Hole mobilities in hydrazone-polycarbonate dispersions.
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Biomedical subjects
Publications and source records attributed to A Peled.
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The surface negative charge distribution of fresh leukemic cells from patients with acute leukemia was examined with cationized ferritin (CF), an electron dense label of anionic sites and compared with leukemic cells from phase-cycle fractionated populations of a human leukemic cell line K-562. Normal-untreated and phytohemagglutinin (PHA)-transformed lymphocytes were also tested. A CF-induced redistribution of anionic sites into clusters and patches within a wide range of variations in density was observed electron microscopically both in fresh acute leukemic cells and in unseparated cells of the K-562 line. Cells of the G0/G1 fraction from a phase-cycle separated K-562 population exhibit a higher density of CF label per unit length of membrane as compared with the G2 + M cell fraction. PHA-benign transformed normal lymphocytes exhibit an even and continuous CF labeling, similar to that of normal-untreated lymphocytes. An attempt was made to correlate the CF-induced charge redistribution with the rate of agglutination with the cationic Poly-L-lysine. Our observations indicate that the CF ligand does induce an anionic site redistribution, varying in density, both in fresh leukemic cells and in cells from a K-562 line, and does not in normal untreated and PHA-benign transformed lymphocytes. The particular pattern of anionic site redistribution observed in leukemic cells of this study is apparently phase-cycle dependent.
Injection of a dual tropic virus (DTV) isolated from a T cell lymphoma AKR/J mice into the thymus of 14 day old AKR/J puppies accelerates lymphoma development; 90-100% of the injected mice develop the disease within 120 days. In contrast a cell free centrifuge CFC-666 prepared B cell lymphoma of AKR/J origin injected into the thymus of 14 day old AKR/J mice failed to accelerate T cell lymphomagenesis and actually prevented the spontaneous T cell lymphoma development. However, 50% of the treated mice developed B cell lymphoma with a latency of 417 + 18 days. DTV injection induces amplification of thymic expression of MuLV related antigens, besides changes in thymus subpopulation. Such changes emerge spontaneously in 5-6 month preleukemic AKR/J mice (at the time of spontaneous DTV formation in the thymus). These changes in the thymus were not observed following CFC-666 injection. We assume therefore that CFC-666 interferes with spontaneous DTV formation that contributes to T cell lymphomagenesis.
The karyotype of B-cell leukemias of AKR origin was studied by G-banding. In contrast to previous observations indicating trisomy of chromosome 15 in spontaneous and chemically-induced B-cell leukemias, 11 out of 15 tumors analyzed had normal diploid karyotypes. Four tumors with the modal number 39-41 had different chromosome markers specific for each tumor. The possible correlation between non-random chromosomal changes and the target cell involved in the initial transformation in AKR leukemogenesis is discussed.
The effect of sodium butyrate on mouse and human melanoma cell lines was evaluated. Sodium butyrate (0.1-2mM) is shown to reduce the clonogenic potential of several melanoma cell lines. The antiproliferative effect of sodium butyrate is accompanied by a marked increase in the activity of the plasma-membrane bound enzyme gamma-glutamyl transpeptidase. Sodium butyrate treated cells acquire a well developed rough endoplasmic reticulum and accumulate fat droplets. The development of the endoplasmic reticulum is associated with a marked increase in the activity of the enzyme marker NADPH cytochrome c reductase. It is suggested that the phenotypic alterations induced by sodium butyrate may serve as markers for the action of this agent on melanoma cells and other tumours.
The occurrence of potential leukemia cells (PLC) among bone marrow, spleen, and thymus of AKR mice during the preleukemic period was tested by an in vivo transplantation bioassay. The presence of PLC in 30- and 75-day-old AKR mice was demonstrated mostly among bone marrow cells, less in spleen, and was lacking in thymus. Occurrence of PLC in young AKR mice was shown to be thymus independent. However, progression of PLC from young donors (14-80 days old) into overt leukemia following transplantation into F1 recipients was shown to be dependent on specific host conditions including an intact thymus and an Fv-1nn allele. In contrast, PLC from 7-9-month-old AKR mice or frank leukemic cells when transplanted grew in any intact or thymectomized histocompatible host, thereby indicating their autonomous growth state. Infection of 2-week-old AKR mice with the dual-tropic virus DTV-70 induced characteristic changes in the thymus and accelerated leukemia development. DTV-70 inoculation into 14-day-old AKR mice did not change the spontaneous PLC distribution pattern in the tested host organs within 30 days postinfection, nor did it change PLC-specific host requirements for further progression into leukemic cells; however, it enhanced PLC transition to autonomous leukemic cells. The preferential cell tropism of DTV-70 for target cells (prothymocytes) among bone marrow and young spleen cells rather than for thymocytes was also demonstrated in an in vitro-in vivo test. The dual tropic virus may act as a promoter on preexisting PLC (present mostly among bone marrow cells) by enhancing their ability to progress into autonomous leukemic cells.
We examined the relationship of the leukemia-accelerating properties of a dual-tropic virus (DTV-70) (when injected into the thymus of 14-day-old AKR mice) to its ability to impair T cell functions. Splenic lymphocytes from virus-infected AKR mice were found to have reduced T cell mitogenic responses; moreover, these cells suppressed phytohemagglutinin stimulation of cells from normal, uninfected AKR mice. The response to the B cell mitogen lipopolysaccharide was slightly enhanced at 15 days following DTV-70 infection and was unaffected at later ages. AKR mice infected with DTV-70 showed reduced ability to develop delayed-type hypersensitivity reaction and interleukin 2 production. In contrast, spleen cells from the virus-infected mice responded normally to allogeneic stimulation in mixed lymphocyte culture and mounted an almost normal graft versus host reaction. The data suggest that DTV-70 impairs certain T cell functions that could interfere with immune surveillance and thus permit progression of preleukemic cells into overt leukemia. These T cell functions are suppressed normally by 6 months of age, perhaps by spontaneously arising DTV.
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AKR mice, 6-12 mo after birth, display a high incidence of spontaneous T cell lymphomas that can be prevented by thymus removal at the age of 1-3 mo. We report here the presence of dormant preleukemic cells among bone marrow cells of 8-12-mo-old AKR mice that have been thymectomized when 40-60 d old. Transplantation of bone marrow cells from these thymectomized AKR donors into syngeneic or hybrid (AKR X DBA/2)F1 intact or thymectomized recipients resulted in lymphoma development of AKR origin in 80-100% of the recipients. Analysis, by flow microfluorometry, of the antigenic cell surface phenotypes of the developing lymphomas revealed that all tumors were B cell lymphomas, since the cells stained with class-specific anti-IgM reagents and other reagents specific for B cells (RA3-2C2, RA3-6B2, anti-I-A, and anti-Fc receptor), and were Thy-1-. All these B cell tumors also expressed two T cell differentiation antigens, TL.4, found exclusively on T cell lymphomas, and Lyt-1 antigen, previously shown (11) to be expressed on some B cell neoplasms. The surface markers mu, I-A, RA3-2C2, and TL.4 identified by immunofluorescence, were shown to be integral membrane components synthesized by the tumor cells, rather than passively acquired proteins.
The safety of a flashing amber signal for all directions at off-peak hours as a replacement for regular traffic signal operations was evaluated. The proposed control strategy was motivated by the need for energy conservation through reduced amounts of acceleration and of idling time of vehicles. The methodology of the study employed as a measure a broadened definition of "conflict" that freed observers from the need to detect only emergency evasive manoeuvres and decreased their subjective interpretations. Observations were carried out by trained observers at a sample of intersections, using two control strategies: full signal operation and flashing amber phase. Stationed at each leg of an intersection, the observers noted the travel direction of any two vehicles involved in a conflict. The results showed that the most frequent type of conflict under full signal operation was of the rear-end type; during the flashing amber operation, crossing and merging conflicts were dominant. It was concluded that up to a volume of 600 vehicles per hour, flashing operation does not increase the number of conflicts.
The expression of antigens encoded by the K and D region genes of the major histocompatibility complex on thymocytes of BL/6 mice infected with Radiation Leukemia Virus (RadLV) variants, A-RadLV to which they are sensitive or D-RadLV to which they are resistant, was investigated. Reduced thymus cellularity due to the thymolytic effect of both RadLV variants (30-40% cell reduction within 24 h after intrathymic virus injection) was accompanied with elevated H-2 expression on thymocytes. A high density of H-2D and to a lesser degree increased expression of H-2K were observed following infection with both virus variants. This elevated H-2 expression was maintained transiently for 6-7 weeks in the resistant situation and persisted in the sensitive situation until overt leukemia developed. The occurrence of A-RadLV transformed cells in 75% of the tested thymuses within 10 days after infection (vs 16% in D-RadLV treated mice) and their further expansion until overt leukemia developed could explain the continued expression of elevated H-2 expression on thymocytes in the sensitive situation. The majority (85%) of the primary A-RadLV induced leukemias tested expressed more H-2D/H-2K gene products than normal thymocytes. We conclude that leukemia development due to RadLV infection is not associated with the reduction or disappearance of H-2D/H-2K gene products.
A survey of age-related expression of thymus-leukemia (TL) alloantigens (TL 1,2,4) among bone marrow, spleen and thymus cells of grossly normal and leukemic AKR/J mice is presented. The response of the stained cells to antisera directed against TL antigens was analysed by means of the fluorescence-activated cell sorter (FACS) apparatus. A transient expression of TL antigens on cells among the bone marrow population was observed in 1- to 20-day-old AKR/J mice, followed by an undetectable level up to 3 months and its reappearance thereafter. Thymocytes expressed TL from the age of 4 months onwards, reaching a transient maximal level at the age of 6 months in females and 8 months in males. Subsequently, an age-related decrease took place. In spleen cells from newborn mice TL expression was seen, followed by a rapid decrease to undetectable levels up to the age of 5-6 months. In most tests the expression of TL4 preceded the TL 1,2 phenotype. The frequency of TL+ leukemias was about 50% among the early-occurring spontaneous leukemias (in 5- to 7-month-old mice) and decreased to 20% with age increase. Leukemia development following treatment with methyl-nitrosourea (MNUA) or exposure to X-rays increased the frequency of TL+ tumors to 75-100%. These results suggest that heterogeneous target cells are involved in AKR leukemogenesis.
Studies on the chemotherapeutic potential of methyl-CCNU on experimental leukemias were undertaken. A number of murine transplantable in vivo lines (chemical carcinogen-induced T and B leukemias; radiation- and viral-induced T leukemias of C57BL/6, C3H/eb and SJL/J origin; radiation-induced myeloid leukemias and spontaneous reticulum cell neoplasms of SJL/J mine) were used in these studies. The optimal dose of methyl-CCNU and optimal timing of administration were extensively investigated on two sample lines of T cell leukemias of C57BL/6 mice. Leukemic cell eradication could be achieved in almost all of the different leukemias treated, irrespective of whether induction was brought about by chemical or physical means or due to a viral leukemogenic agent. Studies undertaken to elucidate the effect of methyl-CCNU on the establishment of preleukemic cells following induction of leukemia by the radiation leukemia virus (RadLV) or by total body irradiation, indicated the oncostatic effect of methyl-CCNU on early preleukemic cells.
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The mechanism of resistance to leukemogenesis by two radiation leukemia virus variants, A-RadLV and D-RadLV, was investigated. Resistance to these viruses is linked to H-21 in both B10.S and C57BL/10 mice. The resistance of virus-infected mice to transplantation of syngeneic. A- or D-RadLV-induced lymphoma cells was similar to their resistance to leukemogenesis by the same viruses. This resistance could be transferred by lymphoid cells from immune donors to normal recipients, and it was specific for RadLV lymphomas. Virus-primed (responder x sensitive)F1 hybrids rejected only resistant-type parental lymphoma cells. Hence, it appears that H-21-linked resistance to RadLV leukemogenesis is regulated by Ir genes. Resistant mice immunized by A- or D-RadLV rejected syngeneic lymphoma cells, irrespective of whether they were sensitive or resistant to the RadLV variant used for the induction of the lymphoma cells. It follows that resistant and sensitive type lymphomas are antigenically similar for the effector mechanism, and that the Ir genes may be expressed in the sensitization phase of the reaction. In virus-infected mice which are resistant to A- or D-RadLV we were able to demonstrate the presence of preleukemic lymphocytes. Normal mice could be immunized by these preleukemic cells against lymphoma challenge. These data are interpreted to suggest that mice having H-21-linked resistance to RadLV infection may be sensitized by their preleukemic cells, and that these preleukemic cells are then arrested in their development as a result of the immune response.
The relationship between the local outgrowth of different subcutaneous transplantable tumors (plasmacytoma MOPC-315, mastocytoma P-815; Lewis lung carcinoma-3LL; fibrosarcoma; lymphomas and mammary adenocarcinoma) and tumor cell spread in different organs was evaluated. The presence of tumor cells in thymus, spleen, lung, and liver was demonstrated by using both in vivo and in vitro methods. Sequestration of tumor cells derived from the transplanted solid tumor was indicated within 3 to 7 days after tumor graft, shortly before or after early palpable outgrowth of the primary tumor was observed. Tumor cells present in thymus and spleen might affect immune responses of tumor-bearing mice.