tbuckley/cabot-search huggingface dataset:
A simplified method for monitoring heparin therapy at the bedside: The activated whole blood clotting time
Authors: Walter B. Forman, Gerald Bayer
Journal: American Journal of Hematology (1981)

Abstract Twelve patients receiving heparin during hemodialysis had coagulation parameters monitored using the whole blood clotting time (WBCT), activated partial thromboplastin time (APTT), plasma heparin levels and activated whole blood clotting time (AWBCT). The AWBCT, performed with a battery‐powered portable incubator/timer, correlated with both the corresponding WBCT and the plasma heparin levels. However, the correlation between the AWBCT and the APTT was quite poor. This assay is simply performed, inexpensive, and reproducible. It is recommended as an excellent method for monitoring heparin therapy.
Standing Genetic Variation Drives Repeatable Experimental Evolution in Outcrossing Populations of Saccharomyces cerevisiae
Authors: Molly K. Burke, Gianni Liti, Anthony D. Long
Journal: Molecular Biology and Evolution (2014)

In "evolve-and-resequence" (E&R) experiments, whole-genome sequence data from laboratory-evolved populations can potentially uncover mechanisms of adaptive change. E&R experiments with initially isogenic, asexually reproducing microbes have repeatedly shown that beneficial de novo mutations drive adaptation, and these mutations are not shared among independently evolving replicate populations. Recent E&R experiments with higher eukaryotes that maintain genetic variation via sexual reproduction implicate largely different mechanisms; adaptation may act primarily on pre-existing genetic variation and occur in parallel among independent populations. But this is currently a debated topic, and generalizing these conclusions is problematic because E&R experiments with sexual species are difficult to implement and important elements of experimental design suffer for practical reasons. We circumvent potentially confounding limitations with a yeast model capable of shuffling genotypes via sexual recombination. Our starting population consisted of a highly intercrossed diploid Saccharomyces cerevisiae initiated from four wild haplotypes. We imposed a laboratory domestication treatment on 12 independent replicate populations for 18 weeks, where each week included 2 days as diploids in liquid culture and a forced recombination/mating event. We then sequenced pooled population samples at weeks 0, 6, 12, and 18. We show that adaptation is highly parallel among replicate populations, and can be localized to a modest number of genomic regions. We also demonstrate that despite hundreds of generations of evolution and large effective population sizes, de novo beneficial mutations do not play a large role in this adaptation. Further, we have high power to detect the signal of change in these populations but show how this power is dramatically reduced when fewer timepoints are sampled, or fewer replicate populations are analyzed. As ours is the most highly replicated and sampled E&R study in a sexual species to date, this evokes important considerations for past and future experiments.
Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts.
Authors: M S Brown, J R Faust, J L Goldstein
Journal: Journal of Clinical Investigation (1975)

The transfer of normal human fibroblasts from medium containing whole serum to medium devoid of lipoproteins produced a 90 percent decrease in the cellular content of cholesteryl esters and a 30 percent decrease in the free cholesterol content. When these lipoprotein-deprived cells were subsequently incubated with human low density lipoprotein (LDL), there was a 7-fold increase in the cellular content of esterified cholesterol and a 1.6-fold increase in the cellular content of free cholesterol. The concentration at which LDL produced its half-maximal effect in elevating cellular sterol content (30 mug/ml of LDL-cholesterol) was similar to the half-maximal concentration previously reported for high affinity binding of LDL to its cell surface receptor. High density lipoprotein (HDL) and whole serum from a patient with abetalipoproteinemia (neither of which contains a component that binds to the LDL receptor) did not produce a significant increase in the content of either cholesterol or cholesteryl esters in normal cells. Furthermore, in fibroblasts from patients with the homozygous form of familial hypercholesterolemia, which lack functional LDL receptors, LDL had no effect in raising the cellular content of either free or esterified cholesterol even when present in the medium at concentrations as high as 450 mug sterol/ml. It is concluded that LDL-receptor interactions constitute an important biochemical mechanism for the regulation of the cholesterol content of normal human fibroblasts. Moreover, when considered in light of current concepts of LDL metabolism in intact mammals, the present data suggest that a major function of plasma LDL may be to transport cholesterol from its site of synthesis in liver and intestine to its site of uptake in peripheral tissues.
Preliminary classification criteria for the cryoglobulinaemic vasculitis
Authors: S. De Vita, F. Soldano, M. Isola, G. Monti, A. Gabrielli, A. Tzioufas, C. Ferri, G. F. Ferraccioli, L. Quartuccio, L. Corazza, G. De Marchi, M. R. Casals, M. Voulgarelis, M. Lenzi, F. Saccardo, P. Fraticelli, M. T. Mascia, D. Sansonno, P. Cacoub, M. Tomsic, A. Tavoni, M. Pietrogrande, A. L. Zignego, S. Scarpato, C. Mazzaro, P. Pioltelli, S. Steinfeld, P. Lamprecht, S. Bombardieri, M. Galli
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Summary</h3> The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels. By contrast, a moderate decrease in the SA:V ratio had a marked effect on the equivalent cylinder diameter that is traversable by RBCs of similar stiffness. We developed a finite element model that provides a coherent rationale for the experimental observations, based on the nonlinear mechanical behaviour of the RBC membrane skeleton. We conclude that the SA:V ratio should be given more prominence in studies of RBC pathologies.
Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register
Authors: Moetaza M Soliman, Darren M Ashcroft, Kath D Watson, Mark Lunt, Deborah P M Symmons, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2011)

To evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA).This analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan-Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference.One-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence.These results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.
Piezoelectric lithotripsy and soft tissue injury. Safety limits in the experimental and clinical setting.
Authors: A Darzi, I Reid, E Kay, J R Monson, W A Tanner, F B Keane
Journal: Gut (1990)

Controversy surrounds the capacity of extracorporeal shock wave lithotripsy to cause soft tissue injury. This study examines the influence of different dosages of shock waves on the gall bladder in both humans and an animal model. Sixty one guinea pigs were divided into groups and subjected to different numbers of shock waves (6,000, 24,000, and 48,000) at different frequencies (2.5, 5.0, 10, 20 shock waves per second) and sacrificed at different intervals. Soft tissue damage after lithotripsy seemed to be related to the number of shock waves administered. In addition, repeated administration of low dose lithotripsy (at weekly intervals for six weeks) did not seem to produce a cumulative injury. Finally, in the animals sacrificed one month after receiving high dose lithotripsy, no soft tissue damage was evident, indicating satisfactory healing. Thirty patients were subjected to either high dose (36,000 shock waves) or low dose (6,000 shock waves) lithotripsy 24 hours before elective cholecystectomy. Both macroscopic and microscopic evidence of soft tissue injury were detected in a significantly higher percentage of patients who received a high dose in a single treatment (p less than 0.05). The group who received repeated low dose lithotripsy showed no evidence of cumulative injury. We conclude that low dose lithotripsy produces minimal soft tissue injury and is safe when repeated up to six times at weekly intervals.
Kidney Function After Islet Transplant Alone in Type 1 Diabetes
Authors: Paola Maffi, Federico Bertuzzi, Francesca De Taddeo, Paola Magistretti, Rita Nano, Paolo Fiorina, Andrea Caumo, Paolo Pozzi, Carlo Socci, Massimo Venturini, Alessandro del Maschio, Antonio Secchi
Journal: Diabetes Care (2007)

Islet transplantation alone is an alternative for the replacement of pancreatic endocrine function in patients with type 1 diabetes. The aim of our study was to assess the impact of the Edmonton immunosuppressive protocol (tacrolimus-sirolimus association) on kidney function.Nineteen patients with type 1 diabetes and metabolic instability received islet transplantation alone and immunosuppressive therapy according to the Edmonton protocol. Serum creatinine (sCr), creatinine clearance (CrCl), and 24-h urinary protein excretion (UPE) were assessed at baseline and during a follow-up of 339 patient-months.After islet transplantation we observed 1) sCr within the normal range in all but two patients in whom sCr increased immediately after islet transplantation, and despite withdrawal of immunosuppression, patients progressed to end-stage renal disease (ESRD); 2) CrCl remained within the normal range for those patients who had normal baseline values and decreased, progressing to ESRD in two patients with a decreased baseline CrCl; and 3) 24-h UPE worsened (>300 mg/24 h) in four patients. In the two patients who progressed to ESRD, the worsening of 24-h UPE occurred immediately after islet transplantation. In one patient 24-h UPE worsening occurred at 18 months, and, after withdrawal of immunosuppression, it returned to the normal range. In another patient 24-h UPE increased at 24 months and remained stable while immunosuppression was continued.In type 1 diabetic patients receiving islet transplantation alone, the association of tacrolimus and sirolimus should be used only in patients with normal kidney function. Alternative options for immunosuppressive treatment should be considered for patients with even a mild decrease of kidney function.
Spontaneous rupture of lung echinococcal cyst causing anaphylactic shock and respiratory distress syndrome
Authors: R A Fanne
Journal: Thorax (2006)

A 21 year old woman was admitted to hospital with a persistent productive cough, dyspnoea, and fever. There was no history of sweats or haemoptysis. At admission a chest radiograph showed a 6 cm lesion at the base of the left lower lobe with an air fluid level (fig 1A) and an additional cavitary lesion in the left apex. The blood count was within the normal range with 0.7% eosinophils.



 Figure 1  
 (A) Chest radiograph on admission. …
Racing Alaskan Sled Dogs as a Model of “Ski Asthma”
Authors: Michael S. Davis, Brendan McKiernan, Sheila McCullough, Stuart Nelson, Ronald E. Mandsager, Michael Willard, Karen Dorsey
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Athletes who play sports in cold weather, particularly skaters and cross-country skiers, have an increased prevalence of lower airway disease that is hypothesized to result from repeated penetration of incompletely conditioned air into the lung periphery. In this study, we investigated the hypothesis that canine winter athletes also suffer from increased prevalence of lung disease secondary to hyperpnea with cold air. Bronchoscopy and bronchoalveolar lavage was conducted in elite racing sled dogs 24 to 48 hours after completion of a 1,100-mile endurance race. Bronchoscopic abnormalities were classified as none, mild, moderate, or severe, based on the quantity and distribution of intralumenal debris. Eighty-one percent of the dogs (48 of 59) examined had abnormal accumulations of intralumenal debris, with 46% (27 of 59) classified as moderate or severe, indicating significant accumulation of exudate. Bronchoalveolar lavage obtained from dogs after the race had significantly higher nucleated macrophage and eosinophil counts compared with sedentary control dogs. Our findings support the hypothesis that strenuous exercise in cold environments can lead to lower airway disease and suggest that racing sled dogs may be a useful naturally occurring animal model of the analogous human disease.
The Expression Status and Prognostic Value of Cancer Stem Cell Biomarker CD133 in Cutaneous Squamous Cell Carcinoma
Authors: Rui Xu, Mu-Yan Cai, Rong-Zhen Luo, Xin Tian, Jian-de Han, Mu-Kai Chen
Journal: JAMA Dermatology (2015)

The CD133 protein has been considered a key biomarker of cancer stem cells in various cancers. However, the expression status and prognostic significance of CD133 in cutaneous squamous cell carcinoma (cSCC) are poorly understood.To investigate the expression of cancer stem cell biomarker CD133 in cSCC tissue and its effect on clinicopathological features and outcomes in patients with cSCC.Immunohistochemistry was performed on a tissue microarray to investigate the expression levels of CD133 in cSCC tissue. Receiver operating characteristic curve analysis, Kaplan-Meier plots, and a Cox proportional hazards regression model were applied to analyze the data. Samples were obtained from the archives of the First Affiliated Hospital, Sun Yat-Sen University Cancer Center, and Guangzhou Institute of Dermatology and Venerology. In total, 165 paraffin-embedded clinicopathological samples from 165 patients were obtained from the archives of hospitals between June 1, 1996, and December 31, 2010. Follow-up data were available for these cases.The CD133 expression in cSCC tissue, correlation of CD133 expression with clinicopathological features of cSCC, and association of CD133 expression with prognosis in patients with cSCC.Based on the receiver operating characteristic curves, the cutoff value for high CD133 expression was defined as greater than 65% of tumor cells positively stained. High CD133 expression was observed in 50.9% (84 of 165) of the cSCC samples and in 16.7% (5 of 30) of adjacent nonmalignant epithelial tissue samples (P = .001). High CD133 expression was positively correlated with poorly differentiated cSCC (48.0% [73 of 84] for well to moderately differentiated vs 84.6% [11 of 84] for poorly differentiated, P = .01) and with advanced tumor stage (45.5% [55 of 84] for stage I-II vs 65.9% [29 of 84] for stage III, P = .02). In univariable survival analysis, high CD133 expression was correlated with poor prognosis (mean survival, 63.4 vs 95.7 months; P < .001). In multivariable analysis, CD133 expression was an independent prognostic factor for cSCC (hazard ratio, 1.9152; 95% CI, 1.1950-3.3495; P = .02).High CD133 expression is associated with poorly differentiated and advanced-stage cSCC. High CD133 expression was also correlated with poor prognosis in patients with cSCC. It may serve as a useful biomarker to predict prognosis in patients with cSCC.
Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling
Authors: Jordi Guiu, Ritsuko Shimizu, Teresa D’Altri, Stuart T. Fraser, Jun Hatakeyama, Emery H. Bresnick, Ryoichiro Kageyama, Elaine Dzierzak, Masayuki Yamamoto, Lluis Espinosa, Anna Bigas
Journal: The Journal of Experimental Medicine (2012)

Previous studies have identified Notch as a key regulator of hematopoietic stem cell (HSC) development, but the underlying downstream mechanisms remain unknown. The Notch target Hes1 is widely expressed in the aortic endothelium and hematopoietic clusters, though Hes1-deficient mice show no overt hematopoietic abnormalities. We now demonstrate that Hes is required for the development of HSC in the mouse embryo, a function previously undetected as the result of functional compensation by de novo expression of Hes5 in the aorta/gonad/mesonephros (AGM) region of Hes1 mutants. Analysis of embryos deficient for Hes1 and Hes5 reveals an intact arterial program with overproduction of nonfunctional hematopoietic precursors and total absence of HSC activity. These alterations were associated with increased expression of the hematopoietic regulators Runx1, c-myb, and the previously identified Notch target Gata2. By analyzing the Gata2 locus, we have identified functional RBPJ-binding sites, which mutation results in loss of Gata2 reporter expression in transgenic embryos, and functional Hes-binding sites, which mutation leads to specific Gata2 up-regulation in the hematopoietic precursors. Together, our findings show that Notch activation in the AGM triggers Gata2 and Hes1 transcription, and next HES-1 protein represses Gata2, creating an incoherent feed-forward loop required to restrict Gata2 expression in the emerging HSCs.
MDM2 Gene Amplification and Transcript Levels in Human Sarcomas: Relationship to TP53 Gene Status
Authors: V. A. Florenes, G. M. Maelandsmo, A. Forus, A. Andreassen, O. Myklebost, O. Fodstad
Journal: JNCI Journal of the National Cancer Institute (1994)

Alterations of the TP53 tumor suppressor gene appear to be implicated in the tumorigenesis and progression of several types of human cancer, including different histologic subtypes of sarcomas. The MDM2 (murine double minute-2) gene encodes a nuclear phosphoprotein that may interact with both mutant and wild-type p 53 proteins, there by inhibiting p 53 -mediated transactivation in a dose-dependent manner. Recently it has been suggested that mdm2 and p 53 proteins are components of an autoregulatory loop in which the MDM2 gene is transactivated by p 53 . Our purpose was to examine the frequency of MDM2 amplifications in larger panels of sarcomas, determine if the mRNA level could be elevated in tumors without concomitant gene amplification, and relate MDM2 findings to the TP53 status of the tumors. Sarcoma tissue of different histologic subtypes was obtained from 68 patients at the time of surgery and from 26 human xenografts in nude mice. In addition, two human sarcoma cell lines (OSA and U2OS) were studied. Genomic DNA from tumor tissue, in vitro cell lines, and peripheral blood cells were isolated by Southern-blot analysis methods to determine MDM2 gene amplification. Tumor DNA was analyzed for possible TP53 gene mutations in exons 5, 7, and 8 by constant denaturing gel electrophoresis. To determine the MDM2 and TP53 mRNA levels, Northern-blot analysis was performed. Amplification of the MDM2 gene was detected in 10 tumors (10.3%). Whereas MDM2 amplification and/or over-expression were found only in two (U2OS and OSA cell lines) of 18 osteosarcomas, one of 20 malignant fibrous his-tiocytomas (MFHs), and in none of 14 leiomyosarcomas, such alterations were observed in two of two fibrosarcomas, three of six malignant schwannomas, three of 19 liposar-comas, and in the one hemangiopericytoma examined. MDM2 overexpression was found in all nine examined cases with and in three tumors without amplification. TP53 mutations were detected in 12 cases (five osteosarcomas, four MFHs, and three leiomyosarcomas), of which none showed amplification, but one had increased levels of MDM2 mRNA. None of the fibrosarcomas, malignant schwannomas, and liposarcomas examined had mutated TP53. The six sarcomas that showed high TP53 mRNA expression in the absence of gene mutation also had elevated levels of MDM2 mRNA. The present data provide further indications that increased MDM2 expression level, caused by gene amplification or altered regulation of transcription, is involved in tumor progression of some, but not all, sarcoma subtypes. [J Natl Cancer Inst 86: 1297–1302, 1994]
Cardiovascular Stress Hyperreactivity in Babies of Smokers and in Babies Born Preterm
Authors: Gary Cohen, Silvano Vella, Heather Jeffery, Hugo Lagercrantz, Miriam Katz-Salamon
Journal: Circulation (2008)

Being born preterm, small, and to a mother who smokes are common perinatal complications with major public health implications. Evidence suggests that each affects the body's structure and function in ways that could increase susceptibility to cardiovascular dysfunction later in life. Here, we used 2 routine stress reactivity tests to identify incipient "silent" programming of cardiovascular dysfunction associated with adverse perinatal events.We studied 29 control babies born at term to nonsmokers, 18 term-born babies of mothers who smoked throughout pregnancy (mean, 15 cigarettes a day), and 31 babies born preterm to nonsmokers. All infants were compared at the same age after conception (ie, at 40 to 42 weeks), during sleep. We analyzed blood pressure (BP) and heart rate responses to breathing 4% CO(2) for 4 minutes or to passive head-up tilt to 60 degrees . BP was measured continuously from a wrist cuff. CO(2) exposure raised heart rate and BP in controls by 10%, and tilt increased their BP by 5%. CO(2) elicited the expected BP but no heart rate response from preterm infants but a much-greater-than-expected BP and heart rate response from babies of smokers. Tilt elicited a 3- to 4-fold greater rise in BP from preterm and tobacco-exposed babies.Vascular, cardiac, and blood pressure reactivity is heightened in babies born preterm or to smokers. The findings are consistent with in utero and early postnatal "programming" of human cardiovascular dysfunction by adverse circumstances. This incipient dysfunction may be an early manifestation of processes that lead to other problems or complications later on (eg, higher BP or sudden infant death syndrome).