Expression of latent hematopoietic progenitor cells in cultures of newborn and adult baboon liver

The anatomic site of hematopoiesis changes during fetal development from the yolk sac to the liver and finally to the marrow. Factors controlling this switch in the site of hematopoiesis are unknown. We assayed erythroid colony (CFU-E) and erythroid burst (BFU-E) formation in fetal, newborn, and adult baboon liver and marrow to determine the growth requirements of primate hematopoietic progenitor cells from different anatomic sites and developmental stages. We cocultured fetal, newborn, and adult liver and marrow nonadherent cells with adherent cells from these organs to assess the role adherent cells may play in determining the site of hematopoiesis. Fetal liver, fetal marrow, newborn marrow, and adult marrow cultures formed CFU-E and BFU-E colonies in vitro. In contrast, newborn and adult liver cell cultures very rarely formed colonies. However, when newborn or adult liver nonadherent cells were cocultured with marrow adherent cells, CFU-E and BFU-E colonies were detected. The colonies that formed in the newborn and adult liver cultures were derived from the liver and not from the marrow cells or peripheral blood trapped in the liver. These data suggest that in contrast to fetal liver, newborn and adult liver may not be hematopoietic organs in normal primates in vivo because of changes in the growth requirements of hematopoietic progenitor cells present in these organs.     

Granulocyte colony-stimulating factor "mobilized" peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy

Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to "mobilize" peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with "nonmobilized" PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with "nonmobilized" recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving "mobilized" PBPC.     

Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130

The interleukin-6 (IL-6) signal is transduced through membrane-anchored gp130, which is associated with IL-6 receptor (IL-6R) in the presence of IL-6. Soluble forms of gp130 (sgp130) with molecular weights of 90 and 110 Kd were found in human serum. In the presence of recombinant IL- 6 (rIL-6), serum sgp130 were capable of associating with serum sIL-6R. By the sandwich enzyme-linked immunosorbent assay, healthy human sera was shown to contain 390 +/- 72 ng/mL of sgp130. A mouse pro-B-cell line-derived transfectant, BAF-130, expressing human gp130 was used to examine the function of serum sgp130. When supplemented with rIL-6, human serum induced DNA synthesis in BAF-130 cells, whereas the serum deprived of sIL-6R did not. In contrast, the DNA synthesis induced in BAF-130 cells by rIL-6-supplemented serum was increased when the serum was deprived of sgp130. These results indicated that serum sgp130 could negatively regulate the IL-6 signal. Recently, gp130 has been shown to be involved in the signaling processes of oncostatin M, leukemia inhibitory factor, and ciliary neurotropic factor, in addition to those of IL-6. Recombinant sgp130 showed inhibitory effect on the biologic function of such cytokines. This work implies physiologic roles of naturally produced serum sgp130 in modulating signals through gp130.     

Thrombolytic therapy in refractory unstable angina: the role of Holter monitoring.

We tested the safety and the usefulness of intravenous urokinase (2 million units administered over 30 min) in 44 patients with refractory unstable angina, defined as persistence of ischemic episodes during 48-h Holter monitoring (Phase 1) despite maximal medical therapy. After thrombolysis, recurrence of ischemia was observed during a week of observation in the CCU, including two 24-h Holter monitorings at the beginning and the end of the week (Phase 2). Seventeen patients completed the observation period without either symptomatic or asymptomatic ischemic episodes (Group A); the remaining 27 continued to manifest ischemia (Group B). No bleeding complications occurred. Within a 6-month follow-up, 2 patients of Group A had recurrence of unstable angina while in Group B, 19 patients had refractory angina or a major cardiac event [10 patients underwent coronary artery bypass surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) for refractory angina (p less than 0.001), 6 other patients with refractory angina continued medical therapy, one patient had a myocardial infarction, and two patients died]. In Phase 1 the duration of total ischemia (min/24 h) was a relevant prognostic marker: higher duration correlated with adverse clinical outcome (p less than 0.01). In comparison to Phase 1, duration of total ischemia in Phase 2 was significantly reduced in both groups (16.9 +/- 19.6 vs. 25.4 +/- 17.7; p less than .001). A percent value expressing this variation was calculated for each patient: the variation thus obtained again gave information on the clinical outcome--the greater the reduction, the lower the risk of cardiac events (p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Granulocyte/macrophage progenitor cells from peripheral blood and bone marrow differ in their response to prostaglandin E1

Prostaglandins of the E series (PGE) inhibit proliferation of normal bone marrow granulocyte/macrophage progenitors (CFU-GM). Circulating CFU-GM are known to differ from marrow CFU-GM in many characteristics, and in the present study, we compared the effect of PGE1 on circulating and bone marrow progenitors in normals and in patients with chronic myelogenous leukemia (CML). PGE1 caused a dose-dependent inhibition of normal marrow CFU-GM. Circulating CFU-GM were inhibited only at concentrations of 10(-5) mol/L or greater, and progenitor proliferation was, in fact, significantly stimulated at PGE1 concentrations between 10(-8) and 10(-6) mol/L. Bone marrow CFU-GM from patients with CML were inhibited in a manner similar to that of normal bone marrow. Circulating cells from patients with CML were, however, less sensitive to PGE1 inhibition than CML bone marrow cells and demonstrated a pattern intermediate between normal circulating and normal marrow progenitors. These studies suggest that peripheral blood and bone marrow contain different progenitor cell populations.     

Cell surface expression of c-kit receptors by childhood acute myeloid leukemia blasts is not of prognostic value: a report from the Childrens Cancer Group

The prognostic significance of c-kit receptor expression on leukemic blast cells was determined in 122 children with acute myeloid leukemia (AML) entered onto Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as well as outcome were analyzed according to the percentage of blast cells expressing c-kit receptors and the relative number of c-kit receptors per cell as determined by indirect immunofluorescence. c-kit receptor expression was strongly associated with the expression of the CD34 antigen. However, contrary to findings in adult patients with AML, c-kit receptor expression by childhood AML blast cells was not predictive of a poor response to therapy.     

Regulation of hematopoiesis II: the role of polyamine inhibition on helper or suppressor influences of the thymus

We have previously suggested in murine model systems, that two cell subpopulations with differing proliferative capacity, from the thymus, modify the growth of erythroid progenitor cells in vitro. In order to further characterize these populations, we have specifically inhibited polyamine biosynthesis; this pathway is essential for the process of cell replication. Thus, alpha-difluoromethyl ornithine (DFMO) was used to block the conversion of ornithine to putrescine, the first and rate- limiting step in polyamine biosynthesis. We observed a threefold increase in hematopoietic progenitors (CFU-S and CFU-E) from bone marrow in animals treated with DFMO. We further examined the effect of DFMO on accessory "helper" and "suppressor" cells from the thymus and observed an increase in helper activity with an elimination of suppressor activity. All of these effects of DFMO were specific for inhibition of polyamine biosynthesis, since simultaneous addition of the depleted biosynthetic product, putrescine, restored suppressor activity. We conclude that polyamine biosynthesis is required acutely for accessory cell regulation of hematopoiesis.     

Peri-ictal and inter-ictal headache in children and adolescents with idiopathic epilepsy: a multicenter cross-sectional study

Purpose  

Headache in epileptic population ranges from 8% to 15%. The aim of this paper was to study the clinical and temporal characteristics of primary headache comorbidity in idiopathic epileptic children.     

THE 6‐minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history observations over 48 weeks from a multicenter study

Introduction: Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double‐blind, placebo‐controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6‐minute walk test (6MWT) and other endpoints. Methods: Evaluations performed every 6 weeks included the 6‐minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand‐held myometry. Results: Baseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of <350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation. Conclusion: Findings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials. Muscle Nerve 48 : 343–356, 2013