Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL.

In diffuse large B cell lymphoma (DLBCL), tumors belonging to the ABC but not GCB gene expression subgroup rely upon chronic active B cell receptor signaling for viability, a dependency that is targetable by ibrutinib. A phase III trial ("Phoenix;" ClinicalTrials.gov: NCT01855750) showed a survival benefit of ibrutinib addition to R-CHOP chemotherapy in younger patients with non-GCB DLBCL, but the molecular basis for this benefit was unclear.

Prediction of drowsiness events in night shift workers during morning driving.

The morning commute home is an especially vulnerable time for workers engaged in night shift work due to the heightened risk of experiencing drowsy driving. One strategy to manage this risk is to monitor the driver's state in real time using an in vehicle monitoring system and to alert drivers when they are becoming sleepy. The primary objective of this study is to build and evaluate predictive models for drowsiness events occurring in morning drives using a variety of physiological and performance data gathered under a real driving scenario.

High risk of near-crash driving events following night-shift work.

Night-shift workers are at high risk of drowsiness-related motor vehicle crashes as a result of circadian disruption and sleep restriction. However, the impact of actual night-shift work on measures of drowsiness and driving performance while operating a real motor vehicle remains unknown. Sixteen night-shift workers completed two 2-h daytime driving sessions on a closed driving track at the Liberty Mutual Research Institute for Safety: (i) a postsleep baseline driving session after an average of 7.

Evidence-based chiropractic education: are we equipping graduates for clinical practice with improved patient outcomes?

Evidence-based practice has emerged as a driving factor in current curriculum development in chiropractic education. This commentary discusses educational strategies incorporating evidence-based practices in the doctor of chiropractic curriculum and explores whether all five steps of the evidence-based process and patient outcomes from evidence-based practice are being assessed.

Chiropractic care of a patient with thoracic outlet syndrome and arrhythmia.

Objective: The purpose of this article is to describe a case report and discuss a possible anatomical explanation of the occurrence of arrhythmias in patients with thoracic outlet syndrome (TOS).

Clinical Features: A 60-year-old man experienced arrhythmia when he turned his head to the left and had these symptoms for 7 years. The patient attributed his symptoms to TOS.

The Digital Bridge: A Boomer's View of Course Management Software in the Gen Y Classroom.

Today's Generation Y student population entered adulthood in a world immersed with digital technology. This commentary discusses the migration of educators, primarily from the Baby Boomer generation, in the use of digital technology as part of an educational process designed to engage current student cohorts.

Beyond the didactic classroom: educational models to encourage active student involvement in learning.

In a chiropractic college that utilizes a hybrid curriculum model composed of adult-based learning strategies along with traditional lecture-based course delivery, a literature search for educational delivery methods that would integrate the affective domain and the cognitive domain of learning provided some insights into the use of problem-based learning (PBL), experiential learning theory (ELT), and the emerging use of appreciative inquiry (AI) to enhance the learning experience. The purpose of this literature review is to provide a brief overview of key components of PBL, ELT, and AI in educational methodology and to discuss how these might be used within the chiropractic curriculum to supplement traditional didactic lecture courses. A growing body of literature describes the use of PBL and ELT in educational settings across many disciplines, both at the undergraduate and graduate levels.

Superoxide dismutase specifically inhibits erythroid cell DNA synthesis and proliferation.

The antioxidant enzyme superoxide dismutase (SOD) was previously shown to inhibit both the proliferation of murine erythroid DA-1 cells growing in the presence of Interleukin-3 (IL-3) and the DNA synthesis of marrow erythroid progenitor cells (BFU-E) in vitro. We show here that the inhibition of marrow cell DNA synthesis by SOD is specific for BFU-E and erythroid precursors (CFU-E), with other myeloid progenitors (CFU-GM) and stem cells (CFU-S) being unaffected, and IL-3 blocks the inhibitory effects of SOD on BFU-E in a dose-dependent manner. Extending earlier observations on the effects of SOD on cell proliferation, it was found that SOD was capable of inhibiting DA-1 cell proliferation supported by either IL-3 or erythropoietin (epo), but had no effect on IL-3 dependent FDCP-1 cells, nor on epo-dependent HCD-57 cells.

Purification of an inhibitor of erythroid progenitor cell cycling and antagonist to interleukin 3 from mouse marrow cell supernatants and its identification as cytosolic superoxide dismutase.

We have isolated a protein from media conditioned by a murine marrow-derived cell line (PB6) and from mouse marrow supernatants that antagonizes interleukin 3-dependent proliferation of cells in culture and reversibly inhibits DNA synthesis of erythroid progenitor cells (BFU-E) in vitro. This protein, p16 (monomer Mr = 16 kD on SDS-PAGE), was purified to homogeneity and amino acid sequencing of a polypeptide fragment yielded a sequence identical to that of murine cytosolic Cu,Zn-containing superoxide dismutase (SOD). The identification of p16 as SOD was confirmed by the detection of SOD enzymatic activity in pure p16 fractions, and when a commercial human erythrocytic SOD preparation was tested it showed the same cell inhibitory activities as p16.

Interleukin 3-stimulated proliferation is sensitive to pertussis toxin: evidence for a guanyl nucleotide regulatory protein-mediated signal transduction mechanism.

Interleukin 3 (IL-3) stimulates several biochemical and biological responses in IL-3-dependent tissue culture cells. We examined the possibility that guanyl nucleotide regulatory (G) proteins may transduce signals from IL-3 receptors. We report here that pertussis toxin (PT), which can covalently modify a subclass of G proteins, is capable of inhibiting IL-3-stimulated proliferation in a dose-dependent fashion.

Interleukin 3 and cell cycle progression.

Interleukin 3 (IL-3) is a regulatory glycoprotein required for the proliferation and differentiation of cells from many if not all hemopoietic lineages. With the emergence of the competence-progression model of cell proliferation, which predicts that growth factors function at specific stages of the cell cycle, we examined the possibility that IL-3 functions at a specific stage of the cell cycle. C-63 cells were developed as a cell line from normal murine bone marrow.

A self-renewing, bipotential erythroid/mast cell progenitor in continuous cultures of normal murine bone marrow.

We have established permanent lines of nonadherent cells from fresh normal mouse bone marrow in media containing pokeweed mitogen-stimulated spleen cell conditioned medium (PWSCM). These lines continuously produced erythropoietic progenitor cells (detected by their ability to form erythroid bursts in semi-solid medium containing erythropoietin) together with cells having characteristics of the mast cell lineage (as demonstrated by metachromatic staining with toluidine blue, histamine content and membrane receptors for IgE). Sixteen such cell lines have been established in sixteen attempts.

Long-term culture of murine erythropoietic progenitor cells in the absence of an adherent layer.

Replication of multipotential stem cells in long-term murine bone marrow cell culture is known to depend on the development of an adherent stromal cell layer. In these conditions, restricted haematopoietic progenitor cells have also been generated for up to several months1-3. However, maturation is observed only in the granulocyte/macrophage and megakaryocyte lineages; erythropoiesis appears to be blocked at the earliest burst-forming unit (BFU-E) stage.

Chromosome marker evidence for the bipotentiality of BFU-E.

When mouse bone marrow cells are seeded in agar cultures containing erythropoietin or pokeweed mitogen stimulated spleen cell conditioned medium plus erythropoietin, megakaryocytes are found mixed with erythroid cells in approximately 40% of the erythropoietic bursts that develop in the cultures. Chromosome spreads of C-metaphases in such "megaerythro bursts" were prepared and stained in situ with a modification of the C-banding technique. In cultures seeded with mixtures of male and female cells, metaphases from individual megaerythro bursts were shown to be either all male of all female but not both.

Evidence for the clonal nature of erythropoietic bursts: application of an in situ method for demonstrating centromeric heterochromatin in plasma cultures.

Erythropoietic bursts were produced in plasma cultures seeded with a mixture of male and female murine bone marrow cells. Chromosome spreads of C-metaphases were prepared and stained in situ with a modification of the C-banding technique. In cultures seeded with mixtures of male and female cells, homogeneity of male or female C-metaphases in erythropoietic bursts was established by the presence or absence of the Y-chromosome.

Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation.

The sedimentation velocity profiles of the entities in mouse bone marrow responsible for erythropoietic burst formation (BFU-E) and for erythrocytic colony formation (CFU-E) have been studied under conditions designed to determine whether the values observed are real or result from cell interactions occurring during culture of the fractions. Bone marrow cells of adult C3Hf/Bi mice were subjected to unit gravity sedimentation in a bovine serum albumin gradient, and fractions were assayed in plasma culture. Because it was found that cell concentration affected the efficiency of erythropoietic burst formation in culture, aliquots were plated at two different cell concentrations, as well as at a fixed proportion of each fraction.

Erythroid colony induction without erythropoietin by Friend leukemia virus in vitro.

Erythroid colonies could be produced without the addition of erythropeietin in plasma cultures seeded with bone marrow cells from normal C3Hf/Bi mice by exposure of the cells in vitro to medium from a cell line (IS) that continuously produces Friend leukemia virus in culture. The activity in the culture medium was viral rather than erythropoietin-like, since it was sedimentable by high-speed centrifugation and heat labile. Erythroid colonies did not develop when the bone marrow cells exposed to virus-containing medium were from mice genetically resistant to Friend virus.

Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro.

A culture method has been developed in which erythroid colonies are produced in vitro from hemopoietic cells from the livers of 13-day fetuses of C3H(f)/Bi mice. Heme synthesis by the cultures was correlated with the presence of these colonies, and the hemoglobin produced was shown to be electrophoretically normal. The individual colonies were identified as erythroid since they were erythropoietin-dependent, positively stained by the histochemical "Lepehne" procedure for hemoglobin, and labeled by (59)Fe radioautography.