Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis

Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research. (Blood. 2001;97:3025-3031)     

Comprehensive health status assessment of centenarians: results from the 1999 large health survey of veteran enrollees

BACKGROUND: Information on the health status of centenarians provides a means for understanding the health care needs of this growing population. Therefore, we examined the health status of a national cohort of centenarian veteran enrollees. METHODS: Ninety-three centenarian veteran enrollees returned a complete health history questionnaire, which included questions about sociodemographic information, age-associated conditions, health behaviors, health-related quality of life as measured by the Veterans SF-36, and change in health status. RESULTS: Centenarian veteran enrollees are a group with major impairment across multiple dimensions of health-related quality of life despite having a relatively low prevalence of diseases. They had considerable physical limitations as reflected by their physical health summary scores (26.2 +/- 8.3). However, their mental health was comparatively good (mental health summary score 44.1 +/- 12.5). Compared to younger elderly veterans (ages 85-99), centenarians had a lower prevalence of hypertension, angina or myocardial infarction, diabetes, and chronic low back pain (p <.05). Centenarians had significantly worse physical functioning, role physical, vitality, and social functioning scores than did younger elderly veterans. The two groups did not differ in their general health, bodily pain, role emotional, and mental health scores. Centenarians did not perceive much decline in their physical or mental health during the preceding year. CONCLUSIONS: Centenarian veteran enrollees are a group with a low number of age-associated diseases and good mental health despite substantial physical limitations. These results support future studies of services directed toward improvement of function as opposed to those focused solely on the treatment of diseases.     

Distinct microRNA expression profiles in acute myeloid leukemia with common translocations

MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific miRNAs may play a role in the development of leukemia with these associated genetic rearrangements.     

Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury

Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptor is present in the lungs, and NMDA receptor antagonist MK-801 attenuates oxidant lung injury. We hypothesized that Glu excitotoxicity may participate in the pathogenesis of hyperoxia-induced lung injury. To determine possible pulmonary protective effects, we administered 0.05 ml/kg MK-801 or saline intraperitoneally daily to neonatal rats exposed to more than 95% oxygen in air. After 7 days, MK-801 decreased the hyperoxia-associated elevation of wet-to-dry lung weight, total leukocyte and neutrophil counts, total protein and lactate dehydroase in BAL fluid, total myeloperoxidase activity, and lung pathological injury. MK-801 inhibited hyperoxia-associated increments in reactive oxygen species production and NF-kappaB production. Hence, NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats, and is associated with decreased reactive oxygen species and NF-kappaB. We conclude that Glu may play an important role in hyperoxia-induced lung injury by activation of NMDA receptor.     

磁共振形态学半定量评分对新生儿细菌性脑膜炎出院结局的评估价值

目的 分析MRI形态学半定量评分对新生儿细菌性脑膜炎出院结局的评估价值。方法 收集复旦大学附属儿科医院2011年7月至2013年12月NICU收治的出院诊断为新生儿细菌性脑膜炎的病例,采用基于大脑损伤MRI形态学分析的半定量评分,对头颅MRI图像进行回顾性分析。MRI形态学评价包括脑室扩大、脑室旁白质容积丢失、脑白质囊性病灶、内囊后肢髓鞘化异常、皮质信号异常、颅内脑外间隙异常、基底节信号异常、脑白质非囊性信号异常、脑室内出血、脑室积脓、脑膜异常强化、室管膜异常强化和脑脓肿。将上述13项评分归纳为脑白质异常（WMA）、脑灰质异常（GMA）和非脑实质异常（NPA）。同时采集患儿出生孕周、发病时间、MRI检查时间、发病至MRI检查间隔时间和出院结局。按照出生孕周分为早产儿组和足月儿组,再按照出院结局分为预后良好和预后不良亚组,在各组内比较亚组之间时间因素、MRI单项评分和综合评分的差异。结果 63例新生儿细菌性脑膜炎病例进入分析（早产儿组18例,足月儿组45例）。MRI单项评分构成预后良好和预后不良亚组间差异有统计学意义的指标：早产儿组中有脑室扩大(P=0.012)和脑室旁白质容积丢失(P=0.004);足月儿组有脑室扩大(P=0.002)、脑室旁容积丢失(P=0.040)、颅内脑外间隙异常(P=0.005)和脑室内出血(P=0.038)。MRI综合评分中,早产儿组WMA评分(P=0.001)和NPA评分（P=0.039）、足月儿组NPA评分(P=0.018)在预后不良和预后良好亚组之间分布差异有统计学意义。足月儿组和早产儿组内不同预后亚组的各时间因素差异未发现统计学意义或临床意义。结论 新生儿细菌性脑膜炎MRI脑室扩大和脑室旁白质容积丢失预示早产儿出院不良结局;脑室扩大、脑室旁白质容积丢失、颅内脑外间隙异常和脑室内出血预示足月儿出院不良结局。WMA评分高预示早产儿出院不良结局,NPA评分高预示早产儿和足月儿出院不良结局。     

Hemangiopoietin, a novel human growth factor for the primitive cells of both hematopoietic and endothelial cell lineages

The cells of hematopoietic and vascular endothelial cell lineages are believed to share a common precursor, termed hemangioblast. However, the existence of a growth factor acting relatively specifically on hemangioblasts remains unclear. Here we report the identification of hemangiopoietin (HAPO), a novel growth factor acting on both hematopoietic and endothelial cell lineages. In vitro in the human system, recombinant human HAPO (rhHAPO) significantly stimulated the proliferation and hematopoietic and/or endothelial differentiation of human bone marrow mononuclear cells and of purified CD34+, CD133+, kinase domain receptor-positive (KDR+), or CD34+/KDR+ cell populations. In the murine system, rhHAPO stimulated the proliferation of long-term culture-initiating cells (LTC-ICs) as well as CD34+ and stem cell antigen-1 (Sca-1+) cell subsets. In vivo, subcutaneous injection of rhHAPO into normal mice resulted in a significant increase in bone marrow hematopoietic cells. Furthermore, irradiated mice injected with rhHAPO had an enhanced survival rate and accelerated hematopoiesis. Our data suggest that HAPO is a novel growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages and that HAPO may have a clinical potential in the treatment of various cytopenias and radiation injury and in the expansion of hematopoietic and endothelial stem/progenitor cells.     

Synthesis and evaluation of properties of N,N-bis(perfluorooctyl)imine acetate sodium as a gas-wetting alteration agent

The wettability of a rock’s surface is a vital factor for gas flow and fracturing fluid backflow. As a result of this, novel and effective gas wetting alteration agents are required. In this work, a gas-wetting alteration agent, N,N-bis(perfluorooctyl)imine acetate sodium, was synthesized and characterized by different methods. The wettability of a rock’s surface was evaluated by contact angle and imbibition measurements, the Owens two-liquid method and glass capillary tube rise testing. The results showed that after treatment with 0.5 wt% N,N-bis(perfluorooctyl)imine acetate sodium the contact angles of water and n-hexadecane on the surface of the rock increased from 36° and 0° to 140° and 119°, respectively. The surface free energy rapidly reduced from primeval 72 mN m⁻¹ to 3.4 mN m⁻¹ after treatment with 0.3 wt% N,N-bis(perfluorooctyl)imine acetate sodium. These values agreed with the imbibition measurements and the results of the glass capillary tube rise testing. Moreover, analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) showed that the roughness of the rock surface significantly increased. The above results fully proved that the wettability of the rock surface is altered from its original water-wetting or oil-wetting to gas-wetting. Furthermore, thermal analysis demonstrated that the gas-wetting alteration agent has good thermal stability, which indicates its great potential to be used as a gas-wetting alteration agent for unconventional gas reservoirs under high temperature conditions.

A gas-wetting alteration agent, N,N-bis(perfluorooctyl)imine acetate sodium, was synthesized and characterized by different methods and the wettability of a rock surface was evaluated.