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N Kamada

Publications and source records attributed to N Kamada.

At least 325 records · Page 18Linked to original sources

Hypothermic preservation of the rat liver assessed by orthotopic transplantation. II. Evaluation of citrate solutions.

Rat livers were flushed with isotonic citrate solution (IC), hypertonic citrate solution (HC), or Collins' solution (C2), and were stored at 0 degree C for 8-16 hr. Following 8-hr preservation, the number of animals surviving for one month was greatest with IC grafts (6/8) and least with C2 grafts (2/7). There was no significant difference between the two citrate groups. Following 12-hr preservation, the IC group was superior to the HC group (3/6 vs. 1/6). Following 16-hr preservation, all four animals in each citrate group died within 24 hr. The ability of livers to produce bile was greater in the citrate groups, compared with the C2 group. A bile flow rate less than 0.3 microliter/min/g liver, 15 min after implantation, appeared to predict subsequent poor survival. There were no significant histological differences between biopsies taken from each group at the end of the transplant operation. Biochemical measures of liver function were best in animals that had received IC grafts, and functional damage after preservation was consistently greater in the C2 group than the citrate groups. The best results were obtained with grafts preserved with IC solution.

Animals↗

Successful 48-hour preservation of the rat liver by continuous hypothermic perfusion with haemaccel-isotonic citrate solution.

Eleven rat livers were stored at 7 degrees C for 24 or 48 hr using a continuous nonpulsatile perfusion method. The perfusate was based on the isotonic citrate preservation solution but contained, in addition, gelatin polypeptides (Haemaccel, Hoechst) and fluorocarbon emulsion (FC-43, Green Cross Corp.). Isologous livers were orthotopically transplanted after preservation, and long-term survival was 3/6 following 24 hr preservation and 4/5 following 48 hr preservation. All the biopsies taken immediately after revascularization were histologically normal. The seven surviving animals were killed at two months and histology showed biliary obstruction, but in all cases the hepatocytes appeared to be well preserved. These late histological findings are common in any use of this transplantation model and are believed to be associated with the difficulty of obtaining a satisfactory anastomosis of the bile duct. The perfusate described here is capable of providing reliable 48 hr preservation of the rat liver.

Animals↗

Immunosuppressive activity of serum from liver-grafted rats: in vitro specific inhibition of mixed lymphocyte reactivity by antibodies against class II RT1 alloantigens.

The immunosuppressive activity of serum from PVG rats following orthotopic transplantation of DA liver has been examined in vitro. Liver grafts in this combination are never rejected, but induce a state of specific transplantation tolerance in the recipient. Serum from such tolerant animals was able to inhibit proliferation of normal PVG lymph node cells in response to DA stimulators in the mixed lymphocyte reaction (MLR); inhibition was specific for donor (DA) antigens. Interleukin-2 (IL-2) production during the MLR was also reduced. The production of anti-DA cytotoxic T cells developing in the MLR was not affected, but the total yield of such cells was reduced. Evidence was obtained that part of the inhibitory serum activity was due to IgG antibody against class II RT1a alloantigens. Thus, a purified IgG fraction retained much of the inhibitory activity which could be removed by an anti-IgG absorbent. Studies of MLR inhibition in different rat strains indicated the anti-class II specificity of the inhibitory IgG. Lymph node cells from DA-liver-grafted PVG rats responded normally against DA stimulators in vitro, and this MLR was also blocked by the inhibitory IgG. Our results suggest that anti-class II allo-antibody may play a role in immunosuppression and long-term graft survival following liver transplantation in this combination.

Animals↗

Reciprocal translocation involving the short arms of chromosomes 7 and 11, t(7p-;11p+), associated with myeloid leukemia with maturation.

A reciprocal translocation involving the short arms of chromosomes 7 and 11, t(7;11)(p15;p15), was found in nine patients including eight with acute myelogenous leukemia (AML) and one with Philadelphia (Ph1) chromosome-positive chronic myelogenous leukemia (CML) in blastic crisis. Although a similar chromosome rearrangement has previously been reported in five patients, including three with AML and two with CML, the 7p breakpoint in some of these cases was slightly different from that detected in our patients. Notable cytogenetic and clinicohematologic findings in our patients and those reported in the literature were as follows: (a) t(7;11) occurred in myeloid leukemia, predominantly AML with subtype M2, and occasionally in other AML subtypes and in CML with or without Ph1 chromosome; (b) t(7;11) frequently occurred as the sole chromosome abnormality; (c) most patients showed a low neutrophil alkaline phosphatase score; and (d) Auer rods were present in leukemic cells of most cases including Ph1-positive CML. Our findings suggest that a t(7;11)-associated leukemia constitutes a subgroup of myeloid malignancy involving maturing leukemic cells.

Blast Crisis↗

Chromosome aberrations and transforming genes in leukemic and non-leukemic patients with a history of atomic bomb exposure.

To investigate leukemogenesis in atomic bomb (A-bomb) survivors, chromosome aberrations in bone marrow cells, and T- and B-lymphocytes from 135 healthy persons who had been exposed within 1,000 m of the hypocenter of the Hiroshima A-bomb were sequentially examined. Leukemic marrow cells from 468 patients with acute or chronic type of leukemias, including 25 acute leukemias exposed to 1 rad or more of radiation were also studied cytogenetically. Analysis of breakpoints observed in T-lymphocytes with stable types of abnormalities revealed a nonrandom distribution, and clustering in specific regions of chromosomes such as 22q1, 14q3, and 5q3. Statistical analysis revealed a higher incidence of translocations in 50 bands, including those containing cellular oncogenes such as 8q22, 8q24, and 9q34. Of these 50 bands, 20 were matched with bands specific for leukemia and cancer and 14 with constitutive fragile sites. In leukemic marrow, all 10 patients who had been exposed to radiation of more than 200 rad and then developed acute non-lymphocytic leukemia had chromosome aberrations. Their aberrations were more complex than those in patients exposed to less than 200 rad (33 patients) and in the non-exposed patients (134 patients). DNA samples extracted from bone marrow cells of 13 survivors, including 4 healthy survivors with more than 30% chromosome abnormalities in the bone marrow and 9 leukemia patients were used for in vivo selection assay of transforming genes. Tumor formation in nude mice was observed in 3 of the 4 healthy survivors and 9 leukemia patients. All of the transfectants were shown to contain Alu sequences. The transforming N-ras gene was detected for the first time in the bone marrow cells from 3 heavily exposed survivors and from 7 leukemia patients with a history of radiation exposure.

B-Lymphocytes↗

Serology of liver transplantation in the rat. I. Alloantibody responses and evidence for tolerance in a nonrejector combination.

The antibody response against class I and class II RT1 antigens has been studied in PVG rats grafted with DA liver. In this nonrejector combination, liver grafts survive permanently in all normal recipients and in about 50% of recipients presensitized by a DA skin graft, with concurrent induction of transplant tolerance for other DA organs and skin. Using a two-stage radioimmunoassay, the anti-class I (RT1Aa) levels in sera of normal PVG recipients of DA liver grafts were found to be low (maximal titer 1:50 serum dilution or less); after peaking at 2 weeks posttransplantation, they diminished to background levels by 6 weeks. The anti-RT1Aa response showed a close parallel to cell-mediated rejection events in the liver graft recipients. In contrast, anti-class II (RT1Ba/Da) responses reached much higher titers (over 1:1000), which were maintained for several weeks before declining after 4 months. Similar observations were made in presensitized recipients. The induction of tolerance in the alloantibody response was indicated by the inability of DA skin grafts to restimulate anti-RT1 antibody in liver recipients. The observations support the picture of "split tolerance" indicated by previous cellular studies in this combination.

Animals↗

Immunosuppressive activity of serum from liver-grafted rats. Passive enhancement of fully allogeneic heart grafts and induction of systemic tolerance.

Immunological enhancement of allogeneic heart graft survival by serum from rats tolerized by liver grafting has been studied. Serum taken from long-term-surviving PVG rats carrying orthotopic DA liver transplants (OLT serum) was able to increase the survival time of PVG.RT1a heterotopic heart grafts in PVG recipients. Administration of 1 ml of OLT serum at the time of heart grafting led to permanent survival of the grafts in all animals. The recipients became systemically tolerant of RT1a and several weeks later were able to accept permanently skin grafts from the same donor strain, while rejecting third-party grafts. Enhancement appeared to be mediated initially by IgG antibodies in the OLT serum against class II donor RT1a antigens; significant enhancement was produced by as little as 100 micrograms of antibody. Recipient alloantibody responses following enhancement were studied and showed selective suppression of the anti-class-I (RT1Aa) antibody levels, while the anti-class-II antibody response was apparently unaffected. The implications of these results for mechanisms of unresponsiveness following enhancement and liver transplantation are discussed.

Animals↗

A case of leukemic mastocytoma terminating in metamorphosis.

A case of leukemic mastocytoma terminating in metamorphosis is reported. Three types of mastocytoma cells appeared in the peripheral blood and bone marrow, each differing in cytochemical staining and maturation ability in both in vitro and in vivo cultures. Most immature mastocytoma cells, which contained no granules and were lymphoblast-like cells, differentiated to have basophilic and metachromatically positive granules in the cytoplasm after culture in the diffusion chamber, resembling more mature cells (type II). Mature cells (type II), which had diffusely dispersed and metachromatically positive granules in the cytoplasm, came to have vacuoles with basophilic substances after culture in vitro, resembling most mature cells (type I) which contained large and clumped granules with metachromasia. These findings together with clinical findings and results of morphological studies suggest that most immature cells originate from second mature or most mature cells and effect a blastic transformation.

Adult↗