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Biomedical subjects

N Kamada

Publications and source records attributed to N Kamada.

At least 343 records · Page 19Linked to original sources

Increased sister chromatid exchange frequency in bone marrow cells of myelodysplastic syndromes.

The frequency and distribution of sister chromatid exchange (SCE) was determined in bone marrow and peripheral lymphocytes of patients with preleukemic myelodysplastic syndromes. Patients with refractory anemia (RA), RA with excess of blasts (REAB), RA with ring sideroblasts, and RA in transformation presented a 2-3-fold increase in SCE frequency in the bone marrow cells. In contrast, lymphocytes from these patients showed only a marginal increase in SCE. Analysis of interchromosomal distribution of SCE indicated a preferential involvement of chromosomes in group C in patients with RA with excess of blasts. Furthermore, the SCE in patients was not found to be influenced by the karyotype status.

Aged↗

Intraorgan pressure changes in rejecting kidney, liver, and heart transplants in the rat.

Intraorgan pressure was measured in DA kidneys, livers, and hearts after transplantation into Lewis rats. Recordings were obtained by passing a fine needle into the graft and measuring the resistance to the flow of saline. Rats with organ isografts (Lewis-to-Lewis) were used as controls, and a further control group comprised Lewis rats that had undergone left ureteric ligation. Following transplantation a rise in pressure was recorded from some of the isografts, it returned to base line levels by the second or third day. Similar changes were observed in the organ allografts, except that a second, much greater (P less than .05) rise soon followed. This was observed from day 3 onward in the case of the kidney and liver transplants, and from day 4 in the cardiac transplants. Control experiments showed that ligation of the ureter (as performed in all the kidney transplants) did not influence intrarenal pressure. It is concluded that a rise in intraorgan pressure is an early feature of rejection, and that pressure monitoring might be useful in patients with cardiac or liver transplants--in addition to those with kidney transplants in whom the test has been shown to be of value.

Animals↗

Double minute chromosomes in acute myeloblastic leukemia.

Two patients with acute myeloblastic leukemia (AML) with double minute chromosomes (dmins) are described. One patient had dmins in approximately one-third of bone marrow cells examined at diagnosis; no other karyotypic changes were observed. The dmins disappeared when the patient achieved a complete remission. The second patient developed acute leukemia as a second cancer, having previously received radiotherapy and chemotherapy for a breast carcinoma. At the time of diagnosis of AML, the patient exhibited dmins in 12% of bone marrow cells; other complex karyotypic changes were observed. Data on the clinical and cytogenetic features of these cases are compared with those of other reported cases of acute leukemia with dmins. The possible biologic and clinical significance of dmins in acute leukemia is discussed.

Acute Disease↗

Clonal deletion as the mechanism of abrogation of immunological memory following liver grafting in rats.

In the rat strain combination of DA into PVG, an orthotopic liver graft has the ability to abrogate an existing state of sensitization against donor (DA) antigens. Fifty-four percent of PVG rats sensitized against DA by skin grafting accepted a DA liver graft permanently, and about half of these became systemically tolerant of DA MHC antigens, as demonstrated by permanent acceptance of a subsequent (second-set) DA skin or heart graft. The cellular basis of this tolerant state was studied in vivo. An adoptive transfer assay provided evidence for functional deletion of DA-reactive cells responsible for graft rejection from the recirculating lymphocyte pool. There was no evidence of a role for suppressor T cells in maintaining tolerance. However, a graft-versus-host assay showed normal reactivity in thoracic duct lymphocytes from tolerant animals. Hence, specific clonal deletion is apparently responsible for the abolition of immunological memory by liver grafting, but is selective in respect of the sets of alloreactive lymphocytes affected.

Animals↗

Transfer of specific immunosuppression of graft rejection using lymph from tolerant liver-grafted rats.

The effect on graft rejection of lymph from rats rendered tolerant of donor antigens by liver transplantation has been studied. Transfer, by daily intravenous injection, of lymph from PVG rats grafted with DA livers prolonged the survival of DA skin, kidney and heart grafts in normal PVG recipients. The effect was specific for the antigens of the liver donor. Suppression was short-term only; thus, after lymph injections were stopped, rejection occurred with a time course approximating a normal first-set reaction. The result suggests a reversible interference by materials in the tolerant lymph with early stages of sensitization of the recipients.

Animals↗

The immunology of experimental liver transplantation in the rat.

In many species, the rejection of liver allografts is milder than that of other organs. This is especially so in the rat where, without immunosuppressive treatment, liver grafts between certain strain combinations are accepted permanently, whereas skin, heart and renal allografts undergo acute rejection. Reliable surgical methods, together with the availability of inbred strains and a rapidly developing knowledge of its MHC and immune system in general, have made the rat a prime species in which to study the immunological events which follow liver grafting. In non-rejector combinations, liver allografts possess remarkable properties of tolerance induction and antigen-specific immunosuppression, leading to a state of donor-specific unresponsiveness in which grafts of other organs are also accepted. Moreover, liver transplantation can terminate ongoing rejection reactions in other organs and convert an existing state of sensitization against donor antigens into one of unresponsiveness. This review describes recent progress in understanding the immunological mechanisms behind these phenomena. The topics discussed include the rat MHC (RT1) antigens and their distribution in the liver; the genetic control of rejection and non-rejection, including the role of MHC-linked immune response genes; and cellular and humoral mechanisms involved in tolerance and immunosuppression, such as clonal deletion of alloreactive lymphocytes and antibody-mediated enhancement.

Animals↗

Antigen-specific immunosuppression induced by liver transplantation in the rat.

We have demonstrated that DA hearts grafted into PVG rats were completely protected from rejection by simultaneous liver transplantation from the same donor. In subsequent experiments PVG animals were given DA hearts followed 5 or 6 days later by livers from the same donor strain. Instead of the expected rapid rejection, all the grafts survived for at least 18 days, despite showing definite graft-swelling, a reliable clinical sign of early rejection, immediately prior to liver transplantation. In all 13 rats the heart size returned to normal and a strong beat returned within a few days. 6 animals survived indefinitely with healthy, beating heart grafts and the remaining 7 animals died of liver transplant rejection, but in these animals also the hearts were beating normally immediately prior to death. Histological examination of the hearts revealed no active rejection, but there was extensive myocardial scarring, compatible with resolution of a rejection reaction. It seems, therefore, that the liver grafts had entirely absorbed the vigorous immune response, terminating that which had already begun in the heart. This immunosuppressive effect was donor-specific and far more powerful than that of the immunosuppressive agent cyclosporine.

Animals↗

Defective ultraviolet-induced DNA repair in bone marrow cells and peripheral lymphocytes of patients with refractory anemia with excess of blasts.

The extent of ultraviolet (UV) irradiation-induced DNA repair was measured in bone marrow cells and peripheral lymphocytes of patients with refractory anemia with excess of blasts (RAEB). Bone marrow cells from RAEB, when exposed to a 2 J/m dose of UV, exhibited 50% lower incorporation of tritiated thymidine than those of control subjects. A similar finding was observed in the peripheral lymphocytes. These data suggest that bone marrow cells and peripheral lymphocytes from RAEB are deficient in repair of UV-induced lesions by DNA. Furthermore, this impaired DNA repair efficiency in RAEB was not related to the presence or absence of a karyotype abnormality.

Adult↗

Hexosaminidase isoenzyme profiles in leukemic cells.

The isoenzyme profiles of hexosaminidase in leukemic cells from 39 patients were examined with DEAE-Sephadex chromatography. There was a clear difference in the isoenzyme composition between normal lymphocytes and granulocytes. In acute non-T/non-B lymphocytic leukemia (ALL) a characteristic alteration was found in the intermediate forms of hexosaminidase (Hex I), which was significantly higher than those of normal lymphocytes (p less than 0.001). Subtypes of Hex I (Hex i1-i4) and the heterogeneity of their abnormal expression in ALL was demonstrated. There was no type-specific alteration of the isoenzyme profiles in T-cell leukemia. Leukemic cells of acute myelocytic leukemia (AML) had significantly higher Hex P component than granulocytes (p less than 0.01) and ALL cells (p less than 0.01). The increase of Hex P was evident in childhood AML. There was a significant difference in Hex P level between childhood AML and adult myelo(mono)genous leukemia (p less than 0.001). Chronic myelo(mono)genous leukemia showed similar isoenzyme compositions to normal granulocytes. The isoenzyme profiles in acute undifferentiated leukemia differed from those in other types of leukemia. Isoenzyme analysis might be useful for probing the nature and the intrinsic biochemical abnormality of leukemic cells.

Adolescent↗

A summary of cytogenetic studies on 534 cases of chronic myelocytic leukemia in Japan.

Cytogenetic and clinical data on 534 patients with chronic myelocytic leukemia (CML) were collected from 10 institutions in Japan. The results of the analysis of the data were in substantial accord with those of the First International Workshop on Chromosomes in Leukemia and other published data, but certain differences were noted in the frequency of Philadelphia chromosome (Ph1)-negative cases, unusual and complex Ph1 translocations, and additional chromosome changes. Some of the findings are discussed with respect to the origin of unusual and complex Ph1 translocations, the relationship between chromosome abnormalities and survival, and geographic differences in chromosome abnormalities.

Adult↗