Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS.

OBJECTIVE: Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to play a key roll in amplification of production of inflammatory cytokines. TREM-1 is suggested to be a specific biomarker for sepsis for this reason, but the clinical significance of TREM-1 has not been elucidated. We investigated TREM-1 expression on the cell-surface, and plasma levels of soluble TREM-1 (sTREM-1) in patients with non-infectious systemic inflammatory response syndrome (SIRS) and sepsis admitted to the ICU. METHODS: Thirty-five patients with SIRS and 21 patients with sepsis admitted to ICU were subjected to the study. TREM-1 expressions on the surfaces of monocytes and neutrophils were measured by flow cytometry. Plasma sTREM-1 level and serum interleukin (IL)-6 level were measured. RESULTS: Septic patients had decreased TREM-1 expression, clearly on neutrophils or to a lesser extent on monocyte compared to SIRS patients on ICU admission (neutrophils p<0.001, monocyte p<0.05). TREM-1 expression on neutrophils had a significant inverse correlation with serum IL-6 level (r=-0.64, p<0.0001). Plasma sTREM-1 level in septic patients was significantly higher than that in SIRS patients (p<0.05). Plasma sTREM-1 level positively correlated with severity score and non-survivors had increased plasma sTREM-1 level compared to survivors in all SIRS/sepsis patients (p<0.05). CONCLUSIONS: Patients with sepsis had increased soluble TREM-1 and decreased TREM-1 expression on neutrophil compared to SIRS patients. sTREM-1 may be useful to evaluate disease severity and outcome of patients with SIRS or sepsis.

Cytogenetic remissions induced by interferon alpha and imatinib mesylate are immunologically distinct in chronic myeloid leukemia.

We compared immunologic parameters of chronic myeloid leukemia (CML) patients in cytogenetic remission receiving imatinib mesylate (STI) treatment, CML patients receiving interferon alpha (IFN-alpha), and healthy volunteers. Each group comprised 14 subjects. Median treatment dosages and durations were 6 x 10(6) IU/week and 174 months, respectively, for IFN-alpha and 400 mg/day and 54 months for STI. The numbers of T-cells were significantly lower in the 2 patient groups (P = .0006), whereas the 3 groups were comparable with respect to the numbers of natural killer cells. Not only the absolute numbers of monocytes and B-cells but also serum immunoglobulin G (IgG) and IgA titers were significantly lower in the STI group than in the IFN-alpha group (P < .0001). For T-cell subsets, the ratio of CD4 T-cells to CD8 T-cells was significantly lower in the IFN-alpha group than in the STI group, but the proportion of CD26(high)CD4+ T-cells among CD4+ cells was significantly higher. Collectively, the 2 therapeutic agents induce a distinct immunologic status in CML patients whose hematopoiesis has returned to normal levels.

Freeze-Dried Human Platelet-Rich Plasma Retains Activation and Growth Factor Expression after an Eight-Week Preservation Period.

STUDY DESIGN: Controlled laboratory study. PURPOSE: This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. OVERVIEW OF LITERATURE: PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. METHODS: PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at -80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. RESULTS: Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. CONCLUSIONS: Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.

FET family proto-oncogene Fus contributes to self-renewal of hematopoietic stem cells.

OBJECTIVE: Fus is the gene for a member of the FET family of RNA-binding proteins often involved in chromosomal translocations to generate oncogenic fusion genes in human cancers. Fus participates in multiple cellular functions, including RNA processing and transport, transcriptional regulation, and genome integrity. However, its role in hematopoiesis remains obscure. In this study, we examined its role in the self-renewal of hematopoietic stem cells (HSCs). MATERIALS AND METHODS: HSCs in Fus(-/-) fetal livers were analyzed for proliferative capacity in vitro and long-term repopulating capacity in recipient mice. Radiation sensitivity of Fus(-/-) HSCs was evaluated in recipient mice repopulated by Fus(-/-) fetal liver cells. RESULTS: Fus(-/-) fetal livers developed normally, except for a mild reduction in numbers of hematopoietic stem and progenitor cells compared to wild-type. The proliferation and differentiation of Fus(-/-) hematopoietic progenitors were normal in vitro. However, the number of colony-forming cells present in long-term cocultures of Fus(-/-) hematopoietic progenitors and stromal cells was significantly reduced. Fus(-/-) HSCs had an impaired long-term repopulating capacity and failed to repopulate in tertiary recipient mice. Fus(-/-) HSCs were highly susceptible to radiation both in vitro and in vivo and showed retardation of radiation-induced DNA damage repair. CONCLUSION: Our findings define Fus as a novel regulator of self-renewal and radioprotection of HSCs and also implicate it in stress-resistance and maintenance of the genomic integrity of HSCs.