Biomedical subjects
Publications and source records attributed to Y Yamane.
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The mutagenicity of airborne particles was studied in the Ames Salmonella system. The mutagenic activity of benzene extracts from airborne particles was more active in strain TA98 in the presence and absence of S9 mix than in strain TA100. The presence of mutagens, other than benzo[a]pyrene (B[a]P), which did not require S9 mix, was indicated. However, the monthly variation of direct-acting mutagenic activity showed a pattern similar to that of B[a]P at atmospheric concentration. The monthly variations of atmospheric NO, NO2, NO-2 and NO-3 concentrations were also similar to that of the direct-acting mutagenic activity. Atmospheric concentrations of heavy metals such as Pb, Zn, Cd, V and Cu were also found to be related to direct-acting mutagenic activity. These results suggest that emissions from automobiles, home heaters and power plants etc. may be a primary source of atmospheric, direct-acting mutagens. It is suggested that secondary direct-acting mutagens might be partly formed by the nitration of polycyclic aromatic hydrocarbons (PAH) with NO2 in the atmosphere because concentrations of B[a]P, NO2 and NO-3 increased simultaneously when the highest direct-acting mutagenic activity was observed.
Based on the results of our previous pilot study, we conducted a multi-institutional phase II study of combination chemotherapy consisting of oral UFT (Taiho Pharmaceutical Co. Ltd, Tokyo) plus cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). UFT capsule containing 100 mg tegafur and 224 mg uracil was orally administered in two divided doses on days 1 through 21 making the total tegafur dose 400 mg/m(2)/day (maximum 600 mg/body). CDDP was administered by drip infusion at a dose of 20 mg/m(2) on a 5-day schedule from day 8 to 12. Treatment was repeated every 4 weeks as long as the criteria for initiation of therapy were still met. Between April 1995 and March 1997, 51 patients were entered into the study. The mean age of all 50 eligible patients was 64 years(range: 40-78). There were 21 patients with clinical stage IIIB disease and 29 patients with IV disease. Thirty-two patients had adenocarcinoma, 14 had epidermoid carcinoma, and four had large cell carcinoma. Of the 47 assessable patients, 18 achieved a partial response with an overall response rate of 38.3% (95% confidence interval: 24.4-52.2%). The median response duration was 113 days. The median survival time of the eligible patients was 12.8 months, and the 1-year survival rate was 54%. Among the 51 patients enrolled, grade 3 or 4 leukopenia developed in one patient (2%), neutropenia in six patients (11. 8%), thrombocytopenia in six patients (11. 8%), and anemia in three patients (5. 9%). Non-hematological grade 3 or 4 toxicities included anorexia in 10 patients (19.6%), nausea in ten (19.6%), vomiting in two (3.9%), and diarrhea in two (3. 9%). Grade 3 abnormal laboratory data included bilirubinemia in four (7. 8%), GPT elevation in one (2.0%), and hematuria in one (2.0%). In conclusion, combination of CDDP plus oral UFT is efficacious, with low toxicity, in the treatment of advanced NSCLC. In particular, the low hematological toxicity may warrant application of this regimen to the treatment of elderly patients and in trials of concurrent chemoradiotherapy in patients with locally advanced NSCLC.
OBJECTIVE: To describe the use of a detachable coil for transcatheter closure (TCC) of patent ductus arteriosus (PDA) in 2 dogs. STUDY DESIGN: Clinical study. ANIMALS: Two female Pembroke Welsh Corgi dogs with PDA. METHODS: Using fluoroscopic guidance, an 8-mm-diameter coil stent with 5 loops (detachable coils for PDA closure) was inserted via catheterization of the femoral artery. The catheter was passed through the PDA into the pulmonary artery. The coil was withdrawn so that 1.5 loops remained on the pulmonary side of the orifice of the ductus. The rest of the loops were pushed out from the catheter into the ductus. After confirming the correct placement of the coil and the effectiveness of the occlusion, the delivery wire was detached from the coil. RESULTS: Insertion of the coil was easily performed, even without previous experience. Immediate and marked decrease of the cardiac murmur was auscultated. Only slight residual flow was detected by angiography conducted 3 months' postoperatively. The dogs experienced quick and uneventful recovery after coil placement and required minimal postoperative care. Follow-up evaluation of the dogs showed no functional clinical signs of PDA, and no cardiac abnormalities were detected on electrocardiographic, phonocardiographic, and echocardiographic examination. In dog 1, the residual flow had disappeared on the color-flow Doppler echocardiographic examination at 18 months' postoperatively. CONCLUSION: TCC using a detachable coil was easy, safe, and effective in 2 dogs with PDA. The minimal residual shunting observed only by echocardiography seemed hemodynamically insignificant. CLINICAL RELEVANCE: This method can be used as an alternative to traditional surgical methods.
The safety of a vascular graft that can grow with the growth of its recipients was evaluated during long-term implantation in experimental animals. An acellular matrix made of human saphenous vein was cross-linked with a polyepoxy compound to give controlled biodegradability, hydrophilicity, and antithrombogenic properties. Four millimeter internal diameter (ID) grafts, enveloped with a polyester mesh tube of 10 mm ID were implanted in 15 puppies. The diameter of the graft grew to 9.5 mm after 1 year from the original 4 mm, and remained stable for 2 years and 7 months of observation. The newly formed neointima reinforced with polyester mesh was composed of smooth muscle cells covered with endothelial cells. The original vein graft was completely absorbed, and there were no degenerative changes such as calcification or aneurysmal dilatation. The graft maintained the expected size.
The authors successfully applied a method to accelerate endothelialization by tissue fragmentation to a small diameter fabric vascular prosthesis. Tissue fragment seeded grafts showed rapid healing of the neointima. The thrombogenicity of the collagen fibrils in the fragments, however, caused major problems when the method was applied to small diameter grafts: the positively charged collagen fibrils aggregated the negatively charged platelets. The authors masked the fibrils electrostatically with heparin molecules, which are negatively charged. A canine jugular vein was resected, minced into tissue fragments, and suspended in the heparin solution; it then was sieved through the wall of a fabric prosthesis. The grafts (4 mm internal diameter and 3.5 cm in length) were implanted into both carotid arteries of six dogs (12 grafts). Tissue fragment seeded grafts without heparin also were implanted into six dogs. As a control, preclotted fabric grafts were implanted into six dogs (12 grafts). These grafts occluded within 1 week, whereas all the masked grafts were patent without thrombi. In vitro examination of heparin release revealed that approximately 92% of heparin in the graft was released during the first 5 hr, but approximately 6% remained after 25 hr. These results indicate that the method is applicable to small diameter arterial grafts.
A vascular prosthesis that can induce a neointima similar to a natural arterial wall is reported. The authors have developed a sealing method using autologous tissue fragments. The sealed graft showed many advantages, with characteristic neointima formation in an animal study. The grafts were implanted in the thoracic descending aortae of 40 dogs and were removed from 1 hour to 608 days after implantation. Another 40 dogs, used as controls, had a fabric graft implanted using the preclotting method. The luminal surface of the sealed graft was completely endothelialized and the original adipose tissue fragments were absorbed within 1 month. Smooth muscle cells infiltrated and proliferated at the same time as endothelialization took place. Most of the smooth muscle cells were arranged in parallel rows and oriented circumferentially within the graft. At 1 month, elastic fibers appeared around the smooth muscle cells near the anastomotic sites. In the long-term specimens, these elastic fibers constituted a fine lamina in the neointima. Intimal hyperplasia and degenerative changes in the neointima were not observed. These results indicated that the sealing method could induce a very stable neointima with a smooth muscle cell layer and elastic laminae similar to a natural arterial wall within a short period of time throughout the graft wall, with maintenance of the neointima for a long period of time after implantation.
A new cardiac wall substitute (PC graft) was developed using equine pericardium cross-linked with a polyepoxy compound. Compared with glutaraldehyde cross-linked pericardium (GA graft), the PC graft showed an approximately 10 times higher affinity for fibroblasts as measured by our in vitro cell migration and proliferation test. Six PC grafts (5 x 3 cm) were implanted into the right ventricular-pulmonary outflow tract position as a cardiac wall patch. Three GA grafts were used as controls. The PC grafts showed excellent handling during surgery because of their softness and elasticity. These grafts were explanted at 2 and 7-8 weeks after implantation. All PC grafts showed a white and glistening surface without any thrombus formation except in one case where thrombus deposition was observed in the center of the graft. In the GA grafts, thrombus adhered to the luminal surface. Light microscopic observation showed that the PC graft surface was covered with a connective tissue layer and significant fibroblast infiltration. Approximately 60% of the area infiltrated by these fibroblasts was endothelialized, whereas in the GA graft, endothelialization was limited to within 2-5 mm of the suture line. Other areas were covered with a thrombus layer without any endothelial cells or fibroblast infiltration. PC cross-linking can maintain the biologic and mechanical properties of the original materials. The PC graft offered excellent affinity for fibroblast migration and proliferation, which induced an endothelial cell lining on the surface. The results of this experiment indicated that the PC graft, which obtained the natural antithrombogenic property, was superior to a GA graft in terms of safety as well as mechanical, physiologic, and biologic properties as a cardiac wall substitute.
A fabric vascular prosthesis sealed with succinylated collagen (SC) was developed as an arteriovenous (A-V) shunt graft for hemodialysis. The SC graft was soft, pliable, flexible, and puncturable, with quick hemostasis. A needle puncture made a smaller hole in the SC graft wall than in a control expanded-polytetrafluoroethylene (e-PTFE) graft such as is usually used for an A-V shunt. The SC graft was extremely hydrous, because it is sealed with water, which is absorbed into the intermolecular spaces of negatively charged collagen. The SC suspension was injected with pressure into a knitted fabric vascular prosthesis wall (water permeability, 1,200 ml) so as to become entangled in the Dacron network. The graft then was lyophilized and thermally cross-linked. Water leakage from six holes created by an 18 G needle puncture in vitro under water pressure of 120 mmHg was 34.5 +/- 29.9 ml/min in the SC graft and 169.9 +/- 38.5 ml/min in the control e-PTFE graft. Hemostatic time at six 18G needle puncture sites on grafts implanted in the abdomen of 12 dogs was 4.5 +/- 2.5 mins in the SC graft and 34.2 +/- 11.5 mins in the control graft. After implantation, the luminal surface of the SC grafts had a thinner thrombus layer than did the control grafts. After 1 week, a thin thrombus layer covered the luminal surface of the SC grafts, and puncture sites were recognized as small dots under it, but in the control grafts, the thrombus layer was thick and the puncture sites could not be seen. These results suggest that the SC graft is less thrombogenic and has less blood leakage from the puncture sites than does the control graft.