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71.
Myeloproliferative syndrome induced by MPSV in DBA/2 mice: presence of a mixed-colonies promoting activity (MPA) in the spleen 总被引:1,自引:0,他引:1
Le Bousse-Kerdiles MC; Smadja-Joffe F; Klein B; Jasmin C; Comisso M; Ostertag W 《Blood》1983,61(3):520-524
The myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) in DBA/2 mice stimulates the proliferation of pluripotent hemopoietic stem cells (HSC) and of progenitors committed toward granulomacrophagic and erythroid cell lines. This stimulation may result from a direct effect of the MPSV on HSC or from an indirect effect via locally secreted factors. Normal isogenic bone marrow cells were incubated in the mixed colony-forming unit system in semisolid medium supplemented with conditioned media obtained after incubating neoplastic spleen cells for 3 days at 37 degrees C. These spleen conditioned media contain an activity that is physically separable from MPSV by ultracentrifugation and which, in the presence of a very low quantity of erythropoietin, can induce in vitro the proliferation and differentiation of pluripotent HSC, detected by this Mix-CFU technique. We termed this activity mixed-colonies promoting activity (MPA). These results suggest that the hyperplasia of the nonlymphoid hematopoietic system in the neoplastic spleen results from an indirect effect of the MPSV on pluripotent HSC via locally secreted factors. 相似文献
72.
Yauk C Polyzos A Rowan-Carroll A Somers CM Godschalk RW Van Schooten FJ Berndt ML Pogribny IP Koturbash I Williams A Douglas GR Kovalchuk O 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(2):605-610
Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation. 相似文献
73.
There are remarkable differences of incidence and mortality from cervical cancer between countries and even within small countries. In developed industrial countries, incidence is slowly declining. Age distribution (middle--aged women are mostly afflicted) distinguishes cervical cancer from all other common malignant neoplasms. Known risk factors are: low social class, sexual activity early in youth, instable sexual relationships. Cervical cancer behaves like a veneral disease of low infectious power. Cervical cancer develops stepwise out of epithelial dysplasia and carcinoma in situ. The foundations of a cervical cancer control programme are laid: cytodiagnosis as screening method; well defined high risk groups; effective and not dangerous treatment of prephases and early stages of cancer. In the G.D.R. conditions for effective cancer control are good: cancer registration works stable for more than 20 years; it enables evaluation of effectivity. Cytologic screening can be fully integrated into basic gynecologic care. Medical care including prevention is free of fees and available for all women. The ultimate of goal of a cervical cancer control programme is primary prevention by detection and treatment of preneoplastic lesions (dysplasia and carcinoma in situ). 相似文献
74.
Taylor AJ Bobik A Berndt MC Kalff V Michaelides A Jennings GL 《The American journal of cardiology》2003,92(4):446-450
We assessed glycoprotein (GP) IIb/IIIa independent platelet activation in coronary sinus and peripheral blood from patients who underwent angioplasty for acute myocardial infarction and stable angina. Despite complete blockade of the activated GP IIb/IIIa receptor with abciximab in patients with acute myocardial infarction, unsuppressed local GP IIb/IIIa independent activation was associated with a lack of recovery of left ventricular function. 相似文献
75.
Borsi L Balza E Carnemolla B Sassi F Castellani P Berndt A Kosmehl H Biro A Siri A Orecchia P Grassi J Neri D Zardi L 《Blood》2003,102(13):4384-4392
We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy. 相似文献
76.
Li X Tjwa M Van Hove I Enholm B Neven E Paavonen K Jeltsch M Juan TD Sievers RE Chorianopoulos E Wada H Vanwildemeersch M Noel A Foidart JM Springer ML von Degenfeld G Dewerchin M Blau HM Alitalo K Eriksson U Carmeliet P Moons L 《Arteriosclerosis, thrombosis, and vascular biology》2008,28(9):1614-1620
77.
Under conditions of high shear stress, both hemostasis andthrombosis are initiated by the interaction of the platelet membrane glycoprotein (GP) Ib-IX-V complex with its adhesive ligand, von Willebrand factor (vWF), in the subendothelial matrix or plasma. Thisinteraction involves the A1 domain of vWF and the N-terminal extracellular region of GP Ib (His-1-Glu-282), and it can also beinduced under static conditions by the modulators ristocetin andbotrocetin. In this study, a panel of anti-vWF and anti-GP Ibantibodiespreviously characterized for their effects on ristocetin- and botrocetin-dependent vWF-GP Ib-IX-V interactionswas analyzed fortheir capacity to inhibit either the adhesion of Chinese hamster ovarycells expressing recombinant GP Ib to surface-associated vWF underhydrodynamic flow or shear-stress-induced platelet aggregation. Thecombined results suggest that the shear-dependent interactions betweenvWF and GP Ib closely correlate with ristocetin- rather thanbotrocetin-dependent binding under static conditions and that certainanti-vWF monoclonal antibodies are able to selectively inhibitshear-dependent platelet aggregation. 相似文献
78.
Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia 总被引:1,自引:1,他引:1
Robinson N; Sanders JE; Benyunes MC; Beach K; Lindgren C; Thompson JA; Appelbaum FR; Fefer A 《Blood》1996,87(4):1249-1254
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
79.
Evelyn?Ziehenberger Berndt?Urlesberger Corinna?Binder-Heschl Bernhard?Schwaberger Nariae?Baik-Schneditz Gerhard?PichlerEmail authorView authors OrcID profile 《Journal of clinical monitoring and computing》2018,32(3):465-469
Feasibility of cerebral tissue oxygenation measurements immediately after birth has been published starting with first values 2 min after birth. Aim of this study was to evaluate, the time periods from birth and from arrival at the resuscitation table to obtain the first cerebral tissue oxygenation values with two different near infrared spectroscopy (NIRS) devices. The present study is an analysis of exploratory parameters of two prospective observational studies. Cerebral tissue oxygen saturation was measured by the NIRO 200NX measuring “cerebral-tissue-oxygenation-index” (cTOI) or the INVOS5100C measuring “cerebral-regional-oxygen-saturation” (crSO2). Four time periods (T) were defined: T1 birth to arrival at resuscitation table, T2 arrival to application of NIRS sensor, T3 application to first displayed cTOI or crSO2 value, and T4 from arrival at resuscitation table to first displayed values. Additionally, we compared first displayed values of cTOI and crSO2. Thirty neonates were included. Twenty-four were term and six late-preterm neonates. Fifteen neonates measured with NIRO were compared to 15 measured with INVOS. T1 was 49 (6–163) s with NIRO versus 59 (15–87) s with INVOS, T2 14 (4–20) s versus 12 (15–18) s, T3 33 (13–138) s versus 17 (6–290) s and T4 46 (20–153) s and 34 (14–300) s. The first displayed value tended to be higher for cTOI [54% (18–80)] compared to crSO2 [35% (15–87)]. There were no significant differences between devices in time periods and first values displayed. Cerebral tissue oxygenation can be measured within 1 min after arriving at the resuscitation table in term and preterm neonates after birth without difference between devices. 相似文献
80.
Karl Pillemer Emily K. Chen Catherine Riffin Holly Prigerson MC Reid Leslie Schultz 《American journal of public health》2015,105(11):2237-2244
We employed the research-to-practice consensus workshop (RTP; workshops held in
New York City and Tompkins County, New York, in 2013) model to merge researcher
and practitioner views of translational research priorities in palliative care.
In the RTP approach, a diverse group of frontline providers generates a research
agenda for palliative care in collaboration with researchers. We have presented
the major workshop recommendations and contrasted the practice-based research
priorities with those of previous consensus efforts. We uncovered notable
differences and found that the RTP model can produce unique insights into
research priorities. Integrating practitioner-identified needs into research
priorities for palliative care can contribute to addressing palliative care more
effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach
for addressing the needs of individuals with life-threatening illnesses from a holistic,
interdisciplinary perspective. For this project, we defined palliative care as an
approach that improves the quality of life of patients and families facing the problems
encountered in life-threatening illness by preventing and relieving suffering. Core
components of palliative care include providing relief from pain and other distressing
symptoms, affirming dying as a normal process, integrating psychological and spiritual
aspects of care, enhancing the quality of life of patients, and offering support systems
to patients and their families to help them live as fully as possible until death
occurs.Research suggests that palliative care results in positive patient outcomes, greater
patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the
World Health Organization, and the Institute of Medicine3–6 have identified the
development of a robust palliative care delivery system as a key public health issue
because of the documented ability of palliative care to deliver effective and efficient
patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the
public health implications of palliative care, acknowledged the growing burden of
advanced chronic illness and disease in older adults, and recommended key steps to
address the problem. This policy statement called for federal, state, and local efforts
to promote effective symptom management in populations with serious illness or at the
end of life. Other recommended initiatives included the development of a palliative care
workforce, educational programs to improve uptake and use of palliative and hospice
care, and research funding to support the expansion of palliative care initiatives.
Achieving these goals will require moving beyond traditional medical practices to
include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs
of individuals with advanced illness, significant knowledge gaps impede its reach and
effectiveness. Reports from scientific bodies and consensus workshops have highlighted
weaknesses in the literature and called for more research on palliative care and
improved research methods.7–10 Thus, although both interest in and demand for
palliative care are increasing, reviews of the knowledge base continue to lament the
lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers
who deliver palliative care. The systematic engagement of community practitioners in a
consensus process can lead to particularly useful and actionable recommendations for
research,13–15 which are greatly needed at this stage in the
development of the field. Therefore, to shed new light on research priorities in
palliative care, we used a structured, participatory method designed to solicit
practitioner input on research priorities: the research-to-practice consensus workshop
(RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should
be conducted to improve providers’ ability to deliver palliative care most
effectively. This model harnesses practice wisdom by engaging clinicians, agency staff,
and other practitioners with researchers in a process of articulating and refining
research questions and research priorities that honors scientific expertise and practice
wisdom. 相似文献