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E C Halperin

Publications and source records attributed to E C Halperin.

At least 91 records · Page 5Linked to original sources
PubMed1991

Induction of micronuclei by X-radiation in human, mouse and rat peripheral blood lymphocytes.

We compared the radiosensitivity of human, rat and mouse peripheral blood lymphocytes (PBLs) by analyzing micronuclei (MN) in cytochalasin B-induced binucleated (BN) cells. For each species and dose 4-ml aliquots of whole blood were X-irradiated to obtain doses of 38, 75, 150 or 300 cGy. Controls were sham-irradiated. After exposure to X-rays, mononuclear leukocytes were isolated using density gradients and cultured in RPMI 1640 medium containing phytohemagglutinin to stimulate mitogenesis. At 21 h cytochalasin B was added to produce BN PBLs, and all cultures were harvested at 52 h post-initiation using a cytocentrifuge. Significant dose-dependent increases in the percentage of micronucleated cells and the number of MN per BN cell were observed in all three species. The linear-quadratic regression curves for the total percentage of micronucleated cells for the three species were similar; however, the curve for the mouse PBLs had a larger quadratic component than either of the curves for the rat or human PBLs. Although the correlation between the percentage of cells with MN and those with chromosome aberrations was high (r2 greater than 0.95), the mouse and rat PBLs were over twice as efficient as human PBLs in forming MN from presumed acentric fragments. These data indicate that the induction of MN in BN cells following ionizing radiation is similar in human, rat and mouse PBLs, but care must be taken in using the MN results to predict frequencies of cells with chromosomal aberrations.

Adult↗
PubMed1991

A groundless hypothesis, megaloblastic madness, and the founding of Duke University.

In a recent issue of Medical Hypotheses, Dr H L Newbold repeats the assertion that the cause of James B Duke's death in 1925 was pernicious anemia. Dr Newbold postulates that Mr Duke was neurologically impaired as a result of vitamin B-12 deficiency and that he suffered from depression. In an attempt to relieve this depression, Dr Newbold argues that James B Duke donated the money necessary to found Duke University. Had he been properly treated for pernicious anemia, James Duke might have not been depressed nor made his donation. The historical record does not substantiate this hypothesis. Dr George Minot, Novel Laureate for his work on pernicious anemia, was a consultant to Mr Duke's physicians, and felt that the patient did not have pernicious anemia. There is no independently verifiable evidence to demonstrate that Mr Duke ever suffered from depression. Duke made his first donations to Trinity College, later named Duke University, in 1900--25 years before his death. The available data discounts the hypothesis that depression related to pernicious anemia played any role in the founding of Duke University.

Anemia, Pernicious↗
PubMed1991

The effect of total-body irradiation on corneal neovascularization in the Fischer 344 rat after chemical cauterization.

Previous investigations of corneal neovascularization after irradiation yielded discordant results. Most studies indicated that new blood vessel formation in the cornea is inhibited by irradiation. However, others reported that angiogenesis after corneal cauterization is similar in both irradiated and nonirradiated animals. To assess the effect of total-body irradiation on neovascularization further, the amount of angiogenesis was determined in irradiated rats after chemically induced corneal injury. Corneal tissue was evaluated quantitatively with computerized image analysis 2, 3, or 4 days postcautery in rats perfused with India ink and gelatin immediately after death. The rats were exposed to a single dose (9 Gy) of total-body irradiation 6 days before corneal cauterization. In both the nonirradiated and irradiated rats, neovascularization increased with the duration of the postcautery interval. The amount of corneal neovascularization was not significantly different in the irradiated and nonirradiated rats at any of the postcautery intervals studied. This investigation suggests that endothelial cell migration plays a more important role than cell replication in the pathogenesis of corneal angiogenesis in the Fischer 344 rat. Moreover, the suppression of corneal angiogenesis by irradiation may be dependent on the experimental conditions and species examined.

Animals↗
PubMed1990

Effects of hyperthermia and irradiation on the growth of mouse melanoma tumors following immunotherapy.

Recent investigations suggest that adjuvant hyperthermia enhances the response of human malignant melanoma to ionizing radiation. A study was undertaken to explore the effect of radiation and hyperthermia on the responsiveness of melanoma following active immunization with lethally irradiated B16 melanoma cells in C57 BL 6 mice. Two groups of mice were treated: group 1 received immunotherapy on days 2-5 following tumor inoculation, and group 2 received immunotherapy on days 15-18 following tumor inoculation. The mice in each group were subsequently randomized into one of three subgroups: 1) no further treatment; 2) radiation therapy alone (6 Gy in a single fraction); 3) radiation therapy and regional hyperthermia (43 degrees C x 1 hour). Tumor sizes were measured regularly, and between day 52 and 63 the animals were sacrificed and the lungs sectioned for counting of metastatic tumors. Results from this study show that the immunomodulated B16 murine melanoma is responsive to radiation therapy alone and that this responsiveness is enhanced by the addition of adjuvant regional hyperthermia. There did not appear to be any significant effect of radiation therapy or radiation therapy plus hyperthermia on the development of lung metastases in this tumor model system.

Animals↗
PubMed1990

Irradiation for xenogeneic transplantation.

Xenogeneic transplantation (XT) is the transplantation of organs or tissues from a member of one species to a member of another. Mammalian species frequently have circulating antibody which is directed against the foreign organ irrespective of known prior antigen exposure. This antibody may lead to hyperacute rejection. There is no reliable means to avert hyperacute rejection once it ensues so efforts must be directed towards eliminating the pre-existing antibody. In those species in which hyperacute rejection of xenografts does not occur, cell-mediated rejection, similar to allograft rejection, may occur. It is in the prevention of this latter form of rejection that radiation is most likely to be beneficial in XT. Both total lymphoid irradiation (TLI) and selective lymphoid irradiation (SLI) have been investigated for use in conjunction with XT. TLI has contributed to the prolongation of pancreatic islet-cell xenografts from hamsters to rats. TLI has also markedly prolonged the survival of cardiac transplants from hamsters to rats. A more modest prolongation of graft survival has been seen with the use of TLI in rabbit-to-rat exchanges. Therapy with TLI, cyclosporine, and splenectomy has markedly prolonged the survival of liver transplants from hamsters to rats, and preliminary data suggest that TLI may contribute to the prolongation of graft survival in the transplantation of hearts from monkeys to baboons. SLI appears to have prolonged graft survival, when used in conjunction with anti-lymphocyte globulin, in hamster-to-rat cardiac graft exchanges. The current state of knowledge of the use of irradiation in experimental XT is reviewed.

Animals↗
PubMed1990

High-dose areas are unintentionally created as a result of gap shifts when the prescribed dose in the two adjacent areas are different.

A large number of methods have been described for matching adjacent fields to prevent over- or underdosage at a field junction. Most authors recommend that the location of field junctions be shifted to different locations during the course of the treatment in an effort to "smear out" any dose inhomogeneity regardless of which field matching technique is used. This report focuses on the considerable variation in dose that can occur when the dose in the two adjacent treatment areas is different at the time of the gap shift. In a typical cranio-spinal treatment we found a 16% dose increase over the prescribed central axis dose.

Brain Neoplasms↗
PubMed1990

L-buthionine-sulfoximine-mediated radiosensitization in experimental interstitial radiotherapy of intracerebral D-54 MG glioma xenografts in athymic mice.

An intracranial (i.c.) interstitial radiotherapy model in athymic nude mice bearing i.c. D-54 MG human glioma xenografts was developed, allowing evaluation of the therapeutic benefits seen after L-buthionine-S,R-sulfoximine (L-BSO)-mediated depletion of tumor glutathione levels. Administration of L-BSO [2.5 mmol/kg intraperitoneal injections x 4 doses plus concomitant availability in acidified (pH 3.0) drinking water at a concentration of 20 mM] resulted in depletion of tumor glutathione levels to 0.15 mumol/g wet weight (7.9% of control). The therapeutic activity of i.c. interstitial radiotherapy with an 125I seed was enhanced after L-BSO-mediated glutathione depletion, with increases in median survival of 13.4 to 30.5% over that seen with 125I seeds alone. These studies demonstrate a potential role for BSO in enhancing the therapeutic activity of interstitial radiotherapy.

Animals↗
PubMed1990

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy.

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation.

Animals↗
PubMed1990

The persistence of lymphocytes with dicentric chromosomes following whole-body X irradiation of mice.

Thirty-six male C57B1/6 mice were X-irradiated whole body with 3 Gy to generate lymphocytes with dicentric chromosomes to study the persistence of these lymphocytes in the spleen and peripheral blood to estimate the life span of mature B- and T-cells. Peripheral blood and spleen were removed from groups of four mice immediately after radiation exposure and on Days 1, 3, 7, 14, 28, 56, and 112 thereafter. Peripheral blood lymphocytes were cultured with phytohemagglutinin to stimulate T-cell division, and splenic lymphocytes were cultured with either lipopolysaccharide or phytohemagglutinin to stimulate B- or T-cell division, respectively. The initial frequencies of dicentric chromosomes with accompanying fragments observed in splenic T-cells (0.44), splenic B-cells (0.43), and peripheral blood lymphocyte cultures (0.48) initiated on Day 0 were not significantly different. For both splenic and peripheral blood T-lymphocytes, the frequency of cells containing dicentric chromosomes declined in an exponential manner following irradiation, with a 50% reduction in frequency occurring 14 days after exposure. In contrast, the frequency of B-cells containing dicentric chromosomes remained stable through Day 7 but then declined precipitously between Day 7 and Day 14 and remained relatively stable, although slightly above baseline, through Day 112 post-exposure. For both B- and T-cells, less than 5% of the cells contained a dicentric chromosome with accompanying fragments at Day 112. These data indicate that B- and T-lymphocytes with dicentric chromosomes show different decay kinetics and suggest that they may possess different life spans.

Animals↗
PubMed1989

Micronuclei in binucleated lymphocytes of mice following exposure to gamma radiation.

Experiments were designed to investigate the induction of micronuclei (MN) in mouse peripheral blood lymphocytes (PBLs) after in vitro or in vivo exposure to 60Co gamma radiation. For the in vitro experiments, 4 ml of blood from male C57BL/6J mice were either irradiated in 6 ml Falcon culture tubes as whole blood or isolated to obtain mononuclear leukocytes (MNLs) that were pelleted by centrifugation and then irradiated in RPMI 1640. For the in vivo analysis, mice received whole body irradiation, blood was obtained by cardiac puncture, and the MNLs were isolated for each mouse. Exposures were at a rate of 0.82 to 0.90 Gy/min to yield doses of 0.5, 1, 2, 3, or 4 Gy. MNLs were cultured using cytochalasin B for MN analysis in binucleated PBLs. There was a significant dose-dependent increase in MN observed at all doses. Dose-response curves for the in vivo and in vitro whole blood experiment were not significantly different. However, for isolated pelleted MNLs irradiated in vitro, the MN frequency at 4 Gy was less than one-half that seen in the in vivo experiment. The large difference in MN response is thought to be due to the radioprotective effect of hypoxia.

Animals↗