tbuckley/cabot-search huggingface dataset:
Smooth Muscle Cells Differentiated From Reprogrammed Embryonic Lung Fibroblasts Through DKK3 Signaling Are Potent for Tissue Engineering of Vascular Grafts
Authors: Eirini Karamariti, Andriana Margariti, Bernhard Winkler, Xiaocong Wang, Xuechong Hong, Dilair Baban, Jiannis Ragoussis, Yi Huang, Jing-Dong J. Han, Mei Mei Wong, Can M. Sag, Ajay M. Shah, Yanhua Hu, Qingbo Xu
Journal: Circulation Research (2013)

Rationale: Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited. Objective: We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state. Methods and Results: We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft. Conclusions: We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.
CROSS TRANSFUSION IN SCHIZOPHRENIA
Authors: GEORGE NICKLIN, WILLIAM SACKS, HANS WEHRHEIM, GEORGE SIMPSON, JOHN SAUNDERS, NATHAN KLINE
Journal: American Journal of Psychiatry (1959)

In this study of cross-transfusion in schizophrenia no clinically significant changes occurred in the non-psychotic volunteer, during or after the cross-transfusion. The patient became psychiatrically more ill during the 24 hours immediately following the cross-transfusion.
Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression
Authors: M Nozaki, M Tada, H Kobayashi, C L Zhang, Y Sawamura, H Abe, N Ishii, E G Van Meir
Journal: Neuro-Oncology (1999)

Loss of function of the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is reflected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G1/S transition control genes, either loss of the p16/CDKN2 or RB genes or amplification of the cyclin D gene. The final progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with amplification of the epidermal growth factor receptor (EGFR) genes. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis.
Evaluation of a commercially available pedometer used to promote physical activity as part of a national programme
Authors: S A Clemes, S O'Connell, L M Rogan, P L Griffiths
Journal: British Journal of Sports Medicine (2009)

Objective To assess the accuracy of a pedometer (manufactured by Silva) currently being used as part of a national programme to promote physical activity in the UK. Methods Laboratory study: 68 participants (aged 19.2 years (SD 2.7), body mass index (BMI) 22.5 kg/m 2 (SD 3.3)) wore two Silva pedometers (over the right and left hips) while walking on a motorised treadmill at 2, 2.5, 3, 3.5 and 4 mph. Pedometer step counts were compared with actual steps counted. Free-living study: 134 participants (aged 36.4 years (SD 18.1), BMI 26.3 kg/m 2 (SD 5.1)) wore one Silva pedometer, one New-Lifestyles NL-1000 pedometer and an ActiGraph GT1M accelerometer (the criterion) during waking hours for one day. Step counts registered by the Silva and NL-1000 pedometers were compared with ActiGraph step counts. Percentage error of the pedometers were compared across normal-weight (n = 58), overweight (n = 45) and obese (n = 31) participants. Results Laboratory study: Across the speeds tested percentage error in steps ranged from 6.7 (4 mph) to 46.9% (2 mph). Free-living study: Overall percentage errors of the Silva and NL-1000 pedometers relative to the criterion were 36.3% and 9%, respectively. Significant differences in percentage error of the Silva pedometer were observed across BMI groups (normal-weight 21%, overweight 40.2%, obese 59.2%, p&lt;0.001). Conclusion The findings suggest the Silva pedometer is unacceptably inaccurate for activity promotion purposes, particularly in overweight and obese adults. Pedometers are an excellent tool for activity promotion; however, the use of inexpensive, untested pedometers is not recommended as they will lead to user frustration, low intervention compliance and adverse reaction to the instrument, potentially impacting future public health campaigns.
Doctors condemn "unethical" 55 payment for every new dementia diagnosis
Authors: Z. Kmietowicz
Journal: BMJ (2014)

<i>BACKGROUND AND PURPOSE:</i> Functional MR (fMR) imaging with blood-oxygen-level–dependent (BOLD) contrast enhancement is increasingly used as a noninvasive tool for presurgical mapping in patients with intracranial tumors. Most physiologic studies of task-related BOLD contrast enhancement have involved healthy volunteers. Therefore, it is not known whether BOLD contrast is evoked in the same way in or adjacent to tumor tissue. The purpose of this study was to study the influence of different intracranial tumors on BOLD contrast enhancement. <i>METHODS:</i> fMR mapping of the sensorimotor cortex was successfully performed in 15 of 21 patients with intracranial space-occupying lesions by using a bimanual motor task. Tumors were located either within the sensorimotor area itself or in adjacent brain areas, inducing changes of signal intensity on T2-weighted images along the pre- or postcentral gyrus. Space-occupying lesions were divided into a group comprising gliomas (seven cases) and a group comprising nonglial space-occupying lesions (three metastases, two cavernomas, one abscess, one arteriovenous malformation, one meningioma). A hemispheric activation index was calculated using the volume of activation on the affected and on the contralateral hemisphere. Hemispheric activation indices of gliomas and nonglial lesions were compared statistically. <i>RESULTS:</i> The activated volume in the hemispheres ipsilateral to the nonglial lesions was 14% larger than in the contralateral hemisphere, whereas in the hemispheres ipsilateral to gliomas, the activated volume decreased by 36% in comparison with the contralateral hemisphere. The difference between nonglial lesions and gliomas was significant (<i>P</i> &lt; .05). <i>CONCLUSION:</i> The generation of BOLD contrast enhancement is reduced near gliomas but is not affected by nonglial tumors.
Sentinel node biopsy compared with complete axillary dissection for staging early breast cancer with clinically negative lymph nodes: results of randomized trial
Authors: G. Canavese, A. Catturich, C. Vecchio, D. Tomei, M. Gipponi, G. Villa, F. Carli, P. Bruzzi, B. Dozin
Journal: Annals of Oncology (2009)
Daytime risk factors of nocturnal hyoxemia in COPD patients unqualified for long-term oxygen therapy
Authors: Yijia Wang, Lianqin Tao, Guochao Shi, Huanying Wan, Xiaoting Cai, Haixing Zhu
Journal: European Respiratory Journal (2012)

Objective  To identity daytime variables that are predicative to nocturnal hyoxemia among COPD patients unqualified for long-term oxygen therapy (LTOT).  Methods  Forty-eight stable COPD patients with daytime SaO 2 ≥90% were enrolled to this study and regarded as patients unqualified for LTOT. Patients were divided into 4 groups depending on daytime SaO 2  (SaO 2 ≥98%, group 1; SaO 2 =97%, group 2; SaO 2 =96%, group 3; 90%≤SaO 2 ≤95%, group 4). All patients underwent lung function examination during daytime. Their nocturnal oxygen saturations were monitored with overnight pulse oximetry (OPO).  Results  Daytime oxygen saturation was positively correlated with nocturnal mean SaO 2  ( r =0.79,  P  r = -0.75,  P  2 . Patients with daytime oxygen saturation between 90% and 95% were more likely to have lower nocturnal oxygen saturation and longer TB90 ( P  Conclusions  Daytime oxygen saturation may effectively predict the occurrence of nocturnal hyoxemia in stable COPD patients unqualified for LTOT. To reduce COPD complications and improve prognosis, we suggest a relative indication of LTOT for patients with daytime oxygen saturation between 90% and 95% and diagnosed with nocturnal hyoxemia.
Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial
Authors: Harry D Bear, Gong Tang, Priya Rastogi, Charles E Geyer, Qing Liu, André Robidoux, Luis Baez-Diaz, Adam M Brufsky, Rita S Mehta, Louis Fehrenbacher, James A Young, Francis M Senecal, Rakesh Gaur, Richard G Margolese, Paul T Adams, Howard M Gross, Joseph P Costantino, Soonmyung Paik, Sandra M Swain, Eleftherios P Mamounas, Norman Wolmark
Journal: The Lancet Oncology (2015)
Case of Mediastinal Sarcoma, Simulating 'Callous Mediastino-Pericarditis'
Authors: T. C. Allbutt
Journal: BMJ (1874)

ISept. 5, I874.did not apparently interfere with his general well-being.He was keenly alive to the exciting rumours and incidents of each day, slept well, and fared generously.This internal medication was slightly varied from time to time; but his principal medicines were iron, gentian, cinchona, aid rhubarb.Occasionally, he had a few grains of grey
Fracture experience of patients with coeliac disease: a population based survey
Authors: K Thomason
Journal: Gut (2003)

<b>Background:</b> While coeliac disease is now recognised as being associated with both osteoporosis and osteomalacia, the size of any increase in the risk of fracture in patients with coeliac disease compared with the general population has not been quantified. <b>Aim:</b> To examine the fracture experience of adults with coeliac disease compared with the general population. <b>Subjects:</b> Patients with coeliac disease diagnosed in adulthood and born before 1950, selected from two large population based disease registers, and age and sex frequency matched controls identified from local general practitioner lists. <b>Methods:</b> A four page lifestyle and general health questionnaire which included specific questions about fracture experience. <b>Results:</b> Analysis was performed on 244 patients with coeliac disease and 161 controls, giving response rates of 89% and 72%, respectively. Eighty two (35%) coeliac patients and 53 (33%) controls reported ever having sustained one or more fractures, giving an age and sex adjusted odds ratio of 1.05 (95% confidence interval (CI) 0.68–1.62). The most common fracture site reported was the forearm or wrist, with an adjusted odds ratio of 1.21 (95% CI 0.66–2.25) for patients with coeliac disease having had a forearm or wrist fracture. Low trauma fractures were reported by 37 patients with coeliac disease (15.7%) and by 21 controls (13.8%), with an adjusted odds ratio of 1.16 (95% CI 0.65–2.10). The risk of low trauma fracture was slightly higher in coeliac men than women (odds ratio 1.28 compared with 1.12), but this difference was not statistically significant (p=0.84). After adjustment for age, sex, body mass index, and smoking status, patients with coeliac disease reported 13% more low trauma fractures than controls (odds ratio 1.13, 95% CI 0.60–2.12). There was no difference in low trauma fracture risk before and after diagnosis of coeliac disease. <b>Conclusion:</b> No overall increased fracture risk in patients with coeliac disease was observed. Although severe osteoporosis may develop in a subset of patients, as a whole patients with coeliac disease do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified.
Steatosis: Co-factor in other liver diseases
Authors: Elizabeth E. Powell, Julie R. Jonsson, Andrew D. Clouston
Journal: Hepatology (2005)

Abstract The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol- and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells. In conclusion , active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis. (Hepatology 2005;42:5–13.)
OP04 Synergistic influence of tapasin and HLA class I protection against chronic Hepatitis C virus infection
Authors: S. Ashraf, S. Knapp, C. Becford-Tackoir, C. Brooks, A.-M. Little, G. Alexander, M. Cramp, S. I. Khakoo
Journal: Gut (2011)

<h3>Introduction</h3> HLA class I is associated with the outcome of hepatitis C virus (HCV) infection. Tapasin is a member of the peptide loading complex that loads self and viral peptides onto HLA class I. Presentation of viral peptides by HLA class I is critical in generating an effective cytotoxic T lymphocyte (CTL) response, and hence in clearing HCV infection. However, not all HLA alleles require tapasin for efficient peptide loading. Thus polymorphisms in the tapasin gene could affect clearance of HCV in combination with specific “tapasin-dependent” HLA class I alleles. The SNP rs2071888 is a non-synonymous polymorphism in exon 4 of the <i>Tapasin</i> gene causing an arginine to threonine change that could affect tapasin function. We have investigated the effect of this SNP in resolving hepatitis C virus (HCV) infection in a cohort of 336 patients from the UK. <h3>Aim</h3> We have investigated the effect of the SNP rs2071888 in resolving hepatitis C virus (HCV) infection in a cohort of 336 patients from the UK. <h3>Method</h3> Genomic DNA from 216 chronically infected individuals and 120 spontaneous resolvers of HCV was genotyped with an allele specific PCR designed to identify the G/C SNP in exon 4 of the <i>Tapasin</i> gene. Individuals were also typed for HLA-A, -B and -C. Results were analysed for association with hepatitis C outcome. <h3>Results</h3> Overall the G allele of tapasin was associated with protection against chronic HCV infection (p=0.018, OR=1.99, 95% CI 1.14 to 3.46). Interestingly, in combination with heterozygosity at the HLA-B locus, heterozygosity at the tapasin locus was also protective (Abstract OP04 figure 1, p trend =0.005). Furthermore, we identified specific HLA-B alleles associated with protection in the context of the Tapasin G, but not Tapasin C allele. Specifically the G allele was most protective in the context of B*0702 (p=0.029, OR=4.56, 95% CI 1.2 to 17.27), and B*5701 (p=0.029, OR=12, 95% CI 1.2 to 120). Tapasin has been shown to bind specifically to amino acids 114 and 116 of HLA class I. Consistent with this functional interaction we found that aspartate at position 114 and serine at 116 were most beneficial in the context of both the G allele (D114/TapG, p&lt;0.0001, OR=3.3, 95% CI 1.83 to 5.98; S116/TapG, p&lt;0.0001, OR=2.73, 95% CI 1.57 to 4.76). <h3>Conclusion</h3> The G allele of tapasin was associated with protection from chronic HCV infection, both alone and in combination with specific HLA class I alleles. Individuals who are heterozygous for both tapasin and HLA-B are relatively protected from chronic HCV infection. This heterozygosity may allow them to present a broader range of peptides to CTL and thus mount a more effective anti-HCV immune response.
Serum Apolipoprotein AI and B Are Stronger Biomarkers of Diabetic Retinopathy Than Traditional Lipids
Authors: Muhammad Bayu Sasongko, Tien Y. Wong, Thanh T. Nguyen, Ryo Kawasaki, Alicia Jenkins, Jonathan Shaw, Jie Jin Wang
Journal: Diabetes Care (2011)

To describe and compare the associations of serum lipoproteins and apolipoproteins with diabetic retinopathy.This was a cross-sectional study of 224 diabetic patients (85 type 1 and 139 type 2) from a diabetes clinic. Diabetic retinopathy was graded from fundus photographs according to the Airlie House Classification system and categorized into mild, moderate, and vision-threatening diabetic retinopathy (VTDR). Serum traditional lipids (total, LDL, non-HDL, and HDL cholesterol and triglycerides) and apolipoprotein AI (apoAI), apolipoprotein B (apoB), and the apoB-to-apoAI ratio were assessed.Diabetic retinopathy was present in 133 (59.4%) individuals. After adjustment for age, sex, diabetes duration, A1C, systolic blood pressure, and diabetes medications, the HDL cholesterol level was inversely associated with diabetic retinopathy (odds ratio 0.39 [95% CI 0.16-0.94], highest versus lowest quartile; P(trend) = 0.017). The ApoAI level was inversely associated with diabetic retinopathy (per SD increase, 0.76 [95% CI 0.59-0.98]), whereas apoB (per SD increase, 1.31 [1.02-1.68]) and the apoB-to-apoAI ratio (per SD increase, 1.48 [1.13-1.95]) were positively associated with diabetic retinopathy. Results were similar for mild to moderate diabetic retinopathy and VTDR. Traditional lipid levels improved the area under the receiver operating curve by 1.8%, whereas apolipoproteins improved the area by 8.2%.ApoAI and apoB and the apoB-to-apoAI ratio were significantly and independently associated with diabetic retinopathy and diabetic retinopathy severity and improved the ability to discriminate diabetic retinopathy by 8%. Serum apolipoprotein levels may therefore be stronger biomarkers of diabetic retinopathy than traditional lipid measures.
Irradiation Prolongs Survival of Alport Mice
Authors: Kan Katayama, Mitsuo Kawano, Ichiro Naito, Hitoshi Ishikawa, Yoshikazu Sado, Nagisa Asakawa, Tomohiro Murata, Kazuki Oosugi, Michiyo Kiyohara, Eiji Ishikawa, Masaaki Ito, Shinsuke Nomura
Journal: Journal of the American Society of Nephrology (2008)

Alport syndrome is a hereditary nephropathy that results in irreversible, progressive renal failure. Recent reports suggested that bone marrow transplantation (BMT) has a beneficial, short-term effect on renal injury in Alport (Col4a3(-/-)) mice, but its long-term effects, especially with regard to survival, are unknown. In this study, Alport mice received a transplant of either wild-type or Col4a3(-/-) bone marrow cells. Surprising, laboratory evaluations and renal histology demonstrated similar findings in both transplanted groups. Transplanted cells accounted for >10% of glomerular cells at 8 wk, but type IV collagen alpha3 chains were not detected in glomerular basement membranes of either group by immunofluorescence or Western blot analysis, although Col4a3 mRNA in the kidney could be amplified by reverse transcription-PCR in knockout mice that received a transplant of wild-type bone marrow. Both transplanted groups, however, survived approximately 1.5 times longer than untreated knockout mice (log rank P < 0.05). These data suggested that irradiation, which preceded BMT, may have conferred a survival benefit; therefore, the survival time of knockout mice was assessed after sublethal irradiation (3, 6, and 7 Gy) without subsequent BMT. A strong positive correlation between irradiation dosage and survival time was identified (P < 0.0001). In conclusion, the improved survival observed in Alport mice that received a transplant of wild-type bone marrow might be primarily attributed to as-yet-unidentified effects of irradiation.
Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients
Authors: Kwang Kon Koh, Michael J. Quon, Seung Hwan Han, Yonghee Lee, Jeong Yeal Ahn, Soo Jin Kim, Yesl Koh, Eak Kyun Shin
Journal: Diabetes Care (2008)

We hypothesized that simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients.