Linkage mapping of the mitochondrial aconitase (ACO2) gene to chicken chromosome 1.
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Aconitate Hydratase↗
Biomedical subjects
S Miyagawa
Publications and source records attributed to S Miyagawa.
Genotyping for HLA-A, B and C alleles in Japanese patients with pemphigus: prevalence of Asian alleles of the HLA-B15 family.
BACKGROUND: There have been only limited reports on major histocompatibility complex class I antigens in pemphigus. OBJECTIVES: To characterize HLA-A, B and C class I alleles by genotyping in Japanese patients with pemphigus, and to analyse the possible association of class I alleles with disease susceptibility within a relatively homogeneous ethnic population. METHODS: Alleles of HLA-A, B and C, and DRB1 and DQB1 loci were fully determined in 51 Japanese patients with pemphigus. RESULTS: Asian alleles of the HLA-B15 family, including the allele B*1507, which was significantly increased in comparison with normal controls, were prevalent in patients with pemphigus vulgaris (PV). The prevalence of B*15 alleles in patients with PV was not due to linkage disequilibrium with HLA-DR4 or DR14 alleles, which have been shown to confer strong susceptibility to PV across racial barriers. In contrast to the unique distribution of the HLA-B alleles, HLA-A and C alleles were unremarkable in patients with PV when compared with normal control subjects. CONCLUSIONS: These results suggest that there may be differences in the ethnic concentrations of different HLA-B alleles in patients with PV.
Alleles↗
Myeloma-associated systemic amyloidosis presenting as digital nodules.
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Amyloidosis↗
Improvement of psoriasis during imatinib therapy in a patient with a metastatic gastrointestinal stromal tumour.
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Benzamides↗
Remodeling of the major pig xenoantigen by N-acetylglucosaminyltransferase III in transgenic pig.
We have been successful in generating several lines of transgenic mice and pigs that contain the human beta-d-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galalpha1-3Galbeta1-4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.
Animals↗
Long-term results of living-related donor liver graft transplantation: a single-center analysis of 110 transplants.
BACKGROUND: Difficulties of cadaveric donation and serious donor shortage have led to the development and popularization of living-related donor liver graft transplantation (LRLT). Because the history of this procedure is rather short, important aspects specific to this procedure have not been sufficiently documented. The objective of this study was to analyze a single center's 10-year experience with 110 LRLT in pediatric and adult patients with end-stage liver diseases. METHODS: The medical records of 110 consecutive patients who underwent LRLT were reviewed. The recipients were comprised of 72 children and 38 adults. The graft volume corresponded to 26-192% of the recipient's standard liver volume. The relationship between pretransplant covariates and patient and graft survival was analyzed. Actuarial patient/graft survival rates were determined at 1, 3, and 5 years. The type and incidence of posttransplant complications were analyzed, as was long-term graft function. RESULTS: The 1-, 3-, and 5-year actuarial patient and graft survival rates were 88%, 85%, and 85%, respectively. Log-rank test demonstrated that ABO-compatibility predicted patient survival rate, whereas patient age, underlying disease, patient's clinical status, donor-recipient relation, donor age, and graft volume/standard liver volume ratio did not. Long-term liver function remains excellent. All the donors have returned to normal daily lives with an uneventful course. CONCLUSIONS: LRLT is an efficacious procedure that provides excellent short-term and long-term survival. The indication criteria for both recipient and donor were legitimate in this series, except for transplant across ABO-incompatibility. Cautious expansion of this procedure may be justified under the situation of serious shortage of cadaveric donor.
Adolescent↗
Down-regulation of the alpha-Gal epitope expression in N-glycans of swine endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene. Modulation of the biosynthesis of terminal structures by a bisecting GlcNAc.
The down-regulation of the alpha-Gal epitope (Galalpha1,3Galbeta-R) in swine tissues would be highly desirable, in terms of preventing hyperacute rejection in pig-to-human xenotransplantation. In an earlier study, we reported that the introduction of the beta1,4-N-acetylglucosaminyltransferase (GnT) III gene into swine endothelial cells resulted in a substantial reduction in the expression of the alpha-Gal epitope. In this study, we report on the mechanism for this down-regulation of the alpha-Gal epitope by means of structural and kinetic analyses. The structural analyses revealed that the amount of N-linked oligosaccharides bearing the alpha-Gal epitopes in the GnT-III-transfected cells was less than 10% that in parental cells, due to the alteration of the terminal structures as well as a decrease in branch formation. In addition, it appeared that the addition of a bisecting GlcNAc, which is catalyzed by GnT-III, leads to a more efficient sialylation rather than alpha-galactosylation. In vitro kinetic analyses showed that the bisecting GlcNAc has an inhibitory effect on alpha-galactosylation, but does not significantly affect the sialylation. These results suggest that the bisecting GlcNAc in the core is capable of modifying the biosynthesis of the terminal structures via its differential effects on the capping glycosyltransferase reactions. The findings may contribute to the development of a novel strategy to eliminate carbohydrate xenoantigens.
Acetylglucosamine↗
[Preoperative portal embolization for induction of liver hypertrophy].
Preoperative portal embolization (PVE) is now widely used to induce hypertrophy of the anticipated liver remnant. Here, pathophysiology, indications, technical procedures, and problems of PVE are reviewed and our experience of 105 PVEs is presented. The reported complication rate after PVE is low (0-10%) and the increment of the future remnant liver volume is 12% of total liver volume (range: 7-27%). The resection rate after PVE ranged from 58% to 100%. In our series of 105 PVEs, the morbidity rate was 3.8%, the future remnant liver increased by about 10% of total liver volume, and 34 patients (32.4%) did not undergo planned extended hepatectomy. After hepatectomy, hepatic failure occurred in one patient (< 1%). In conclusion, although PVE is a safe procedure for enlarging the future remnant liver, more appropriate indication criteria should be established.
Adult↗
Analysis of sympathetic nerve activity in end-stage cardiomyopathy patients receiving left ventricular support.
BACKGROUND: The left ventricular assist system (LVAS) has been used increasingly for patients with end-stage heart failure who are awaiting transplantation. Sympathetic nerve activity is known to correlate with cardiac function in chronic heart failure patients, but little is known about sympathetic nerve activity during LVAS support. In this study, we examined the status of sympathetic nerve activity in relation to mechanical support. METHODS: In this study, we included 10 consecutive patients with end-stage cardiomyopathy who were on LVAS support for at least 2 months (duration, 222 +/- 59 days). None of these patients achieved enough functional recovery to be taken off LVAS. In these patients, we used iodine-125-metaiodobenzylguanidine (125I-MIBG) scintigraphy to examine the change of sympathetic nerve activity after LVAS implantation, and compared the results with the change of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels as well as with histologic optional findings. Samples for ANP and BNP measurement were obtained before and 30 days after LVAS implantation. Specimens for histologic analysis were obtained at the time of LVAS implantation and at the time of cardiac transplantation or autopsy. RESULTS: We observed marked decrease in serum levels of ANP and BNP 1 month after LVAS implantation. But myocardial sympathetic nerve function, which was evaluated with 125I-MIBG scintigraphy and expressed as the heart-to-mediastinum activity ratio, remained below normal even 2 months after the LVAS implantation (1.57 +/- 0.19; normal, 2.34 +/- 0.36). Serial histologic analysis in these 10 patients showed continuous increase in percentage of fibrosis and cell diameter despite ventricular unloading by the LVAS. CONCLUSIONS: Sympathetic nerve function, which was evaluated on 125I-MIBG scintigraphy, did not improve during left ventricular support. Because none of the patients included in our study showed improvement in cardiac function or histologic findings, the recovery of myocardial sympathetic nerve function may be an important factor in myocardial recovery for cardiomyopathy patients on LVAS support.
3-Iodobenzylguanidine↗
Quantitation and visualization of ultraviolet-induced DNA damage using specific antibodies: application to pigment cell biology.
The major types of DNA damage induced by sunlight in the skin are DNA photoproducts, such as cyclobutane pyrimidine dimers (CPDs), (6-4)photoproducts (6-4PPs) and Dewar isomers of 6-4PPs. A sensitive method for quantitating and visualizing each type of DNA photoproduct induced by biologically relevant doses of ultraviolet (UV) or sunlight is essential to characterize DNA photoproducts and their biological effects. We have established monoclonal antibodies specific for CPDs, 6-4PPs or Dewar isomers. Those antibodies allow one to quantitate photoproducts in DNA purified from cultured cells or from the skin epidermis using an enzyme-linked immunosorbent assay. One can also use those specific antibodies with in situ laser cytometry to visualize and measure DNA photoproducts in cultured cells or in the skin, using indirect immunofluorescence and a laser-scanning confocal microscope. This latter method allows us to reconstruct three-dimensional images of nuclei containing DNA photoproducts and to simultaneously examine DNA photoproducts and histology in multilayered epidermis. Using those techniques, one can determine the induction and repair of these three distinct types of DNA photoproducts in cultured cells and in the skin exposed to sublethal or suberythematous doses of UV or solar simulated radiation. As examples of the utility of these techniques and antibodies, we describe the DNA repair kinetics following irradiation of human cell nuclei and the photoprotective effect of melanin against DNA photoproducts in cultured pigmented cells and in human epidermis.
Animals↗
In situ visualization of ultraviolet-light-induced DNA damage repair in locally irradiated human fibroblasts.
We have developed a novel method that uses a microfilter mask to produce ultraviolet-induced DNA lesions in localized areas of the cell nucleus. This technique allows us to visualize localized DNA repair in situ using immunologic probes. Two major types of DNA photoproducts [cyclobutane pyrimidine dimers and (6-4) photoproducts] were indeed detected in several foci per nucleus in normal human fibroblasts. They were repaired at those localized sites at different speeds, indicating that DNA photoproducts remain in relatively fixed nuclear positions during repair. A nucleotide excision repair protein, proliferating cell nuclear antigen, was recruited to the sites of DNA damage within 30 min after ultraviolet exposure. The level of proliferating cell nuclear antigen varied with DNA repair activity and diminished within 24 h. In contrast, almost no proliferating cell nuclear antigen fluorescence was observed within 3 h in xeroderma pigmentosum fibroblasts, which could not repair either type of photolesion. These results demonstrate that this technique is useful for visualizing the normal nucleotide excision repair process in vivo. Interestingly, however, in xeroderma pigmentosum cells, proliferating cell nuclear antigen appeared at ultraviolet damage sites after a delay and persisted as late as 72 h after ultraviolet exposure. This result suggests that this technique is also valuable for examining an incomplete or stalled nucleotide excision repair process caused by the lack of a single functional nucleotide excision repair protein. Thus, the technique provides a powerful approach to understanding the temporal and spatial interactions between DNA damage and damage-binding proteins in vivo.
Cell Line↗
Cutaneous mastocytosis associated with a mixed germ cell tumour of the ovary: report of a case and review of the literature.
A 10-year-old girl with a mixed germ cell tumour of the ovary, treated by surgery and chemotherapy, developed cutaneous mastocytosis approximately 8 months after starting chemotherapy. This is the sixth report of a germ cell tumour associated with mastocytosis. c-kit receptor point mutations, including Asp816Val and Val560Gly were absent in a biopsy specimen obtained from lesional skin.
Antineoplastic Combined Chemotherapy Protocols↗
The possible use of HLA-G1 and G3 in the inhibition of NK cell-mediated swine endothelial cell lysis.
The splicing isoform of HLA-G that is expressed in xenogeneic cells, and its effect on NK-mediated direct cytotoxicity was examined, using stable Chinese hamster ovary (CHO) cell or swine endothelial cell (SEC) transfectants. cDNAs of HLA-G (G1 and G3) and human beta2-microglobulin were prepared and subcloned into the expression vector, pCXN. The transfected HLA-G1 was easily expressed on SEC, and co-transfection with human beta2-microglobulin led to an enhanced level of HLA-G1 expression, as evidenced by flow cytometry. The expressed HLA-G1 significantly suppressed NK-mediated SEC cell lysis, which is an in vitro delayed-type rejection model of a xenograft. On the other hand, the swine leucocyte antigen (SLA) class I molecules could be up-regulated as the result of the transfection of human beta2-microglobulin, but did not down-regulate human NK-mediated SEC lysis. The HLA-G3 was not expressed on CHO and SEC in contrast to HLA-G1, as the result of the transfection. The gene introduction of HLA-G3 in SEC showed no protective effect from human NK cells. However, indirect evidence demonstrated that HLA-G3 transfection resulted in HLA-E expression, but not itself, when transfected to the human cell line, 721.221, thus providing some insight into its natural function in human cells. The present findings suggest that the expression of HLA-G1 on the cell surface could serve as a new approach to overcoming NK-mediated immunity to xenografts.
Animals↗
A synthetic dDAF (CD55) gene based on optimal codon usage for transgenic animals.
The human DAF (CD55) gene was chosen as a representative molecule in a xenotransplantation study. The gene was synthesized in order to adapt its codons to those which are more frequent in mammals, especially pigs, and the expression levels were then examined in Chinese hamster ovarian (CHO) cells, swine endothelial cell (SEC) and transgenic mice. A significant increase in protein production with no detectable mRNA elevation was observed in the transfectants of synthetic DAF (sDAF), compared with the wild-type DAF (wtDAF) and delta-SCR1 wild-type DAF (Delta1wtDAF). Consistent with the in vitro data, the expression of DAF in mice that carry sDAF was higher than Delta1wtDAF in many organs, especially the pancreas. The sDAF showed a high level of expression in SEC and transgenic mice, suggesting that it will be useful in the development of transgenic pigs with high levels of expression.
Animals↗
Value of lipiodol computed tomography and digital subtraction angiography in the era of helical biphasic computed tomography as preoperative assessment of hepatocellular carcinoma.
OBJECTIVE: To compare the diagnostic accuracies of Lipiodol computed tomography (CT) and helical biphasic CT as preoperative imaging modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Lipiodol CT after digital subtraction angiography has long been used as a highly sensitive imaging modality for HCC. The recent advent of helical CT has allowed scanning the entire liver during both the arterial and portal venous phase of contrast enhancement. METHODS: The authors analyzed data from 164 patients who underwent hepatic resection for HCC to calculate the sensitivity and specificity of these modalities. Findings of intraoperative ultrasonography followed by histologic confirmation were set as the gold standard. RESULTS: Although sensitivity decreased with both modalities as tumors became small and well differentiated, helical CT showed a higher sensitivity than Lipiodol CT in detecting well-differentiated HCC nodules smaller than 2 cm. In contrast, Lipiodol CT was superior to helical CT for the detection of small but moderately to poorly differentiated nodules. The overall sensitivity of helical CT was higher than that of Lipiodol CT. These findings suggest that helical CT is superior in delineating early HCC, whereas Lipiodol CT is specific to the detection of intrahepatic metastases. In terms of specificity, helical CT was superior to Lipiodol CT. CONCLUSIONS: Helical CT and Lipiodol CT are complementary modalities. At present, helical biphasic CT does not obviate the need for invasive techniques such as angiography and Lipiodol CT as preoperative examinations for HCC.
Adult↗
Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver.
Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.
Animals↗
Insulin and somatostatin releasing islet cell tumor caused hypoglycemia.
We report a hypoglycemic case with normal insulin levels, which was caused by an islet cell tumor that was releasing insulin and somatostatin. A fasting test suggested the over secretion of insulin. Moreover, this hypoglycemia was enhanced by the inhibitory effect of somatostatin on the secretion of insulin counter-regulatory hormones, such as glucagon, in addition to the autonomous secretion of insulin from the tumor. In cases of hypoglycemia with apparently normal insulin levels, the measurement of somatostatin and various provocative tests are recommended. Arterial stimulation venous sampling (ASVS) was useful to detect the location of this functioning islet cell tumor.
Adenoma, Islet Cell↗