Spontaneously relapsing clonal, mucosal cytotoxic T-cell lymphoproliferative disorder: case report and review of the literature

Primary T-cell lymphoma of the gastrointestinal tract is a rare and usually aggressive disorder that may be associated with celiac disease. The authors describe a unique case of a clonal proliferation of CD8+ T cells involving the oral mucosa, ileum, and colon of a 35-year-old man that has regressed spontaneously and recurred numerous times over a 9-year period without treatment. The patient's symptoms were limited to occasional rectal bleeding and recurring painful oral ulcers. Within the intestine, these collections of small T cells induced minimal architectural distortions and did not show extensive epitheliotrophism. Polymerase chain reaction and sequencing analyses revealed that the identical T-cell clone has been present for more than 9 years and in different mucosal locations in this patient. This may represent a unique T-cell lymphoproliferative process akin to a mucosal counterpart of lymphomatoid papulosis of the skin.     

Embodied reflection in practice—‘Touching the core of caring’

Ranheim A, Kärner A, Arman M, Rehnsfeldt AW, Berterö C. International Journal of Nursing Practice 2010; 16 : 241–247
Embodied reflection in practice—‘Touching the core of caring’ A study was performed with the aim of clarifying the integration of the caring act of touch with reflection on caring theory. Seven participant nurses in elderly care volunteered as ‘coresearchers’ and performed a caring act called Rhythmical Embrocation, together with reflective dialogues on caring theory. The project lasted for 6 months and at the end qualitative interviews with participants were used to evaluate the study. The findings showed an opening of awareness, embodied moments of presence and an extended ability to act creatively in caring. In this study, the movement between theory and practice was the integration of the caring act with reflection on basic caring concepts. Implications for praxis development are that implementation and reflection by teams over certain caring acts might open the door to an expanded view of one's own caring ability that in the long run will benefit the patient.     

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells

Crosslinking the CD27 antigen on T cells provides a costimulatory signal that, in concert with T-cell receptor crosslinking, can induce T- cell proliferation and cellular immune activation. We find that chronic lymphocytic leukemia (CLL) B cells from most patients coexpress both membrane-bound and soluble CD27, along with its newly identified ligand, CD70. The expression of soluble CD27 may preclude leukemic B cells from stimulating T cells via CD70, thereby potentially impairing their ability to function as effective antigen-presenting cells. We find that leukemic B-cell expression of soluble and membrane-bound CD27 can be downmodulated through a CD40-dependent signal. This signal also induces enhanced expression of CD70 on both normal and leukemic B cells. We find that tumor necrosis factor (TNF)-alpha, or the Th1 cytokine interferon (IFN)-gamma, also can induce downmodulation of CD27, whereas Th2-associated cytokines interleukin-4 (IL-4) or IL-10 can enhance leukemic B-cell expression of this accessory molecule. The modulation of CD27 induced by these conditions is accompanied by reciprocal changes in the expression levels of CD70, suggesting that these accessory molecules may be engaged in reciprocal receptor-ligand downmodulation. Consistent with this, we observe that co-culture of CLL B cells with transfected murine plasmacytoma cells that express human CD70 affects downmodulation of CD27 and enhanced expression of CD70 on leukemic B cells, but does not affect expression of CD27 mRNA. However, we find that CD40-crosslinking, in addition to reducing the level of CD27 protein, also reduces leukemic B-cell expression of CD27 mRNA. This argues that the changes in the expression levels of CD27 following CD40-signaling are not simply due to induced increases in the expression levels of CD70. Finally, we demonstrate that reciprocal changes in expression of CD27 and CD70 may contribute to the enhanced antigen-presenting capacity of CLL B cells after CD40-dependent leukemic B-cell activation. These findings expand the understanding of the regulation of costimulatory molecules important in antigen presentation and also have implications for the immunobiology of and therapy for CLL.     

8-iso-prostaglandin F(2alpha) increases expression of LOX-1 in JAR cells

Lectinlike oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL (ox-LDL), is proposed to be involved in endothelial dysfunction and in the pathogenesis of atherosclerosis. Preeclampsia is a pregnancy complication diagnosed by hypertension and proteinuria, characterized by endothelial dysfunction, and supposedly caused by compounds from hypoxic uteroplacental tissues. A feature of preeclampsia is formation of foam cells in maternal arterial walls of gestational tissue ("acute atherosis"). Oxidative stress is believed to play a role in the pathophysiology of preeclampsia. 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) is a marker of oxidative stress in vivo, is biologically active in vitro, and is elevated in preeclamptic plasma and gestational tissue. In the present article, we hypothesized that 8-iso-PGF(2alpha) could induce the expression of LOX-1 in trophoblastic cells (JAR). We demonstrated augmented cellular uptake of (125)I-tyraminylcellobiose ox-LDL in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) versus control cells. Ligand blots revealed an increased binding of ox-LDL to LOX-1 in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L). Incubation with 8-iso-PGF(2alpha) (10 micromol/L) also resulted in augmented LOX-1 protein levels (Western blots) and mRNA levels (Northern blots). JAR cells transfected with 3 copies of a nuclear factor-kappaB binding site demonstrated dose-dependent activation of the reporter gene luciferase after incubation with 8-iso-PGF(2alpha) (0 to 10 micromol/L). We also demonstrated increased accumulation of neutral fats in JAR cells incubated with 8-iso-PGF(2alpha) (10 micromol/L) and ox-LDL compared with controls by oil red O staining. We speculate a potential role of isoprostanes and LOX-1 in preeclampsia in the development of "acute atherosis" of gestational spiral arteries.     

VEGF mRNA is unaltered in decidual and placental tissues in preeclampsia at delivery

BACKGROUND: VEGF (vascular endothelial growth factor) is a growth factor which is central in blood vessel formation. We wanted to determine whether the mRNA levels of VEGF are altered in preeclampsia in decidual and placental tissues compared to control pregnancies. METHODS: Decidua basalis was obtained by vacuum aspiration during cesarean section in 25 preeclamptic and 19 uneventful pregnancies. Placental biopsies were taken immediately after delivery. Relative mRNA levels of VEGF were quantified and compared to those of the housekeeping gene beta-actin. RESULTS: No statistically significant differences in VEGF mRNA levels were found between the preeclampsia and the control group for either the decidual or placental tissues. Furthermore, there were no significant differences between VEGF mRNA levels in the preeclamptic and control group with respect to gestational age of the women. CONCLUSIONS: This study provides no evidence of abnormal VEGF expression at delivery in decidua basalis or placenta in pregnancies complicated by preeclampsia.     

Design-for-Six-Sigma To Develop a Bioprocess Knowledge Management Framework

Owing to the high costs associated with biopharmaceutical development, considerable pressure has developed for the biopharmaceutical industry to increase productivity by becoming more lean and flexible. The ability to reuse knowledge was identified as one key advantage to streamline productivity, efficiently use resources, and ultimately perform better than the competition. A knowledge management (KM) strategy was assembled for bioprocess-related information using the technique of Design-for-Six-Sigma (DFSS). This strategy supported quality-by-design and process validation efforts for pipeline as well as licensed products. The DFSS technique was selected because it was both streamlined and efficient. These characteristics permitted development of a KM strategy with minimized team leader and team member resources. DFSS also placed a high emphasis on the voice of the customer, information considered crucial to the selection of solutions most appropriate for the current knowledge-based challenges of the organization. The KM strategy developed was comprised of nine workstreams, constructed from related solution buckets which in turn were assembled from the individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the KM strategy project charter and design inputs. Gaps and risks were identified and mitigated as necessary to improve the robustness of the proposed strategy. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and divisional/corporate information technology efforts were leveraged to minimize the additional bioprocess resources required for implementation. Finally, leading and lagging indicator metrics were selected to track the success of pilots and eventual implementation. LAY ABSTRACT: A knowledge management framework was assembled for bioprocess-related information using a streamlined and efficient technique that minimized team leader and member resources. The technique also highly emphasized input from the staff, who generated and used the knowledge, information considered crucial to selection of solutions most appropriate for the current knowledge-based challenges in the organization. The framework developed was comprised of nine workstreams, constructed from related solution buckets which were assembled from individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the project charter and design inputs. Gaps and risks were identified and mitigated to improve robustness of the proposed framework. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and information technology efforts were leveraged to minimize additional bioprocess resources required for implementation. Finally, metrics were selected to track the success of pilots and eventual implementation.