Collagen as a vehicle for drug delivery. Preliminary report.
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Biomedical subjects
Publications and source records attributed to T Miyata.
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A heuristic approach to search for the maximum-likelihood (ML) phylogenetic tree based on a genetic algorithm (GA) has been developed. It outputs the best tree as well as multiple alternative trees that are not significantly worse than the best one on the basis of the likelihood criterion. These near-optimum trees are subjected to further statistical tests. This approach enables ones to infer phylogenetic trees of over 20 taxa taking account of the rate heterogeneity among sites on practical time scales on a PC cluster. Computer simulations were conducted to compare the efficiency of the present approach with that of several likelihood-based methods and distance-based methods, using amino acid sequence data of relatively large (5-24) taxa. The superiority of the ML method over distance-based methods increases as the condition of simulations becomes more realistic (an incorrect model is assumed or many taxa are involved). This approach was applied to the inference of the universal tree based on the concatenated amino acid sequences of vertically descendent genes that are shared among all genomes whose complete sequences have been reported. The inferred tree strongly supports that Archaea is paraphyletic and Eukarya is specifically related to Crenarchaeota. Apart from the paraphyly of Archaea and some minor disagreements, the universal tree based on these genes is largely consistent with the universal tree based on SSU rRNA.
BACKGROUND: To identify the appropriate puncture points in the bile duct to avoid catheter dislodgement. METHODS: Percutaneous transhepatic biliary drainage catheters (n = 300) were placed in 242 patients. The frequency of dislodgement (complete dislodgement or bending of the catheter) was prospectively investigated. The puncture site of the bile duct was classified on the ultrasonographic findings as follows: Main-B3, main branch of the lateral inferior segment; peripheral-B3, peripheral branch of the lateral inferior segment; B2, lateral superior segment; left hepatic duct, proximal portion of the left hepatic duct; B8, anterior superior segment; B5, anterior inferior segment; B5 + 8, main bile duct of the anterior segment; B6, bile duct of posterior inferior segment; and right hepatic duct, proximal portion of the right hepatic duct. RESULTS: When a catheter without an outer sheath was used, catheter dislodgement in peripheral-B3 (2/11, 18%) was more common than in main-B3 (0/32, 0%; p < 0.05). In B5, catheter dislodgement (6/12, 50%) was more frequent than in B8 (3/20, 15%; p < 0.05) and in B6 (0/14, 0%; p < 0.005). When a catheter with an outer sheath was used, catheter dislodgement (2/207, 1%) was rare. CONCLUSION: Drainage from B5 and peripheral-B3 is associated with a high risk of dislodgement of the catheter. A catheter with an outer sheath was useful to prevent catheter dislodgement.
BACKGROUND: Patients with papillary adenocarcinoma survive longer than do patients with other histologic types of bile duct tumors. We evaluated the usefulness of intraductal ultrasonography (IDUS) for predicting the histology. METHODS: Preoperative tumor assessment was performed by using IDUS through a percutaneous tract or the transpapillary route in 37 patients with extrahepatic bile duct cancer. In 30 of 37 patients, imaging results were compared prospectively with histologic findings in resected specimens. Probes 2.0 mm in diameter and 20 MHz in frequency were mainly used. When IDUS showed a "narrow-based polypoid pattern" or a "papillary surface pattern," the patients were judged as having papillary adenocarcinoma. RESULTS: The accuracy, sensitivity, and specificity of IDUS in predicting papillary adenocarcinoma were 90%, 89%, and 90%, respectively. When intraductal ultrasonography showed a papillary surface pattern or a narrow-based polypoid pattern, lymph node metastases and perineural invasion were rarely seen when compared with other patients with bile duct cancer (p < 0.05). CONCLUSION: IDUS is useful for assessing the histologic type of bile duct cancer.
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In infected cells, the RNA genomes of RNA tumour viruses are copied into DNA by a virus-encoded reverse transcriptase enzyme. This transfer of information from RNA into DNA was thought to be a unique feature of RNA tumour viruses, but recent results suggest it may be a more general strategy. Hepatitis B virus (HBV) has a double-stranded DNA genome, and it has recently been shown that the minus DNA strand of the HBV genome is copied from a plus-strand RNA template, leading to the suggestion that reverse transcription is central to the life cycle of HBV. More recently it has been suggested that the replication cycle of a plant virus, cauliflower mosaic virus (CaMV), includes a reverse transcription step. We report here the existence of amino acid sequence homology between retroviral reverse transcriptase and the putative polymerases of HBV and CaMV.
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Immunoglobulin-binding factors are known to regulate the synthesis of B-cell-derived immunoglobulin heavy-chain isotypes. Cloning and nucleotide sequence determination of complementary DNA encoding rodent IgE-binding factors (IgE-BF) revealed that messenger RNA encodes a glycoprotein of 557 amino acids which is expressed as a precursor of relative molecular mass (Mr) 60,000 (60K) in COS7 monkey cells. We report here that the 3' two-thirds of the IgE-BF coding sequence shows a surprising homology (72%) at the DNA level with coding sequences of the gag and pol (DNA endonuclease) genes of the Syrian hamster intracisternal A particle (IAP H18), an endogenous retrovirus. This marked homology demonstrates that the rodent gene encoding IgE-BF is a hybrid gene which evolved very recently by integrating genes of viral origin, and that the encoded polypeptide comprises three separate domains: an IgE-BF domain and retrovirus-derived gag and DNA endonuclease-like domains. This may represent the first report of a cellular gene containing a virus-derived coding sequence.
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Previous work showed that the authors' vascular graft had satisfactory antithrombogenicity because of high hydrophilicity. The authors developed a small-caliber xenograft using new technology and evaluated the potential application for aortocoronary bypass grafting. Fresh sheep carotid artery with an internal diameter of 3 mm was obtained, and cross-linked with hydrophilic polyepoxy compounds. A 6 cm segment of the graft was then used between the aorta and the left circumflex coronary artery without cardiopulmonary bypass in 17 dogs. Sodium heparin was given during the surgery, but no anticoagulant was used thereafter. After the surgery, the dogs were randomly assigned to two groups according to the observation period. In 11 animals (Group 1), the observation period was up to 24 hr, at which time the grafts were evaluated; the patency rate was 72.7%. The patent grafts were clean and without thrombi. At the distal anastomotic lines of the occluded grafts, a thrombus was observed and a technical error was highly suspected. In six dogs (Group 2), angiography was performed to confirm graft patency between 2 and 3 weeks. The patency rate was 50% during the mean observation period of 17.5 days. One graft was evaluated at postoperative day 23. It was patent and soft, and the inner surface was shiny and smooth. Microscopic observation showed nice healing characteristics. These results indicate that it is possible for this new graft to be used for aortocoronary bypass grafting.
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.
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.
Dialysis-related amyloidosis (DRA) is a major complication of chronic renal failure and long-term renal replacement therapy. Beta2-Microglobulin is a major constituent of amyloid fibrils in DRA. Amyloid deposition mainly involves bone and joint structures, presenting as carpal tunnel syndrome, destructive arthropathy, and subchondral bone erosions and cysts. While a definitive diagnosis of DRA can only be made by histological findings, various imaging techniques often support diagnosis. The molecular pathogenesis of this complication remains unknown. Recent studies, however, have suggested a pathogenic role of a new modification of beta2-microglobulin in amyloid fibrils, i.e. the advanced glycation end products (AGEs). Increased carbonyl compounds derived from autoxidation of both carbohydrates and lipids modify proteins in uremia, leading to augment not only AGE production but also the advanced lipoxidation end product production. Thus, uremia might be a state of carbonyl overload with potentially damaging proteins ('carbonyl stress'). Therapy of DRA is limited to symptomatic approaches and surgical removal of amyloid deposits. High-flux biocompatible dialysis membranes could be used to delay DRA development.
Total parenteral nutrition (TPN) has been shown to alter the serum concentration of certain gastrointestinal hormones. However, the effects of surgical and nutritional techniques have not been evaluated adequately. This study examined the effects of those techniques on serum gastrin and secretin levels in Fischer 344 rats fed TPN. After aseptic superior vena cava cannulation and a 4-day postoperative recovery period with ad libitum access to food and water, 18 rats were randomly and equally (n = 6) assigned to either (1) a baseline group, killed after the recovery period; (2) a TPN group fed sufficient nutrients (67% dextrose, 21.7% amino acid, 11.3% fat) and kilocalories (1.45 kcal/mL) for normal growth and development; or (3) an orally fed (OF) group fed ad libitum a powdered diet isocaloric and isonitrogenous to the TPN solution. Both the TPN and OF groups were fed for 5 days and then killed. Another set of six rats without surgery served as a control (CON) group and had the same diet protocol as the OF group. Serum was analyzed for gastrin and secretin by radioimmunoassay. The OF group had significantly (p < .01) lower gastrin levels than the CON group. Gastrin levels of OF rats were twofold lower (p < .04) than those of the TPN rats and were threefold greater (p < .02) than those of the baseline group. Secretin levels in OF rats were twice as high (p < .02) as those in CON rats. The OF group showed a trend toward significantly (p < .09) higher serum secretin levels when compared with the TPN group.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of experimental occlusal overload on peri-implantitis in monkeys (Macaca fascicularis) has been examined to explain the pathology of the disease that develops in the tissue around osseointegrated implants. In the first article of this series, it was reported that bone resorption was not observed around implants when occlusal trauma was produced by a super-structure that was in supraocclusal contact with an excess occlusal height of approximately 100 microns, provided there was no inflammation in the peri-implant tissue. In the second part of the study, experimental inflammation was created in the peri-implant tissue, and occlusal overload was produced by a superstructure with an excess occlusal height of 100 microns. Notable bone resorption was observed around the implant with the passage of time. These results suggested that, in addition to the control of inflammation in peri-implant tissue, traumatic occlusion may play a role in bone breakdown around the implant. In the present study, while the peri-implant tissue was kept in an inflammation-free state, bone level changes around the implants were investigated when various levels of traumatic force were exerted. The supraoccluding prostheses were defined as excessively high by 100 microns, 180 microns, and 250 microns, respectively. The heights were determined with an image analysis device, and the bone responses around the implants induced by the traumatic forces were investigated. The results showed that bone resorption around implants tended to increase with 180 microns or more excessive height of the superstructure. This suggests that the threshold of excessive height of the superstructures at which peri-implant tissue breakdown may start is approximately 180 microns. It is also suggested that there is a possibility of bone resorption around the implants caused by excess occlusal trauma, even when there is no inflammation in peri-implant tissue.