tbuckley/cabot-search huggingface dataset:
Bradykinin Decreases Plasminogen Activator Inhibitor-1 Expression and Facilitates Matrix Degradation in the Renal Tubulointerstitium under Angiotensin-Converting Enzyme Blockade
Authors: Hirokazu Okada, Yusuke Watanabe, Tomohiro Kikuta, Tatsuya Kobayashi, Yoshihiko Kanno, Takeshi Sugaya, Hiromichi Suzuki
Journal: Journal of the American Society of Nephrology (2004)

A number of experimental and clinical investigations support the notion that angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II type 1 receptor blocker (ARB) compounds attenuate renal fibrosis. Fibrosis can be attenuated by either suppressing matrix formation or facilitating matrix degradation. In this study, drugs of ACEi and ARB classes were tested for their ability to facilitate matrix degradation in the kidney. A murine model system in which cyclosporin A (CsA) treatment for a specified period caused interstitial matrix deposition in the kidney was used. CsA was then discontinued, and experimental procedures were initiated to investigate matrix degradation. Benazepril, an ACEi, facilitated matrix degradation via the bradykinin (BK) B2 receptor on tubular epithelial cells in the kidney, whereas CGP-48933, an ARB, did not. In this murine model of CsA nephropathy under ACE blockade, plasminogen activator inhibitor-1 (PAI-1) expression was decreased in tubular epithelial cells, possibly leading to conversion of plasminogen to plasmin by plasminogen activator and subsequent activation of matrix metalloproteinases. These findings were confirmed in this study by measurements of plasmin activity, collagenolytic activity, and matrix metalloproteinase activities in the kidneys. In tubular epithelial cells stimulated in vitro, BK suppressed PAI-1 gene expression. All of these results suggest that ACEi can decrease PAI-1 expression via BK, thereby facilitating matrix degradation via activation of degradative enzymes to reduce interstitial matrix deposition.
Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis–associated glomerular injury
Authors: Uma Potla, Jie Ni, Justin Vadaparampil, Guozhe Yang, Jeremy S. Leventhal, Kirk N. Campbell, Peter Y. Chuang, Alexei Morozov, John C. He, Vivette D. D’Agati, Paul E. Klotman, Lewis Kaufman
Journal: Journal of Clinical Investigation (2014)

Injury to the specialized epithelial cells of the glomerulus (podocytes) underlies the pathogenesis of all forms of proteinuric kidney disease; however, the specific genetic changes that mediate podocyte dysfunction after injury are not fully understood. Here, we performed a large-scale insertional mutagenic screen of injury-resistant podocytes isolated from mice and found that increased expression of the gene Rap1gap, encoding a RAP1 activation inhibitor, ameliorated podocyte injury resistance. Furthermore, injured podocytes in murine models of disease and kidney biopsies from glomerulosclerosis patients exhibited increased RAP1GAP, resulting in diminished glomerular RAP1 activation. In mouse models, podocyte-specific inactivation of Rap1a and Rap1b induced massive glomerulosclerosis and premature death. Podocyte-specific Rap1a and Rap1b haploinsufficiency also resulted in severe podocyte damage, including features of podocyte detachment. Over-expression of RAP1GAP in cultured podocytes induced loss of activated β1 integrin, which was similarly observed in kidney biopsies from patients. Furthermore, preventing elevation of RAP1GAP levels in injured podocytes maintained β1 integrin-mediated adhesion and prevented cellular detachment. Taken together, our findings suggest that increased podocyte expression of RAP1GAP contributes directly to podocyte dysfunction by a mechanism that involves loss of RAP1-mediated activation of β1 integrin.
Air pollution effects in the elderly: introduction
Authors: M. Decramer, R. Loddenkemper, J. Boe, J. Roca, M. Zelter
Journal: European Respiratory Journal (2003)

At the 1998 European Respiratory Society (ERS) Congress in Geneva, M. Decramer (at the time Chairman of the Scientific Programme Committee) and R. Loddenkemper (President) had the idea to follow a new avenue in the activity of the Society: i.e. to foster the participation of the European respirologists in the research activity funded by the European Union.

They asked A. Davies, an experienced British retired professor of molecular biology, to be the ERS consultant for the European Union (EU)-related activities, and gathered a bunch of ERS members. Among them, G. Viegi (a respiratory epidemiologist, newly elected Head of the Occupation and Epidemiology Assembly) and T. Sandstrom (a pulmonary physician and basic scientist, member of the Occupational and Environmental Health Working Group) were invited to submit a project on air pollution effects. They identified the elderly ( i.e. ≥65 yrs) as a segment of the general population which might be particularly vulnerable to the effects of air pollution and for whom there was lack of knowledge, according to the MEDLINE search.

G. Viegi and T. Sandstrom prepared, with the invaluable assistance of T. Davies, a proposal which was submitted to the EU in October 1999, approved in April 2000 and the contract started to be effective in October 2000.

The proposal concerned holding a conference as an accompanying measure to Key Action 4, Environment and Health, of the Quality of Life work program. A …
VOLTAGE-GATED ION CHANNELOPATHIES: Inherited Disorders Caused by Abnormal Sodium, Chloride, and Calcium Regulation in Skeletal Muscle
Authors: Eric P. Hoffman, Ph.D
Journal: Annual Review of Medicine (1995)

▪ Abstract The pathological genetic defects in the inherited myotonias and periodic paralyses were recently elucidated using molecular genetic studies. These disorders are usually transmitted as a dominant trait from an affected parent to a child. The many clinical symptoms include cold-induced uncontrollable contraction of muscle, potassium-induced contraction and paralysis, myotonia with dramatic muscular hypertrophy, muscle stiffness, and insulin-induced paralysis (in males). Horses afflicted with the disorder can suddenly collapse, despite an impressive physique. In the past three years, these clinically defined disorders have been shown to share a common etiology: subtle defects of ion channels in the muscle-fiber membrane. Although the specific ion channel involved varies depending on the disease, most patients have single amino acid changes in the channel proteins, with both normal and mutant channels present in each muscle fiber. For each patient, we can now establish a precise molecular diagnosis in the face of overlapping clinical symptoms and begin specific pharmacological treatment based on the primary problem. These studies have also provided insight into basic muscle biology and emphasize the careful regulation of ions in muscle excitation.
Trial of 2009 Influenza A (H1N1) Monovalent MF59-Adjuvanted Vaccine
Authors: Tristan W. Clark, Manish Pareek, Katja Hoschler, Helen Dillon, Karl G. Nicholson, Nicola Groth, Iain Stephenson
Journal: New England Journal of Medicine (2009)

The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority.We conducted a single-center study, involving 176 adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms. Subjects were randomly assigned to receive two intramuscular injections of vaccine containing 7.5 microg of hemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21; or two 3.75-microg doses of MF59-adjuvanted vaccine, or 7.5 or 15 microg of nonadjuvanted vaccine, administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay and a microneutralization assay on days 0, 14, 21, and 42 after injection of the first dose.The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively; reactions were more common with the MF59-adjuvanted vaccine than with nonadjuvanted vaccine. Three subjects reported fever, with a temperature of 38 degrees C or higher, after either dose. Antibody titers, expressed as geometric means, were higher at day 21 among subjects who had received one dose of MF59-adjuvanted vaccine than among those who had received one dose of nonadjuvanted vaccine (P<0.001 by the microneutralization assay). By day 21, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 77 to 96% and 92 to 100% of subjects receiving MF59-adjuvanted vaccine, respectively, and in 63 to 72% and 67 to 76% of those receiving nonadjuvanted vaccine, respectively. By day 42, after two doses of vaccine, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 92 to 100% and 100% of recipients of MF59-adjuvanted vaccine, respectively, and in 74 to 79% and 78 to 83% of recipients of nonadjuvanted vaccine, respectively.Monovalent 2009 influenza A (H1N1) MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection after a single dose is administered. (ClinicalTrials.gov number, NCT00943358).
Mechanism of immediate recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation
Authors: Aman Chugh, Hiroshi Tada, Sohail Hassan, Christoph Scharf, Radmira Greenstein, Mehmet Ozaydin, Frank Pelosi, Bradley P. Knight, S.Adam Strickberger, Fred Morady, Hakan Oral
Journal: Journal of the American College of Cardiology (2002)
Prevalence of working smoke alarms in local authority inner city housing: randomised controlled trial
Authors: D. Rowland
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To identify which type of smoke alarm is most likely to remain working in local authority inner city housing, and to identify an alarm tolerated in households with smokers. <b>Design:</b> Randomised controlled trial. <b>Setting:</b>Two local authority housing estates in inner London. <b>Participants:</b> 2145 households. <b>Intervention:</b> Installation of one of five types of smoke alarm (ionisation sensor with a zinc battery; ionisation sensor with a zinc battery and pause button; ionisation sensor with a lithium battery and pause button; optical sensor with a lithium battery; or optical sensor with a zinc battery). <b>Main outcome measure:</b> Percentage of homes with any working alarm and percentage in which the alarm installed for this study was working after 15 months. <b>Results:</b> 54.4% (1166/2145) of all households and 45.9% (465/1012) of households occupied by smokers had a working smoke alarm. Ionisation sensor, lithium battery, and there being a smoker in the household were independently associated with whether an alarm was working (adjusted odds ratios 2.24 (95% confidence interval 1.75 to 2.87), 2.20 (1.77 to 2.75), and 0.62 (0.52 to 0.74)). The most common reasons for non-function were missing battery (19%), missing alarm (17%), and battery disconnected (4%). <b>Conclusions:</b> Nearly half of the alarms installed were not working when tested 15 months later. Type of alarm and power source are important determinants of whether a household had a working alarm. <h3>What is already known on this topic</h3> Functioning smoke alarms can reduce the risk of death in the event of a house fire Many local authorities install smoke alarms in their properties Several different types of smoke alarm are available <h3>What this study adds</h3> Only half of the smoke alarms installed in local authority housing were still working 15 months later Ionising smoke alarms with long life lithium batteries were most likely to remain functioning Installing smoke alarms may not be an effective use of resources
A Post-Freudian Comment on Sexuality
Authors: MORRIS GELFMAN
Journal: American Journal of Psychiatry (1969)

There exists a large gap in our knowledge and understanding of the correlations between adequate sexual functioning and maturity. From the classic psychoanalytic viewpoint, only those who have reached the genital stage of psychosexual development should be able to function in a sexually adequate way. The author suggests that this is unrealistic and that if in a sexual setting where there is rapprochement a neurotic person is accepted on his terms, adequate functioning may well be possible. Responsibility as part of the patient's interpersonal relationships is also examined.
ICAM-1 mediates lung leukocyte recruitment but not pulmonary fibrosis in a murine model of bleomycin-induced lung injury
Authors: T Matsuse, S Teramoto, H Katayama, E Sudo, H Ekimoto, H Mitsuhashi, Y Uejima, Y Fukuchi, Y Ouchi
Journal: European Respiratory Journal (1999)

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p&lt;0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.
Intestinal failure after bariatric surgery
Authors: Olivier Corcos, Dominique Cazals-Hatem, François Durand, Nathalie Kapel, Marie Guinhut, Carmen Stefanescu, Xavier Treton, Vanessa Bondjemah, Alain Attar, Jean-Pierre Marmuse, Yoram Bouhnik, Francisca Joly
Journal: The Lancet (2013)
Effect of Impaired Recognition and Expression of Emotions on Frontocingulate Cortices: An fMRI Study of Men With Alexithymia
Authors: Sylvie Berthoz, Eric Artiges, Pierre-François Van de Moortele, Jean-Baptiste Poline, Stéphanie Rouquette, Silla M. Consoli, Jean-Luc Martinot
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Although the brain areas involved in emotional response and in the recognition of others' emotions have been reported, the neural bases of individual differences in affective style remain to be elucidated. Alexithymia, i.e., impairment of the ability to identify and communicate one's emotional state, influences how emotions are regulated. Alexithymia has been hypothesized to involve anterior cingulate dysfunction. Therefore, the authors searched for differential cerebral regional activation in response to emotional stimuli in subjects with alexithymia. METHOD: Two groups of eight men each were selected from 437 healthy subjects on the basis of high or low scores on the 20-item Toronto Alexithymia Scale. Using functional magnetic resonance imaging (fMRI), the authors compared the two groups for their regional cerebral activation in response to the presentation of pictures with validated positive or negative arousal capabilities. RESULTS: Men with alexithymia demonstrated less cerebral activation in the left mediofrontal-paracingulate cortex in response to highly negative stimuli and more activation in the anterior cingulate, mediofrontal cortex, and middle frontal gyrus in response to highly positive stimuli than men without alexithymia. CONCLUSIONS: These findings provide direct evidence that alexithymia, a personality trait playing a role in affect regulation, is linked with differences in anterior cingulate and mediofrontal activity during emotional stimuli processing.
Abstract 13601: Long Term Clinical Outcome of Cardiac Resynchronization Therapy According to Baseline QRS Duration: a Multi-National, Ten-Year Experience. Data From the Mulin-Crt (Multicenter International -Crt) Study
Authors: Maurizio Gasparini, Cristophe Leclercq, Cheuk-Man Yu, Angelo Auricchio, Jonathan S Steinberg, Barbara Lamp, Catherine Klersy, Francisco Leyva
Journal: Circulation (2013)
Two independent sets of monoclonal antibodies define neoepitopes linked to soluble ligand binding and leukocyte adhesion functions of activated alpha M beta 2.
Authors: G S Elemer, T S Edgington
Journal: Circulation Research (1994)

The integrin alpha M beta 2 mediates a variety of events, adhesive, phagocytic, and inflammatory. Evidence has suggested that the functional events may be mediated by the "activated" conformational forms of alpha M beta 2 produced by appropriate stimulation of myeloid and monocytic lineage. The activation of alpha M beta 2 may be associated with new epitopes on alpha M beta 2, sites that may be related to the acquired receptor functions. Monoclonal antibodies were produced that preferentially bind neoepitopes expressed by activated alpha M beta 2. These anti-neo antibodies each inhibited three activation-associated specific receptor alpha M beta 2 functions, though to different extents. One set of anti-neo antibodies inhibited in a concordant manner the binding of factor X and of fibrinogen by &gt; 90%, abolished the alpha M beta 2-initiated cellular coagulant response, and inhibited monocyte adhesion to unstimulated endothelial monolayers. A second set of anti-neo antibodies only diminished factor X and fibrinogen binding by approximately 40% to 50% but markedly suppressed Xa generation and only partially inhibited monocyte adherence to unstimulated endothelium. Concordance was observed between binding of factor X or fibrinogen and competence for leukocyte adhesion to unstimulated endothelium. Antibody competition assays segregated the anti-neo antibodies into the same two distinct sets, consistent with recognition of separate neoepitopes that are linked to alpha M beta 2 function. These data support the conclusion that the activated conformer of alpha M beta 2 that binds fibrinogen and factor X also mediates monocyte-endothelial interactions as well as the alternative cellular coagulation pathway.
Early Childhood Gut Microbiomes Show Strong Geographic Differences Among Subjects at High Risk for Type 1 Diabetes
Authors: Kaisa M. Kemppainen, Alexandria N. Ardissone, Austin G. Davis-Richardson, Jennie R. Fagen, Kelsey A. Gano, Luis G. León-Novelo, Kendra Vehik, George Casella, Olli Simell, Anette G. Ziegler, Marian J. Rewers, Åke Lernmark, William Hagopian, Jin-Xiong She, Jeffrey P. Krischer, Beena Akolkar, Desmond A. Schatz, Mark A. Atkinson, Eric W. Triplett
Journal: Diabetes Care (2014)

Gut microbiome dysbiosis is associated with numerous diseases, including type 1 diabetes. This pilot study determines how geographical location affects the microbiome of infants at high risk for type 1 diabetes in a population of homogenous HLA class II genotypes.
The Risk of Colorectal Cancer in Patients With Type 2 Diabetes: Associations With Treatment Stage and Obesity
Authors: Paul J.H.L. Peeters, Marloes T. Bazelier, Hubert G.M. Leufkens, Frank de Vries, Marie L. De Bruin
Journal: Diabetes Care (2014)

OBJECTIVE To assess the risk of colorectal cancer associated with type 2 diabetes, as compared with a nondiabetic reference population, and to study additional associations between treatment stage and duration of obesity and colorectal cancer risk. RESEARCH DESIGN AND METHODS We conducted an observational population-based cohort study within the Clinical Practice Research Datalink (1987–2012). All patients (≥18 years) with at least one prescription for an antidiabetic drug (n = 300,039) were matched (1:1) by birth year, sex, and practice to a comparison cohort without diabetes. Cox proportional hazards models were used to derive adjusted hazard ratios (HRs) for colorectal cancer associated with type 2 diabetes. Within the diabetic cohort, associations of colorectal cancer with treatment stages and duration of obesity (BMI ≥30 kg/m2) were studied. RESULTS After a median follow-up of 4.5 years, 2,759 cases of colorectal cancer were observed among the diabetic study population. Type 2 diabetes was associated with a 1.3-fold increased risk of colorectal cancer (HR 1.26 [95% CI 1.18–1.33]). Among diabetic patients, no association was found with treatment stages. A trend of increased colorectal cancer risk was observed with longer duration of obesity. Risk of colorectal cancer was significantly increased for patients with recorded duration of obesity of 4–8 years (HR 1.19 [1.06–1.34]) and &amp;gt;8 years (1.28 [1.11–1.49]). CONCLUSIONS Type 2 diabetes is associated with a moderately increased risk of colorectal cancer. Among diabetic patients, an increased risk was observed for patients who suffered from obesity for a total duration of 4 years or more.
The <i>SLC22A12</i> gene is associated with gout in Han Chinese and Solomon Islanders: Table 1
Authors: Hung-Pin Tu, Chung-Jen Chen, Chien-Hung Lee, Silent Tovosia, Albert Min-Shan Ko, Shu-Jung Wang, Tsan-Teng Ou, Gau-Tyan Lin, Shang-Lun Chiang, Hung-Che Chiang, Ping-Ho Chen, Shun-Jen Chang, Han-Ming Lai, Ying-Chin Ko
Journal: Annals of the Rheumatic Diseases (2009)

Gout is characterised by monosodium urate crystals in hyperuricaemic individuals.1 2 Impaired excretion of urate exacerbates this condition.1 Urate transporter 1 (encoded by SLC22A12 ) is an urate–anion exchanger in the kidneys mediating urate transportation across the apical membrane of the proximal tubules.3 4 SLC22A12 has been reported to influence urate homeostasis in Caucasian and Japanese populations5,–,8 but single nucleotide polymorphism (SNP) genotype effects on gout are unclear. We studied four SLC22A12 SNP associations with gout and urate levels in male Han Chinese from Taiwan and Solomon Islanders.

Clinical rheumatologists confirmed gout/tophi cases using American College of Rheumatology (ACR) criteria.9 Our controls had no diagnosis of gout and were not medicated with hypouricaemic agents during outpatient visits. We enrolled 115 …
Identification, purification, and characterization of antigen-activated and antigen-specific human B lymphocytes.
Authors: J H Kehrl, A S Fauci
Journal: The Journal of Experimental Medicine (1983)

Activated pneumococcal polysaccharide (PPS)-specific human B lymphocytes have been purified and examined in vitro. They are large cells that are refractory to further activation by antigen, anti-Ig, or Staphylococcus aureus Cowan strain I, but they respond directly by proliferation to B cell growth factors. In addition, they express the isotype pattern of activated cells and a surface marker of activated lymphocytes called 4F2. Finally, they contain a subset of cells that spontaneously secrete PPS-specific antibody.