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Biomedical subjects

N Kamada

Publications and source records attributed to N Kamada.

At least 163 records · Page 9Linked to original sources
PubMed1995

Isolation of a 40 kDa immunoinhibitory protein induced by rat liver transplantation.

In certain combinations of donor and recipient rat strains, such as DA (RT1a) donors into PVG (RT1c) recipients, rejection after orthotopic liver transplantation (OLT) is overcome without immunosuppressive drugs, although other organs transplanted between these combinations are promptly rejected. The mechanisms involved in achieving drug-free liver allograft tolerance still remain poorly understood. In the present study, OLT (DA into PVG) serum from various postoperative times was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and two unique proteins of 40 kDa and 37 kDa were found to be in large concentrations in 60 day post-OLT serum. These proteins could only be detected at specific times after OLT in the DA into PVG combination and could not be detected in the serum of syngenically transplanted animals (DA into DA) and (PVG into PVG), rejector combinations (DA into LEW) requiring immunosuppressive treatment or induced by other organ transplants. When these proteins were purified and sequenced they were found to have an identical N-terminal sequence which is not listed in sequence databases. Mixed lymphocyte assays revealed that only the 40 kDa protein has a immunosuppressive capability which additionally appears to be donor specific. The 40 kDa protein will aid further in the understanding of how drug-free tolerance is attained in certain liver allografts and may also act as a marker of when treatment with conventional immunosuppressive drugs can be stopped in clinical OLT providing a homologue of the molecule can be found. This possibility appears likely as case reports already exist of patients who have successfully been able to cease treatment with such drugs.

Amino Acid Sequence↗
PubMed1995

A specific chromosome abnormality of t(4;12)(q11-12;p13) in CD7+ acute leukaemia.

Three cases of acute leukaemia with t(4;12) (q11-12;p13) karyotypic abnormalities were analysed. They had the following common clinical and biological characteristics: (1) dysplasia of three haemopoietic lineages: (2) absent or low myeloperoxidase activity: and (3) retention of platelets in the peripheral blood and megakaryocytes in the bone marrow. There were increased numbers of basophils in the bone marrow and peripheral blood in two of the cases. In all, the blast cells displayed the unique immunophenotype CD7+CD13+CD34+HLA-DR+. The blasts analysed in one case expressed c-kit on the membrane surface. These findings suggest that the t(4;12) (q11-12;p13) abnormality is associated with a particular type of acute leukaemia, one in which the morphology and immunophenotype suggest that the translocation may have occurred at an early stage of haemopoiesis.

Acute Disease↗
PubMed1995

Emergence of karyotypically unrelated clone in remission of de novo acute myeloblastic leukaemias.

Serial cytogenetic analysis revealed karyotypically unrelated clones in four patients with acute myeloblastic leukaemia (AML) in remission. At diagnosis, three patients had t(8;21)(q22;q22) and one had an inv(16)(p13q22). After 18-22 months in remission, different clones emerged in each patient with myelodysplastic features of the bone marrow cells. The emergence of clones with abnormalities of chromosome 7 in remission seems to be an unfavourable factor for prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Syngeneic small-bowel grafting increases susceptibility to lethal graft-versus-host disease in the rat.

The rat model has been used to present evidence of the effect of surgical damage on the immune system. Syngeneic small bowel transplantation (SBT) has been used to show an increased incidence of graft-versus-host disease (GVHD) as well as thymic atrophy and altered host T cell proliferative response. Syngeneic auxiliary SBT was carried out between (LEW x BN)F1 hybrids. Varying amounts of LEW mesenteric lymphocytes were injected into the last animals to induce GVHD. Results showed that in the SBT recipients the incidence of lethal GVHD was increased when compared with untreated or sham-laparotomy controls. Marked thymic atrophy was also observed, while the number of hepatic lymphocytes increased transiently. Lymphocyte proliferation in response to concanavalin A or interleukin-2 was impaired for up to 21 days postoperatively, whereas the mixed lymphocyte reaction reactivity was not affected. These results show that the number and proliferative activity of thymic T cells were impaired after major small bowel transplantation surgery and that extrathymic lymphocytes were developed in the liver.

Animals↗
PubMed1995

Production of mice entirely derived from embryonic stem (ES) cell with many passages by coculture of ES cells with cytochalasin B induced tetraploid embryos.

Mice entirely derived from ES cells were obtained from aggregates of TT2 ES cells and cytochalasin B induced tetraploid embryos. Tetraploid embryos were cocultured with ES cells in a well on the Multiplate-Terasaki. After embryo transfer of the aggregates, the male newborns were recovered normally after Cesarean section and reached adulthood. The male mice exhibited complete pigmentation of the eye and coat, suggesting ES cell contributions alone. Alkaline phosphatase-1 analysis yielded no evidence of tetraploid cells in the kidney or liver. The TT2-derived males were fertile, produced normal offspring, and exclusively transmitted the TT2 genotype to their progeny. This result clearly shows that ES cells are able to support complete fetal development.

Animals↗
PubMed1995

[Fate of two different stages of embryos transferred to an identical recipient in mice].

To define the developmental fate of two different stages of embryos existing together in the mouse reproductive tract, different stages of fresh and frozen-thawed embryos were transferred separately into the oviducts of identical recipients. ICR and FvB embryos were flushed from the oviducts and/or uterus of superovulated females on Day 1 (2-4-cell stage) and Day 2 (8-cell-morula stage) of pregnancy. Day 1 embryos were transferred separately to the right or left oviduct of recipients, while the other oviduct received Day 2 embryos. There were no significant differences between Day 1 and Day 2 embryos with respect to the number of implantation sites and live fetuses in either the fresh or frozen-thawed embryos. These results concerning to the embryonic stage were similar to those of control experiments, in which Day 1 or Day 2 embryos were transferred to both right and left oviducts of recipients. Furthermore, no strain differences were observed in this study. No developmental retardation or anomalies were observed in fetuses derived from either Day 1 or Day 2 embryos. The embryo transfer in this study revealed that differences in developmental stage at preimplantation were synchronized by the maternal uterine environment.

Animals↗
PubMed1995

Independent clones of trisomy 12 and retinoblastoma gene deletion in Japanese B cell chronic lymphocytic leukemia, detected by fluorescence in situ hybridization.

Trisomy 12 and a deletion of chromosome 13 are the most common chromosome abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL). We determined the frequencies of these abnormalities in Japanese B-CLL patients by FISH in interphase nuclei. Specimens from 42 patients were analyzed using both DNA probes specific to the centromeric region of chromosome 12 and the retinoblastoma (RB) gene. Among 42 patients, eight had trisomy 12 and 12 had the RB gene deletion. We found aberrations of trisomy 12 and the RB gene deletion in a totally different group of patients. This suggested that the trisomy 12 and the RB gene deletion occur in different clones and the presence of which in the same patient may be rare. Furthermore, the frequency of trisomy 12 (19%) found in Japanese B-CLL was lower than that in Western countries (30-35%). On the contrary, the frequency of the RB gene deletion (28.6%) was almost the same as in European B-CLL (30-35%). These results will be helpful in understanding the leukemogenesis of B-CLL.

Adult↗
PubMed1995

Expression of AML1 and ETO Transcripts in hematopoietic cells.

Recently, two genes, AML1 and ETO have been isolated from the chromosomal breakpoint of t(8;21). In this study, we isolated and identified fusion transcripts from a leukemic cell line carrying t(8;21). We demonstrated by PCR analysis that these transcripts are consistently expressed in fresh leukemic cells with t(8;21). On the other hand, the wild type of ETO is expressed in several hematopoietic cells from different lineage, while the expression of AML1 was present in all hematopoietic cells investigated. These widespread expression suggests these molecules play an essential role in hematopoiesis.

Base Sequence↗
PubMed1995

Migration of donor cells into the thymus is not essential for induction and maintenance of systemic tolerance after liver transplantation in the rat.

In this study, we show that cells encoded by donor-type major histocompatibility complex (MHC) class I antigens effectively migrate into the thymus of the host after liver transplantation. However, the thymus is not essential for the induction and maintenance of tolerance after orthotopic rat liver transplantation (OLT). Liver allografted rats in the DA(RT1a) into PVG (RT1c) combination survived without immunosuppressive agents. The thymus of the host showed a transitory atrophy and returned to normal weight 4 weeks after OLT. Donor antigens were detected in the host thymus after OLT. Adult PVG rats that had been thymectomized 1 week before implantation of DA liver grafts showed liver graft survival without immunosuppression. DA heart grafts were heterotopically transplanted into the PVG thymectomized, liver-grafted rats 1-4 weeks after OLT. No rejection of the cardiac allografts was observed. Systemic tolerance was induced and maintained in the absence of the thymus.

Animals↗
PubMed1994

Induction of natural chimerism after retransplantation of the liver in rats.

Immunological aspects after orthotopic rat liver retransplantation (re-OLT) were examined in association with cell migration and mixed chimerism. At day 2 after the first orthotopic liver transplantation (day 0) in the combination of DA (MHC haplotype, RT1a) donor into PVG (RT1c) recipient, the grafted DA liver was removed and a new PVG liver was implanted into the same PVG recipient (re-OLT). In the PVG recipient at various times after the re-OLT, DA-derived antigen and cells were detected using a DA-specific anti-class I mAb R3/13 in conjunction with ELISA, immunoblotting, and immunohistochemistry. The level of soluble class I antigen, which had risen to 270 ng/ml after the first OLT, substantially decreased within 24 hr after re-OLT. Using immunoblotting, DA class I antigen was detected in the PVG recipient's lymphoid organs at day 3 after DA liver grafting and persisted for up to 21 days after the DA liver was replaced by a new PVG liver. Immunohistochemistry on sections of spleen from re-OLT rats showed that the level of migratory cells expressing DA class I correlated with the findings obtained by immunoblotting. While the DA-derived antigen and cells were detected in the re-OLT recipient, the DA-specific inhibition of mixed lymphocyte reaction was observed in re-OLT serum. Our results suggest that the implanted DA liver graft was the source of DA soluble class I antigen, but DA-derived antigen and cells detected in the re-OLT recipient organs could persist for a relatively long time under immunosuppression after the implanted DA liver was removed by re-OLT.

Animals↗
PubMed1994

Hepatoprotection by a PGI2 analogue in complete warm ischemia of the pig liver. Prostanoid release from the reperfused liver.

We examined the hepatoprotective effect of a prostaglandin (PG)I2 analogue by analyzing the endogenous release of prostanoid from the pig liver. Fourteen female pigs underwent 1 hr complete hepatic vascular exclusion (HVE); the portal and vena caval circulation was actively decompressed. The animals were divided into one of two groups (n = 7, each) according to pretreatment with the prostacyclin analogue (OP 2507, OP) administered via a mesenteric vein branch for 30 min at a rate of 2 micrograms/kg/min immediately prior to HVE. The plasma levels of prostaglandin E2 (PGE2), 6-keto-prostaglandin F1-alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2), from the blood samples from the aorta, the hepatic vein, and the portal vein were serially compared for 60 min after the restoration of blood flow. Other parameters included 7-day survival rate, serum biochemistry, and endotoxin assay. A significant improvement in 7-day survival rate (6/7 vs. 1/7 for the control, P < 0.02) was observed in the OP-treated animals, associated with amelioration of serum transaminase activities but with no differences in plasma endotoxin levels. The reperfused liver progressively and substantially released PGE2 but did not generate other prostanoids (TXB2 and 6-keto-PGF1 alpha). OP pretherapy substantially suppressed hepatic generation of the PGE2 postreflow, correlating with serum transaminase levels (rs = 0.80; P < 0.01, at 60 min). We conclude that the PGI2 analogue ameliorates hepatic ischemia/reperfusion injury by down-regulating PGE2 production from the reperfused liver.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI1 gene in acute myelogenous leukemias with inv(3)(q21q26).

Structural alterations occur in the long arm of chromosome 3 in approximately 2% of patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). The major alterations are inv(3)(q21q26) and t(3:3)(q21;q26) and are often classified as the 3q21q26 syndrome. We previously reported that the EVI1 gene is transcriptionally activated in AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) and that the chromosomal breakpoints at 3q26 in the translocations were 5' of the EVI1 gene, whereas the breakpoints in the inversion cases were 3' of the gene. In these studies, four additional cases of AML with inv(3)(q21q26) are shown to express the EVI1 gene and to have breakpoints 3' of the gene. To characterize the 3q21 breakpoint region, cosmid and phage clones were isolated that cover approximately 100 kb. At 3q21, the breakpoints for both AMLs with t(3;3)(q21;q26) and inv(3)(q21q26) were found to cluster over a region of approximately 50 kb downstream of the Ribophorin I gene. The results indicate a common mechanism for the translocations and inversions and support the hypothesis that the transcriptional activation of the EVI1 gene is mediated by enhancer elements associated with the Ribophorin I gene.

Adult↗