Liver transplantation regulates a graft-versus-host reaction in the rat.
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Animals↗
Biomedical subjects
N Kamada
Publications and source records attributed to N Kamada.
The value of hepatic artery reconstruction as a technique in rat liver transplantation.
The importance of hepatic artery reconstruction in the success of liver transplantation in the rat has been studied. Rat liver grafts were performed with or without reanastomosis of the hepatic artery, both in rejector and nonrejector donor/recipient combinations. No significant improvement in recipient survival was found when arterialization was performed, and histologic studies showed no differences in hepatocyte or bile duct architecture between arterialized and nonarterialized groups. Thus, arterialization does not make an important contribution to the outcome of liver transplantation in the rat; biliary complications associated with the nonarterialized method appear to be technique-related rather than the result of ischemia.
Anastomosis, Surgical↗
Molecular studies of chronic myelogenous leukemia using the polymerase chain reaction.
Thirty-two cases of chronic myelogenous leukemia (CML) were studied to determine whether there was a correlation between the position of the chromosome breakpoint within the breakpoint cluster region (bcr) on chromosome 22 and the type of chimeric mRNA expression. One case with the chromosome breakpoint in zone 2 of the major bcr (Mbcr) and six cases with breakpoints in zone 3 expressed Mbcr exon 2-abl (b2-a) mRNA, and they were in distinguishable at the level of mRNA expression. The remaining ten cases with breakpoints in zone 3 and all ten cases with breakpoints in zone 4 expressed Mbcr exon 3-abl (b3-a) mRNA with or without b2-a mRNA. Three cases with breakpoints in zone 5 expressed b3-a mRNA, and none of these expressed Mbcr exon 4-abl(b4-a) mRNA. The cases with breakpoints in zones 4 or 5 had b3-a mRNA expression indistinguishable from those with breakpoints in zone 3. In two patients, the breakpoint in the bcr could not be determined by Southern hybridization using the 3' bcr probe or the large bcr probe. However, when analyzed for chimeric mRNA expression, both of them exhibited b3-a chimeric mRNA, suggesting the possibility that the entire Mbcr is deleted in the majority of leukemic cells in these patients. These studies indicate that Southern hybridization analysis combined with the polymerase chain reaction assay is a useful approach to understanding the pathologic role of bcr-abl gene recombination and expression in the development of CML.
Adolescent↗
Lymphoproliferative disorders after FK 506.
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Anti-Bacterial Agents↗
Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation.
A novel leukemic cell line with an 8;21 chromosome translocation, designated as Kasumi-1, was established from the peripheral blood of a 7-year-old boy suffering from acute myeloid leukemia (AML). The Kasumi-1 cells were positive for myeloperoxidase showing a morphology of myeloid maturation. The response in proliferation assay was observed in the culture with interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor (G-CSF), and granulocytemacrophage CSF (GM-CSF), but not with IL-1 or IL-5. Neither granulocytic nor eosinophilic maturation was observed in the liquid culture by the addition of dimethyl sulfoxide, G-CSF, or IL-5, respectively. In contrast, induction of macrophagelike cells was seen by the addition of phorbol ester. This is the first report of a human AML cell line with t(8;21) that has characteristics of myeloid and macrophage lineages. The cell line could be a useful tool for elucidating the pathophysiology of AML with t(8;21).
Antigens, CD↗
Establishment and characterization of human signet ring cell gastric carcinoma cell lines with amplification of the c-myc oncogene.
Two unique human signet ring cell gastric carcinoma cell lines (designated HSC-39 and HSC-40A) were established in vitro from the ascites of a 54-year-old male patient. Both cell lines were biologically quite similar, grew in vitro in suspension with a population doubling time of 28-30 h, and had cytological features of mucinous epithelial tumor cells. They formed colonies in soft agar, with a cloning efficiency of 0.8-1.0%. Ultrastructurally, numerous granules were observed in the cytoplasm, suggesting secretory activity. The frequent presence of desmosome and the tight junction at the cell boundary certifies the epithelial origin of the lines. Immunocytochemistry and radioimmunoassay showed production of tumor marker antigens (carcinoembryonic antigen, CA 19-9, and sialyl-Lex-i) and gastrin in both lines. These lines were transplantable in athymic BALB/c nude mice. The histopathology of each line growing in athymic BALB/c nude mice was similar to that of the original tumor. The karyotype of the cells was highly aberrant with structural and numerical changes. The presence of numerous double minute chromosomes and loss of the 13 chromosome and Y-chromosome characterize these lines. In addition, the amplified c-myc oncogene (16-32-fold) was found in both cell lines and original ascitic tumor cells. Overexpression of the c-myc mRNA was noted. These cell lines may be a useful tool, providing both in vivo and in vitro systems for further studies of the biology and therapy of human signet ring cell (or Borrmann's type IV carcinoma) gastric carcinoma.
Adenocarcinoma, Mucinous↗
Localization and ultrastructure of the Kupffer cells in orthotopically transplanted liver grafts in the rat.
Kupffer cells play an important role in the acceptance or rejection of liver grafts. We examined the ultrastructure of the Kupffer cells in transplanted rat livers, from an early to a late stage where the graft is accepted, using a DA-to-PVG combination. Two days after surgery, endocytic activity of the Kupffer cells had increased, as evidenced by worm-like structures and many endocytic vacuoles. There was often close apposition to the monocytes or lymphocytes. By day 4, infiltration of mononuclear cells into the sinusoids was readily noticeable. By day 7, several Kupffer cells had migrated into the space of Disse through the openings in endothelial linings. The number of Kupffer cells reached a maximum at 14 days. They were located mostly outside the sinusoid, adhering to the hepatocytes. At this point in time, however, the Kupffer cells contained few endocytic vacuoles and phagolysosomes, in contrast to those at 2 days. The number and location of Kupffer cells became almost normal at 2 months. The present results indicate that Kupffer cells are highly activated before mononuclear cell infiltration becomes manifest in the sinusoid, and that when a rejecting reaction reaches a peak, they are usually located extrasinusoidally and show a morphologically immature profile.
Animals↗
Effect of sugars in the preservation solution on liver storage in rats.
We have performed 128 rat liver transplants in order to examine the effect of sugars in preservation solutions on cold storage of rat livers. Glucose (Mw. 180), sucrose (Mw. 348), and raffinose (Mw. 594) were tested. Rat livers were preserved at 4 degrees C for 12, 16, 18, and 24 h in standard Eurocollins solution (EC solution) (solution A) or in one of three modified EC solutions in which 194 mM/liter glucose in standard EC solution was replaced by 140 mM/liter of glucose (solution B), sucrose (solution C), or raffinose (solution D). The osmolarity of the modified solutions (solution B-D) was 320 mOsm/liter. Using standard EC solution (solution A), the 1-week survival rate of rats receiving livers preserved for 12, 16, 18, or 24 h was 6/8, 4/8, 1/8, and 0/4, respectively. With solution B, in which 194 mM/liter glucose was replaced by 140 mM/liter glucose, 1 week survivors following transplantation of livers preserved for 12, 16, 18 or 24 h were 4/8, 3/8, 2/8 and 0/4, respectively. Solution C, which was identical to solution A except for the replacement of 194 mM/liter glucose by 140 mM/liter sucrose, gave the following 1-week survival rates: 5/8 for 12 h, 5/8 for 16 h, 2/8 for 18 h, and 0/4 for 24 hours preservation, respectively. Using solution D, which differed from A in the replacement of glucose by 140 mM/liter raffinose, the 1-week survival rates of rats grafted with livers preserved for 12, 16, 18, and 24 h were 6/8, 5/8, 3/8 and 0/4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A comparison of a new solution combining histidine and lactobionate with UW solution and eurocollins for rat liver preservation.
Forty-six rat liver transplants were performed to investigate the effectiveness of a simplified lactobionate solution containing histidine as a buffer (histidine-lactobionate solution) and to compare it with University of Wisconsin solution. This new solution is isoosmotic (320 mOsm/L) and has a higher sodium content and a lower potassium content (Na: 90 mEq/L, K: 45 mEq/L) than standard UW solution. Buffering capacity is increased by adding histidine (90 mM/L) together with KH2PO4 (20 mM/L) and is greater than that of Eurocollins solution or UW solution. Adenosine, insulin, hydroxyethyl starch, and dexamethasone that are included in UW solution are not included in the new solution. The 1-week survival rate of rats transplanted with livers preserved in this solutions at 4 degrees C was 85% (11/13) following 24-hr preservation and 33% (2/6) after 30-hr preservation. By contrast, UW solution gave only a 29% (5/17) survival rate after 24-hr preservation and 0% (0/6) survival after 30-hr preservation, demonstrating that this simplified UW solution with histidine is superior to UW solution in rat liver preservation. No rats (0/4) receiving livers preserved for 24 hr in Eurocollins solution survived. These findings show that the inclusion of histidine as a buffer dramatically improves the effectiveness of lactobionate-based preservation solutions and justify application in a large-animal model and subsequently in clinical liver transplantation.
Adenosine↗
Immunological tolerance induced by liver grafting in the rat: splenic macrophages and T cells mediate distinct phases of immunosuppressive activity.
In the rat combination DA into PVG, liver grafts are not rejected but induce donor-specific transplantation tolerance. We have examined the immunosuppressive properties of spleen cells from PVG recipients of DA liver grafts at various times post-grafting. The results indicate the development of two phases of cell-mediated suppressor activity, which appear to be mediated by separate spleen cell populations. Mitomycin-C-treated spleen cells taken from animals between 5 and 28 days post-grafting were able to suppress rat mixed lymphocyte reactions (MLRs). These 'early' suppressor cells were glass adherent and absent from populations purified by passage through nylon wool or G10 Sephadex columns. Suppression of MLR by purified glass adherent cells was not specific for either stimulator or responder haplotypes and was blocked by indomethacin. Nylon wool purified T cells were not suppressive at this time. Spleen cell suppressor activity declined to background levels after 35 days post-grafting. However, spleen cells from long-term surviving liver graft recipients (20 weeks or more) were again able to suppress MLR; the 'late' suppressor cells were nylon wool non-adherent and suppression was specific for the donor (DA) MHC type. We conclude that liver grafting in this combination generates early and late phases of suppression among spleen cells, that the early phase is produced by macrophages and mediated by prostaglandins and that the late phase is dependent on allospecific suppressor T cells.
Animals↗
Mutation of RAS oncogene in atomic bomb radiation-exposed leukemia.
To determine what the role of RAS oncogene is in radiation-induced leukemia, we investigated the frequency of mutations and the sites of the base substitution of activated N- and K-RAS oncogenes in 25 leukemic patients who had been exposed to the atomic bomb and compared the results with those for 47 non-exposed leukemic patients. To detect the presence of mutated RAS oncogene, we used the PCR method to analyze DNAs from leukemic cells and from nude mouse tumors formed by in vivo selection assay. Eight of the 25 exposed leukemic patients (32%) and 13 of the 47 non-exposed leukemic patients (27.6%) had RAS oncogene mutations. No significant differences were found between the exposed and non-exposed groups in frequency of mutation and the sites of base substitution on the RAS oncogene sequence. This study should prove valuable for understanding the role of RAS oncogene mutation in the genesis of radiation-induced leukemias.
Base Sequence↗
Cytogenetic and molecular changes in leukemia among atomic bomb survivors.
Seventy five radiation-related leukemia patients in Hiroshima including 16 patients exposed to more than one Gray were cytogenetically examined. Statistical analysis of data on the frequencies of chromosomal aberrations in the survivor groups according to bone marrow doses by DS86 estimation revealed that the heavily exposed group tended to have significantly higher aberration rates compared to the non-exposed group. Furthermore, the chromosomal aberrations in the survivors were observed to be of a more complex nature and had the characteristic findings of secondary leukemia. These observations therefore suggest that patients with a history of heavy exposure to atomic bomb radiation had leukemic cells originating from a stem cell which had been damaged by irradiation at the time of the bombing as well as cells involved in complex chromosome abnormalities. Molecular biologic studies on ras genes in acute and chronic leukemias and the bcr gene in chronic myelocytic leukemia were performed in exposed and non-exposed groups. So far, no distinctive differences have been observed in the frequency and sites of point mutations in N- and K-ras genes or in the rearrangement of the bcr gene. Further, retrospective analysis using DNA from leukemia patients who developed this disease in the early period from atomic bomb radiation exposure would be useful for the elucidation of the mechanisms of radiation-induced leukemia.
Aged↗
Cytogenetic and molecular changes in leukemia found among atomic bomb survivors.
Seventy five radiation-related leukemias (acute non-lymphocyte) in Hiroshima including 16 patients exposed to more than one Gray were cytogenetically examined. Statistical analysis of the data on the frequencies of chromosomal aberrations in survivors according to the bone marrow doses of DS86 estimation revealed that heavily exposed patients tended to have significantly higher aberration rates as compared with non-exposed patients. Furthermore, the chromosomal aberrations in the survivors were observed to be of a more complex nature and had characteristic findings of secondary leukemia. These observations therefore suggest that patients with a history of heavy exposure to atomic bomb radiation exhibit leukemic cells that originated from a stem cell which had been damaged by irradiation at the time of bombing and had been involved in the complex chromosome abnormalities. Molecular biological studies on transforming genes in acute and chronic leukemia and the bcr gene in chronic myelocytic leukemia have been performed in exposed and non-exposed groups. So far, no distinctive differences have been observed in the frequency and the sites of point mutations in N- and K-ras genes or in the rearrangement of the bcr gene, for a final conclusion of the specificity of radiation induced leukemia. Further retrospective studies require patient DNAs that developed in the early period of the atomic bomb exposure.
Chromosome Aberrations↗
A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Chromosome abnormality in early entrants.
A preliminary study was performed to estimate radiation dose in 10 individuals who had entered Hiroshima city one day after the explosion and worked around the hypocenter area for a week. The numbers of cells with chromosome aberrations differed in each subject, ranging from one to 18 (median: 11 abnormalities) in 500 metaphases of lymphocytes cultured for 48 hours with Phytohemagglutinin. Five individuals had more than 1.6 percent stable type aberrations and were estimated to have been exposed to 6-13 rad. The other five individuals and the controls were estimated to be less than two rad.
Aged↗
Cytogenetic, molecular biological and clinical study of B-cell lymphomas with 14;18 translocation in Japanese patients.
To investigate the role of the BCL-2 gene in Japanese patients with B-cell non-Hodgkin's lymphoma, karyotypic analysis, DNA analysis and clinical characterization were studied. Ten of 73 patients showed t(14;18) and two patients had variant translocations [t(2;18) and t(18;22), respectively]. Of 42 patients examined at the molecular level, eight patients showed the BCL-2 gene rearrangement detected by mbr probe and two patients by 5'BCL-2 probe. Of the eight patients with the BCL-2 gene rearrangement by the mbr probe, t(14;18) was detected in six patients. A discrepancy in the relationship between the occurrence of t(14;18) and BCL-2 gene rearrangement was recognized. Two patients with obvious t(14;18) showed no rearrangement of the BCL-2 gene by mbr, mcr, nor 5' probe. Cytogenetic analysis is an indispensable tool for investigating lymphomogenesis. The two patients with the variant translocations, t(2;18) and t(18;22), showed breakpoints at the 5' site of the BCL-2 gene and both were histologically of the small lymphocytic type. No examples with the co-existence of both the BCL-2 and c-MYC gene rearrangements were found. The median survival time of the patients with the BCL-2 rearrangement and/or t(14;18) was longer than the patients without the BCL-2 gene rearrangement and translocation and also patients with the c-MYC gene rearrangement and/or translocation. Racial and geographical heterogeneities, variant translocations of t(14;18) and the clinical characteristics of B-cell non-Hodgkin's lymphoma with t(14;18) are discussed.
Chromosome Aberrations↗
[The significance of cytogenetic analysis in the diagnosis of leukemia].
The results of a comprehensive study on 1,000 patients who had been cytogenetically diagnosed to have leukemia in our department since 1962 are reported, and the value of cytogenetic diagnosis for leukemia emphasized. In our series, we detected patients with FAB L1 and L2 showing an abnormality rate of 60 and 66%, respectively. They included 20% with Ph1 positive ALL. In FAB L3, we found t(8;14) in 5 of the 6 patients. The FAB M1 group showed the lowest abnormality rate (50%). Forty percent of the M2 patients exhibited t(8;21), 60% of which also showed loss of sex chromosome of either X or Y. Seventy-eight percent of the M3 patients presented t(15;17) (two patients with no detectable t(15;17) showed rearrangements of retinoic acid receptor alpha gene). Inversion of chromosome 16 was found in 10% of the patients with FAB M4. Patients with M6 exhibited relatively complex chromosomes aberrations. RAEB patients showed more frequent and complex type of chromosome aberrations than PARA patients. Cytogenetic and molecular-biological analyses provided valuable information on the pathophysiology of leukemia and suggested the possible localization of novel oncogene(s).
Chromosome Aberrations↗
Cellular basis of transplantation tolerance induced by rat liver transplantation: evidence for suppressor cell activity in vivo.
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Animals↗
Mechanisms in passive enhancement of cardiac and renal allografts by serum from liver-grafted rats.
The ability of serum from PVG (haplotype RT1c) rats carrying long-term surviving orthotopic DA (RT1a) liver grafts (OLT serum) to enhance cardiac allografts has been confirmed and extended to renal allografts. One millilitre of OLT serum given at the time of allografting was sufficient to cause permanent acceptance of PVG.RT1a heart or kidney grafts in PVG recipients ('enhanced recipients'); the PVG.RT1a being congenic with respect to PVG, and sharing the RT1a haplotype with DA. Adoptive transfer of thoracic duct lymphocytes (TDL) from rats carrying enhanced liver grafts into irradiated recipients indicated that specific alloreactive clones had been functionally inactivated or deleted; this was accompanied by active suppression in which specific alloreactivity of normal TDL was partially inhibited. In vitro, splenic T cells from rats with enhanced grafts mediated allospecific suppression in mixed lymphocyte reaction (MLR). The serum of rats carrying enhanced grafts was able to specifically suppress MLR of the same donor/recipient combination. Thus enhancement by orthotopic liver transplantation (OLT) serum leads to cellular and serological changes in the recipient associated with maintenance of unresponsiveness. Such changes are similar to those seen in liver graft recipients themselves.
Animals↗