tbuckley/cabot-search huggingface dataset:
Effects of interferon-gamma on expression of cell surface receptors for collagen and deposition of newly synthesized collagen by cultured human lung fibroblasts.
Authors: J G Clark, T F Dedon, E A Wayner, W G Carter
Journal: Journal of Clinical Investigation (1989)

We used cultured human diploid lung fibroblasts as a model system to examine the effects of recombinant IFN-gamma on synthesis of collagen, matrix deposition of newly synthesized collagen, and the expression of cell surface receptors for collagen. Using [3H]proline-labeled cells we found that IFN-gamma resulted in dose-dependent inhibition of fibroblast collagen synthesis. Pulse-chase experiments to analyze compartmentalization of newly synthesized collagen showed that the decrease in collagen synthesis was confined to the soluble pool of procollagen in the medium, while extracellular matrix associated collagen was not changed, indicating that a larger proportion of newly synthesized collagen was deposited into the matrix in IFN-gamma exposed fibroblasts (34.2 vs. 25.3%). This increase in the efficiency of collagen matrix deposition was associated with enhanced expression of a cell surface receptor for collagen as detected by indirect immunofluorescence labeling and analysis by flow cytometry. Fibroblasts (IMR-90) cultured in the presence of IFN-gamma (1,000 U/ml) exhibited a twofold increase in mean linear fluorescence intensity compared with cells cultured under control conditions. The distribution of log fluorescence intensity in both control and IFN-gamma exposed cells was normally distributed about the mean, indicating that discrete subpopulations with respect to receptor expression were not present. Increased fluorescence intensity and log normal distribution of fluorescence intensity also were identified in IFN-gamma-treated lung fibroblasts from a normal adult individual and two strains obtained from patients with pulmonary fibrosis. These results indicate that IFN-gamma modulates fibroblast collagen matrix deposition as well as collagen synthesis. The associated increase in collagen receptors suggests that cytokine-mediated modulation of the cell surface maybe a contributing factor in regulation of fibroblast collagen accumulation in the extracellular matrix or in cellular interaction with collagen-containing matrix. Such an effect could modulate the interaction of fibroblasts with extracellular matrix at sites of inflammation and play an important role in the remodeling of matrix during repair from tissue injury.
Effects of heavy resistance exercise on fatigue and recovery during period of 48 h post-exercise in females
Authors: M Touba, A Lees
Journal: British Journal of Sports Medicine (2010)

The objective of study two was to establish the heavy resistance exercise volume and intensity to produce a fatigue effect of a 40% reduction in measured force variables and to establish the fatigue and recovery responses over 48-h period. Subjects were familiarised with the same testing procedures in the pilot study. All subjects performed three sets of six different exercises (lying leg curls, dumbbell lunges, barbell squats, leg extensions, straight leg deadlift, leg presses) at an intensity corresponding to 70% of 1 RM (8-10 repetitions). A 1-min rest period was allowed between exercises and a 3-min rest period between sets. The isometric force measurements were also obtained 2 h, 24 h and 48 h recovery for maximal voluntary contraction (MVC) and rate of force development (RFD). The data showed that there was a significant main effect of time on MVC for both legs (p=0.001). Post hoc analysis revealed a significant difference between pre- and post-exercise (p=0.001), pre-exercise and 2 h, 24 h (p=0.002) but no significant difference for 48 h (p=1.00). A significant main effect of time on MVC (p&lt;0.001) for the dominant leg. Pairwise comparisons showed a significant difference between pre- and post-exercise at 2 h (p=0.001), but no significant difference between pre-exercise and after 24 h and 48 h (p=1.00). The RFD for both legs (p&lt;0.001). Post-hoc analysis revealed a significant difference between pre- and post-exercise (p=0.001) and at 2 h, but no significant difference among pre-exercise, 24 h and 48 h (p=1.00). There was a significant main effect of time on RFD (p&lt;0.001) for the dominant leg. Pairwise comparisons showed a significant difference between pre- and post-exercise (p=0.000) but no significant difference between pre-exercise and 2, 24 and 48 h (p=1.00). In this study it was found that using both legs at 70% of 1 RM was still not enough for the desired reduction, so further studies should increase the intensity of 1 RM.
Alcohol and gastric acid secretion in humans.
Authors: S Chari, S Teyssen, M V Singer
Journal: Gut (1993)

The secretory response of gastric acid to pure ethanol and alcoholic beverages may be different because the action of the non-ethanolic contents of the beverage may overwhelm that of ethanol. Pure ethanol in low concentrations (&lt; 5% vol/vol) is a mild stimulant of acid secretion whereas at higher concentrations it has either no effect or a mildly inhibitory one. Pure ethanol given by any route does not cause release of gastrin in humans. Alcoholic beverages with low ethanol content (beer and wine) are strong stimulants of gastric acid secretion and gastrin release, the effect of beer being equal to the maximal acid output. Beverages with a higher ethanol content (whisky, gin, cognac) do not stimulate gastric acid secretion or release of gastrin. The powerful stimulants of gastric acid secretion present in beer, which are yet to be identified, are thermostable and anionic polar substances. The effect of chronic alcohol abuse on gastric acid secretion is not as predictable. Chronic alcoholic patients may have normal, enhanced, or diminished acid secretory capacity; hypochlorhydria being associated histologically with atrophic gastritis. There are no studies on the acute effect of alcohol intake on gastric acid secretion in chronic alcoholic patients. The acid stimulatory component of beer and wine needs to be characterised and its possible role in the causation of alcohol induced gastrointestinal diseases needs to be investigated.
Dexamethasone-induced increase in in vitro clonogenicity of human neoplasms.
Authors: J C Sloman, M J Murphy
Journal: Journal of Clinical Oncology (1984)

The addition of the corticosteroid hormone, dexamethasone, to the culture medium results in a significant enhancement of tumor colony growth in the human tumor clonogenic assay. Taking 20 as the mean minimum number of colonies per dish that allows evaluation of 122 cultured tumors, 67 were fully evaluable in the presence of dexamethasone whereas only 34 were evaluable when it was omitted. The addition of dexamethasone significantly (P less than .05) increased the number of evaluable tumors by 23. Tumors cultured included those of the breast, lung, colon, ovary, kidney, and stomach. The response to dexamethasone showed a dose-response relationship over a concentration range typical of corticosteroid receptor-mediated reactions, and it appeared to be steroid specific. Possible mechanisms for this hormone effect are discussed.
An Overnight High-Dose Dexamethasone Suppression Test for Rapid Differential Diagnosis of Cushing's Syndrome
Authors: J. BLAKE TYRRELL
Journal: Annals of Internal Medicine (1986)

We have developed a high-dose dexamethasone suppression test that can be administered overnight with a single 8-mg dose and used the new procedure in the differential diagnosis of 83 patients with Cushing's syndrome. In 76 patients with surgically or pathologically proven cause—60 with Cushing's disease, 7 with the ectopic adrenocorticotropic hormone syndrome, and 9 with adrenal tumors—suppression of plasma Cortisol levels to less than 50% of baseline indicated a diagnosis of Cushing's disease. The test had a sensitivity of 92%, a specificity of 100%, and a diagnostic accuracy of 93%. These values equal or exceed those of the standard 2-day test whether based on suppression of urinary 17hydroxycorticosteroids or plasma Cortisol. We conclude that this overnight, high-dose dexamethasone suppression test is practical and reliable in the differential diagnosis of Cushing's syndrome.
The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial
Authors: Philippe Menasché, Ottavio Alfieri, Stefan Janssens, William McKenna, Hermann Reichenspurner, Ludovic Trinquart, Jean-Thomas Vilquin, Jean-Pierre Marolleau, Barbara Seymour, Jérôme Larghero, Stephen Lake, Gilles Chatellier, Scott Solomon, Michel Desnos, Albert A. Hagège
Journal: Circulation (2008)

Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfarction scars. However, they have failed to determine whether this procedure was functionally effective and arrhythmogenic.This multicenter, randomized, placebo-controlled, double-blind study included patients with left ventricular (LV) dysfunction (ejection fraction < or = 35%), myocardial infarction, and indication for coronary surgery. Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar. All patients received an implantable cardioverter-defibrillator. The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography. The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias. Ninety-seven patients received myoblasts (400 or 800 million; n=33 and n=34, respectively) or the placebo (n=30). Myoblast transfer did not improve regional or global LV function beyond that seen in control patients. The absolute change in ejection fraction (median [interquartile range]) between 6 months and baseline was 4.4% (0.2; 7.3), 3.4% (-0.3; 12.4), and 5.2% (-4.4; 11.0) in the placebo, low-dose, and high-dose groups, respectively (P=0.95). However, the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group. Despite a higher number of arrhythmic events in the myoblast-treated patients, the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups.Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function. The increased number of early postoperative arrhythmic events after myoblast transplantation, as well as the capability of high-dose injections to revert LV remodeling, warrants further investigation.
T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B
Authors: Ying Ju, Nan Hou, Jing Meng, Xiaoyan Wang, Xiaoning Zhang, Di Zhao, Ying Liu, Faliang Zhu, Lining Zhang, Wensheng Sun, Xiaohong Liang, Lifen Gao, Chunhong Ma
Journal: Journal of Hepatology (2010)
Modification of Breast Cancer Risk in Young Women by a Polymorphic Sequence in the <b> <i>egfr</i> </b> Gene
Authors: Burkhard Brandt, Silke Hermann, Kurt Straif, Nicola Tidow, Horst Buerger, Jenny Chang-Claude
Journal: Cancer Research (2004)

The regulation of the epidermal growth factor receptor (egfr) gene in human cancer is not yet fully understood. Recent data on a polymorphic CA repeat located at the 5'-regulatory sequence in intron 1 of the egfr gene [egfr CA simple sequence repeat (SSR) I] point to a possible inheritance of cancer risk associated with the egfr gene. Furthermore, we have detected frequent allelic imbalances restricted to the egfr CA SSR I in breast cancer tissue and nontumorous breast tissue adjacent to invasive and in situ breast cancer representing amplifications. Therefore, we conducted a population-based case-control study to assess the relationship between the egfr polymorphism and breast cancer risk. Cases with a first primary breast cancer by age 50 years and age-matched population controls provided information on known and suspected risk factors. The allelic length of the egfr CA SSR was determined in 616 cases and 1072 population-sampled controls. Genotypes were categorized for analysis by allele length. Multivariate logistic regression was used to compare genotype distributions, accounting for other risk factors, and to investigate gene-environment interactions. We found a modifying effect, albeit no main effect, of the allelic length of the egfr polymorphism on breast cancer risk. The presence of two long alleles (>/==" BORDER="0">19 CA) was associated with a significantly elevated odds ratio (OR) of 10.4 [95% confidence interval (CI), 1.85-58.70] among women with a first-degree family history of breast cancer (P = 0.015 for interaction). The risk increase associated with high red meat consumption (OR, 10.68; 95% CI, 1.57-72.58) and the protective effect of high vegetable intake (OR, 0.07; 95% CI, 0.004-1.07) was also most pronounced among carriers of two long alleles (>/==" BORDER="0">19 CA). The length of the egfr CA SSR may increase the risk for familial breast cancers, and its effect could be modulated by dietary factors.
Functional Heterogeneity of Cancer-Associated Fibroblasts from Human Colon Tumors Shows Specific Prognostic Gene Expression Signature
Authors: Mercedes Herrera, Abul B.M.M.K. Islam, Alberto Herrera, Paloma Martín, Vanesa García, Javier Silva, Jose M. Garcia, Clara Salas, Ignacio Casal, Antonio García de Herreros, Félix Bonilla, Cristina Peña
Journal: Clinical Cancer Research (2013)

Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells.Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics.Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this "CAF signature" showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the "CAF signature."In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified.
Loss-of-function mutations in the filaggrin gene: no contribution to disease susceptibility, but to autoantibody formation against citrullinated peptides in early rheumatoid arthritis
Authors: U Huffmeier, U Boiers, J Lascorz, A Reis, H Burkhardt
Journal: Annals of the Rheumatic Diseases (2007)

Autoantibody formation to citrullinated (pro)filaggrin has proven to be a highly specific serological marker for rheumatoid arthritis (RA). To test the potential relevance of mutations of the filaggrin (FLG) gene for disease susceptibility and elicitation of humoural autoimmunity in RA, a case-control association study of three loss-of-function FLG variants was performed.DNA was obtained from 282 patients with early RA (mean disease duration: 6.5 months) and from 376 control individuals. Three loss-of-function variants of the FLG gene (*R501X, *2282del4 and *3702del1) were genotyped.No significant differences in genotype frequencies were observed between control probands and the population of RA patients. The FLG*3702del1 allele was not identified in any of the patients nor controls, and none of the probands was homozygous or compound heterozygous. In the RA cohort, heterozygous carriers of either of the FLG variants exhibited a significantly elevated prevalence of autoantibodies to citrullinated peptides (CCP-2) (80%) compared to non-carriers (51.9%) (p = 0.018, odds ratio: 3.71 (1.20-11.46)).The investigated FLG variants do not confer an overall risk for the development of RA. However, loss-of-function mutations in the FLG gene may contribute to the development of humoural autoimmunity, targeting citrullinated determinants in early RA.
Association of <i>Chlamydia pneumoniae</i> With Coronary Artery Disease and Its Progression Is Dependent on the Modifying Effect of Mannose-Binding Lectin
Authors: Szabolcs Rugonfalvi-Kiss, Valéria Endrész, Hans O. Madsen, Katalin Burián, Jenô Duba, Zoltán Prohászka, István Karádi, László Romics, Éva Gönczöl, George Füst, Peter Garred
Journal: Circulation (2002)

Background— The possible association between coronary artery disease (CAD) and Chlamydia pneumoniae (C pneumoniae) infection is controversial. On the basis of the recent suggestion that mannose-binding lectin (MBL) variant alleles are related to an increased risk of severe atherosclerosis, and on the in vitro interaction of MBL with C pneumoniae , we asked whether MBL might contribute to CAD in conjunction with C pneumoniae . Methods and Results— Antibodies to C pneumoniae were measured by immunofluorescence and MBL alleles were determined by polymerase chain reaction technique in samples from 210 patients with CAD and 257 healthy subjects from Hungary collected between 1995 and 1996. A higher percentage of patients with CAD were anti- C pneumoniae positive as compared with the control group ( P =0.058). However, at logistic regression analysis adjusted to age, sex, and serum lipid levels, this difference was confined only to subjects carrying MBL variant alleles ( P =0.035, odds ratio 2.63, [95% CI: 1.07 to 6.45]). In contrast, no significant difference was seen in those homozygous for the normal MBL allele ( P =0.412). During a 65±5.8-month follow-up period, major outcomes (new myocardial infarction, and/or bypass operation or cardiovascular death) occurred in 11 C pneumoniae positive and 3 C pneumoniae negative patients. In the C pneumoniae positive group, the odds ratio of development of outcomes was 3.27 (95% CI: 1.10 to 9.71, P =0.033) in the carriers of the MBL variant alleles compared with the homozygous carriers of the normal MBL allele. Conclusions— These results indicate that infection with C pneumoniae leads mainly to the development and progression of severe CAD in patients with variation in the MBL gene.
Eph-Dependent Tyrosine Phosphorylation of Ephexin1 Modulates Growth Cone Collapse
Authors: Mustafa Sahin, Paul L. Greer, Michael Z. Lin, Heather Poucher, Johann Eberhart, Susanne Schmidt, Tracy M. Wright, Steven M. Shamah, Sinead O’Connell, Christopher W. Cowan, Linda Hu, Jeffrey L. Goldberg, Anne Debant, Gabriel Corfas, Catherine E. Krull, Michael E. Greenberg
Journal: Neuron (2005)
<i>PIK3CA</i> Mutations May Be Discordant between Primary and Corresponding Metastatic Disease in Breast Cancer
Authors: Jeanette Dupont Jensen, Anne-Vibeke Laenkholm, Ann Knoop, Marianne Ewertz, Raj Bandaru, Weihua Liu, Wolfgang Hackl, J. Carl Barrett, Humphrey Gardner
Journal: Clinical Cancer Research (2010)

PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome. In a cohort of patients where both primary and metastatic lesions were available, the objective was to assess changes in PIK3CA mutations. We wished to discern whether selective pressures occur and the influence of PIK3CA mutation on time to recurrence.Formalin-fixed paraffin-embedded tumor blocks were obtained from 104 patients with paired samples from primary tumors and corresponding asynchronous metastatic breast tumors. Samples were analyzed for PIK3CA mutations (exons 9 and 20) as well as immunohistochemical evaluation for PTEN, pAKT, Ki67, ER, and HER2.PIK3CA mutation was detected in 45% of the primary tumors. Overall, there was a net gain in mutation in metastatic disease, to 53%; nonetheless, there were instances where metastases were wild type in patients with PIK3CA mutant primary tumors. Laser capture microdissection on a subset of cases revealed microheterogeneity for PIK3CA mutational status in the primary tumor. PIK3CA mutants overall showed a significantly longer time to first recurrence than wild type cases (P = 0.03).PIK3CA mutations occur at high frequency in primary and metastatic breast cancer; these may not necessarily confer increased aggressiveness as mutants had a longer time to recurrence. Because PIK3CA status quite frequently changes between primary and metastatic disease, it emphasizes the necessity of assessing the PIK3CA status in the metastatic lesion for selection of PIK3CA inhibitor therapy.
Bacteraemia in outpatients with community-acquired pneumonia
Authors: Catia Cillóniz, Albert Gabarrús, Jordi Almirall, Rosanel Amaro, Mariano Rinaudo, Chiara Travierso, Michael Niederman, Antoni Torres
Journal: European Respiratory Journal (2015)

Community-acquired pneumonia (CAP) is a frequent cause of morbidity and mortality worldwide. Approximately 20% of CAP patients require hospital admission [1, 2], leaving a large percentage of patients treated in the community as outpatients. In addition, bacteraemia is associated with worse outcomes, such as a higher prevalence of intensive care unit (ICU) admission and longer length of stay. Current international guidelines [1, 3, 4] do not recommend blood cultures as part of routine microbiological tests in patients managed in the community. However, there is little information regarding the prevalence and clinical impact of bacteraemia in CAP patients treated outside the hospital. Previous studies reported incidences of 2.1–7%, respectively [5–8]. However, few data exist regard predictive factors and the clinical outcomes associated with positive blood cultures in this population [8]. The current study aimed to determine the predictive factors and the clinical outcomes of bacteraemic outpatients with CAP, and describe their clinical, epidemiological and microbiological characteristics. CAP patients who are discharged but have a high risk of bacteraemia can be identified using risk factors <http://ow.ly/TcMiq>
Pneumatosis cystoides intestinalis in Iran.
Authors: F Namdaran, W Dutz, A Ovasepian
Journal: Gut (1979)

Nineteen cases of pneumatosis cystoides intestinalis all affecting adults and all involving the small intestine have been collected in two centres of Iran (Shiraz and Tehran) over a 20 year period, the pathological findings being divided into three groups: pure submucosal, combined submucosal and subserosal, and pure subserosal cysts. Experimental PCI was produced in cadavers using high pressure oxygen insuflation of the lungs, thus lending support to the theory that it has a mechanical origin. Other theories of aetiology include tumour, nutritional deficiencies, gas-forming organisms, alveolar rupture, and acid-base disturbance. In most of the cases presented high intraluminal pressure produced by obstruction appeared to force intraluminal gas through a breach in the mucosa into either the lymphatics or perivascular tissue to produce PCI. It is concluded that the aetiology in the vast majority of adult cases is mechanical in nature and that bacteria seem to play very little part, unlike their role in the PCI of infants.