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51.
Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane 总被引:3,自引:6,他引:3
Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane. 相似文献
52.
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
53.
Methylation of TIMP3 in esophageal squamous cell carcinoma 总被引:1,自引:0,他引:1
Smith E De Young NJ Tian ZQ Caruso M Ruszkiewicz AR Liu JF Jamieson GG Drew PA 《World journal of gastroenterology : WJG》2008,14(2):203-210
AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China. METHODS: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2′-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by immunohistochemistry.
RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.
CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China. 相似文献
RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.
CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China. 相似文献
54.
Heron Jon Low Nicola Lewis Glyn Macleod John Ness Andy Waylen Andrea 《Archives of sexual behavior》2015,44(3):669-678
Archives of Sexual Behavior - Various factors are associated with sexual activity in adolescence and it is important to identify those that promote healthy and adaptive romantic and sexual... 相似文献
55.
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
56.
Soo Khai Ng MBBS John PM Wood DPhil Glyn Chidlow DPhil Guoge Han MBBS Thaksaon Kittipassorn MD Daniel J Peet PhD Robert J Casson DPhil FRANZCO 《Clinical & experimental ophthalmology》2015,43(4):367-376
The retina, like many cancers, produces energy from glycolysis even in the presence of oxygen. This phenomenon is known as aerobic glycolysis and eponymously as the Warburg effect. In recent years, the Warburg effect has become an explosive area of study within the cancer research community. The expanding knowledge about the molecular mechanisms underpinning the Warburg effect in cancer promises to provide a greater understanding of mammalian retinal metabolism and has motivated cancer researchers to target the Warburg effect as a novel treatment strategy for cancer. However, if the molecular mechanisms underlying the Warburg effect are shared by the retina and cancer, treatments targeting the Warburg effect may have serious adverse effects on retinal metabolism. Herein, we provide an updated understanding of the Warburg effect in mammalian retina. 相似文献
57.
58.
Intracellular pH Measurements of the Whole Head and the Basal Ganglia in Chronic Liver Disease: A Phosphorus-31 MR Spectroscopy Study 总被引:2,自引:0,他引:2
Patel N Forton DM Coutts GA Thomas HC Taylor-Robinson SD 《Metabolic brain disease》2000,15(3):223-240
The purpose of this study was to determine the intracellular pH of the whole head and in voxels localized to the basal ganglia
in patients with chronic liver disease using phosphorus-31 magnetic resonance spectroscopy (31P MRS). The study group compromised 82 patients with biopsy-proven cirrhosis (43 Child's grade A, 25 Child's grade B and 14
Child's grade C). Eleven subjects showed no evidence of neuropsychiatric impairment on clinical, psychometric and electrophysiological
testing, 37 showed evidence of minimal hepatic encephalopathy and 34 had overt hepatic encephalopathy. Unlocalized31P MRS of the whole head was performed in 48 patients and 10 healthy volunteers. Localized31P MRS of the basal ganglia was performed in the 34 patients and in 20 healthy volunteers. The intracellular pH values were
calculated from the chemical shift difference between the inorganic phosphate (Pi) and phosphocreatine (PCr) resonances. The percentage inorganic phosphate (%Pi), phosphocreatine (%PCr) and βNTP signals, relative to the total31P signal, and peak area ratios of inorganic phosphate and phosphocreatine, relative to βNTP were also measured. There were
no differences between patients and volunteers in intracellular pH in31P MR spectra measured from the whole head or the basal ganglia. There was no correlation between the severity of encephalopathy
(West Haven criteria) or liver dysfunction (Child score) and intracellular pH values. There was also no significant change
in the inorganic phosphate, phosphocreatine or βNTP resonances in spectra acquired from the whole head. However, in spectra
localized to the basal ganglia, there was a significant increase in mean Pi/NTP (p=0.02) and PCr/NTP (p=0.009). The mean %Pi and mean %PCr were also increased (p=0.06; p=0.05, respectively), but there was no significant change in mean %βNTP. When
the patient population was classified according to the severity of encephalopathy, those with overt disease had a higher mean
Pi/NTP and %Pi (p=0.03; p=0.01), compared to the reference population. Our results suggest that there are detectable bioenergetic abnormalities
in patients with minimal hepatic encephalopathy or stable, overt chronic hepatic encephalopathy, but any associated intracellular
pH change is probably a secondary, rather than a primary phenomenon. 相似文献
59.
Richmond L Rajappan K Voth E Rangavajhala V Earley MJ Thomas G Harris S Sporton SC Schilling RJ 《Journal of cardiovascular electrophysiology》2008,19(8):821-827
Introduction: The complex anatomy of the left atrium (LA) makes location of ablation catheters difficult using fluoroscopy alone, and therefore 3D mapping systems are now routinely used. We describe the integration of a CT image into the EnSite NavX System with Fusion and its validation in patients undergoing atrial fibrillation (AF) or left atrial tachycardia (AT) catheter ablation. Methods and Results: Twenty‐three patients (61 ± 9.2 years, 16 male) with paroxysmal (14) and persistent (8) AF and persistent (1) AT underwent ablation using CT image integration into the EnSite NavX mapping system with the EnSite Fusion Dynamic Registration software module. In all cases, segmentation of the CT data was accomplished using the EnSite Verismo segmentation tool, although repeat segmentation attempts were required in seven cases. The CT was registered with the NavX‐created geometry using an average of 24 user‐defined fiducial pairs (range 9 to 48). The average distance from NavX‐measured lesion positions to the CT surface was 3.2 ± 0.9 mm (median 2.4 mm). A large, automated, retrospective test using registrations with random subsets of each patient's fiducial pairs showed this average distance decreasing as the number of fiducial pairs increased, although the improvement ceased to be significant beyond 15 pairs. In confirmation, those studies which had used 16 or more pairs had a smaller average lesion‐to‐surface distance (2.9 ± 0.7 mm) than those using 15 or fewer (4.3 ± 0.8 mm, P < 0.02). Finally, for the 13 patients who underwent left atrial circumferential ablation (LACA), there was no significant difference between the circumference computed using NavX‐measured positions and CT surface positions for either the left pulmonary veins (178 ± 64 vs. 177 ± 60 mm; P = 0.81) or the right pulmonary veins (218 ± 86 vs. 207 ± 81 mm; P = 0.08). Conclusion: CT image integration into the EnSite NavX Fusion system was successful in all patients undergoing catheter ablation. A learning curve exists for the Verismo segmentation tool; but once the 3D model was created, the registration process was easily accomplished, with a registration error that is comparable with registration errors using other mapping systems with CT image integration. All patients went on to have subsequent successful ablation procedures. Where LACA was performed (13 patients), only four patients required segmental ostial lesions to achieve electrical isolation. 相似文献
60.
Abstract We examined object identification in two simultanagnosic patients, ES and GK. We show that the patients tended to identify animate objects more accurately than inanimate objects (Experiments 1 and 4). The patients also showed relatively good identification of objects that could be recognised from their global shape, but not objects whose recognition depended on their internal detail (Experiment 2). Indeed, the presence of local segmentation cues disrupted global identification (Experiment 3). Identification was aided, though, by the presence of surface colour and texture (Experiment 4). We suggest that the patients could derive global representations of objects that served to recognise animate items. In contrast, they were impaired at coding parts-based representations for the identification of inanimate objects. 相似文献