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Biomedical subjects

M S Hamilton

Publications and source records attributed to M S Hamilton.

11 recordsLinked to original sources

Sustained engraftment of mice transplanted with IL-1-primed blood-derived stem cells.

IL-1 is considered the primary mediator of the acute phase response. One of the characteristic manifestations of this response is early neutrophilia that is probably caused by release of mature neutrophils from the bone marrow into the peripheral blood. In the present study, we assessed whether IL-1 had a similar releasing effect on the number of circulating progenitor cells and stem cells. Female BALB/c mice were injected i.p. with increasing (0.1-1.0 micrograms/mouse) concentrations of rhu-IL-1 alpha. IL-1 injection resulted in a marked dose-dependent increase in the number of polymorphonuclear neutrophils, granulocyte-macrophage colony-forming units (CFU-GM), and cells forming spleen colonies (CFU-S day 8 and day 12). The maximal increase was found at 4 to 8 h after injection of 1 micrograms IL-1 per mouse, yielding a mean fivefold elevation in neutrophil count, and a mean 30-fold and 10-fold increase in the number of circulating CFU-GM and CFU-S, respectively. In a subsequent series of experiments, lethally irradiated (8.5 Gy) female recipient animals were transplanted with 5 x 10(5) blood mononuclear cells derived from male IL-1-treated animals. Long-term survival was obtained in 68% of mice transplanted with peripheral blood cells derived from donor animals at 6 h after a single injection of 1 micrograms IL-1. The mean number of circulating CFU-GM in these donor animals was 557/ml blood. At 6 mo after transplantation, greater than 95% of the bone marrow cells were of male origin, as determined using in situ hybridization with a Y-chromosome specific probe. In contrast, long-term survival was reached in less than 10% of mice transplanted with an equal number of blood cells derived from saline-treated controls or donor animals treated with a dose of 0.1 micrograms IL-1. These results indicate that a single injection of IL-1 induces a shift of hematopoietic progenitor cells and marrow repopulating cells into peripheral blood and that these cells can be used to rescue and permanently repopulate the bone marrow of lethally irradiated recipients.

Animals

Granulocytic sarcomas of small intestine and brain are associated with acute myelomonocytic leukaemia with abnormal eosinophils and inversion of chromosome 16.

We report two cases of acute myelomonocytic leukaemia with abnormal eosinophils (M4Eo) in which the presenting feature was small bowel obstruction. We suggest there is a unique clinicopathological association between small intestine involvement with leukaemia and the M4Eo subtype. Central nervous system involvement by myeloblastoma occurred in one of the two cases which is a recognised feature of M4Eo and should necessitate prophylaxis with intrathecal therapy. Inversion of chromosome 16 which is a cytogenetic marker for M4Eo was demonstrable in one of the two cases.

Biomarkers, Tumor

Akathisia, suicidality, and fluoxetine.

BACKGROUND: The propose link between fluoxetine and suicidal ideation is explained by fluoxetine-induced akathisia and other dysphoric extrapyramidal reactions. METHOD: The following literature is reviewed: (1) the subjective response of schizophrenics to akathisia, including evidence that akathisia gives rise to suicidal ideation; (2) the subjective reports of patients taking fluoxetine; and (3) preclinical studies describing the role of serotonin in the extrapyramidal system and suggesting a mechanism whereby fluoxetine can induce extrapyramidal side effects. RESULTS: The literature suggests that fluoxetine-induced extrapyramidal reactions may be a mediator of de novo suicidal ideation. CONCLUSION: We propose a syndrome which we name Extrapyramidal-Induced Dysphoric Reactions, one extreme manifestation of which is the emergence of suicidal ideation. We further propose a heuristic "Four Neuron Model of the Extrapyramidal Motor System" in which increased serotonin activity, by inhibiting the nigrostriatal dopamine tract, is capable of inducing extrapyramidal side effects.

Akathisia, Drug-Induced

Privileged status of the subcutaneous site for skin allografts in rats.

Evidence is presented that in rats the subcutaneous site can extend privilege to both major histocompatibility complex (MHC)-incompatible (FI X DA)F1 leads to FI and MHC-compatible LEW leads to FI skin allografts, approximately doubling the median survival time of similar grafts transplanted orthotopically. Unlike graft dosage, "gene" dosage was an important variable in that grafts from (FI X DA)F1 donors significantly outlived those from DA strain donors. Prior splenectomy of the hosts did not prejudice the capacity of their subcutaneous sites to extend privilege. It was found that the hemagglutinin response incited by subcutaneous grafts was significantly delayed compared with that evoked by similar grafts transplanted orthotopically or intraperitoneally. This observation, coupled with our inability to demonstrate the passage of India ink to regional lymph nodes after its injection into the dermis of established subcutaneous grafts of syngenic skin, is consistent with the concept that poor endowment of the subcutaneous milieu with both blood and lymph vessels is the principal factor underlying its hospitality to allografts.

Animals

Altered immune responses in pregnant mice.

The immune responses of pregnant mice to alloantigens were studied using the 51chromiun release assay. Four populations of lymphoid effector cells were studied. Control lymphoid cells were from normal, virgin BALB/c females, and BALB/c females specifically immunized to (BALB/c X C3H) F1 spleen cells. Experimental lymphoid cells were from BALB/c females pregnant by BALB/c males (syngeneically pregnant) or C3H males (allogeneically pregnant). Target cells were 51chromiumlabeled phytohemagglutinin-induced lymphoblasts from BALB/c and (BALB/c X C3H) F1 animals. Pooled lymph node and spleen cells from BALB/c females pregnant by C3H males were not cytotoxic for (BALB/c X C3H) F1 target cells. Lymphoid cells were transferred to sublethally irradiated syngeneic recipients that were simultaneously challenged with (BALB/c X C3H) F1 alloantigens. One week later, the spleen cells of the recipient animals were used as effector lymphoid cells. Lymphoid cells from normal, syngeneically pregnant, and allogeneically pregnant animals were equally cytotoxic for (BALB/c X C3H) F, target cells. Lymphoid cells from BALB/c animals specifically immunized to (BALB/c X C3H) F, alloantigens were highly cytotoxic for these target cells. Compared with the unmixed cell populations, mixtures of lymphoid cells from norman and syngeneically or allogeneically pregnant animals were hyporesponsive to alloantigenic challenge. Serum from neither syngeneically pregnant nor allogeneically pregnant animals inhibited the response of normal lymphoid cells to alloantigen. Immunoregulation in pregnancy was discussed.

Animals

Pelvic exenteration.

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Adaptation, Psychological