Stability of a perturbed Leslie model.

A small perturbation introduced in the stochastic Leslie model leads to a long-lived stable population in a region or parameter space where the stochastic model predicts the demise of the population. This somewhat surprising result is understood by considering a related model with a density-dependent sex ratio which exhibits similar features.

Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein.

Repair of a uracil-guanine base pair in DNA has been reconstituted with the recombinant human proteins uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta and DNA ligase III. The XRCC1 protein, which is known to bind DNA ligase III, is not absolutely required for the reaction but suppresses strand displacement by DNA polymerase beta, allowing for more efficient ligation after filling of a single nucleotide patch. We show that XRCC1 interacts directly with DNA polymerase beta using far Western blotting, affinity precipitation and yeast two-hybrid analyses.

FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors.

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus-host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment.

Calystegine B4, a novel trehalase inhibitor from Scopolia japonica.

GLC-MS analysis has been developed for screening plants of the family Solanaceae for new calystegines. GLC-MS analyses of the extract of Scopolia japonica showed the presence of a new tetrahydroxy-nor-tropane alkaloid in addition to the known calystegines A3, A5, B1, B2, B3, and C1. We gave this new alkaloid the trivial name calystegine B4.

Graft-versus-host effect after allogeneic hematopoietic stem cell transplantation: GVHD and GVL.

The development of a graft-versus-host reaction after allogeneic hematopoietic stem cell transplantation is an important determinant of the transplant outcome. A better understanding and improved management of the graft-versus-host reaction should allow improved prevention and treatment of graft-versus-host disease and the development of new strategies to enhance a graft-versus-leukemia effect and to decrease the incidence of leukemic relapse after transplantation.

Canine CD34: cloning of the cDNA and evaluation of an antiserum to recombinant protein.

Increasingly, enriched populations of hematopoietic progenitors are used in experimental and clinical transplantation studies. The separation of progenitors is based on the expression of CD34, a marker preferentially expressed on progenitor cells. The dog model has been important for preclinical transplant studies, because it has proven predictive for outcomes in human hematopoietic stem cell transplantation.

Core competencies create value.

In the past, healthcare providers have created value by delivering care on demand to their patients. In the future, however, providers will create value by mastering four core competencies: effective management of health and wellness, effective care delivery, effective population enrollment, and effective management of financial risk.

Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation.

Tumor-specific aneuploidy not detected in CD19+ B-lymphoid cells from myeloma patients in a multidimensional flow cytometric analysis.

Aneuploidy and lg light chain restriction were used as separate, independent tumor specific markers to study 26 patients with multiple myeloma to determine whether bone marrow B cells, as defined by CD19 expression, are clonally related to myeloma plasma cells. Specimens were characterized using multidimensional flow cytometry to identify the presence of clonality in both the B lymphoid and plasma cell populations using both surface and cytoplasmic staining with antibodies specific for kappa or lambda lg light chain In none of the patients with multiple myeloma were CD19+ cells found to be clonally restricted to kappa or lambda. The monoclonal plasma cells (MPC) were found to be uniformly negative for CD10, CD19, and CD34, while the CD19+ B lymphoid cells present within the samples expressed normal intensities and relationships of these antigens, which allowed them to serve as internal positive controls.

Delay of radiation-induced decline and recovery of hematopoiesis following treatment with anti-HLA-DR antibody.

A dose of 200 cGy of total-body irradiation (TBI) is nonlethal in dogs: Following a granulocyte nadir in the third week post-TBI, peripheral blood cell counts recover to normal values by about 5 weeks. In the context of studies on a potential role of major histocompatibility (MHC) class II antigens in the regulation of stress hematopoiesis, we tested the effect of anti-MHC class II monoclonal antibodies (mAbs) on hematologic recovery after TBI. Thirteen dogs were given 200 cGy of TBI not followed by marrow infusion.

The problem of thrombocytopenia after hematopoietic stem cell transplantation.

Thrombocytopenia after hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of bleeding and utilization of significant resources. This review presents an analysis of risk factors associated with delayed platelet engraftment. The retrospective analysis included 1,468 recipients of autologous or allogeneic transplants treated between January 1, 1990 and July 1, 1995.

The Problem of Thrombocytopenia after Hematopoietic Stem Cell Transplantation.

Thrombocytopenia after hematopoietic stem cell transplantation (HSCT) is associated with an increased risk of bleeding and utilization of significant resources. This review presents an analysis of risk factors associated with delayed platelet engraftment. The retrospective analysis included 1,468 recipients of autologous or allogeneic transplants treated between January 1, 1990 and July 1, 1995.

Thermoradiotherapy of intraocular tumors in an animal model: concurrent vs. sequential brachytherapy and ferromagnetic hyperthermia.

Purpose: To compare concurrent vs. sequential ferromagnetic thermoradiotherapy in vivo.

Methods And Materials: Greene melanomas were implanted subretinally in rabbits and observed until they were 3-5 mm in diameter.

Comparison of scleral tensile strength after transscleral retinal cryopexy, diathermy, and diode laser photocoagulation.

Objectives: To determine the effect of transscleral diode photocoagulation on the tensile strength of sclera in an experimental rabbit model and to compare it with that of transscleral cryotherapy and diathermy.

Methods: Twenty-four Dutch-belted rabbits received one of the following three treatment modalities in one eye: (1) transscleral cryotherapy, (2) transscleral diathermy, or (3) transscleral diode laser photocoagulation. The opposite eye served as a paired control.

Thrombocytopenia in dogs induced by granulocyte-macrophage colony-stimulating factor: increased destruction of circulating platelets.

Administration of recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) to normal dogs in previous studies induced an increase in peripheral blood neutrophils and a dose-dependent decrease in platelet counts. In six dogs that received the highest tested dose of rcGM-CSF (50 micrograms/kg/d) for a minimum of 12 days, the mean nadir of the platelet count was 46,000/microL (range, 4,000 to 91,000/microL) on day 9 +/- 1.1 after starting therapy, compared with a mean baseline platelet count of 398,000/microL (range, 240,000 to 555,000/microL).