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Biomedical subjects

M T Gallagher

Publications and source records attributed to M T Gallagher.

At least 37 records · Page 2Linked to original sources

Augmentation of erythroid burst formation by the addition of thymocytes and other myelo-lymphoid cells.

Bone marrow from barrier-sustained specific pathogen-free (SPF) CBA and C57BL/6 mice gave relatively low numbers of BFU-E colonies in methylcellulose culture, as compared to conventional mice. Addition of thymocytes to the marrow cultures increased the yield of BFU-E colonies more than fourfold in SPF mice but only 1.5-fold in conventional mice. Colony size was also increased. Increased yield of BFU-E colonies was also obtained by co-culture of bone marrow with lymph node cells or with bone marrow or spleen cells from 900R whole-body irradiated mice. The effect appeared to be cellular rather than humoral. It was not reproduced by conditioned medium from thymus or pokeweed mitogen stimulated spleen cells. The helper effect of thymus cells was eliminated or reduced by freezing and thawing, or by 48 hours of incubation after irradiation. Treatment of bone marrow cells in vitro with anti-theta serum and complement did not decrease the number of BFU-E colonies. The putative helper cells appear not to be T cells, were non-adherent to the plastic culture dish, and were cortisone resistant and radioresistant. The low BFU-E colony yield from SPF mouse marrow is presumed to be largely the result of deficiency of these non-T helper cells in SPF bone marrow, rather than of BFU-E progenitor cells.

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Genetic resistance to bone marrow transplantation as a leukemia-lymphoma defense mechanism: correlation of "in vivo" lymphoma resistance and "in vitro" NK activity.

(C57 X AKR) F1 hybrid mice, which show genetic resistance to C57 parental bone marrow cells and to AKR lymphoma but not to AKR bone marrow cells in vivo, also show high natural killer cell lysis versus lymphoma cells in vitro. (C3H X AKR) F1 hybrids which show no genetic resistance to parental bone marrow cells or to lymphoma cells in vivo have low levels of NK activity like those of the low responding AKR strain. Thus genetic resistance to bone marrow transplantation and to lymphoma in vivo, correlates with NK lytic activity versus lymphoma cells in vitro, adding to the evidence linking these phenomena.

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The abrogation of in vivo resistance to parental bone marrow transplantation and of in vitro natural cell-mediated cytotoxicity to the YAC lymphoma by in vivo growth of a transformed thymus-derived cell culture.

A thymus-derived monolayer culture, referred to as E1, from (C57Bl/6 X A)F1 hybrid mice was continuously passaged in vitro for over three years and formed rapidly growing, non-metastasizing tumors when injected s.c. into syngeneic mice. The spleens of tumor-bearing mice were greatly enlarged, but no tumor cells were detected in these spleens. The natural cell-mediated cytotoxic activity of spleen cells of tumor-bearing mice decreased with increasing tumor size. In addition, the expression of genetic resistance to transplantation of C57Bl/6 parental bone marrow cells was decreased in the spleens of irradiated tumor-bearing mice. This correlation between the expressions of natural cell-mediated cytotoxicity and of genetic resistance to bone marrow transplantation is consistent with the hypothesis that both of these responses are mediated by the same population of effector cells.

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Comparative effects of different strains of Corynebacterium parvum on natural cell-mediated cytotoxicity.

Because there are conflicting reports regarding the effects of Corynebacterium parvum (CP) on natural killer (NK) cell activity, several different strains of CP were compared. In replicate experiments, age- and sex-matched mice received 0.25-mg i.p. injections of one of four types of CP; formalin-killed strain 6134; heat-killed strain 6134; formalin-killed strain 5888 (actually Corynebacterium granulosum); or formalin-killed CP from the Pasteur Institute. At various days thereafter, two to three mice from each group were sacrificed to determine spleen weight, cellularity, and NK cell activity versus YAC-1 lymphoma cells. The CP from the Pasteur Institute augmented NK cell activity 3 days following injections; however, the activity returned to normal by Day 7 and remained at that level. On the other hand, strain 5888 did not cause as great an increase in lytic activity as did the Pasteur Institute CP at Day 3; but by Day 10 after injection, NK cell levels were above control, and they remained elevated through Day 21. Both the heat-killed and formalin-killed preparations of strain 6134 stimulated NK cell activity initially but resulted in a loss of activity at the later times tested. Experiments done with different doses and routes of injection yielded similar results. Thus, we were able to demonstrate that different types of CP have different effects on NK cell activity in mice and that the general kinetics of these effects were independent of dose or route of administration.

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Apparent identity of mechanisms of genetic resistance to marrow transplantation and natural killer cell activity.

Because the phenomenon of in vitro lysis of lymphoma cells by spleen natural killer (NK) cells bears genetic and effector cell resemblances to genetic resistance to bone marrow transplantation, they were compared for additional known unique characteristics of the latter phenomenon. Like GR to BMT, NK cell activity first appeared abruptly at about 3 weeks of post-natal age; was radioresistant to 1 100 R whole body irradiation, but was quantitatively diminished by higher exposures or delay of test post-irradiation; was suppressed by pretreatment with either cyclophosphamide, carrageenan, silica particles, anti-bone marrow serum or anti-thymus serum. The many unique identical characteristics of these two effector mechanisms indicates that they represent two manifestations of the same basic phenomenon of natural immunity. This is in accord with other data indicating that GR to BMT is directed at Hh antigens which, like TL antigens, may in some mouse strains appear on both leukemic cells and normal hemopoietic cells.

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Genetic resistance to marrow transplantation as a leukemia defense mechanism.

(C57 X AKR) F1 hybrid mice show genetic resistance to C57 parental bone marrow cells, but not to AKR parental bone marrow cells. (C3H X AKR) F1 hybrids show no genetic resistance to bone marrow transplantation from either parental strain. Transplantation of AKR lymphoma cells into lethally irradiated "resistant" (C57 X AKR) F1 and "non-resistant" (C3H X AKR) F1 hybrids produce lymphomatous spleen colonies in "non-resistant" hybrids but not in "resistant" hybrids. Thus "resistant" (C57 X AKR) F1 hybrids can recognize and reject AKR lymphoma cells, but not normal AKR bone marrow cells. A normal biological role of lymphoma surveillance is postulated for genetic resistance.

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"Xenogeneic resistance" to rat bone marrow transplantation. III. Maturation age, and abrogation with cyclophosphamide, Corynebacterium parvum and fractionated irradiation.

Lethally irradiated C57 Bl/6 mice and (C57 X A) F1 hybrids fail to accept doses of rat bone marrow cells (5 X 10(6)) which give confluent splenic repopulation in "non-resistant" strains of mice. This phenomenon has been termed "xenogeneic resistance" (XR). XR in (C57 X A) F1 mice can be overridden by a very large inoculum of rat bone marrow (26 X 10(6) cells). XR is not manifest in mice of a resistant strain at ages of 18 days or younger, but is manifest at ages of 22 days and older. XR can be abrogated by agents as varied as: 1) cyclophosphamide, which abrogates XR in a dose dependent manner when given 1 hr prior to lethal irradiation and bone marrow transplantation 2) C. parvum, which abrogates resistance when given 7 days prior to lethal irradiation and bone marrow transplantation, and 3) Fractionated irradiation, which, while capable of abrogating XR, is much less potent than either cyclophosphamide or C. parvum.

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Involvement of macrophages in genetic resistance to bone marrow grafts. Studies with two specific antimacrophage agents, carrageenan and silica.

Carrageenans and silica, agents toxic for macrophages, were used in this study to examine the role of macrophages in resistance of irradiated mice to inbred parental and rat bone marrow grafts. Administration of 2.5 mg of carrageenans or 2.5-5 mg of silica particles intravenously to prospective graft recipients resulted in a prompt abrogation of hybrid and xenogeneic resistance. The macrophage stabilizer poly-2-vinylpyridine N-oxide (PVNO) injected subcutaneously in the dose of 150 mg/kg, 24 hr before silica prevented or reduced the suppression of resistance. PVNO, however, did not antagonize the suppression of resistance by carrageenen, horse anti-mouse thymocyte serum and cyclophosphamide. These results suggest that a) a subpopulation is involved in marrow graft rejection by irradiated mice; b) carrageenan and silica apparently act on macrophages by different mechanisms c) horse anti-mouse thymocyte serum and cyclophosphamide may act on cells other than macrophages or they act on macrophages by a different mechanism than silica, to resistance to bone marrow transplantation.

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