Dual chemical barriers protect a plant against different larval stages of an insect.

The host plants of the native American butterfly, Pieris napi oleracea, include most wild mustards. However, garlic mustard, Alliaria petiolata, a highly invasive weed that was introduced from Europe, appears to be protected from this insect. Although adults will oviposit on the plant, most larvae of P. n. oleracea do not survive on garlic mustard. We used feeding bioassays with different larval stages of the insect to monitor the isolation and identification of two bioactive constituents that could explain the natural resistance of this plant. A novel cyanopropenyl glycoside (1), alliarinoside, strongly inhibits feeding by first instars, while a flavone glycoside (2), isovitexin-6"-D-beta-glucopyranoside, deters later instars from feeding. Interestingly, the first instars are insensitive to 2, and the late instars are little affected by 1. Furthermore, differential effects of dietary experience on insect responses suggest that 1 acts through a mechanism of post-ingestive inhibition, whereas 2 involves gustatory deterrence of feeding.

GM-CSF clinical trials: pediatric aplastic anemia and Fanconi's anemia.

Two clinical trials were undertaken to evaluate the effect of human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) in pancytopenic pediatric patients with aplastic anemia and Fanconi's anemia. In the aplastic anemia trial, 9 out of 12 patients had some improvement when treated with GM-CSF. In the Fanconi's anemia trial, 6 of 7 patients showed some improvement when treated with GM-CSF. For both groups, improvement in white blood cell count and absolute neutrophil count were the most common response. Side effects observed during these studies were fever, rash, urticaria, and flu-like symptoms. Nursing care of both groups focused on the effects of pancytopenia, as well as the potential adverse effects of GM-CSF. Patient education focused on teaching drug preparation and storage, subcutaneous injection, and potential side effects.

Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia.

Fanconi anemia is a congenital syndrome characterized by multiple specific physical anomalies, progressive marrow failure, and a predisposition to acute leukemia. We studied the toxicity and efficacy of daily subcutaneous administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with Fanconi anemia and pancytopenia. The toxicity of GM-CSF at the doses and schedule used was minimal. Six of seven patients entered had an increase in the neutrophil count of 7- to 25-fold, which was maintained during the course of study. Despite increases in the reticulocyte count, increases in hemoglobin concentration were rare. No improvement in platelet count was evident in any patient. No patient has evidence of leukemia after up to 19 months of continuous GM-CSF exposure, and all five surviving patients remain responsive to treatment. Although the optimal dose, schedule, and choice of cytokine for patients with marrow failure and Fanconi anemia are not established by this preliminary study, the data indicate that (1) GM-CSF may be able to palliate at least the neutropenia and potentially the neutropenic complications of the disease, (2) this effect can be sustained for more than 1 year, and (3) rapid evolution of acute leukemia is unlikely to be a frequent outcome of such treatment. The clinical impact of GM-CSF or other cytokines in patients with Fanconi anemia and pancytopenia remains to be established by further studies.

Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia.

Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU-MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT.