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Biomedical subjects

Y Tomizawa

Publications and source records attributed to Y Tomizawa.

At least 19 recordsLinked to original sources

Allelic losses on chromosome 3p are accumulated in relation to morphological changes of lung adenocarcinoma.

We performed allelotyping analysis at nine regions on chromosome 3p using 56 microdissected samples from 23 primary lung adenocarcinomas to examine the process of progression within individual lung adenocarcinoma with various grades of differentiation. Identical allelic patterns among various grades of differentiation were found in eight cases. Accumulation of allelic losses from high to lower differentiated portions was found in seven cases and accumulation of allelic losses from low to higher differentiated portions was found in five cases. Various allelic patterns among various grades of differentiation were found in three cases. These results suggested that allelic losses on 3p play an important role in morphological changes of lung adenocarcinomas. We also investigated the relationship between allelic losses on 3p and histological subtypes of lung adenocarcinoma. The frequencies of allelic losses at 3p14.2 and telomeric region of 3p21.3 were higher in papillary type tumour (nine out of 14, 64% and 11 out of 15, 73%) than in bronchioloalveolar carcinoma-type tumour (one out of 8, 13%; P=0.031 and four out of 12, 33%; P = 0.057). These results indicated that allelic losses at 3p14.2 and telomeric region of 3p21.3 are related to pattern of the proliferation of lung adenocarcinoma.

Adenocarcinoma↗

[Surgical repair of left ventricular aneurysm; long-term results].

OBJECTIVE: The aim of this study was to evaluate the late results of left ventricular (LV) aneurysm repair. METHODS: From July 1968 to 1999, 86 consecutive patients (74 male, 12 female, mean age 56.0 +/- 9.3) underwent LV aneurysm repair at our institute. The surgical methods were as follows; linear repair in 71 patients, endoaneurysmorrhaphy in 5, endoventricular circular plasty in 4, Jatene method in 1 and plication of aneurysm in 5. Thirty-nine patients underwent concomitant myocardial revascularization. Major arrhythmias occurred in 38 patients. The results were retrospectively reviewed and follow-up was achieved in 95.3%. RESULTS: There were 6 operative deaths and 4 hospital deaths. Actuarial survival rate including the 10 deaths was 72.7% at 5 years and 46.3% at 10 years. In patients with coronary artery bypass grafting (CABG), survival rate was 82.2% at 5 years and 56.3% at 10 years, and was significantly higher than that in those without revascularization (p = 0.01). In patients without arrhythmias, survival rate was 79.2% at 5 years and 55.0% at 10 years, and was significantly higher than that in patients with arrhythmias. CONCLUSIONS: The patients were not homologous and the techniques were not the same; however, in spite of these study limitations, patients who underwent revascularization, and were without major arrhythmias preoperatively, had better long-term survival.

Adult↗

An experimental study of self-expanding ureteric metallic stents: macroscopic and microscopic changes in the canine ureter.

OBJECTIVE: To evaluate the efficacy and safety of self-expanding metallic stents after insertion into the canine ureter. MATERIALS AND METHODS: Actively expanding metallic (Nitinol) stents (diameter 8-10 mm, length 4-6 cm) were placed in eight mongrel dogs (18-34 kg). Under general anaesthesia, a midline abdominal incision was made and a stent inserted directly into the ureter through a small incision; each animal was stented on one side. The dogs were assessed after 6 or 19 days or 2, 5 (two), 6 (two) and 7 months. Ureteric specimens were evaluated both macroscopically and microscopically. RESULTS: Macroscopically there was no leakage of urine in any of the animals. On day 6 the inserted stent was patent despite blood clots in the mesh. The lumen was smooth and shiny in three dogs examined at 5, 6 and 7 months. One of the two dogs assessed at both 5 and 6 months had hydronephrosis associated with papillary hyper-epithelialization inside the stent, while the other animals had no dilatation of the renal pelvis. Microscopically there was loss of epithelium and bleeding of the ureteric wall at 6 days. Epithelial regeneration started after 19 days and was complete in the lumen at 2 months, with the stent incorporated into the wall of the ureter. Epithelialization was maintained up to 7 months, after which the problem of urothelial hyperplasia persisted, but an adequate lumen was maintained by epithelial regeneration. This epithelium was smooth and shiny, and composed of thin layers of cells. CONCLUSION: Self-expanding metallic stents may be effective if hyperplastic epithelialization does not occur, as the stent was epithelialized within 2 months and the regenerated epithelium maintained for up to 7 months. Metallic stents may be useful for treating patients with renal failure caused by ureteric stenosis from malignant tumours.

Animals↗

[Dissecting aneurysm of ventricular septum following acute inferior myocardial infarction].

Dissecting aneurysm of the ventricular septum as a complication after myocardial infarction (MI) is very rare. The patient was a 70-year-old women who was diagnosed with acute inferior MI. Three months after MI, catheterization showed a left ventricular aneurysm of the inferior wall, and left-to-right ventricular shunt flow was detected in the aneurysm. Echocardiography showed that the inferior left ventricular free wall was aneurysmal and dissected from the septal wall. Nine months after MI, chronic heart failure was uncontrollable by medication. At surgery, a tear (5 mm long) in the dissecting aneurysm of the ventricular septum was found and closed directly using 2 felt patches, and aneurysmectomy was performed using felt strips. The postoperative course was uneventful and she has been free from any complication for over 1 year.

Aged↗

[Early and mid-term results of all arterial graft coronary artery bypass grafting using bilateral internal thoracic and radial arterial conduits].

From March 1996 to May 2000, 41 patients [age 39-78 (mean 63.5 +/- 8.8) years, 90.2% male] underwent all arterial multiple coronary artery bypass grafting (CABG) using bilateral internal thoracic (BiITA) and radial (RA) arterial conduits. The reason for using RA was that the right gastroepiploic artery (RGEA) was small or occluded on preoperative angiography, a history of upper abdominal surgery or disease, or the right coronary arterial lesion was proximal and mild. The BiITA were used as in situ grafts and the proximal anastomosis of RA was to the ascending aorta in all cases. All patients underwent conventional elective CABG with median sternotomy using cardiopulmonary bypass. The mean number of anastomoses was 3.3 +/- 0.5 branches and complete revascularization rate was 80.5%. Postoperative follow-up averaged 20 months and the longest was 50 months. There was no early death, and overall graft patency 2-3 weeks after surgery was 96.2% (LITA 94.0%, RITA 97.6%, RA 97.6%). Four-year actuarial survival rate was 96.4 +/- 3.5% (1 patient: 9 months, no cardiac death), and cardiac event-free rate after surgery was 89.7 +/- 4.9% [4 patients: percutaneous transluminal coronary angioplasty (PTCA)]. However, once patients were discharged from hospital, cardiac event-free rate was 100%. These excellent results suggest that all arterial graft CABG was satisfactory, and RA can be used as a third suitable arterial bypass conduit, if RGEA cannot be used or is unsuitable for use.

Adult↗

Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B.

Semaphorins SEMA3B and its homologue SEMA3F are 3p21.3 candidate tumor suppressor genes (TSGs), the expression of which is frequently lost in lung cancers. To test the TSG candidacy of SEMA3B and SEMA3F, we transfected them into lung cancer NCI-H1299 cells, which do not express either gene. Colony formation of H1299 cells was reduced 90% after transfection with wild-type SEMA3B compared with the control vector. By contrast, only 30-40% reduction in colony formation was seen after the transfection of SEMA3F or SEMA3B variants carrying lung cancer-associated single amino acid missense mutations. H1299 cells transfected with wild-type but not mutant SEMA3B underwent apoptosis. We found that lung cancers (n = 34) always express the neuropilin-1 receptor for secreted semaphorins, whereas 82% expressed the neuropilin-2 receptor. Because SEMA3B and SEMA3F are secreted proteins, we tested conditioned medium from COS-7 cells transfected with SEMA3B and SEMA3F and found that medium from wild-type SEMA3B transfectants reduced the growth of several lung cancer lines 30-90%, whereas SEMA3B mutants or SEMA3F had little effect in the same assay. Sequencing of sodium bisulfite-treated DNA showed dense methylation of CpG sites in the SEMA3B 5' region of lung cancers not expressing SEMA3B but no methylation in SEMA3B-expressing tumors. These results are consistent with SEMA3B functioning as a TSG, the expression of which is inactivated frequently in lung cancers by allele loss and promoter region methylation.

Animals↗

Inactivation of human SRBC, located within the 11p15.5-p15.4 tumor suppressor region, in breast and lung cancers.

A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors. hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70%) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60%) of 5 primary breast tumors and 11 (79%) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5'azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.

Amino Acid Sequence↗

Benefit of bilateral over single internal mammary artery grafts for multiple coronary artery bypass grafting.

BACKGROUND: The aim of this study was to evaluate the performance of bilateral internal mammary artery (BIMA) grafts in isolated CABG. METHODS AND RESULTS: Beginning in April 1985, elective primary multiple CABG for multivessel disease was performed in 1131 patients. The early and late results of 688 patients who received single internal mammary artery (SIMA) grafts and 443 patients who received BIMA grafts were compared (median follow-up, 6.15 years). Hospital mortality was not significantly different in the SIMA (0.9%) and BIMA (0.9%) groups. Graft patency was 97.3% in the BIMA group and 94.3% in the SIMA group (P<0.0001). The 7-year repeated CABG-free rate was significantly higher in the BIMA group (P=0.026). The 7-year new myocardial infarction-free rate in all patients tended to be higher in the BIMA group (P=0.06). The hazard ratio for all death or repeated CABG in patients with ejection fractions >0.4 and age <71 years was lower in the BIMA group (P=0.0499). CONCLUSIONS: Our data suggest that the use of BIMA grafts in patients with in situ coronary artery anastomoses achieves a significantly higher repeated CABG-free rate in all patients compared with the use of SIMA.

Adolescent↗

Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells.

Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in the 120 kb 3p21.3 critical region contained in nested lung and breast cancer homozygous deletions. Mutation of FUS1 is infrequent in lung cancers which we have confirmed in 40 other primary lung cancers. In addition, we found no evidence for FUS1 promoter region methylation. Because haploinsufficiency or low expression of Fus1 may play a role in lung tumorigenesis, we tested the effect of exogenously induced overexpression of Fus1 protein and found 60-80% inhibition of colony formation for non-small cell lung cancer lines NCI-H1299 (showing allele loss for FUS1) and NCI-H322 (containing only a mutated FUS1 allele) in vitro. By contrast, a similar level of expression of a tumor-acquired mutant form of FUS1 protein did not significantly suppress colony formation. Also, induced expression of Fus1 under the control of an Ecdysone regulated promoter decreased colony formation 75%, increased the doubling time twofold, and arrested H1299 cells in G1. In conclusion, our data are consistent with the hypothesis that FUS1 may function as a 3p21.3 TSG, warranting further studies of its function in the pathogenesis of human cancers.

Alleles↗

Coronary artery bypass with only in situ bilateral internal thoracic arteries and right gastroepiploic artery.

BACKGROUND: With the rapid advance of catheter intervention, the direction taken by surgeons is not only to make conventional CABG less invasive but also to pursue better long-term results by using more arterial conduits. METHODS AND RESULTS: Between July 1989 and April 2000, 239 patients (218 men, 21 women) with a mean age of 59.7 (range 39 to 79) years underwent CABG with exclusive use of both internal thoracic arteries (ITAs) and the right gastroepiploic artery (RGEA). ITA grafts were harvested by using the skeletonization technique. Most patients (96%) had either triple-vessel or left main disease. Fifty percent of the patients were diabetic, and 16 were being treated with insulin. The left ventricular ejection fraction was </=40% in 46 patients (19%). Eleven patients (5%) had chronic renal failure and were on hemodialysis. Follow-up was completed in 235 patients (98%). Postoperative follow-up averaged 43 (range 1 to 129) months. Sequential grafting was performed in 64 patients, and the mean number of anastomoses was 3.3. One patient (0.4%) died of mediastinitis on the 53rd postoperative day. Graft patency was confirmed angiographically in 230 patients (96%) 2 to 3 weeks after surgery. The patency rate was 97.1% for the left ITA, 99.6% for the right ITA, and 95.5% for the RGEA. Five-year actuarial survival rate was 92.9%, and the cardiac death-free rate was 97.8%. CONCLUSIONS: Complete arterial grafting with both ITAs and RGEA was associated with minimal operative risk, a high early graft patency rate, and excellent long-term results.

Adult↗

Reconstruction of the left ventricle in a patient with cardiac hemangioma at the apex.

Cardiac hemangiomas in the left ventricle are extremely rare. A 34-year-old woman, without symptoms, with a diagnosis of cardiac tumor at the apex of the left ventricle was referred to us. The tumor was surgically resected, and the diagnosis was hemangioma. The Jatene technique, originally introduced for left ventricular aneurysmectomy was excellent for repair after resection of a cardiac tumor at the apex.

Adult↗

Electrovaporization using a rollerball electrode for flat or small papillary tumors of the bladder: basic study in dogs.

PURPOSE: We investigated electrovaporization of flat bladder tumors with a rollerball electrode 3 mm in diameter as a substitute for conventional transurethral resection with a cutting loop. MATERIALS AND METHODS: A basic study of the action of electrovaporization was performed in dogs. The bladder was exposed under general anesthesia in three mongrel dogs. The rollerball electrode was attached to the resectoscope and inserted into the bladder via a cystostomy. Then electrovaporization was performed with a low or high pressure on the electrode tip and a speed of about 1 cm/sec using a Force 40 generator. The cutting mode power was set at 100 W or 200 W. The effects of the rollerball and cutting loop electrodes were also examined in the coagulation mode (45 W) as a control. RESULTS: A deeper vaporization zone was obtained by using a power of 200 W in the cutting mode than with a power of 100 W, and a desiccation zone was found below the vaporization zone (VZ). The VZ was thicker with a high contact pressure than with a low contact pressure. This VZ was deeper than the tissue defect and heat-affected zone obtained using a rollerball electrode or cutting loop electrode in the 45 W coagulation mode. CONCLUSION: Although caution is required because the VZ can become too deep with excessive pressure, the rollerball electrode seems to be safer and more useful than the cutting loop electrode for resection of flat or small papillary bladder tumors.

Animals↗

Off-pump reimplantation of anomalous origin of the right coronary artery.

A 30-year-old man was diagnosed to have an anomalous origin of the right coronary from the pulmonary artery. Through a mini-sternotomy, without extracorporeal circulation, reimplantation of the anomalous origin of the right coronary artery from the pulmonary artery to the aorta was successfully performed. This is a successful case of off-pump cardiac correction of this type of isolated anomaly, using a minimally invasive approach.

Adult↗

Coronary artery bypass grafting in 105 patients with hemodialysis-dependent renal failure.

This study was proposed to define early and long-term results of coronary artery bypass grafting (CABG) in dialysis-dependent renal failure (RF) patients, and preoperative patient characteristics. This study included 105 patients (87 males and 18 females; mean age 60.0 +/- 9.0 years, range 39-79) with RF on maintenance dialysis (hemodialysis 100, peritoneal dialysis 5) who underwent isolated CABG between August 1985 and April 2000. Postoperative follow-up was completed in 100% and averaged 3.1 years. There were 22 emergency and 2 re-CABG cases. Previous myocardial infarction (MI) was found in 55 patients (52%), and unstable angina was noted in 53 patients (50%). Diabetes mellitus was the cause of RF in 50 patients (48%; 24 patients required insulin). There was 1 case of single vessel disease, 31 cases of double vessel disease, 54 cases of triple vessel disease, and 19 cases of left main disease. Preoperative left ventriculography was performed in 92 patients (88%). Left ventricular ejection fraction (LVEF) was 48.3 +/- 15.8% (range 11-74%) and was 40% or less in 25 patients (27%). The mean number of distal anastomoses was 2.5 (range 1-5). Three patients received only vein grafts, but all were cases of emergency CABG. The remaining 102 patients (97%) received at least 1 arterial conduit. Among them, 64 patients received only arterial conduits, and 72 patients received 2 or more distal anastomoses with arterial conduits. Five patients (4.8%) died within 30 days after CABG (2 cardiac deaths and 3 noncardiac deaths), and 8 patients (7.6%) died beyond 30 days after CABG before discharge (all noncardiac deaths). The cause of 2 cardiac deaths was abrupt circulatory collapse during or after hemodialysis in patients with severe left ventricular dysfunction (LVEF; 11% and 28%) in the early postoperative period. The causes of 8 noncardiac deaths included infection in 4 and rupture of aortic aneurysm, stroke, sleep apnea syndrome, and mesenteric infarction. During the follow-up period, there were 29 late deaths (8 cardiac, 13 noncardiac, and 8 sudden death), 6 MIs, 13 percutaneous transluminal coronary angioplasty, and 1 re-CABG. The 5-year actuarial survival rate was 59.8%, the cardiac death-free rate was 83.0%, and the cardiac event-free rate was 62.4%. Although CABG in patients on hemodialysis is associated with high early and long-term mortality in terms of both cardiac and noncardiac deaths in proportion to the severity of the preoperative condition, long-term survival was still better than that of general dialysis patients. Meticulous perioperative management may be the key factor in the improvement of early results.

Adult↗

[Postoperative rupture of abdominal aortic aneurysm in patients with ischemic heart disease and other organ disease].

We experienced two cases of rupture of an abdominal aortic aneurysm during the early postoperative period of coronary artery bypass grafting (CABG). A 71-year-old man on hemodialysis (HD) was diagnosed with ischemic heart disease (IHD) and abdominal aortic aneurysm (AAA) of 70 mm in size. After CABG, he developed symptoms of acute pancreatitis and died of rupture of AAA on the 12th postoperative day. A 74-year-old man with early gastric cancer was diagnosed with IHD and AAA of 70 mm. After CABG and gastrectomy, he died of rupture of AAA due to anticoagulant therapy on the 3rd postoperative day. One-stage operation should be performed in patients with IHD, AAA more than 60 mm in size and other organ disease. It is important to control blood pressure and anticoagulant therapy appropriately during the early postoperative period when graft replacement for AAA is not performed simultaneously. Careful observation is required to establish the differential diagnosis of acute pancreatitis and impending rupture of AAA in patients on HD.

Aged↗

Sextuple coronary artery bypass grafting using only in situ arterial conduits.

Sequential bypass in coronary artery bypass grafting with in situ arterial conduits, the bilateral internal thoracic arteries and the right gastroepiploic artery, is one of the most important procedures using a limited number of in situ arterial conduits to revascularize a wide area, although it demands rather difficult techniques. We report a case of a 50-year-old man who underwent sextuple bypass using only in situ arterial grafts with three sequential anastomoses.

Coronary Artery Bypass↗

Autologous tissue-fragmented extracardiac conduit with rapid, stable endothelialization due to angiogenesis.

OBJECTIVES: Autologous angiogenic cytokines are known to activated by mincing stimulation, and well regulated in vivo. We applied this tissue fragmentation technique to a low-pressure pulmonary extracardiac conduit to obtain rapid endothelialization and stable neointima formation due to angiogenesis. METHODS: Subcutaneous adipose tissue was obtained, minced, suspended, and sieved through highly porous fabric vascular prosthesis by pressurized injection. The adipose tissue fragmented graft with an autologous fresh pericardial monocusp valve was implanted between the right ventricle and the pulmonary artery in 13 dogs. The same grafts without fragments were implanted in 8 dogs as controls. No anticoagulation therapy was given. RESULTS: Grafts were removed 6 to 1,128 days after implantation. In the developed grafts, angiogenesis occurred throughout the interstices of the graft wall from the adventitial side, and host cells proliferated and migrated. Endothelialization was completed throughout developed grafts at 2 weeks. The intima was still thin up to 1,128 days and free of degenerative changes. In control grafts, however, capillary infiltration was limited to perigraft tissue at 2 weeks and endothelialization was not completed by 3 months. Under the endothelial cell layer, laminal elastic fibers were formed through the developed graft wall by 4 months and still maintained at 1,128 days. CONCLUSIONS: The results demonstrated that adipose tissue fragmented extracardiac conduits induce rapid endothelialization and maintained thin intima with laminal elastic fibers. Long-term durability is expected based on results from using this technique in a low-pressure pulmonary system in dogs.

Adipose Tissue↗

[Open heart surgery in three patients receiving dialysis for more than 20 years].

In Japan, the number of chronic hemodialysis (HD) patients is increasing, and there are 7,000 cases with a more than 20 year history of HD. At our institute, we have experienced 135 cases of open heart surgery in patients on HD, including 92 isolated CABG cases and 43 other open heart surgery cases. However, open heart surgery for patients with a more than 20 year history on HD is rare. Open heart surgery on HD patients is rather difficult, since perioperative management can be complicated and special care must be taken for prophylaxis of infection, fluid and electrolyte management and anticoagulation therapy. Many complications have been published in HD patients. At our institute, 3 cases of open heart surgery in patients with more than a 20 year history of HD have been performed. These included triple CABG, double CABG + AVR and double CABG in a post-kidney transplantation patient. They were discharged uneventfully with angiographically patent grafts. It is concluded that for CABG in patients on HD, aggressive use of arterial conduits for revascularization is recommended. For patients with a transplanted kidney, careful management against dysfunction and rejection is necessary.

Angina, Unstable↗