal end of LCA was directly anastomosed to the ascending aorta. The postoperative course was excellent. It appears that this surgical procedure might be the most ideal repair both anatomically and hemodynamically to reconstruct the left coronary artery in Bland-White-Garland syndrome.

Adolescent↗

PubMed1993

[A case of discrete type of subpulmonary stenosis].

We reported a 8-year-old girl having discrete type of subpulmonary stenosis. This patient was associated with atrial septal defect (ASD), valvular pulmonary stenosis, and persistent left superior vena cava (PLSVC). The incidence of this type of subpulmonary stenosis is less frequent than that of subaortic lesion. ASD was closed by the autologous pericardium and a transannular patch was used for enlargement of the right ventricular outflow tract followed by commissurotomy of the pulmonary valve and resection of subpulmonary discrete lesion. She was uneventful and postoperative pulsed doppler echocardiogram showed good results.

Child↗

PubMed1993

Clinical evaluation with exercise performance in twenty patients who underwent coronary artery bypass grafting with both the gastroepiploic and internal thoracic arteries.

Postoperative exercise performance was evaluated in 20 patients who underwent complete coronary revascularization with simultaneous right gastroepiploic artery and internal thoracic artery grafts for ischemic heart disease and exhibited patency of all grafts on postoperative angiograms. Three patients received only arterial grafts, and 17 simultaneously received a saphenous vein graft. Forty five right gastroepiploic artery grafts were harvested during this study, but two were not used because of foci of severe calcification. The right gastroepiploic artery was grafted to the distal right coronary artery in 17 patients and to the distal obtuse marginal branches in three patients, accompanied by an internal thoracic artery graft to the left anterior descending artery in seventeen, to the diagonal branch in three, and to the proximal right coronary artery in one patient. A postoperative exercise test with a bicycle ergonometer was administered 6 to 12 weeks after the operation, and the results are reported after conversion into metabolic units. The preoperative exercise test resulted in 3.6 +/- 1.9 metabolic units for 18 patients tested, and the postoperative metabolic units were 7.8 +/- 1.3 for 20 patients. Left ventricular wall motion was analyzed by regional ejection fraction before and after coronary artery bypass grafting in 14 patients who received an right gastroepiploic artery graft for the right coronary system. The mean regional ejection fraction of the posterobasal or diaphragmatic wall was 28.0% or 28.2% before operation and improved to 43.1% or 43.2% after coronary artery bypass graft, respectively. The flow of right gastroepiploic artery seemed to distribute adequately to the revascularized area. Long-term results have not yet been proved; the use of simultaneous right gastroepiploic artery and internal thoracic artery grafts, however, thus produced excellent results, as seen from improvements in both left ventricular wall motion and early postoperative exercise performance.

Adult↗

PubMed1992

RFP is a DNA binding protein associated with the nuclear matrix.

We reported that the RFP gene encodes a protein with putative zinc finger domains and was involved in the activation of the ret proto-oncogene. To further characterize the RFP protein, we developed a polyclonal antibody against the product synthesized from a fragment of the RFP cDNA expressed in Escherichia coli. Western blot analysis showed that RFP was identified as a 58 kDa protein in cell lysates from four human and rodent cell lines and from mouse testis. In addition, a unique 68 kDa protein was detected in the testis. Using AH7974 (rat ascites hepatoma) and Raji (human Burkitt lymphoma) cells, we demonstrated strong association of RFP with the nuclear matrix. Furthermore, RFP solubilized from the nuclear matrix had DNA-binding activity although it appears to bind more preferentially to double-stranded DNA than to single-stranded DNA. These results thus suggest that RFP may play a role in molecular processes which occur in the nuclear matrix.

Amino Acid Sequence↗

PubMed1992

Accelerated proliferation and interleukin-2 production of thymocytes by stimulation of soluble anti-CD3 monoclonal antibody in transgenic mice carrying a rabbit protein kinase C alpha.

Protein kinase C (PKC) has been believed to play an important role in the differentiation/proliferation of various kinds of mammalian cells. To analyze its function in living animals, we have established a transgenic mouse line carrying rabbit protein kinase C alpha cDNA under the control of the regulatory element of human CD2. Thymocytes of these transgenic mice overexpressed PKC alpha. Interestingly, the increase of PKC alpha was detected mainly in membrane fractions of transgenic thymocytes. Although the transgenic thymocytes did not show any distinct proliferative features in vivo, they displayed a unique property to extensively proliferate and produce interleukin-2 (IL-2) in response to the stimulation by a soluble form of anti-CD3 monoclonal antibody (mAb), an incomplete agonist for proliferation of normal thymocytes. Furthermore, co-stimulation of the phorbol 12-myristate 13-acetate and anti-CD3 mAb intensely provoked the transgenic thymocytes to release IL-2. For the first time this result provided the direct evidence that PKC alpha translocated to the cell membrane of thymocytes works as an active second messenger of the T cell receptor-CD3 complex-delivered signal for proliferation and IL-2 production.

Animals↗

PubMed1992

Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature.

During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome.

Adult↗

PubMed1992

Morphological and functional study of free arterial grafts.

Morphological and functional changes of free arterial grafts in dogs were studied for 3 weeks after implantation and the changes were compared to those in implanted free vein grafts. In the arterial grafts, endothelial cells with abundant pinocytotic vesicles and some cytoplasmic folds were observed by transmission and scanning electron microscope and cell detachment was seen only at the site of anastomosis, while most cells were detached in the vein grafts. The site of mechanical damage in the arterial grafts was covered by regenerated endothelial cells which showed similar morphological findings to the normal arterial endothelial cells. In contrast, regenerated cells in the vein grafts started to cover the denuded area 7 days after the implantation and had completely covered it by 3 weeks. Prostacyclin was produced more abundantly in arterial grafts than in vein grafts at any phase after implantation. The level of prostacyclin production was between 30 and 40 pg/mg in any phase after implantation of free arterial grafts, while in vein grafts the level was 2.5 pg/mg at the day of implantation and increased to 13.6 pg/mg at 21 days. This study showed that the endothelial cells were well preserved and the level of prostacyclin production was high in the arterial grafts, and thus the grafts seemed to show potent anti-thrombogenicity after implantation. Although late changes in arterial and vein grafts were not investigated in this experimental protocol, these results may suggest that the arterial graft is superior to the vein graft even in the early period after its implantation as a free graft.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

The effectual level of ursodeoxycholic acid in therapy for non-advanced chronic cholestasis is fifty percent of total serum bile acids.

Ursodeoxycholic acid therapy (600 mg/day) was evaluated in twelve patients with non-advanced chronic cholestasis. Within four months, ursodeoxycholic acid replaced more than 50% of total bile acids in 8 patients and the reduction of serum gamma-glutamyltranspeptidase, alkaline phosphatase and transaminases averaged 30% or more. The serum levels of chenodeoxycholic acid depend on those of ursodeoxycholic acid, but are not related to those of biochemical parameters. Drug therapy was continued in three poor responders for 2-3 four-month periods. In one case an increase of the serum proportion of ursodeoxycholic acid was associated with a reduction in biochemical parameters. The other two cases had high serum levels of chenodeoxycholic acid and/or cholic acid throughout the entire course of treatment. While the treatment of chronic cholestasis requires an effectual serum proportion of ursodeoxycholic acid, it is important to distinguish endogenous persistent hyper-bile-acidemia from ursodeoxycholic acid-related acidemia.

Adult↗

PubMed1992

Long-term follow-up results after reconstruction of the mitral valve by leaflet advancement.

In this study, we discuss the clinical results of mitral leaflet advancement performed on 29 patients over the past 10 years and attempt to determine the indication. Preoperative diagnosis of mitral valve lesion consisted of mitral regurgitation in 21 patients and mitral stenosis in 8 patients. Mitral valve repair was applied to the anterior mitral leaflet in 2, the posterior mitral leaflet in 25, and bilateral leaflets in 2 patients. Reoperation was performed on 13 patients, and 1 patient died of renal failure immediately after reoperation. No reoperation was needed for 96.6% of the patients at 1 year, 89.5% at 5 years, 75.0% at 8 years, 63.8% at 10 years, and 52.6% at 15 years postoperatively. At reoperation, the repaired mitral leaflet was found to be calcified in 3 patients more than 9 years after the initial operation. Of the 12 survivors without reoperation, mitral stenosis associated with regurgitation was obvious in 6 patients. Of the 21 patients with preoperative mitral regurgitation, 90.0% showed no deterioration at 5 years, 79.7% at 8 years, and 69.1% at 10 years. On the other hand, for the 8 patients with mitral stenosis, the rates were 87.5% at 1 year, 62.5% at 5 years, 50.0% at 8 years, and 25% at 10 years. Our results suggest that mitral leaflet advancement shows satisfactory results in patients with mitral regurgitation but is not successful for patients with mitral stenosis in the long term because the repaired valve tends to be stenotic in the late postoperative period.

Adolescent↗