tbuckley/cabot-search huggingface dataset:
The influence of sensitisation to pollens and moulds on seasonal variations in asthma attacks
Authors: Cristina Canova, Joachim Heinrich, Josep Maria Anto, Benedicte Leynaert, Matthew Smith, Nino Kuenzli, Jan-Paul Zock, Christer Janson, Isa Cerveri, Roberto de Marco, Kjell Toren, Thorarinn Gislason, Dennis Nowak, Isabelle Pin, Matthias Wjst, Jure Manfreda, Cecilie Svanes, Julian Crane, Michael Abramson, Michael Burr, Peter Burney, Deborah Jarvis
Journal: European Respiratory Journal (2013)

No large study has described the seasonal variation in asthma attacks in population-based asthmatics in whom sensitisation to allergen has been measured. 2,637 young adults with asthma living in 15 countries reported the months in which they usually had attacks of asthma and had skin-prick tests performed. Differences in seasonal patterns by sensitisation status were assessed using generalised estimating equations. Most young adults with asthma reported periods of the year when their asthma attacks were more common (range: 47% in Sweden to 86% in Spain). Seasonal variation in asthma was not modified by sensitisation to house dust mite or cat allergens. Asthmatics sensitised to grass, birch and Alternaria allergens had different seasonal patterns to those not sensitised to each allergen, with some geographical variation. In southern Europe, those sensitised to grass allergens were more likely to report attacks occurred in spring or summer than in winter (OR March/April 2.60, 95% CI 1.70-3.97; OR May/June 4.43, 95% CI 2.34-8.39) and smaller later peaks were observed in northern Europe (OR May/June 1.25, 95% CI 0.60-2.64; OR July/August 1.66, 95% CI 0.89-3.10). Asthmatics reporting hay fever but who were not sensitised to grass showed no seasonal variations. Seasonal variations in asthma attacks in young adults are common and are different depending on sensitisation to outdoor, but not indoor, allergens.
Comparative clinical impact of endoscopic pancreatography, grey-scale ultrasonography, and computed tomography (EMI scanning) in pancreatic disease: preliminary report.
Authors: P B Cotton, M E Denyer, L Kreel, J Husband, H B Meire, W Lees
Journal: Gut (1978)

Grey-scale ultrasound scanning (US), computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) were performed in a series of 50 patients with known or suspected pancreatic disease. The impact of the individual tests were assessed in the relevant clinical context. With a maximum of 100, the overall clinical impact score of ERCP (75) exceeded that of CT(63) and US (36). In patients with obscure pain, and in those with relapsing pancreatitis, a combination of US and ERCP provides good clinical guidance. Computed tomography scanning can currently be reserved for documentation of patients with a major mass lesion. None of the techniques can detect early pancreatic cancer, except of the papilla of Vater, where ERCP is diagnostic. Recommendations for future diagnostic strategies may alter as grey-scale ultrasonography and computed tomography develop, and, in any case, depend on many factors including local expertise, availability, and cost.
Evolutionary History of Caenorhabditis elegans Inferred from Microsatellites: Evidence for Spatial and Temporal Genetic Differentiation and the Occurrence of Outbreeding
Authors: M. Haber
Journal: Molecular Biology and Evolution (2004)

Although diverse biological disciplines employ the nematode Caenorhabditis elegans as a highly efficient laboratory model system, little is known about its natural history. We investigated its evolutionary past using 10 polymorphic trinucleotide and tetranucleotide microsatellites, derived from across the whole genome. These microsatellites were analyzed from the 35 previously available natural isolates from different parts of the world and also 23 new strains isolated from northwest Germany. Our results highlight that C. elegans lineages differentiate genetically with respect to geographic distance and, to a lesser extent, differences in the time of strain isolation. The latter indicates some turnover of strain genotypes at specific locations. Our data also demonstrate the coexistence of highly diverse genotypes in the population from northwest Germany, which is best explained by recent migration events. Furthermore, selfing is confirmed as the primary mode of reproduction for this hermaphroditic nematode in nature. Importantly, we also find evidence for the occurrence of occasional outbreeding. Taken together, these results support the previous notion that C. elegans is a colonizer, whereby selfing may permit rapid dispersal within new habitats even in the absence of potential mates, whereas occasional outcrossing may serve to compensate for the disadvantages of inbreeding. Such information about the natural history of C. elegans should be of great value for an in-depth understanding of the complexity of this organism, including its multifaceted developmental, neurological, or molecular genetic pathways.
Osteopenia and decreased bone formation in osteonectin-deficient mice
Authors: A.M. Delany, M. Amling, M. Priemel, C. Howe, R. Baron, E. Canalis
Journal: Journal of Clinical Investigation (2000)

Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely, osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates.
Mammography Before Diagnosis Among Women Age 80 Years and Older With Breast Cancer
Authors: Brian D. Badgwell, Sharon H. Giordano, Zhigang Z. Duan, Shenying Fang, Isabelle Bedrosian, Henry M. Kuerer, S. Eva Singletary, Kelly K. Hunt, Gabriel N. Hortobagyi, Gildy Babiera
Journal: Journal of Clinical Oncology (2008)

Screening mammography guidelines for patients age 80 years and older are variable. We determined the effect of mammography use on stage at breast cancer diagnosis and survival among women of this age range.We used the linked Surveillance, Epidemiology, and End Results-Medicare database to evaluate 12,358 women >or= 80 years of age diagnosed with breast cancer between 1996 and 2002. Patients were grouped according to number of mammograms during the 60 months before diagnosis: nonusers (0 mammograms), irregular users (one to two mammograms), and regular users (three or more mammograms). Effects of mammography on disease stage (I to IIa v IIb to IV) and survival were determined by logistic regression and Cox proportional hazards analyses.Percentages of women with nonuse, irregular use, and regular use of mammography during the 5 years preceding diagnosis were 49%, 29%, and 22%, respectively. On multivariate analysis, patients were 0.37 times less likely to present with late-stage cancer for each mammogram obtained (odds ratio, 0.63; 95% CI, 0.63 to 0.67). Breast cancer-specific 5-year survival among nonusers was 82%, that among irregular users was 88%, and that among regular users was 94%. However, survival from causes other than breast cancer was also associated with mammography use, suggesting a bias for healthier patients to undergo mammography.Regular mammography among women >or= 80 years of age was associated with earlier disease stage, although improved survival remains difficult to demonstrate. Health care providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity.
A randomized controlled trial of pretransplant antiviral therapy to prevent recurrence of hepatitis C after liver transplantation
Authors: Gregory T. Everson, Norah A. Terrault, Anna S. Lok, Del R. Rodrigo, Robert S. Brown, Sammy Saab, Mitchell L. Shiffman, Abdullah M.S. Al-Osaimi, Laura M. Kulik, Brenda W. Gillespie, James E. Everhart
Journal: Hepatology (2012)

Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 μg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR ( P = 0.29); per-protocol values were 13 (22%) and 0 (0%) ( P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for &lt;8, 8-16, and &gt;16 weeks, respectively ( P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003). Conclusion : Pretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with &gt;16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.
Renal functional reserve in patients with severe chronic obstructive pulmonary disease
Authors: R. A. Sharkey, E. M. Mulloy, I. A. Kilgallen, S. J. O'Neill
Journal: Thorax (1997)

Renal functional reserve is the normal increase in renal blood flow after a protein load, and reduced or absent renal functional reserve is an early index of renal impairment. Renal blood flow is frequently reduced during acute oedematous exacerbations of chronic obstructive pulmonary disease (COPD). It is possible that patients with severe COPD in the stable state may have a reduced or absent renal functional reserve which could be a factor in oedema formation.Sixteen stable patients with severe COPD and five normal controls were studied. The mean (SD) arterial oxygen and carbon dioxide tensions (PaO2, PaCO2) and forced expiratory volume in one second (FEV1) of patients with COPD were 8.1 (1.04) kPa, 6.3 (0.69) kPa, and 0.74 (0.27) 1, respectively. The pulsatility index (PI), an index of renovascular resistance, was measured non-invasively by Doppler ultrasonography at baseline and at intervals after a protein load of 250 g steak.The PI fell after the protein load in the normal subjects from 1.04 (0.19) to 0.84 (0.17), mean difference 0.20, 95% confidence interval of difference (CI) 0.14 to 0.27, p < 0.001. In the COPD group there was no change; baseline PI = 1.04 (0.16), PI after protein load = 1.08 (0.19), mean difference = -0.04, 95% CI-0.11 to 0.04, p = NS. Six of the patients with COPD were normocapnic and 10 were hypercapnic (PaCO2 > or = 6.0 kPa). The normocapnic patients had no significant change in PI (baseline PI = 1.07 (0.15), PI after protein load = 1.01 (0.16), mean difference = 0.06, 95% CI -0.03 to 0.15) while in the hypercapnic patients the PI tended to rise (baseline PI = 1.03 (0.17), PI after protein load = 1.12 (0.21), mean difference = -0.09, 95% CI 0.18 to 0.007, p = 0.06).Renal haemodynamics were unchanged after a protein load in patients with severe COPD, suggesting that they had no renal functional reserve. This may be a factor in the development of oedema frequently seen in patients with severe COPD, particularly in hypercapnic patients.
Dysferlin-mediated membrane repair protects the heart from stress-induced left ventricular injury
Authors: Renzhi Han, Dimple Bansal, Katsuya Miyake, Viviane P. Muniz, Robert M. Weiss, Paul L. McNeil, Kevin P. Campbell
Journal: Journal of Clinical Investigation (2007)

Dilated cardiomyopathy is a life-threatening syndrome that can arise from a myriad of causes, but predisposition toward this malady is inherited in many cases. A number of inherited forms of dilated cardiomyopathy arise from mutations in genes that encode proteins involved in linking the cytoskeleton to the extracellular matrix, and disruption of this link renders the cell membrane more susceptible to injury. Membrane repair is an important cellular mechanism that animal cells have developed to survive membrane disruption. We have previously shown that dysferlin deficiency leads to defective membrane resealing in skeletal muscle and muscle necrosis; however, the function of dysferlin in the heart remains to be determined. Here, we demonstrate that dysferlin is also involved in cardiomyocyte membrane repair and that dysferlin deficiency leads to cardiomyopathy. In particular, stress exercise disturbs left ventricular function in dysferlin-null mice and increases Evans blue dye uptake in dysferlin-deficient cardiomyocytes. Furthermore, a combined deficiency of dystrophin and dysferlin leads to early onset cardiomyopathy. Our results suggest that dysferlin-mediated membrane repair is important for maintaining membrane integrity of cardiomyocytes, particularly under conditions of mechanical stress. Thus, our study establishes what we believe is a novel mechanism underlying the cardiomyopathy that results from a defective membrane repair in the absence of dysferlin.
Faecal microbiota composition and host–microbe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome
Authors: Jonna Jalanka-Tuovinen, Jarkko Salojärvi, Anne Salonen, Outi Immonen, Klara Garsed, Fiona M Kelly, Abed Zaitoun, Airi Palva, Robin C Spiller, Willem M de Vos
Journal: Gut (2013)

Background About 10% of patients with IBS report the start of the syndrome after infectious enteritis. The clinical features of postinfectious IBS (PI-IBS) resemble those of diarrhoea-predominant IBS (IBS-D). While altered faecal microbiota has been identified in other IBS subtypes, composition of the microbiota in patients with PI-IBS remains uncharacterised. Objective To characterise the microbial composition of patients with PI-IBS, and to examine the associations between the faecal microbiota and a patient's clinical features. Design Using a phylogenetic microarray and selected qPCR assays, we analysed differences in the faecal microbiota of 57 subjects from five study groups: patients with diagnosed PI-IBS, patients who 6 months after gastroenteritis had either persisting bowel dysfunction or no IBS symptoms, benchmarked against patients with IBS-D and healthy controls. In addition, the associations between the faecal microbiota and health were investigated by correlating the microbial profiles to immunological markers, quality of life indicators and host gene expression in rectal biopsies. Results Microbiota analysis revealed a bacterial profile of 27 genus-like groups, providing an Index of Microbial Dysbiosis (IMD), which significantly separated patient groups and controls. Within this profile, several members of Bacteroidetes phylum were increased 12-fold in patients, while healthy controls had 35-fold more uncultured Clostridia . We showed correlations between the IMD and expression of several host gene pathways, including amino acid synthesis, cell junction integrity and inflammatory response, suggesting an impaired epithelial barrier function in IBS. Conclusions The faecal microbiota of patients with PI-IBS differs from that of healthy controls and resembles that of patients with IBS-D, suggesting a common pathophysiology. Moreover, our analysis suggests a variety of host–microbe associations that may underlie intestinal symptoms, initiated by gastroenteritis.
QUANTITATIVE FACTORS IN "TEST-TUBE INFECTION."
Authors: Arthur L. Bloomfield, Augustus R. Felty
Journal: The Journal of Experimental Medicine (1924)

In the preceding experiments an attempt has been made to work out on a mathematical basis certain laws of "test-tube infection" with special reference to the relation of dosage and activity of culture to resulting growth in favorable and unfavorable media. It has been shown that neither lag nor dosage is of great importance when dealing with a highly favorable medium, but that with an unfavorable medium both determine very directly the outcome of the inoculation. Certain analogies have been drawn between these test-tube results and the observed phenomena of human and animal infection. If conditions are actually similar in the latter there is a simple explanation of several of the puzzles of epidemiology. It becomes intelligible why a carrier of pathogenic bacteria may reside in a community without producing infection of the susceptibles about him in spite of the fact that they actually acquire the organisms, why crowding results in the spread of infection, and why the introduction of unusually susceptible people into a community where carriers are present leads not only to infection of these susceptibles but to infection of the general population. The experiments further raise the query whether alterations in natural vegetative activity of bacteria as well as specific alterations in virulence are of importance in explaining the spread of infection. Finally, it should be said that the present experiments are not regarded as evidence for any hypothesis of human infection. They merely furnish interesting analogies. Further work with animals along the same lines is in progress.
Diaphragm Injury in Individuals with Airflow Obstruction
Authors: NORI A. MACGOWAN, KENNETH G. EVANS, JEREMY D. ROAD, W. DARLENE REID
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The purpose of this study was to describe the nature of diaphragm injury, to quantify the injury and number of macrophages at the light microscopic level, and to determine their association with airflow obstruction in humans. Partial-thickness diaphragm biopsies were obtained from 21 subjects going for thoracotomy surgery (FEV1: 74 ± 34% predicted; range: 16 to 122% predicted). Cross sections cut from frozen diaphragm were processed with H&E or processed for immunohistochemistry using the monoclonal antibody Ber-MAC3 (DAKO Corp., Carpinteria, CA) to label macrophages. Area fractions (AA) or the proportions of the cross- sectional area were determined by point counting all viable fields of H&E-stained diaphragm cross sections. AA were 66.2 ± 9.0% for normal muscle, 17.6 ± 7.2% for abnormal muscle, and 16.3 ± 4.2% for connective tissue. Percent predicted FEV1 was inversely related to the AA of abnormal muscle (r = − 0.53, p < 0.01) and directly related to the AA of normal muscle (r = 0.37, p < 0.05). The number of macrophages was not related to % predicted FEV1 (mean ± SD: 0.41 ± 0.18/fiber; 52 ± 19/mm2). We conclude that increasing severity of airflow obstruction is associated with an increased AA of abnormal diaphragm and a decreased AA of normal diaphragm.
Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research
Authors: Wei Wei, Young Shik Shin, Chao Ma, Jun Wang, Meltem Elitas, Rong Fan, James R Heath
Journal: Genome Medicine (2013)

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing approaches for directly elucidating phosphoprotein signaling networks in cancer cells or for capturing high-resolution snapshots of immune system function in patients with various disease conditions. We discuss advances in single-cell proteomics platforms, with an emphasis on microchip methods. These methods can provide a direct correlation of morphological, functional and molecular signatures at the single-cell level. We also provide examples of how those platforms are being applied to both fundamental biology and clinical studies, focusing on immune-system monitoring and phosphoprotein signaling networks in cancer.
High frequency of TERT promoter mutation in small cell carcinoma of bladder, but not in small cell carcinoma of other origins
Authors: Xiaoyong Zheng, Jian Zhuge, Stephania M Bezerra, Sheila F Faraj, Enrico Munari, John T Fallon, Ximing J Yang, Pedram Argani, George J Netto, Minghao Zhong
Journal: Journal of Hematology & Oncology (2014)

TERT promoter mutations were recently discovered in melanoma by next generation sequencing. Subsequently, several malignancies including urothelial carcinoma were also found to be associated with the same TERT promoter mutations. Small cell carcinoma (SCC) of the urinary bladder is a rare subtype with an aggressive clinical course. Despite the frequent occurrence of TERT promoter mutations in urothelial carcinoma, the incidence of the mutations in SCC of the urinary bladder is unknown. In addition, as a potential molecular marker to distinguish SCC of the urinary bladder from SCC of the prostate, lung (SCLC) and other origins, this information may be clinically useful. We collected a total of 11 cases of SCC of the urinary bladder (10 cases are primary SCC of the urinary bladder; 1 case has primary SCC of the urinary bladder and liver metastasis). We also included 20 cases of SCLC, 2 cases of SCC of the prostate, 5 cases of Merkel cell carcinoma, and 6 cases of SCC from other sites (cervical, GE junction, breast, and soft tissue). In addition, 3 cases of non-neoplastic tissue from the matched SCC of bladder patient and 14 cases of benign urinary bladder were also included. All tumor sections have been examined to confirm the diagnosis and to make sure more than 20% are of tumor content. Genomic DNA was isolated from FFPE tissue and a fragment of the TERT promoter (145 bp) was amplified by PCR. The TERT promoter mutations are determined by bi-directional Sanger sequencing. All (11/11) SCC of the urinary bladder bear TERT promoter mutation C228T. Neither of SCC from all other origins nor matched non-neoplastic tissue contains the TERT promoter mutations. We demonstrated a high frequency TERT promoter mutation in SCC of the urinary bladder, but not in SCC of other origin, such as the prostate. The findings further illustrate molecular differences between SCC of the urinary bladder and SCC of other origins, despite their shared morphologic and immunophenotypic similarities. The TERT promoter mutation may be a biomarker differentiating SCC of the urinary bladder from SCC of other origins.