Selection and immunomagnetic purging of peripheral blood CD34+ cells for autologous transplantation in B-cell non-Hodgkin's lymphomas

Background: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. Patients and methods: We examined the feasability and safety of a CD34-selection followed by purging with anti-B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophospha-mide, BCNU and etoposide with retransfusion of autologous HPC's. Results: A mean number of 340 × 108 mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2× 106/kg (range 0.6-2.2 ×106/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5×109/1 and 17 days (range 13-25 days) to platelet recovery of 50 × 109/1. Mean number of intravenous antibiotics and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. Conclusions: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphoma

Noise Induced Coherence in Neural Networks

We investigate numerically the dynamics of large networks of $N$ globally pulse-coupled integrate and fire neurons in a noise-induced synchronized state. The powerspectrum of an individual element within the network is shown to exhibit in the thermodynamic limit ($N\to \infty$) a broadband peak and an additional delta-function peak that is absent from the powerspectrum of an isolated element. The powerspectrum of the mean output signal only exhibits the delta-function peak. These results are explained analytically in an exactly soluble oscillator model with global phase coupling.Comment: 4 pages ReVTeX and 3 postscript figure

Selection and immunomagnetic purging of peripheral blood CD34+ cells for autologous transplantation in B-cell non-Hodgkin's lymphomas

Background: Clonogenic tumor cells in the hematopoietic progenitor cell harvest may contribute to relapse after high dose therapy for B-cell malignancies. Purging of the HPC harvest requires large amounts of anti-B-cell antibodies, whereas CD34-selection enriches self renewing HPC's but malignant cells are still detectable in many CD34+ fractions. Patients and methods: We examined the feasability and safety of a CD34-selection followed by purging with anti-B-cell antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high-dose therapy with cyclophospha-mide, BCNU and etoposide with retransfusion of autologous HPC's. Results: A mean number of 340 × 108 mononuclear cells was used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells was 1.2× 106/kg (range 0.6-2.2 ×106/kg) body weight with a median of 11 days (range 10-13 days) to neutrophil recovery of 0.5×109/1 and 17 days (range 13-25 days) to platelet recovery of 50 × 109/1. Mean number of intravenous antibiotics and inpatient days were 8 (range 0-14) and 22 (range 19-26) respectively. Major toxicity consisted in four septicemias. Conclusions: CD34-selected and purged HPC's are safe and mediate rapid hematological recovery after high dose therapy for B-cell non-Hodgkin's lymphoma

Collective dynamics of two-mode stochastic oscillators

We study a system of two-mode stochastic oscillators coupled through their collective output. As a function of a relevant parameter four qualitatively distinct regimes of collective behavior are observed. In an extended region of the parameter space the periodicity of the collective output is enhanced by the considered coupling. This system can be used as a new model to describe synchronization-like phenomena in systems of units with two or more oscillation modes. The model can also explain how periodic dynamics can be generated by coupling largely stochastic units. Similar systems could be responsible for the emergence of rhythmic behavior in complex biological or sociological systems.Comment: 4 pages, RevTex, 5 figure

IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo

Interleukin 21 (IL-21) is a member of the common gamma-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we generated IL-21R-deficient mice and have investigated the role of IL-21R signaling using a series of in vivo experimentally induced disease models. We first addressed the role of IL-21R signaling in Th2 immune responses by examining allergic airway inflammation, and Nippostrongylus brasiliensis and Heligmosomoides polygyrus antihelminth responses. In each of these systems, IL-21R signaling played a clear role in the development of Th2 responses. Comparatively, IL-21R signaling was not required for the containment of Leishmania major infection or the development of experimental autoimmune myocarditis, indicative of competent Th1 and Th17 responses, respectively. Adoptive transfer of T cells and analysis of IL-21R+/+/IL-21R-/- chimera mice revealed that IL-21R-signaling was central to Th2-cell survival or migration to peripheral tissues. Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses

Coherence Resonance and Noise-Induced Synchronization in Globally Coupled Hodgkin-Huxley Neurons

The coherence resonance (CR) of globally coupled Hodgkin-Huxley neurons is studied. When the neurons are set in the subthreshold regime near the firing threshold, the additive noise induces limit cycles. The coherence of the system is optimized by the noise. A bell-shaped curve is found for the peak height of power spectra of the spike train, being significantly different from a monotonic behavior for the single neuron. The coupling of the network can enhance CR in two different ways. In particular, when the coupling is strong enough, the synchronization of the system is induced and optimized by the noise. This synchronization leads to a high and wide plateau in the local measure of coherence curve. The local-noise-induced limit cycle can evolve to a refined spatiotemporal order through the dynamical optimization among the autonomous oscillation of an individual neuron, the coupling of the network, and the local noise.Comment: five pages, five figure

Phase synchronization and noise-induced resonance in systems of coupled oscillators

We study synchronization and noise-induced resonance phenomena in systems of globally coupled oscillators, each possessing finite inertia. The behavior of the order parameter, which measures collective synchronization of the system, is investigated as the noise level and the coupling strength are varied, and hysteretic behavior is manifested. The power spectrum of the phase velocity is also examined and the quality factor as well as the response function is obtained to reveal noise-induced resonance behavior.Comment: to be published in Phys. Rev.

CD28/CD154 Blockade Prevents Autoimmune Diabetes by Inducing Nondeletional Tolerance After Effector T-Cell Inhibition and Regulatory T-Cell Expansion

OBJECTIVE—Blocking T-cell signaling is an effective means to prevent autoimmunity and allograft rejection in many animal models, yet the clinical translation of many of these approaches has not resulted in the success witnessed in experimental systems. Improved understanding of these approaches may assist in developing safe and effective means to treat disorders such as autoimmune diabetes

HVEM Signalling Promotes Colitis

Background Tumor necrosis factor super family (TNFSF) members regulate important processes involved in cell proliferation, survival and differentiation and are therefore crucial for the balance between homeostasis and inflammatory responses. Several members of the TNFSF are closely associated with inflammatory bowel disease (IBD). Thus, they represent interesting new targets for therapeutic treatment of IBD. Methodology/Principal Findings We have used mice deficient in TNFSF member HVEM in experimental models of IBD to investigate its role in the disease process. Two models of IBD were employed: i) chemical-induced colitis primarily mediated by innate immune cells; and ii) colitis initiated by CD4+CD45RBhigh T cells following their transfer into immuno-deficient RAG1-/- hosts. In both models of disease the absence of HVEM resulted in a significant reduction in colitis and inflammatory cytokine production. Conclusions These data show that HVEM stimulatory signals promote experimental colitis driven by innate or adaptive immune cells