tbuckley/cabot-search huggingface dataset:
Geometric Vascular Remodeling After Balloon Angioplasty and β-Radiation Therapy
Authors: Manel Sabaté, Patrick W. Serruys, Willem J. van der Giessen, Jurgen M.R. Ligthart, Veronique L.M.A. Coen, I. Patrick Kay, Anthonie L. Gijzel, Alexander J. Wardeh, Ad den Boer, Peter C. Levendag
Journal: Circulation (1999)

Background —Endovascular radiation appears to inhibit intimal thickening after overstretching balloon injury in animal models. The effect of brachytherapy on vascular remodeling is unknown. The aim of the study was to determine the evolution of coronary vessel dimensions after intracoronary irradiation after successful balloon angioplasty in humans. Methods and Results —Twenty-one consecutive patients treated with balloon angioplasty and β-radiation according to the Beta Energy Restenosis Trial-1.5 were included in the study. Volumetric assessment of the irradiated segment and both edges was performed after brachytherapy and at 6-month follow-up. Intravascular ultrasound images were acquired by means of ECG-triggered pullback, and 3-D reconstruction was performed by automated edge detection, allowing the calculation of lumen, plaque, and external elastic membrane (EEM) volumes. In the irradiated segments, mean EEM and plaque volumes increased significantly (451±128 to 490.9±159 mm 3 and 201.2±59 to 241.7±74 mm 3 ; P =0.01 and P =0.001, respectively), whereas luminal volume remained unchanged (250.8±91 to 249.2±102 mm 3 ; P =NS). The edges demonstrated an increase in mean plaque volume (26.8±12 to 32.6±10 mm 3 , P =0.0001) and no net change in mean EEM volume (71.4±24 to 70.9±24 mm 3 , P =NS), resulting in a decrease in mean luminal volume (44.6±16 to 38.3±16 mm 3 , P =0.01). Conclusions —A different pattern of remodeling is observed in coronary segments treated with β-radiation after successful balloon angioplasty. In the irradiated segments, the adaptive increase of EEM volume appears to be the major contributor to the luminal volume at follow-up. Conversely, both edges showed an increase in plaque volume without a net change in EEM volume.
Should Human Beings Have Sex? Sexual Dimorphism and Human Enhancement
Authors: Robert Sparrow
Journal: The American Journal of Bioethics (2010)

Since the first sex reassignment operations were performed, individual sex has come to be, to some extent at least, a technological artifact. The existence of sperm sorting technology, and of prenatal determination of fetal sex via ultrasound along with the option of termination, means that we now have the power to choose the sex of our children. An influential contemporary line of thought about medical ethics suggests that we should use technology to serve the welfare of individuals and to remove limitations on the opportunities available to them. I argue that, if these are our goals, we may do well to move towards a "post sex" humanity. Until we have the technology to produce genuine hermaphrodites, the most efficient way to do this is to use sex selection technology to ensure that only girl children are born. There are significant restrictions on the opportunities available to men, around gestation, childbirth, and breast-feeding, which will be extremely difficult to overcome via social or technological mechanisms for the foreseeable future. Women also have longer life expectancies than men. Girl babies therefore have a significantly more "open" future than boy babies. Resisting the conclusion that we should ensure that all children are born the same sex will require insisting that sexual difference is natural to human beings and that we should not use technology to reshape humanity beyond certain natural limits. The real concern of my paper, then, is the moral significance of the idea of a normal human body in modern medicine.
Expiratory muscle pressure and breathing mechanics in chronic obstructive pulmonary disease
Authors: S. Yan, C. Sinderby, P. Bielen, J. Beck, N Comtois, P Sliwinski
Journal: European Respiratory Journal (2000)

Expiratory muscle recruitment is common in stable chronic obstructive pulmonary disease (COPD) patients. Due to airway obstruction, there is little reason to believe that active expiration in COPD would be mechanically effective in lowering operating lung volume. The physiological significance of expiratory muscle recruitment in COPD, therefore, remains unknown. The purpose of this study was to assess, in COPD patients breathing at rest, the effect of expiratory muscle contraction on force generating ability of the diaphragm. The force generating ability of the diaphragm was evaluated from its pressure swing (Pdi) for a given diaphragm electrical activity (Edi), where Edi was normalized as % of its maximal value (Pdi/Edi/Edi,max). Phasic expiratory muscle contraction was measured as the total expiratory rise in gastric pressure (Pga,exp.rise). Nineteen seated patients with moderate to severe COPD, participated in the study and 10 exhibited phasic rise in Pga during expiration with a mean Pga,exp.rise of 1.91+/-0.89 cmH2O. The patients were thus divided into passive expiration (PE) and active expiration (AE) groups. There was no significant difference in various lung function and breathing pattern parameters between the two groups. Pdi/Edi/Edi,max was 0.63+/-0.07 and 0.54+/-0.07 cmH2O/% in PE and AE groups, respectively, and was not significantly different between each other. Compared with PE group, AE group not only recruited expiratory muscles, but also preferentially recruited inspiratory rib cage muscles and derecruited the diaphragm. The results do not support a significant improvement of the force-generating ability of the diaphragm by phasic contraction of expiratory muscles at rest in chronic obstructive pulmonary disease patients.
Association of Preoperative Plasma Levels of Vascular Endothelial Growth Factor and Soluble Vascular Cell Adhesion Molecule-1 With Lymph Node Status and Biochemical Progression After Radical Prostatectomy
Authors: Shahrokh F. Shariat, Veronica A. Anwuri, Dolores J. Lamb, Nina V. Shah, Thomas M. Wheeler, Kevin M. Slawin
Journal: Journal of Clinical Oncology (2004)

Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis.Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer.Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P <.001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P <.001). VEGF levels were elevated in patients with biopsy and final Gleason sum > or = 7 (P =.036 and P =.020, respectively) and extraprostatic extension (P =.047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P <.001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P =.014 and P =.039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P =.019).Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.
Msx2 and Necdin Combined Activities Are Required for Smooth Muscle Differentiation in Mesoangioblast Stem Cells
Authors: Silvia Brunelli, Enrico Tagliafico, Fernanda G. De Angelis, Rossana Tonlorenzi, Silvia Baesso, Sergio Ferrari, Michio Niinobe, Kazuaki Yoshikawa, Robert J. Schwartz, Irene Bozzoni, Stefano Ferrari, Giulio Cossu
Journal: Circulation Research (2004)

Little is known about the molecular mechanism underlying specification and differentiation of smooth muscle (SM), and this is, at least in part, because of the few cellular systems available to study the acquisition of a SM phenotype in vitro. Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm, including SM. We performed a DNA microarray analysis of a mesoangioblast clone that spontaneously expresses an immature SM phenotype and compared it with a sister clone mainly composed of undifferentiated progenitor cells. This study allowed us to define a gene expression profile for "stem" cells versus smooth muscle cells (SMCs) in the absence of differentiation inducers such as transforming growth factor beta. Two transcription factors, msx2 and necdin, are expressed at least 100 times more in SMCs than in stem cells, are coexpressed in all SMCs and tissues, are induced by transforming growth factor beta, and, when coexpressed, induce a number of SM markers in mesoangioblast, fibroblast, and endothelial cell lines. Conversely, their downregulation through RNA interference results in a decreased expression of SM markers. These data support the hypothesis that Msx2 and necdin act as master genes regulating SM differentiation in at least a subset of SMCs.
Pseudotumour of the lung caused by Mycobacterium malmoense infection in an HIV positive patient
Authors: K Yoganathan, M W Elliott, J Moxham, M Yates, A L Pozniak
Journal: Thorax (1994)

Abstract A case of pulmonary Mycobacterium malmoense infection presenting as a pseudotumour of the lung in a severely immunosuppressed HIV infected patient is reported.
Mouse embryogenesis requires the tissue factor extracellular domain but not the cytoplasmic domain
Authors: Graham C.N. Parry, Nigel Mackman
Journal: Journal of Clinical Investigation (2000)

Recent studies indicate that tissue factor (TF) acts in embryogenesis, metastasis, and angiogenesis. Three independent groups showed that targeted disruption of the murine TF (mTF) gene results in 90% lethality of mTF null embryos at embryonic days 9.5–10.5. We have demonstrated that expression of wild-type human TF (hTF) from a minigene rescues the embryonic lethality of mTF null embryos. To investigate the role of TF in embryogenesis, we made mutant hTF minigenes whose products either bound FVII/VIIa at a reduced level or lacked the cytoplasmic domain. Two independent transgenic lines expressing the hTF extracellular domain mutant failed to rescue the embryonic lethality of mTF null embryos, suggesting that FVII/VIIa binding by TF, proteolytic activity by the TF/FVIIa complex, or both were required for embryogenesis. In contrast, two transgenic lines expressing the hTF cytoplasmic domain mutant rescued the embryonic lethality of mTF null embryos, indicating that the cytoplasmic domain of TF was not required for embryogenesis. We propose that TF/FVIIa-dependent extracellular protease activity is required for embryogenesis.
Involvement of Plasmacytoid Dendritic Cells in the Immunological Response Against Orf Infection
Authors: Dana Saadeh, Mazen Kurban, Abdul-Ghani Kibbi, Ossama Abbas
Journal: JAMA Dermatology (2014)

Plasmacytoid dendritic cells (PDCs) are specialized dendritic cells with a significant role in antiviral resistance. 1,2lasmacytoid dendritic cells have never been studied in orf infection.Methods | Our institutional review board approved the study.Archival materials with a diagnosis of orf infection and inflamed molluscum contagiosum (I-MC) were retrieved from our dermatopathology database.A total of 5 orf and 5 comparable I-MC cases fit the inclusion criteria.As described before, 2 immunohistochemical analysis was performed on sections obtained from formalin-fixed, paraffin-embedded tissue using antibodies to BDCA-2 (mouse IgG1, clone 124B3.13,dilution 1:50; Dendritics) and myxovirus protein A (MxA) (M143, University of Freiburg, Germany; dilution 1:100). 1,2Although anti-BDCA-2 antibody is a specific PDC marker, anti-MxA antibody indirectly assesses PDC activity because MxA is an interferon (IFN)-α/β-inducible intracellular protein well established as a surrogate marker for local type I IFN production. 1,2We used a semiquantitative scoring system to assess PDC recruitment and MxA staining (Table ).Results | Demographic data and results are summarized in the Table .Although PDCs were present in all orf (Figure ) and I-MC cases, they were significantly less abundant in orf cases.Although the difference was not significant, orf cases tended to have less type I IFN production than I-MC cases.Discussion | Plasmacytoid dendritic cells exhibit plasma cell morphologic characteristics and express CD4, CD123, BDCA-2, and toll-like receptors 7 (TLR-7) and TLR-9 in endosomal compartments. 1They are capable of producing large quantities of type I IFNs against pathogenic agents. 1 They not only
Relationship Between Delay in Performing Direct Coronary Angioplasty and Early Clinical Outcome in Patients With Acute Myocardial Infarction
Authors: Peter B. Berger, Stephen G. Ellis, David R. Holmes, Christopher B. Granger, Douglas A. Criger, Amadeo Betriu, Eric J. Topol, Robert M. Califf
Journal: Circulation (1999)

Background —Time to treatment with thrombolytic therapy is a critical determinant of mortality in acute myocardial infarction. Little is known about the relationship between the time to treatment with direct coronary angioplasty and clinical outcome. The objectives of this study were to determine both the time required to perform direct coronary angioplasty in the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb) trial and its relationship to clinical outcome. Methods and Results —Patients randomized to direct coronary angioplasty (n=565) were divided into groups based on the time between study enrollment and first balloon inflation. Patients randomized to angioplasty who did not undergo the procedure were also analyzed. The median time from study enrollment to first balloon inflation was 76 minutes; 19% of patients assigned to angioplasty did not undergo an angioplasty procedure. The 30-day mortality rate of patients who underwent balloon inflation ≤60 minutes after study enrollment was 1.0%; 61 to 75 minutes after enrollment, 3.7%; 76 to 90 minutes after enrollment, 4.0%; and ≥91 minutes after enrollment, 6.4%. The mortality rate of patients assigned to angioplasty who never underwent the procedure was 14.1% ( P =0.001). Logistic regression analysis revealed that the time from enrollment to first balloon inflation was a significant predictor of mortality within 30 days; after adjustment for differences in baseline characteristics, the odds of death increased 1.6 times ( P =0.008) for a movement from each time interval to the next. Conclusions —The time to treatment with direct PTCA, as with thrombolytic therapy, is a critical determinant of mortality.
Sonic Hedgehog Signaling Pathway Is Activated in ALK-Positive Anaplastic Large Cell Lymphoma
Authors: Rajesh R. Singh, Jeong Hee Cho-Vega, Yogesh Davuluri, Shuguang Ma, Fatan Kasbidi, Cristiane Milito, Patrick A. Lennon, Elias Drakos, L. Jeffrey Medeiros, Rajyalakshmi Luthra, Francisco Vega
Journal: Cancer Research (2009)

Deregulation of the sonic hedgehog (SHH) signaling pathway has been implicated in several cancers but has not been explored in T-cell lymphomas. Here, we report that the SHH/GLI1 signaling pathway is activated in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL). We show that SHH, but not its transcriptional effector GLI1, is amplified in ALK+ ALCL tumors and cell lines, and that SHH and GLI1 proteins are highly expressed in ALK+ ALCL tumors and cell lines. We also show that inhibition of SHH/GLI1 signaling with cyclopamine-KAAD, as well as silencing GLI1 gene expression by small interfering (si)RNA, decreased cell viability and clonogenicity of ALK+ ALCL cells. Transfection of wild-type or mutant NPM-ALK into 293T cells showed that only wild-type NPM-ALK increased GLI1 protein levels and activated SHH/GLI1 signaling as shown by increase of CCND2 mRNA levels. Inhibition of ALK tyrosine kinase and phosphatidylinositol 3-kinase (PI3K)/AKT or forced expression of pAKT down-regulated or up-regulated SHH/GLI1 signaling, respectively. Inhibition of GSK3beta in 293T cells also increased protein levels of GLI1. In conclusion, the SHH/GLI1 signaling pathway is activated in ALK+ ALCL. SHH/GLI1 activation is the result of SHH gene amplification and is further mediated by NPM-ALK through activation of PI3K/AKT and stabilization of GLI1 protein. There is a positive synergistic effect between the SHH/GLI1 and PI3K/AKT pathways that contributes to the lymphomagenic effect of NPM-ALK.
A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: A randomized trial
Authors: Chiun Hsu, Chao A. Hsiung, Ih-Jen Su, Wei-Shou Hwang, Ming-Chung Wang, Sheng-Fung Lin, Tseng-Hsi Lin, Hui-Hua Hsiao, Ji-Hsiung Young, Ming-Chih Chang, Yu-Min Liao, Chi-Cheng Li, Hung-Bo Wu, Hwei-Fang Tien, Tsu-Yi Chao, Tsang-Wu Liu, Ann-Lii Cheng, Pei-Jer Chen
Journal: Hepatology (2008)

Lamivudine is effective to control hepatitis B virus (HBV) reactivation in HBV-carrying cancer patients who undergo chemotherapy, but the optimal treatment protocol remains undetermined. In this study, HBV carriers with newly diagnosed non-Hodgkin's lymphoma (NHL) who underwent chemotherapy were randomized to either prophylactic (P) or therapeutic (T) lamivudine treatment groups. Group P patients started lamivudine from day 1 of the first course of chemotherapy and continued treatment until 2 months after completion of chemotherapy. Group T patients received chemotherapy alone and started lamivudine treatment only if serum alanine aminotransferase (ALT) levels elevated to greater than 1.5-fold of the upper normal limit (ULN). The primary endpoint was incidence of HBV reactivation during the 12 months after starting chemotherapy. During chemotherapy, fewer group P patients had HBV reactivation (11.5% versus 56%, P = 0.001), HBV-related hepatitis (7.7% versus 48%, P = 0.001), or severe hepatitis (ALT more than 10-fold ULN) (0 versus 36%, P &lt; 0.001). No hepatitis-related deaths occurred during protocol treatment. Prophylactic lamivudine use was the only independent predictor of HBV reactivation. After completion of chemotherapy, the incidence of HBV reactivation did not differ between the 2 groups. Two patients, both in group P, died of HBV reactivation–related hepatitis, 173 and 182 days, respectively, after completion of protocol treatment. When compared with an equivalent group of lamivudine-naïve lymphoma patients who underwent chemotherapy, therapeutic use of lamivudine neither reduced the severity of HBV-related hepatitis nor changed the patterns of HBV reactivation. Conclusion: Prophylactic lamivudine use, but not therapeutic use, reduces the incidence and severity of chemotherapy-related HBV reactivation in NHL patients.
Regional lung function in patients with increased unilateral transradiancy of the lung in the presence of cardiac disease
Authors: W. A. Littler, C. C. Evans, J. B. Meade
Journal: Thorax (1972)

Regional lung function has been studied with xenon-133 in two patients with unilateral transradiancy of the lung and coincidental cardiac disease. One patient had severe mitral stenosis with pulmonary venous and pulmonary arterial hypertension, the other had a secundum type of atrial septal defect with a pulmonary blood flow which was increased to 25 litres per minute. In both instances the overall perfusion of the transradiant lung was diminished but the regional distribution of blood flow was the same within both the `normal9 and the transradiant lung. In the patient with mitral stenosis there was an abnormal increase in upper zone perfusion resulting in a reversal of the normal pattern of pulmonary blood flow while in the patient with an atrial septal defect the blood flow difference between the upper and lower zones was decreased and thus the normal vertical gradient was less. These studies suggest that the hypoplastic pulmonary arteries in the transradiant lung reacted in the same way to alterations in pressure and flow as the vessels in the other lung.
Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats
Authors: B. Tyler, S. Wadsworth, V. Recinos, V. Mehta, A. Vellimana, K. Li, J. Rosenblatt, H. Do, G. L. Gallia, I.-M. Siu, R. T. Wicks, M. A. Rudek, M. Zhao, H. Brem
Journal: Neuro-Oncology (2011)

Rapamycin, an anti-proliferative agent, is effective in the treatment of renal cell carcinoma and recurrent breast cancers. We proposed that this potent mammalian target of rapamycin inhibitor may be useful for the treatment of gliomas as well. We examined the cytotoxicity of rapamycin against a rodent glioma cell line, determined the toxicity of rapamycin when delivered intracranially, and investigated the efficacy of local delivery of rapamycin for the treatment of experimental malignant glioma in vivo. We also examined the dose-dependent efficacy of rapamycin and the effect when locally delivered rapamycin was combined with radiation therapy. Rapamycin was cytotoxic to 9L cells, causing 34% growth inhibition at a concentration of 0.01 µg/mL. No in vivo toxicity was observed when rapamycin was incorporated into biodegradable caprolactone-glycolide (35:65) polymer beads at 0.3%, 3%, and 30% loading doses and implanted intracranially. Three separate efficacy studies were performed to test the reproducibility of the effect of the rapamycin beads as well as the validity of this treatment approach. Animals treated with the highest dose of rapamycin beads tested (30%) consistently demonstrated significantly longer survival durations than the control and placebo groups. All dose-escalating rapamycin bead treatment groups (0.3%, 3% and 30%), treated both concurrently with tumor and in a delayed manner after tumor placement, experienced a significant increase in survival, compared with controls. Radiation therapy in addition to the simultaneous treatment with 30% rapamycin beads led to significantly longer survival duration than either therapy alone. These results suggest that the local delivery of rapamycin for the treatment of gliomas should be further investigated.
Shared adaptiveness is not group adaptation
Authors: Cédric Paternotte
Journal: Behavioral and Brain Sciences (2013)

Abstract Climate stresses and monetary resources seem to lead to different collective adaptations. However, the reference to adaptation and to ambiguous collective dimensions appears premature; populations may entertain nothing more than shared adaptiveness. At this point, the intricacy of the underlying evolutionary processes (cultural selection, fitness-utility decoupling) very much obscures any diagnosis based on correlations.
Racial disparity in arthroplasty remains disjointed
Authors: Matthew J Koster
Journal: Annals of the Rheumatic Diseases (2014)

I read with interest the article entitled ‘Racial disparities in knee and hip total joint arthroplasty: an 18-year analysis of national medicare data’ by Singh et al .1 I congratulate the authors for successfully contributing to the increasing literature of racial disparity in total joint arthroplasty (TJA) research by analysing trends over an 18-year period and including both usage and outcomes. The persistently reduced standardised utilisation rates among black patients for both primary and revision total knee (TKA) and total hip arthroplasty (THA) procedures throughout the entire duration of the study are concerning; however, it is even more alarming …