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Biomedical subjects

Shin Yamamoto

Publications and source records attributed to Shin Yamamoto.

31 records · Page 2Linked to original sources

Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis.

BACKGROUND: Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine. METHODS: Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells. RESULTS: Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60. CONCLUSIONS: Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.

Animals↗

Development and evaluation of a health-related quality of life questionnaire for the elderly with dementia in Japan.

OBJECTIVES: The purpose of this study was the development of the quality of life (QOL) questionnaire for dementia (QOL-D) in Japan. METHODS: We performed a questionnaire survey of QOL assessment in elderly patients with dementia in Japan, and developed QOL-D. RESULTS: The final version consists of only 31 items grouped into six response sets, each with its own scale. Reliability is good to excellent, and validity is, to some extent, established. The six domains of health-related QOL are divided into two groups. One is the positive and the other is the negative aspects of health-related QOL. The positive aspects have been shown to correlate positively with cognitive function and activities of daily living (ADL) score, whereas the negative aspects have not. The concept of QOL for elderly patients with dementia in Japan is similar to that in Western countries. CONCLUSION: We demonstrated that QOL-D is a reliable and valid instrument for QOL assessment in elderly patients with dementia in Japan.

Activities of Daily Living↗

Papillary fibroelastoma of the aortic valve: report of a case.

This report describes a case of aortic papillary fibroelastoma causing transient ischemic attack (TIA), and is followed by a review of the relevant literature. A tumor measuring 1.5 x 1.5 cm was located in the right coronary cusp of the aortic valve, which was found to have a "sea anemone-like" configuration due to collagenous or elastic papillary projections. Aortic fibroelastoma can cause cerebrovascular symptoms, and this patient presented with TIA. Moreover, aortic fibroelastoma usually causes chest symptoms and occasionally results in death despite its small size of generally less than 1 cm. According to the literature, all of the patients who died of fibroelastoma had an aortic valve tumor in the right or left coronary cusp, which indicates that the location of the tumor rather than its size may be an important factor contributing to the case of death. Surgical treatment is usually indicated especially for aortic fibroelastoma because of the high associated risk or cerebrovascular and chest diseases. The recent evolution of echocardiography will promote the chance of establishing a preoperative diagnosis of this lesion. However, because it is not possible to differentiate fibroelastoma from other lesions, including malignancies, by echocardiography alone, this may be another reason for performing surgical removal.

Aortic Valve↗

Depressive disorders preceding temporal lobe epilepsy.

In this study, we investigated three female patients given a diagnosis of temporal lobe epilepsy preceded by depression. It is notable that all the patients complained of abnormal sensations, either in the throat or oral. The depression in the three patients showed no improvement with antidepressants, but carbamazepine was effective for both epileptic seizures and depression. EEG should be performed on patients who develop antidepressant treatment-refractory depression accompanied by hypochondriacal complaints.

Aged↗

Putative regulatory gene for polysaccharide synthesis of Streptococcus agalactiae type Ia.

The DNA sequence of downstream and upstream regions of capsular polysaccharide biosynthesis (cps) gene cluster of Streptococcus agalactiae type Ia was determined. The overall structure of this region is very similar to a portion of the genome of S. pyogenes, although S. pyogenes does not contain cps genes. In the upstream region, a putative regulatory gene was identified and designated as cpsIaR. From the similarity of the amino acid sequences, the gene product seems to belong to an LysR family of transcriptional regulatory proteins. cpsIaR seems to be transcribed in the direction opposite to cps genes from two different but closely positioned promoters. GST-fused CpsIaR protein binds to the cpsIaA promoter region, suggesting that the protein controls the expression of cpsIa gene cluster.

Journal Article↗

Diagnosis of common bile duct calculi with intraductal ultrasonography during endoscopic biliary cannulation.

BACKGROUND: Choledocholithiasis can be difficult to diagnose, even with direct cholangiography. We examined the role of biliary intraductal ultrasonography in detecting common bile duct stones that had been overlooked during endoscopic retrograde cholangiopancreatography. METHODS: Eighty consecutive patients who underwent endoscopic retrograde cholangiography for suspected choledocholithiasis with negative results were evaluated with intraductal ultrasonography (20 MHz) for the presence of biliary concrements. The diagnostic criterion for stones was a strong-echo structure with acoustic shadowing. Materials of low amplitude echoes without acoustic shadowing were considered sludge. RESULTS: Intrabile duct scanning was successful in all patients. Of the 80 patients, 20 (25%) had ultrasonic evidence of common bile duct stones. The stones measured 5 mm or less on ultrasound and their presence was confirmed macroscopically during endoscopic (17 patients) or laparoscopic (three patients) bile duct clearance. Another 37 patients (46%) had biliary sludge alone and have been followed up uneventfully. CONCLUSIONS: Biliary intraductal ultrasonography may become a useful adjunct to establish the diagnosis of occult bile duct concrements and a guide to appropriate therapeutic selection during endoscopic biliary cannulation.

Adult↗

Activation of cytomegalovirus in pig-to-primate organ xenotransplantation.

Xenotransplantation of porcine organs carries the risk of reactivation of latent virus in donor and recipient tissues as well as transmission of viruses between species. We have investigated the activation of baboon cytomegalovirus (BCMV) and porcine CMV (PCMV) in a pig-to-primate model of xenotransplantation. Tissues originating from a series of six swine-to-baboon composite thymokidney xenotransplants were investigated. Four immunosuppressed baboons died (survival range, 7 to 27 days) with the graft in situ. Increases in BCMV DNA copy numbers occurred in three (75%) of these baboons and was thought to be responsible for pneumonitis and the death of one animal. In two baboons, disseminated intravascular coagulation was successfully treated by graftectomy and discontinuation of immunosuppression. PCMV was upregulated in five of six xenografts (83%). PCMV infection was associated with ureteric necrosis in one xenograft. Although significantly increased in native tissues, low levels of BCMV and PCMV were also detected in tissues other than that of the native viral host species. The cross-species presence of CMV did not appear to cause clinical or histological signs of invasive disease. Thus, viral infections with clinical disease were restricted to tissues of the native species of each virus. Intensive immune suppression currently required for xenotransplantation results in a significant risk of reactivation of latent infections by BCMV and PCMV. It is not yet known whether viral DNA detected across species lines represents cellular microchimerism, ongoing viral infection, or uptake of free virus. The observation of graft injury by PCMV demonstrates that CMV will be an important pathogen in immunosuppressed xenograft recipients. Strategies must be developed to exclude CMV from porcine organ donors.

Animals↗

Gene therapy--its potential in surgery.

Advances in techniques have resulted in practical applications for gene therapy, which is becoming applicable for the treatment of human disease. This review outlines the advantages and disadvantages of the techniques available. Examples of research efforts in the treatment of diseases of relevance to the surgeon (cardiovascular diseases, cancer, wound healing, fracture repair, and in organ transplantation) are presented.

Adenoviridae↗

Vascularized islet cell transplantation in miniature Swine: islet-kidney allografts correct the diabetic hyperglycemia induced by total pancreatectomy.

We have previously reported the preparation of vascularized islet-kidneys (IKs) by transplantation of islets under the autologous kidney capsule. Here, we compare the efficacy of transplanting vascularized versus nonvascularized islets into diabetic allogeneic swine recipients. In the vascularized islet transplantation (5,000 islet equivalents [IE]/kg), recipients received minor-mismatched (n = 4) or fully-mismatched (n = 2) IKs after pancreatectomy, with a 12-day course of cyclosporine A (CyA) or FK506, respectively. For the nonvascularized islet transplantation (7,000 IE/kg), three recipients received minor-mismatched islets alone and two recipients received minor-mismatched donor islets placed in a donor kidney on the day of transplantation. All recipients of nonvascularized islets were treated with a 12-day course of CyA. With vascularized islet transplantation, pancreatectomized recipients were markedly hyperglycemic pretransplant (fasting blood glucose >300 mg/dl). After composite IK transplantation, all recipients developed and maintained normoglycemia (<120 mg/dl) and stable renal function indefinitely (>3 months), and insulin therapy was not required. Major histocompatibility complex-mismatched recipients demonstrated in vitro donor-specific unresponsiveness. In contrast, recipients of nonvascularized islets remained hyperglycemic. In conclusion, IK allografts cured surgically induced diabetes across allogeneic barriers, whereas nonvascularized islet transplants did not. These data indicate that prevascularization of islet allografts is crucial for their subsequent engraftment and that composite IKs may provide a strategy for successful islet transplantation.

Animals↗

Identification of sialyltransferases of Streptococcus agalactiae.

Group B streptococci, Streptococcus agalactiae, produce high-molecular-weight polysaccharides containing N-acetylneuraminic acid. Although the type-specific capsular polysaccharide (CP) synthesis (cps) genes of several S. agalactiae strains have been extensively analyzed, to date, no sialyltransferase activity has been detected from any gene product of the cps gene cluster. Among the cps genes, the cpsK gene products of S. agalactiae types la and Ib showed weak similarity to several bacterial sialyltransferases. In this study, the cpsIaK and cpsIbK gene products were found to show sialyltransferase activity specific for lacto-N-neotetraose and lacto-N-tetraose, respectively. This acceptor specificity seems to reflect the respective CP structure, since the repeating unit of type la CP is sialyllacto-N-neotetraose and that of type Ib CP is sialyllacto-Ntetraose. We also found that the C-terminal regions of CpsKs were almost completely conserved in various S. agalactiae strains.

Journal Article↗

The effect of biliary decompression on antibiotic biliary excretion.

BACKGROUND/AIMS: Raised biliary pressure may affect antibiotic biliary excretion. We evaluated whether biliary decompression for patients with biliary obstruction could improve antibiotic biliary excretion. METHODOLOGY: Eight patients with common bile duct obstruction undergoing endoscopic nasobiliary drainage were evaluated. During endoscopic cannulation, biliary pressure above the obstruction and antibiotic concentrations in the bile and peripheral blood were determined 60 min after the intravenous antibiotic (panipenem) administration. RESULTS: Biliary pressure was initially elevated above normal in all the patients, but normalized after biliary drainage for 5 to 7 days. At the initial endoscopic retrograde cholangiopancreatography, the aspirated bile contained low or undetectable levels of the antibiotic, but the mean bile panipenem concentration and the mean bile/plasma ratio of panipenem concentrations significantly improved after biliary decompression. CONCLUSIONS: The results suggest an important role of biliary pressure in determining antibiotic transfer into the bile.

Aged↗

Neutrophil chemotaxis in bile duct-obstructed rats, and effect of internal biliary drainage.

BACKGROUND/AIMS: Our previous studies demonstrated enhanced neutrophil chemotaxis in bile duct-ligated, obstructive jaundice rats. In the present study, we produced a reversible obstructive jaundice model in rats. The efficacy of the present model in producing sufficient bile flow blockade and subsequent internal biliary drainage was assessed. Furthermore, the effect of internal biliary drainage on neutrophil chemotaxis was evaluated. METHODOLOGY: Bile duct was obstructed with a polyester tape attached with a stainless steel coil. Internal biliary drainage was performed by removing the tape. Rats were subjected to either 10 days' bile duct obstruction or 4 days' bile duct obstruction followed by 6 days' internal biliary drainage. Some animals underwent conventional bile duct ligation and dissection for 4 or 10 days. Neutrophil chemotaxis was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-beta) as chemoattractant. RESULTS: The present technique produced sufficient obstructive jaundice as evidenced by increases in serum alanine aminotransferase and total bilirubin throughout the observation period, the values of which were insignificant with those induced by the conventional method. Internal biliary drainage effectively normalized these values. Similarly, neutrophil chemotaxis was enhanced with both procedures, and increased neutrophil chemotaxis was significantly decreased after drainage. CONCLUSIONS: The present reversible obstructive jaundice method is as efficacious as the conventional method for producing obstructive jaundice, and internal biliary drainage could be readily available. With the present model, neutrophil overactivity in obstructive jaundice was effectively alleviated by internal biliary drainage. The result may support the role of preoperative biliary drainage in the prevention of postoperative septic complications.

Animals↗

Cepharanthine exerts antitumor activity on oral squamous cell carcinoma cell lines by induction of p27Kip1.

Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. The drug has been widely used for the treatment of many acute and chronic diseases and can exert antitumor effects on several human cancer cells. In this study, we examined the mechanism of the antitumor effects by cepharanthine on a human oral squamous cell carcinoma (SCC) cell line. Treatment of oral SCC cells with cepharanthine (10-20 micrograms/ml) resulted in a significant suppression of cell growth. Cepharanthine preferentially suppressed the growth of B88 cells when compared with other human oral SCC cells. Moreover, it was found, by flow cytometry analysis and Hoechst 33258 staining, that G1 arrest and DNA fragmentation occurred in cepharanthine-treated B88 cells. Furthermore, induction of p27Kip1 and reduction of cyclin E and Skp2 were detected by Western blotting. B88 tumor-bearing nude mice were treated with cepharanthine, which was administered subcutaneously (40 mg/kg/day). The cepharanthine treatment results in a significant suppression of tumor growth. Overall these results indicate that cepharanthine may inhibit the growth of human oral SCC cells by down-regulating cyclin E to induce G1 arrest through a pathway of p27Kip1 induction.

Alkaloids↗