Living donor liver transplantation for fulminant hepatic failure.
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Biomedical subjects
Publications and source records attributed to M Minagawa.
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In contrast to the T cell receptor (TCR) diversity of major alpha beta T cells in lymphoid tissues, epithelial T cells of the murine skin, called dendritic epidermal T cells (DETC), express exclusively an invariant gamma delta TCR. Fetal thymic precursors of DETC immigrate to the skin before birth, and in adult mice T cells expressing the canonical gamma delta TCR identical to that of DETC are not found in other lymphoid or epithelial tissues. Here, we show that DETC precursors migrate to the gut as well as to the skin during fetal periods, but preferentially survive and expand in the skin after birth. We propose that similar to the thymic selection of the diverse alpha beta T cell repertoire, 'peripheral selection' of the homogeneous epithelial gamma delta T cell repertoire may be mediated by TCR signaling upon the recognition of the self-ligand, because the ligand for the DETC TCR was expressed only in the skin.
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Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each of XPA, CS, and control groups. All oxidative products, including nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE) were deposited in large amounts in the globus pallidus of CS patients compared to XPA patients. They were frequently recognized in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of HNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA patients. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They were also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may be involved in pallidal and/or cerebellar degeneration in hereditary nucleotide repair disorders.
OBJECTIVE: To examine the usefulness of the authors' method involving preoperative transcatheter arterial chemoembolization followed by hepatectomy. SUMMARY BACKGROUND DATA: The presence of portal vein tumor thrombus in a patient with hepatocellular carcinoma is one of the most significant factors for a poor prognosis. No standard therapy has been established. METHODS: Forty-five of 455 patients with hepatocellular carcinoma (10%) from 1989 to 1998 were included in this study. These patients had gross portal vein tumor thrombus but no distant metastases. The 23 patients (50%) who had indications for surgery received preoperative transcatheter arterial chemoembolization: 18 underwent hepatic resection and 5 underwent ligation of the hepatic artery or portal vein on laparotomy. Among the remaining 22 patients who did not have indications for hepatectomy, 10 received regional chemotherapy and 12 underwent transcatheter arterial chemoembolization. RESULTS: The mean duration of survival was 3.4 +/- 2.7 years in the 18 patients who received transcatheter arterial chemoembolization and hepatectomy and 0.36 +/- 0.26 years in the 27 patients who did not receive hepatectomy. The survival rate of the 18 patients who received hepatic resection with preoperative transcatheter arterial chemoembolization was 82% at 1 year, 42% at 3 years, and 42% at 5 years. Portal trunk occlusion by tumor thrombus, three or more primary nodules, an indocyanine green retention rate at 15 minutes of 20% or worse, and therapeutic choice other than hepatectomy were significant predictors of a poor prognosis on univariate analysis. Hepatectomy was the only factor that was significant on multivariate analysis. CONCLUSIONS: Patients may enjoy long-term survival if they receive hepatectomy with preoperative transcatheter arterial chemoembolization, when the number of primary nodules is no more than two, the portal trunk is not occluded by tumor thrombus, and the indocyanine green retention rate at 15 minutes is better than 20%.
Hypocalcemia and hyperphosphatemia caused by PTH resistance are the only discernible abnormalities in pseudohypoparathyroidism type 1b (PHP-1b). Because of the selective resistance toward PTH, inactivating mutations in its receptor, the PTH/PTH-related peptide receptor (PTHR1), were thought to be responsible for PHP-1b. However, gene abnormalities responsible for PHP-1b have not been identified in the coding region and well conserved promoters (P1 and P2) of the PTHR1 gene. The purpose of the present study was to analyze the structure of the P3 promoter, the main promoter of the human PTHR1 gene in kidney, in patients with PHP-1b. Southern analysis of genomic DNA from lymphoblastoid cell lines of eight nonfamilial patients with PHP-1b revealed neither gross rearrangements nor methylation abnormalities in the P3 promoter region of the PTHR1 gene. Sequencing revealed no abnormalities in the P3 promoter region, although one patient was homozygous for an (AAAG)n polymorphic variant. In conclusion, despite the selective resistance toward PTH in the kidney, which mainly uses the PTHR1 P3 promoter, PHP-1b in eight cases is not associated with structural abnormalities in this promoter. This study also indicates that inactivation of the P3 promoter is not achieved by methylation as tested in patients' genomic DNA from lymphoblastoid cell lines. The influence of alterations in the polymorphic A-rich repeat sequence on promoter activity warrants further study.
The cellular mechanisms of abnormal calcium regulation and excitation-contraction coupling in relation to glucose metabolism in the hypertrophied heart are not well understood. The present study evaluated the myocardial mechanics of 6-7-week-old pressure overload hypertrophied rabbit hearts in response to dobutamine by (1) serial echocardiograms in vivo and (2) isolated Langendorff perfusion. Cytosolic Ca2+([Ca2+]i) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2) expression were measured by fluorescence spectroscopy and Western immunoblotting, respectively. The effect of glycolytic inhibition by 2-deoxy-D-glucose +/- pyruvate was also evaluated. Both systolic and diastolic [Ca2+]i tended to be higher and diastolic calcium removal (tauCa) significantly slower in the hypertrophied heart. The myocardial response to dobutamine was blunted and dobutamine insignificantly improved tauCa. The SERCA2 protein level was higher in early hypertrophy, but was significantly reduced by 6 weeks of age, with progressive contractile failure. Inhibition of glycolysis or SERCA2 caused an increase in [Ca2+]i as well as a slower tauCa. Pyruvate completely preserved myocardial function and [Ca2+]i handling during glycolytic inhibition. It was concluded that in this model of advanced pressure overload hypertrophy, contractile failure and inotrope insensitivity are associated with increased [Ca2+]i, slower tauCa and reduced sensitivity of the contractile proteins to Ca2+. These changes occur in association with downregulation of the SERCA2, probably caused by impaired glucose metabolism.
UNLABELLED: We have performed 321 cases of coronary artery bypass grafting (CABG), between October 15 1995 and November 20 2000. We have evaluated the operative results of 142 cases (44.2%) of conventional CABG and 179 cases (55.8%) of off-pump CABG performed during this period. The average numbers of bypassed grafts was 3.53 for conventional CABG, and 1.62 for off-pump CABG. The total number of 369 grafts were anastomosed to 501 coronary arteries for conventional CABG, and 283 grafts were anastomosed to 290 coronary arteries for off-pump CABG. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using RITA, LITA, GEA and RA. Three site of stenosis in 18 LITAs and 2 in 16 RITAs were recognized in off-pump CABG without the use of stabilizers. One site of stenosis in 130 LITAs and 3 string signs in 44 GEA were recognized in off-pump CABG with the use of stabilizers. Postoperative angiography in 52 off-pump CABG cases at one year later showed no new lesion. CONCLUSION: The use of stabilizers and LIMA suture enables adaptation of the MIDCAB procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.
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We examined dietary intakes among 69 people of three ethnic groups (Yao Chinese, Zhung Chinese and Han Chinese) in the autonomous country of Bama in China where many elderly people have a long life span in 1998. Dietary intake was evaluated using carbon and nitrogen isotope ratios of human hair (delta 13C, delta 15N) standardized by standard gas. The distributions of delta 13C in Yao Chinese and Han Chinese were scattered from -21 to -17/1000, which were close to that of C4 plants such as corn and millet. The distribution of delta 13C in Zhung Chinese was located from -25 to -22/1000, which was near that of C3 plants such as rice, wheat and potato. These values showed a much wider range when compared with delta 13C in Chinese living in urban areas. On the other hand, delta 15N in each group was distributed in the area ranged from 8 to 11/1000. The result of delta 13C was consistent with data obtained from a nutritional survey, but that of delta 15N was a little higher than expected. The carbon and nitrogen isotope ratios of human hair among three ethnic groups showed characteristic distributions, although the relation between these isotope ratios and longevity is uncertain.
Expression of the human parathyroid hormone (PTH)/PTH-related peptide receptor (PTHR) gene is controlled by three promoters, P1-P3. P1 functions specifically in kidney, whereas P2 is ubiquitously active. P3 is also widely active, although more so in kidney than other tissues. However, only P2 functions at midgestation. We examined the role of methylation in controlling PTHR promoter activity. Function of all promoters was inhibited by CpG methylation in vitro. Significantly, P1 is selectively hypomethylated in adult kidney in vivo, strongly suggesting that demethylation is required for renal P1 function. Moreover, this pattern is established by 11. 75 weeks of fetal age, several weeks prior to the onset P1 activity. P3 is unmethylated at midgestation, although it is inactive at this stage of development, and thus exhibits characteristics of both tissue-specific and ubiquitously active promoters. These results show that adult methylation patterns of P1 and P3 are established several weeks prior to their induction, indicating that their function requires factors expressed late in development.
OBJECTIVES AND METHOD: We have performed 225 cases of coronary artery bypass grafting (CABG), between October 15 1995 and September 8 1999. We have evaluated the operative results of 121 cases (53.8%) of conventional CABG and 104 cases (46.2%) of minimally invasive coronary artery bypass grafting performed during this period. The average numbers of bypassed grafts was 3.45 for conventional CABG, and 1.41 for minimally invasive coronary artery bypass grafting. Sixty-seven right internal thoracic arteries, 145 left internal thoracic arteries, 71 gastroepiploic arteries, 38 radial arteries and 12 saphenous veins were used for conventional CABG, and 29 right internal thoracic arteries, 81 left internal thoracic arteries, 18 gastroepiploic arteries, 3 radial arteries, 10 saphenous veins and 2 inferior epigastric arteries were used for minimally invasive coronary artery bypass grafting. The total number of 303 grafts were anastomosed to 417 coronary arteries for conventional CABG, and 143 grafts were anastomosed to 147 coronary arteries for minimally invasive coronary artery bypass grafting. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using right internal thoracic arteries, left internal thoracic arteries, gastroepiploic arteries and radial arteries. Three site of stenosis in 18 left internal thoracic arteries and 2 in 16 right internal thoracic arteries were recognized in minimally invasive coronary artery bypass grafting without the use of stabilizers. One site of stenosis in 63 left internal thoracic arteries was recognized in minimally invasive coronary artery bypass grafting with the use of stabilizers. CONCLUSION: The use of stabilizers enables adaptation of the minimally invasive coronary artery bypass grafting procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.
c-kit+Lin- cells are present in various immune organs, including the liver, thymus, and bone marrow, where lymphoid, myeloid, or erythroid cells are generated. To compare their properties as lymphoid precursors, c-kit+Lin- cells purified from various organs of B6.Ly5.1 mice were injected into 6.5 Gy-irradiated B6.Ly5.2 mice. Depending on the source of the c-kit cells, the degree of entrance and expansion of lymphoid cells differed in the liver and thymus of recipient mice. c-kit+ cells isolated from the bone marrow entered and expanded prominently in both the liver and thymus, whereas c-kit+ cells from the thymus did not do so at all. On the other hand, c-kit+ cells isolated from the liver and spleen showed an intermediate pattern, namely, they took a long time to enter and expand in the liver and thymus of recipient mice. All of these c-kit+ cells had the potential to give rise to lymphoid cells, which were specific to the liver and thymus, respectively. We previously showed that progenitor cells for extrathymic T cells in the liver and those for conventional T cells in the thymus are not always supplied by the bone marrow, as shown by experiments using parabiosis. Taken together with those previous data, the present results suggest that c-kit+Lin- cells isolated from various immune organs have organ specific properties.
When C57Bl/6 mice were exposed to restraint stress for 12 h or 24 h, lymphocytopenia was induced in the liver, spleen, and thymus. We examined which types of lymphocytes were sensitive or resistant to such stress by a immunofluorescence test. T cells of thymic origin were sensitive while NKT and NK cells were resistant. In contrast to the increase in the proportion of NK cells, NK activity of liver lymphocytes against YAC-1 targets decreased at 24 h after stress. On the other hand, their NKT cytotoxicity against syngeneic thymocytes increased in parallel with an increase in their proportion. In perforin -/- B6 mice and B6-gld/gld (Fas ligand-) mice, NK cells were found to mediate cytotoxicity through perforin while NKT cells mediated self-reactive cytotoxicity through Fas ligand. These results suggest that stress increases the proportion of both NK and NKT cells, but that NK cytotoxicity is suppressed while self-reactive NKT cytotoxicity is not, due to a diversity of their functional mechanisms.
When C57BL/6 mice were partially hepatectomized (PHx), severe lymphocytosis was induced in the liver in the early phase of hepatocyte regeneration (4 to 12 hours after PHx). A major lymphocyte subset expanding in this organ was estimated to be natural killer 1.1(+) (NK1.1(+)) intermediate CD3 (CD3(int)) cells (i.e., NKT cells). CD3(int) cells are extrathymic T cells generated in situ in the liver. These changes were suppressed when mice with PHx were pretreated with a beta-adrenergicD antagonist (i.e., beta-blocker), propranolol (PPL). This might have been caused by sympathetic nerve stimulation during hepatocyte regeneration. An alpha-blocker showed a similar effect, although the magnitude of suppression was lower than that of the beta-blocker. We previously showed that NK and NKT cells express surface beta-adrenergic receptors and are activated in number by sympathetic nerve stimulation. In the present study, NK cytotoxicity mediated by liver lymphocytes obtained from mice with PHx decreased, whereas NKT cytotoxicity against syngeneic thymocytes increased. Purified CD3(int) cells were also found to be able to mediate NKT cytotoxicity against regenerating hepatocytes. These results suggest that sympathetic nerve stimulation after PHx results in subsequent activation of NKT cells and that these NKT cells might be associated with immunologic surveillance during hepatocyte regeneration.
OBJECTIVE: To evaluate retrospectively the long-term results of an approach consisting of performing surgery in every patient in whom radical removal of all metastatic disease was technically feasible. SUMMARY BACKGROUND DATA: The indications for surgical resection for liver metastases from colorectal cancer remain controversial. Several clinical risk factors have been reported to influence survival. METHODS: Between March 1980 and December 1997, 235 patients underwent hepatic resection for metastatic colorectal cancer. Survival rates and disease-free survival as a function of clinical and pathologic determinants were examined retrospectively with univariate and multivariate analyses. RESULTS: The overall 3-, 5-, 10-, and 15-year survival rates were 51%, 38%, 26%, and 24%, respectively. The stage of the primary tumor, lymph node metastasis, and multiple nodules were significantly associated with a poor prognosis in both univariate and multivariate analyses. Disease-free survival was significantly influenced by lymph node metastasis, a short interval between treatment of the primary and metastatic tumors, and a high preoperative level of carcinoembryonic antigen. The 10-year survival rate of patients with four or more nodules (29%) was better than that of patients with two or three nodules (16%), and similar to that of patients with a solitary lesion (32%). CONCLUSIONS: Surgical resection is useful for treating liver metastases from colorectal cancer. Although multiple metastases significantly impaired the prognosis, the life expectancy of patients with four or more nodules mandates removal.
We treated an extremely tall 13-year-old girl with a growth hormone (GH)-secreting macroadenoma and GH levels of 120-495 ng/ml with a combination of preoperative octreotide infusion, surgery and postoperative octreotide infusion plus estrogen, which resulted in reduced tumor size prior to surgery, reduced GH levels and completely suppressed growth after surgery. 20K GH is produced by alternative splicing of 22K GH mRNA and the ratio of 20K GH to 22K GH is within a small range in the normal population and high in a GH-secreting tumor. The 20K/22K GH ratio in this patient was persistently elevated during each phase of the treatment and may serve as a sensitive index of tumor-derived GH secretion.