tbuckley/cabot-search huggingface dataset:
Phenotypic Heterogeneity of the Endothelium
Authors: William C. Aird
Journal: Circulation Research (2007)

Endothelial cells, which form the inner cellular lining of blood vessels and lymphatics, display remarkable heterogeneity in structure and function. This is the second of a 2-part review on the phenotypic heterogeneity of blood vessel endothelial cells. The first part discusses the scope, the underlying mechanisms, and the diagnostic and therapeutic implications of phenotypic heterogeneity. Here, these principles are applied to an understanding of organ-specific phenotypes in representative vascular beds including arteries and veins, heart, lung, liver, and kidney. The goal is to underscore the importance of site-specific properties of the endothelium in mediating homeostasis and focal vascular pathology, while at the same time emphasizing the value of approaching the endothelium as an integrated system.
Pulmonary granuloma infiltration in sarcoidosis, inflamatory markers and domestic exposure to fungi
Authors: Marjeta Tercelj-Zorman, Barbara Salobir, Mirjana Zupancic, Branka Wraber, Ragnar Rylander
Journal: European Respiratory Journal (2013)

Background. Previous studies have demonstrated high levels of inflammatory mediators in sarcoidosis patients and an increased exposure to fungi in their homes. This study was performed to measure the amount of β-glucan, different inflammatory mediators in serum, and to relate the levels to the degree of pulmonary granuloma infiltration.

Material and Methods. The subjects comprise 98 patients with sarcoidosis and 27 controls. Exposure to fungi at home was determined by taking air samples and analysing for N-acetylhexosaminidase (NAHA). β-glucan was measured in broncho-alveolar lavage (BAL), and TNF-α, IL-6, IL-10, IL-12, ACE, and chitotrioxidase in serum. X-rays were taken and the degree of granuloma infiltration was judged, using a numerical score.

Results. The NAHA values in the homes of sarcoidosis than in controls (p = 0.017). Significantly higher levels of β-glucan were found in BAL in sarcoidosis as compared to controls (p<0.001). The relation between β-glucan in BAL and NAHA home in sarcoidosis was significant (p=0.002). There were significant relationships between the degree of granuloma infiltration on x-ray and the levels of the different inflammatory mediators TNF-α (p<0.001), IL-6 (p=0.006) and IL-12 (p<0.001). In contrast to the other mediators, IL-10 values were not related to the x-ray scores and showed a biphasic relationship.

Conclusions. A specific agent, previously suspected to be related to the risk of sarcoidosis, has been detected in high levels in the lung of subjects with the disease. The levels were related to the home exposure to fungi. The results suggest that a possible exposure to fungi should be explored when dealing with patients with sarcoidosis.
Improving the Biomarker Pipeline to Develop and Evaluate Cancer Screening Tests
Authors: Stuart G. Baker
Journal: JNCI Journal of the National Cancer Institute (2009)

The biomarker pipeline to develop and evaluate cancer screening tests has three stages: identification of promising biomarkers for the early detection of cancer, initial evaluation of biomarkers for cancer screening, and definitive evaluation of biomarkers for cancer screening. Statistical and biological issues to improve this pipeline are discussed. Although various recommendations, such as identifying cases based on clinical symptoms, keeping biomarker tests simple, and adjusting for postscreening noise, have been made previously, they are not widely known. New recommendations include more frequent specimen collection to help identify promising biomarkers and the use of the paired availability design with interval cases (symptomatic cancers detected in the interval after screening) for initial evaluation of biomarkers for cancer screening.
Sarcoidosis possibly predisposing to disseminated histoplasmosis.
Authors: J G Tebib, M A Piens, M Guillaux, D Colomb, J P Garin, R Tete
Journal: Thorax (1988)

InEurope mostauthors consider that histoplasmosis dueto Histoplasma capsulatum isarare imported fungal disease that isonly diagnosed whenitappears inthedisseminated form. Suchapresentation isveryunusual inareas whereitis endemic.' This paradox isexplicable because inmostcases infection islocalised, sothatinendemic areas cases of dissemination represent avery small proportion ofthetotal; where histoplasmosis isnotendemic butisseen amongthose whohavelived ortravelled inregions whereitisendemic, disseminated disease maypresent manyyears after their return andrepresents alarge proportion ofconfirmed cases. Underlying immunosuppression hasbeenreported in44%of patients withdisseminated disease2: predisposing factors include haematological malignancy, useofimmunosuppressive drugs (corticosteroids, cytotoxic drugs), orimmunologically depressive disease suchasAIDS,3 systemic lupus erythematosus, anddiabetes mellitus.4 Whendissemination occurs itpredominantly affects the lungs, theadrenal glands, andthereticuloendothelial system, butmayalso affect other organs, suchasthepharynx, liver, andthecentral nervous system, leading tothepeculiar aspects thathavebeendescribed.5 Theeffects maybe confused withthose ofother systemic diseases, suchas tuberculosis andconnective tissue diseases. Thediagnosis becomes particularly difficult whensystemic diseases suchas these predispose todissemination ofhistoplasmosis. We report acase offatal subacute histoplasmosis developing ina patient withprobable sarcoidosis.
THE ANTIBODY-FORMATION BY POLYSACCHARIDS
Authors: Shoji Nishimura
Journal: The Journal of Experimental Medicine (1929)

1. By complement fixation tests, it has been clearly demonstrated that the sera of rabbits immunized with inulin, soluble starch and dextrine contain specific antibodies. 2. All these immune sera gave a negative precipitation reaction. 3. The kind of dextrine which has a construction very near to starch has an antigenic property, but those in a state of further decomposition do not give rise to antibodies. 4. All the three kinds of polysaccharids have power to produce antibodies without any vehicle. Dextrine is the only one of the three that gives rise to immune bodies more readily when pig serum is added to it. 5. Regarded as antigens, inulin stood first and soluble starch and dextrine next in order. 6. All three kinds of polysaccharids that were employed gave a negative protein color reaction. All of them, however, contained nitrogen. It has been proved that the large portion of the nitrogen contained in the soluble starch is derived from its protein contents. 7. It is suggested that in the production of immune bodies by these three kinds of polysaccharids, proteins might play the part of the vehicle. This is, however, still to be determined.
Supraumbilical cutaneous lesions after transcatheter arterial chemoembolization for hepatocellular carcinoma
Authors: Elena del Alcázar Viladomiu, Arantxa López Pestaña, Anna Tuneu Valls, Iñaki Prieto Argarate, Juan Ignacio Arenas Ruiz Tapiador
Journal: Journal of the American Academy of Dermatology (2014)
LIPASES AND CARBOXYLESTERASES: Possible Roles in the Hepatic Metabolism of Retinol
Authors: Earl H. Harrison
Journal: Annual Review of Nutrition (1998)

▪ Abstract The formation and hydrolysis of retinyl esters are key processes in the metabolism of the fat-soluble micronutrient vitamin A. Long-chain acyl esters of retinol are the major chemical form of vitamin A (retinoid) stored in the body. Retinyl esters are found in a variety of tissues and cell types, but most of the total body retinoid is accounted for by the retinyl esters stored in the liver. Thus, these esters represent the major endogenous source of retinoid that can be delivered to peripheral tissues for conversion to biologically active forms. This review summarizes current knowledge about the identity, function, and regulation of the hepatic enzymes potentially involved in catalyzing the hydrolysis of retinyl esters. These enzymes include several known and characterized lipases and carboxylesterases. Although there is accumulating evidence that these enzymes function as retinyl ester hydrolases in vitro, it is not clear which play important physiological roles in hepatic retinyl ester metabolism.
Pre- and post-operative symptoms of patients with stomal ulcers.
Authors: J H Jones, M J Langman
Journal: Gut (1967)

EDITORIAL COMMENT This study of 309 patients suffering from stomal ulcer after operation for duodenal (not gastric) ulcer shows that patients with duodenal ulcer who have had a perforation are more likely to develop a stomal ulcer after operation than those who have not perforated.
Hyperplasia of Smooth Muscle in Mild to Moderate Asthma without Changes in Cell Size or Gene Expression
Authors: Prescott G. Woodruff, Gregory M. Dolganov, Ronald E. Ferrando, Samantha Donnelly, Steven R. Hays, Owen D. Solberg, Roderick Carter, Hofer H. Wong, Peggy S. Cadbury, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Bronchial hyperresponsiveness in mild to moderate asthma may result from airway smooth muscle cell proliferation or acquisition of a hypercontractile phenotype. Because these cells have not been well characterized in mild to moderate asthma, we examined the morphometric and gene expression characteristics of smooth muscle cells in this subgroup of patients with asthma. Using bronchial biopsies from 14 subjects with mild to moderate asthma and 15 control subjects, we quantified smooth muscle cell morphology by stereology and the expression of a panel of genes related to a hypercontractile phenotype of airway smooth muscle, using laser microdissection and two-step real-time polymerase chain reaction. We found that airway smooth muscle cell size was similar in both groups, but cell number was nearly twofold higher in subjects with asthma (p = 0.03), and the amount of smooth muscle in the submucosa was increased 50-83% (p < 0.005). Gene expression profiling in smooth muscle cells showed no difference in the expression of genes encoding phenotypic markers in cells from healthy subjects and subjects with asthma (all p > 0.1). We conclude that airway smooth muscle proliferation is a pathologic characteristic of subjects with mild to moderate asthma. However, smooth muscle cells in mild to moderate asthma do not show hypertrophy or gene expression changes of a hypercontractile phenotype observed in vitro.
Calcium Intake and Risk of Colon Cancer in Women and Men
Authors: K. Wu
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Calcium has been hypothesized to reduce the risk of colon cancer, and in a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. We examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Methods: Our study population included 87 998 women in NHS and 47 344 men in HPFS who, at baseline (1980 for NHS and 1986 for HPFS), completed a food frequency questionnaire and provided information on medical history and lifestyle factors. Dietary information was updated at least every 4 years. During the follow-up period (1980 to May 31, 1996 for the NHS cohort; 1986 to January 31, 1996 for the HPFS cohort), 626 and 399 colon cancer cases were identified in women and men, respectively. Pooled logistic regression was used to estimate relative risks (RRs), and all statistical tests were two-sided. Results: In women and men considered together, we found an inverse association between higher total calcium intake (>1250 mg/day versus ≤500 mg/day) and distal colon cancer (women: multivariate RR = 0.73, 95% confidence interval [CI] = 0.41 to 1.27; men: RR = 0.58, 95% CI = 0.32 to 1.05; pooled RR = 0.65, 95% CI = 0.43 to 0.98). No such association was found for proximal colon cancer (women: RR = 1.28, 95% CI = 0.75 to 2.16; men: RR = 0.92, 95% CI = 0.45 to 1.87; pooled RR = 1.14, 95% CI = 0.72 to 1.81). The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal. Conclusions: Higher calcium intake is associated with a reduced risk of distal colon cancer. The observed risk pattern was consistent with a threshold effect, suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction. Future investigations on this association should concentrate on specific cancer subsites and on the dose–response relationship.
Hospital admission rates for COPD: the inverse care law is alive and well
Authors: R. C. M. Jones
Journal: Thorax (2010)

In times of fiscal restrictions, health services need to invest resources where they will give the best return. Reducing hospital admissions by investing in improved disease management in the community is a prime target for those trying to save money.1 In their paper on the association of population and primary healthcare factors with hospital admissions for chronic obstructive pulmonary disease (COPD), Calderon-Larranaga et al 2 have shone an overdue spotlight on the determinants of admission rates. The authors have integrated routinely collected data sources on a breathtaking scale, using data from over 8000 practices caring for over 53 million people in England. They report a dramatic variation in admission rates from 125 to 646 per 100 000 of population, which demands an explanation.

Among population factors, smoking rates and deprivation were unsurprisingly associated with higher prevalence and admission rates. The prevalence of undiagnosed COPD was also found to be an important contributor. To calculate undiagnosed prevalence it was necessary to estimate the expected prevalence rate using a mathematical model and to subtract the diagnosed prevalence determined by primary care disease registers. Several problems arise from this approach. Among others, disease registers are inaccurate—in one study 27% of those on COPD registers did not meet the spirometric criteria for COPD.3 Furthermore, the mathematical model was based on deprivation according to post codes, a process which may underestimate deprivation in practice populations.4

Various explanations can be postulated as to why the undiagnosed prevalence may affect admission rates. For instance, undiagnosed patients are likely to be denied interventions which might prevent admissions. On the other hand, a high undiagnosed prevalence rate may simply reflect a high disease burden due to …
Pseudochylothorax in pleural effusion due to coronary artery bypass surgery
Authors: E Garcia-Pachon, LC Fernandez, F Lopez-Azorin, I Padilla-Navas
Journal: European Respiratory Journal (1999)

This study describes a 64-yr-old male with a chronic left pleural effusion following a coronary artery bypass 3 yrs earlier. On thoracocentesis, turbid fluid was obtained with crystals of cholesterol on microscopic examination, establishing the diagnosis of pseudochylothorax. The pleural fluid cholesterol level was 207 mg x dL(-1) (5.36 mmol x L(-1)). This is the first report of pseudochylothorax in a chronic pleural effusion due to coronary artery bypass surgery.
Gene Expression Profiling for Survival Prediction in Pediatric Rhabdomyosarcomas: A Report From the Children's Oncology Group
Authors: Elai Davicioni, James R. Anderson, Jonathan D. Buckley, William H. Meyer, Timothy J. Triche
Journal: Journal of Clinical Oncology (2010)

We investigated whether tumors from diagnostic biopsies of primary rhabdomyosarcoma (RMS) contain relevant prognostic information in the form of gene expression signatures that can be used to model and predict outcome of patients.A 22,000-probe set microarray was used to evaluate 120 RMS specimens and correlate gene expression patterns to survival. Multivariate gene expression models or metagenes were developed using cross-validated Cox regression proportional hazards modeling and were evaluated using Kaplan-Meier analysis.A 34-metagene, based on expression patterns of 34 genes, was highly predictive of outcome. It was not highly correlated with individual clinical risk factors such as patient age, stage, tumor size, or histology. However, it was correlated with a risk classification used by the Children's Oncology Group and the biologic subsets of alveolar histology tumors.These data support further evaluation of RMS metagenes to discriminate patients with good prognosis from those with poor prognosis, with the potential to direct risk-adapted therapy.
Dependence of Oxalate Absorption on the Daily Calcium Intake
Authors: Gerd E. von Unruh, Susanne Voss, Tilman Sauerbruch, Albrecht Hesse
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Two to 20% of ingested oxalate is absorbed in the gastrointestinal tract of healthy humans with a daily 800 mg calcium intake. Calcium is the most potent modifier of the oxalate absorption. Although this has been found repeatedly, the exact correlation between calcium intake and oxalate absorption has not been assessed to date. Investigated was oxalate absorption in healthy volunteers applying 0.37 mmol of the soluble salt sodium [13C2]oxalate in the calcium intake range from 5 mmol (200 mg) calcium to 45 mmol (1800 mg) calcium. Within the range of 200 to 1200 mg calcium per day, oxalate absorption depended linearly on the calcium intake. With 200 mg calcium per day, the mean absorption (± SD) was 17% ± 8.3%; with 1200 mg calcium per day, the mean absorption was 2.6% ± 1.5%. Within this range, reduction of the calcium supply by 70 mg increased the oxalate absorption by 1% and vice versa. Calcium addition beyond 1200 mg/d reduced the oxalate absorption only one-tenth as effectively. With 1800 mg calcium per day, the mean absorption was 1.7% ± 0.9%. The findings may explain why a low-calcium diet increases the risk of calcium oxalate stone formation.
Accelerated Rates of Intron Gain/Loss and Protein Evolution in Duplicate Genes in Human and Mouse Malaria Parasites
Authors: C. I. Castillo-Davis
Journal: Molecular Biology and Evolution (2004)

Very little is known about molecular evolution in the human malaria parasite Plasmodium falciparum. Given the potentially important role that introns play in directing transcription and the posttranscriptional control of gene expression, we compare rates of intron/gain loss and intronic substitution in P. falciparum and the rodent malaria P. y. yoelii in both orthologous and duplicate genes. Specifically, we test the hypothesis that intron gain/loss and protein evolution is accelerated in duplicate genes versus orthologous genes in both parasites using the genome sequence of both species. We find that duplicate genes in both P. falciparum and P. y. yoelii exhibit a dramatic acceleration of both intron gain/loss and protein evolution in comparison with orthologs, suggesting increased directional and/or relaxed selection in duplicate genes. Further, we find that rates of intron gain/loss and protein evolution are weakly coupled in orthologs but not paralogs, supporting the hypothesis that selection acts on genes as functionally integrated units after speciation but not necessarily after gene duplication. In contrast, we find that rates of nucleotide substitution do not differ significantly between intronic sites and synonymous sites among duplicate genes, implying that a large fraction of intronic sites in Plasmodium evolve under little or no selective constraint.
Endocytosis in Entamoeba histolytica. Evidence for a unique non-acidified compartment.
Authors: S B Aley, Z A Cohn, W A Scott
Journal: The Journal of Experimental Medicine (1984)

Our studies on endocytosis in Entamoeba histolytica trophozoites suggest that there are two vacuolar compartments in this organism. The first compartment consists of large vacuoles (greater than 2 microns diameter). As measured by the fluid phase markers, fluorescein isothiocyanate (FITC)-dextran and horseradish peroxidase (HRP), this compartment is a rapid equilibrium with the external milieu and is constantly exchanging (1-2 h) its contents with the external medium. The contents of these vacuoles are not acidified. This together with the absence of degradation of fluid phase markers clearly differentiates these vacuoles from lysosomes of eucaryotes. By labeling externally disposed peptides on the surface membrane of trophozoites with 125I, we could show that the surface membrane was rapidly internalized over a 2-h period and then reached a plateau. All major 125I surface proteins, with the exception of a set of peptides in the 40,000 molecular weight range, were interiorized and approximately 60% of the total radiolabel were found to be in the internal membrane fraction at any given time. The kinetics of this process were similar to those for the uptake of fluid phase markers and are best explained by cycling of the surface membrane into the vacuolar compartment(s) and then back to the cell surface. The second vacuolar compartment consisted of small vesicles (less than 2 microns diameter) with acidified contents as indicated by acridine orange uptake. The endocytic nature of these vesicles was shown by their slow (days) labeling with FITC-dextran, and spectral analysis of internalized FITC-dextran confirmed that this second compartment is acidified (pH 5.2).
Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology
Authors: Masahito Kamanaka, Samuel Huber, Lauren A. Zenewicz, Nicola Gagliani, Chozhavendan Rathinam, William O'Connor, Yisong Y. Wan, Susumu Nakae, Yoichiro Iwakura, Liming Hao, Richard A. Flavell
Journal: The Journal of Experimental Medicine (2011)

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RBlo (regulatory T cell [Treg cell]–depleted CD45RBlo) but not CD45RBhi CD4+ T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of Treg cell–depleted CD45RBlo CD4+ T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RBhi T cells. In contrast to the CD45RBhi transfer colitis model, in which IL-22 is protective, we found that T cell–derived IL-22 was pathogenic upon transfer of Treg cell–depleted CD45RBlo T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RBhi) and memory/effector (Treg cell–depleted CD45RBlo) cells and different ways that IL-22 impacts inflammatory bowel disease.