tbuckley/cabot-search huggingface dataset:
Binding of avian IgY to type VII collagen does not activate complement and leucocytes and fails to induce subepidermal blistering in mice
Authors: A. Sesarman, S. Mihai, M.T. Chiriac, F. Olaru, A.G. Sitaru, J.M. Thurman, D. Zillikens, C. Sitaru
Journal: British Journal of Dermatology (2008)

Background Epidermolysis bullosa acquisita (EBA) is a severe autoimmune skin disease characterized by tissue-bound and circulating autoantibodies to type VII collagen, the major component of anchoring fibrils. When passively transferred into mice, rabbit IgG against type VII collagen induces Fc-dependent activation of complement, the recruitment of leucocytes into the skin, and subepidermal blistering. In addition to these inflammatory mechanisms, clinical and experimental evidence suggests that antibodies against type VII collagen might induce blisters by disrupting the ligand function of type VII collagen by an Fc-independent mechanism. Objectives To study noninflammatory mechanisms of blister formation in experimental EBA. Methods We generated chicken IgY antibodies directed to recombinant type VII collagen and examined their pathogenic activity using ex vivo and animal models. Results Mice injected with these chicken IgY antibodies showed binding of the antibodies to the dermal–epidermal junction of skin sections. However, IgY antibodies did not fix complement C3 in enzyme-linked immunosorbent assay and immunofluorescence complement-binding assays. In addition, IgY antibodies did not induce dermal–epidermal separation ex vivo. Following their passive transfer into Balb/c mice, chicken IgY antibodies against type VII collagen bound at the dermal–epidermal junction, but, in contrast to rabbit IgG, did not fix complement C3, recruit granulocytes, or induce skin blisters. Conclusions These findings demonstrate that binding of avian IgY to type VII collagen is not pathogenic in vivo and strongly suggest that in experimental EBA, antibodies to type VII collagen induce blisters not by direct disruption of the ligand function of type VII collagen, but rather by an Fc-dependent engagement of humoral and cellular inflammatory factors.
Feasibility of implanted upper airway nerve stimulation therapy to treat obstructive sleep apnea
Authors: Wilfried De Backer, Johan Verbraecken, Joachim Maurer, Lennart Knaack, Arie Oliven
Journal: European Respiratory Journal (2011)

We studied a second generation Upper Airway Stimulation system (Inspire Medical Systems, Inc) in OSA with an attempt to identify baseline predictors of therapy success.  Moderate-to-severe OSA patients who failed, or were intolerant of, continuous positive airway pressure were included. The study was conducted in 2 phases. In Phase 1, patients were enrolled with broad selection criteria. In Phase 2, patients were enrolled using selection criteria derived from the experience in Phase 1.  20 of 22 patients enrolled in Phase 1 (2 exited the study) were examined for factors predictive of a response (AHI   We conclude that site of obstruction, baseline AHI, and BMI may be important therapy success predictors.
Transmission ratio distortion at the INS-IGF2 VNTR
Authors: Iain A. Eaves, Simon T. Bennett, Peter Forster, Karin M. Ferber, David Ehrmann, Amanda J. Wilson, Sumit Bhattacharyya, Anette-G. Ziegler, Bernd Brinkmann, John A. Todd
Journal: Nature Genetics (1999)
Recombinant human growth hormone poly(lactic-co-glycolic acid) microsphere formulation development1This manuscript is dedicated to the memory of Dr. Michael J. Cronin. Dr. Cronin was a brilliant endocrine scientist with an incredible ability to objectively evaluate any problem, no matter how complex. His spirit and knowledge contributed to the success of the work described herein and his wisdom continues to guide those of us fortunate enough to have known him.1
Authors: Jeffrey L Cleland, OluFunmi L Johnson, Scott Putney, Andrew J.S Jones
Journal: Advanced Drug Delivery Reviews (1997)
Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease
Authors: Chang-Hyuk Kwon, Xiaoyan Zhu, Junyuan Zhang, Lori L. Knoop, Ruby Tharp, Richard J. Smeyne, Charles G. Eberhart, Peter C. Burger, Suzanne J. Baker
Journal: Nature Genetics (2001)
Focal Fat Sparing of the Liver
Authors: Chidambaram Natrajan Balasubramanian Harisankar
Journal: Clinical Nuclear Medicine (2014)

Fat spared area of liver can appear as focal areas of elevated FDG uptake on a PET scan. This may mimic metastases. PET scan performed for metastatic workup in a 35-year-old female patient, a case of exocrine tumor of the pancreas, showed focal areas of increased FDG uptake. Contrast-enhanced CT performed as a part of the PET/CT study showed enlarged fatty liver with focal hyperdense areas suggesting fat sparing. Sulfur colloid scan showed physiological colloid uptake in the suspicious areas indicating preserved Kupffer cell function. The patient is on close follow-up without any evidence of metastatic disease.
Abstract 2736: Thymidine catabolic and salvage pathways are responsible for the heterogeneity of anticancer agent dT-QX in liver cancer cells
Authors: Qibing Zhou, Qiong Wei, Dejun Zhang
Journal: Cancer Research (2014)

Abstract Thymidine analog 3′-deoxythymidine phenylquinoxaline conjugate (dT-QX) can selectively kill cancer cell lines while is low cytotoxic towards normal liver cells. However, the cytotoxicity of dT-QX varied among cell lines of the same type cancer. Thus, the mechanism of the heterogeneity towards dT-QX was investigated. Considering that dT-QX is a thymidine analog, pathways of cellular thymidine metabolism were studied including catabolic and salvage pathways. The expression levels of enzymes of these two pathways among different cell lines of liver cancer were determined and compared. In addition, the impact on the activity of dT-QX by overexpressing and silencing the enzymes of these two pathways was assessed. Furthermore, a series of dT-QX analogs were synthesized and tested to reveal the potential structure-activity relationship to address the heterogeneity. Our initial results indicated that there was dramatic difference on the enzyme levels of thymidine catabolic and salvage pathways among the different cell lines of liver cancer. Modulation of the level of these enzymes resulted in significant impact on the activity of dT-QX. Variation on the cytotoxic activity was even observed with different structural analogs tested on these liver cancer cell lines. Our data suggested that thymidine catabolic and salvage pathways counteracted toward each other and thus were responsible for the heterogeneity of dT-QX in liver cancer cells. Citation Format: Qibing Zhou, Qiong Wei, Dejun Zhang. Thymidine catabolic and salvage pathways are responsible for the heterogeneity of anticancer agent dT-QX in liver cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2736. doi:10.1158/1538-7445.AM2014-2736
772. Adenoviral-Mediated Antioxidant Gene Transfer: A Gene Therapy Approach towards Diminishing Pancreatic β-Cell Susceptibility to Cytokine-Induced Oxidative Damage
Authors: Cillian T. McCabe, Timothy O'Brien
Journal: Molecular Therapy (2004)

Objective: To investigate the effect of single and combined antioxidant gene overexpression on β-cell viability following cytokine exposure in a rat insulinoma (RIN) cell line.
Peri-operative Anti-thrombotic Therapy and Clinical Outcomes in Patients With Prior Coronary Stenting Undergoing Non-Cardiac Surgery
Authors: Nicholas L. Cruden, Chun H. Teh, Jon L. Rodrigues, Scott A. Harding, Jill P. Pell, Andrew D. Flapan, David E. Newby
Journal: Circulation (2009)

Background: Non-cardiac surgery performed following coronary stent implantation is associated with an increased risk of cardiovascular events. This risk is greatest for up to 8 weeks following stent implantation. The influence of anti-thrombotic therapy on outcomes in patients undergoing surgery beyond 8 weeks remains to be determined.  Methods: We examined clinical outcomes for 128 patients who underwent non-cardiac surgery at least 8 weeks following coronary stent implantation in Edinburgh between November 2003 and December 2008. The primary endpoint was death, acute coronary syndrome (ACS) or stroke occurring within 30 days of surgery.  Results: Patients were predominantly male (73%) with a mean age of 66 years. Twenty-three (18%) received at least 1 drug-eluting stent. The median duration from stent implantation to surgery was 15 months (range 2–51). The primary endpoint occurred in 9 patients (8 ACS and 1 stroke). Patients who suffered a cardiovascular event were older (74±9 vs 65±10 years, p=0.02) but had similar comorbidities and index coronary revascularization profiles compared to those who did not. Thirty-eight (30%) patients received no oral anti-platelet agent peri-operatively, 78 (61%) received 1, and 12 (9%) received 2 agents. Patients receiving no anti-platelet therapy peri-operatively had more cardiovascular events compared to patients treated with at least 1 anti-platelet agent (16% vs 3%, p=0.02). Pre-operative discontinuation of aspirin was associated with more cardiovascular events compared to maintenance of therapy (16% vs 4%, p=0.04). There were no differences in peri-operative anti-platelet therapy or outcomes according to stent type (bare metal vs drug-eluting) and no association between anti-platelet therapy and bleeding. Patients treated with low-molecular-weight heparin peri-operatively had more major bleeding (18% vs 6%, p=0.04).  Conclusions: Patients undergoing non-cardiac surgery at least 8 weeks following coronary stent implantation should be maintained on at least 1 anti-platelet agent peri-operatively. Pre-operative discontinuation of aspirin should be avoided. Low-molecular-weight heparin use appears to increase major peri-operative bleeding without preventing cardiovascular events.
Abstract 13300: Quantitative Coronary Plaque Analysis on Coronary Computed Tomography Can Detect High-Risk Plaque Characteristics Associated with Acute Coronary Syndrome - Results from the ROMICAT II Trial
Authors: Maros Ferencik, Stefan B Puchner, Michael T Lu, Pal Maurovich-Horvat, Thomas Mayrhofer, Ting Liu, Khristine Ghemigian, Pieter Kitslaar, Alexander Broersen, Udo Hoffmann
Journal: Circulation (2014)

Introduction:  Novel analytical methods in coronary computed tomography angiography (CCTA) permit quantitative assessment of coronary atherosclerotic plaque and detection of high-risk features. We determined the association of high-risk plaque features with the outcome of acute coronary syndrome (ACS) in patients with acute chest pain.   Methods:  We studied 501 patients who presented to the emergency department with acute chest pain, negative troponin and electrocardiogram at the time of presentation, and were randomized to the CCTA arm of the ROMICAT II trial. Quantitative analysis was performed in 260 patients in whom coronary plaques were detected by visual assessment. Readers used a semi-automated software (QAngio, CT RE 2.0, MEDIS Medical Imaging Systems BV) to measure high-risk plaque features (volume of plaque with    Results:  The baseline characteristics and quantitative plaque analysis stratified by ACS are summarized in the Table. There were more men in the ACS group. In univariate analysis, patients with ACS had larger volume of plaque with 70%, and minimal luminal area    Conclusions:  Quantitative measures of high-risk plaque (volume of plaque with low HU
Teach yourself statistics
Authors: Christopher Martyn
Journal: BMJ (2001)

A glance at this week's (or any week's) BMJ will show that medical research inevitably involves statistics. In his self help book of the 1930s, Mathematics for the Million , Lancelot Hogben included a chapter on statistics entitled “The Arithmetic of Human Welfare”—a warm, almost touchy-feely description of a subject that many doctors still regard as repellently algebraic. Unfortunately the …
Modeling prostate epithelial cancer cells in three-dimensional cultures in Matrigel.
Authors: Marcia V. Fournier, Xueping Zhang, Joy L. Ware, Mina J. Bissell, Zendra E. Zehner
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Growth of prostate epithelial cells in three-dimensional (3D) culture allows cells to form structures that more closely resemble their in vivo architecture. This permits further investigation into signaling pathways that control tumorigenesis in a biologically relevant context. In this study our objective was to assess whether the 3D assay (Petersen et al.1992) recapitulates the growth characteristics of human prostate epithelial cell lines in vivo . We used three human prostate epithelial cell lines, all derived from the same lineage: P69, an SV40 large T antigen immortalized human nonmalignant epithelial cell line that is non-tumorigenic; M12, a highly tumorigenic and metastatic subline derived from the P69 line, which displays a novel 16;19 chromosomal translocation resulting in the deletion of one copy of 19p-q13.1; and M12(F6), a slow growing, poorly tumorigenic subline created from M12 by the stable re-introduction of an intact human chromosome 19. The non-tumorigenic P69 line, when grown in Matrigel, organized into spheroids, commonly called acini, with a clearly defined lumen. Moreover, immunostaining with antibodies to α6- and β1-integrins showed polarization typical of glandular epithelium. The tumorigenic and metastatic M12 subline developed into highly disorganized clusters of cells exhibiting no polarization. The M12(F6) subline, which was converted to a slow growing and poorly tumorigenic line by the re-introduction of chromosome 19, reverted to forming acini-like structures with limited polarity. In the presence of the β1-integrin inhibitory antibody, AIIB2, M12 cells also reverted to forming acini. These findings indicate that growth in 3D culture closely parallels the phenotype of these prostate cells as observed in vivo in athymic nude mice, i.e., the inability to form organized acini with polarized epithelial structure in 3D parallels tumorigenicity. Moreover, β1-integrin must play a key role in acini formation as has been shown previously for the breast cells in 3D cultures (Weaver et al.1977).. These results suggest a highly relevant model system for further investigation of cancer genes and signaling pathways important to tumorigenesis and/or metastasis. This work was supported in part by DOD grant PC040763 to ZEZ and by funding from the DOE, NIH and DOD to MJB.
Prolonged cyclosporine administration after antithymocyte globulin delays but does not prevent relapse in severe aplastic anemia
Authors: Phillip Scheinberg, Olga Rios, Priscila Scheinberg, Barbara Weinstein, Colin O. Wu, Neal S. Young
Journal: American Journal of Hematology (2014)

In severe aplastic anemia, approximately one‐third of responders to standard horse antithymocyte globulin (h‐ATG) plus cyclosporine (CsA) will relapse. Anecdotal experience has suggested that a gradual CsA taper might avoid relapse, but this practice has not been rigorously assessed prospectively. In 2003, we adopted a strategy to taper CsA beyond 6 months, with the intention to reduce hematologic relapse compared with our extensive historical experience. In total, 102 patients received h‐ATG/CsA for 6 months in two sequential clinical protocols: 67 patients (66%) responded and all had the CsA dose tapered per protocol over the subsequent 18 months (total of 2 years). The rate of relapse at 5 years was 33% (95% CI 27–44%), which did not differ from our large historical relapse experience (patients treated before 2003) of 30–40%, in protocols in which CsA was simply discontinued at 6 months. However, time to relapse was prolonged by about 1 year with the longer CsA course. The rates of clonal evolution and overall survival did not differ between the two cohorts. We infer from this large prospective study that CsA taper as implemented delayed but did not prevent relapse. The kinetics of relapse with long course CsA does suggest that a lower long‐term dose might be adequate to maintain patients in remission. Am. J. Hematol. 89:571–574, 2014. © Published 2014.
Abstract 18071: Integrating Three-Dimensional Imaging for Aortic Valve Stenosis Assessment. A Pilot Multimodality Imaging Study Comparing Classic vs. Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis
Authors: Joao L Cavalcante, Mitika T Patel, William E Katz, John T Schindler, Frederick W Crock, Sameer J Khandhar
Journal: Circulation (2013)

BACKGROUND: Assessment of aortic stenosis (AS) severity is critical for treatment decisions but challenging in patients with severe AS (aortic valve area, AVA &lt;1.0 cm2) and low gradients (mean AV gradient &lt;40 mmHg). We sough to evaluate the incremental utility of 3D multidetector computed tomography (MDCT) over TTE for assessment of AS severity in patients with either depressed (classic low-flow, low-gradient, CLFLG, LVEF &lt;50%) or preserved LV systolic function (paradoxical low-flow, low-gradient, PLFLG, LVEF ≥50%) is unknown. METHODS: Sixteen patients who underwent TTE, invasive hemodynamics with a right heart catheterization and dual lumen pigtail catheter, and MDCT studies within 30 days were prospectively studied (10 CLFLG and 6 PLFLG). Mean age was 76±10 years with 26% females. TTE parameters included LVEF, systolic LVOT diameter (LVOT-D) and conventional AV Doppler assessment. MDCT evaluated ratio of maximal to minimal LVOT-D (eccentricity index), mean systolic LVOT-D, and AVA by planimetry. Corrected AVA was calculated by substituting the MDCT-derived mean LVOT-D into continuity equation (MDCT-AVA). RESULTS: Figure 1 shows hemodynamics and imaging parameters measured. Despite good correlation between TTE-AVA and MDCT-AVA (r=0.85, p&lt;0.0001), AVA was underestimated in 10/16 of patients by either TTE or invasive hemodynamics, irrespective of the baseline LVEF (p &lt; 0.0001 for both). Dimensionless index also correlated better with MDCT-AVA (r=0.71, p=0.002) then with TTE-derived AVA (r=0.58, p=0.003) or by cath-derived AVA (r=0.47, p=0.02). CONCLUSION: In patients with severe AS and low-gradients, MDCT imaging revealed eccentric LVOT in most patients, resulting in underestimation of 2D TTE-AVA. Integration of 3D imaging dataset with either 3D-transesophageal echocardiography or MDCT may improve AS severity classification of these challenging patients. Larger cohort studies will be needed to ascertain the impact on treatment decisions.
Baseline IgG Antibody Titers to <i>Chlamydia pneumoniae</i>, <i>Helicobacter pylori</i>, Herpes Simplex Virus, and Cytomegalovirus and the Risk for Cardiovascular Disease in Women
Authors: Paul M. Ridker, Charles H. Hennekens, Julie E. Buring, Ruth Kundsin, Jessie Shih
Journal: Annals of Internal Medicine (1999)

Background: Results of cross-sectional and retrospective studies have suggested that chronic infection may be a risk factor for cardiovascular disease. However, prospective data evaluating the relation between baseline antibody titers against various plausible agents and risk for cardiovascular disease are sparse, particularly among women. Objective: To determine whether previous exposure to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, or cytomegalovirus is associated with increased risk for cardiovascular events. Design: Prospective, nested, case–control study. Setting: Women's Health Study. Participants: Apparently healthy postmenopausal women. Measurements: IgG antibody titers against C. pneumoniae, H. pylori, herpes simplex virus, and cytomegalovirus were measured in baseline blood samples obtained from 122 study participants who subsequently reported a first cardiovascular event (case-patients) and 244 participants matched for age and smoking status who did not report a cardiovascular event (controls) during 3 years of follow-up. Results: Little evidence was found of an association between risk for cardiovascular events and baseline IgG seropositivity for antibodies against C. pneumoniae (rate ratio, 1.1 [95% CI, 0.7 to 1.8]), H. pylori (rate ratio, 0.90 [CI, 0.6 to 1.4]), herpes simplex virus (rate ratio, 1.2 [CI, 0.6 to 2.1]), and cytomegalovirus (rate ratio, 0.9 [CI, 0.6 to 1.5]). In addition, there was little evidence of an association between a participant's total number of infections and subsequent cardiovascular risk (P > 0.2). Conclusion: In apparently healthy postmenopausal women, little evidence was found that previous infection, as measured by IgG antibody titers to C. pneumoniae, H. pylori, herpes simplex virus, and cytomegalovirus, is associated with subsequent risk for cardiovascular disease.
Depth profiling of stratum corneum biophysical and molecular properties
Authors: D. Mohammed, P.J. Matts, J. Hadgraft, M.E. Lane
Journal: British Journal of Dermatology (2011)

The barrier function of the skin may be characterized by a number of biophysical and molecular methods. Variation in the barrier properties as a function of depth has not been explored in detail.To characterize changes in corneocyte surface area, corneocyte maturity, selected protease activities and transepidermal water loss (TEWL) in the ventral forearm with increasing depth.The left mid-ventral forearm of 22 healthy volunteers was selected as the study site. After tape stripping, corneocyte maturity and surface area were assessed. The protease activity of the desquamatory kallikrein proteases, KLK5 and KLK7, and inflammatory tryptase was measured using a fluorogenic probe assay. Protein content and TEWL were also recorded.Corneocyte maturity and surface area decreased with increasing number of tape strippings, i.e. depth into the skin. More mature corneocytes were typically larger than less mature corneocytes. The protease activities of both the desquamatory and inflammatory enzymes together with the protein content were highest in the outer layers of the stratum corneum and decreased with depth. As expected, TEWL increased as more stratum corneum layers were removed. There were no statistical differences between men and women or caucasian and black subjects for all of the parameters studied.The techniques used in this study provide rapid noninvasive measures of the spatial distribution of corneocyte maturity and surface area as well as protease activity and protein content within different levels of the stratum corneum layers. The methods used will allow mechanistic insight into the effects of formulation excipients and active ingredients on epidermal turnover and skin barrier function.