tbuckley/cabot-search huggingface dataset:
Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome
Authors: Avlin B. Imaeda, Azuma Watanabe, Muhammad A. Sohail, Shamail Mahmood, Mehdi Mohamadnejad, Fayyaz S. Sutterwala, Richard A. Flavell, Wajahat Z. Mehal
Journal: Journal of Clinical Investigation (2009)

Hepatocyte death results in a sterile inflammatory response that amplifies the initial insult and increases overall tissue injury. One important example of this type of injury is acetaminophen-induced liver injury, in which the initial toxic injury is followed by innate immune activation. Using mice deficient in Tlr9 and the inflammasome components Nalp3 (NACHT, LRR, and pyrin domain–containing protein 3), ASC (apoptosis-associated speck-like protein containing a CARD), and caspase-1, we have identified a nonredundant role for Tlr9 and the Nalp3 inflammasome in acetaminophen-induced liver injury. We have shown that acetaminophen treatment results in hepatocyte death and that free DNA released from apoptotic hepatocytes activates Tlr9. This triggers a signaling cascade that increases transcription of the genes encoding pro–IL-1β and pro–IL-18 in sinusoidal endothelial cells. By activating caspase-1, the enzyme responsible for generating mature IL-1β and IL-18 from pro–IL-1β and pro–IL-18, respectively, the Nalp3 inflammasome plays a crucial role in the second step of proinflammatory cytokine activation following acetaminophen-induced liver injury. Tlr9 antagonists and aspirin reduced mortality from acetaminophen hepatotoxicity. The protective effect of aspirin on acetaminophen-induced liver injury was due to downregulation of proinflammatory cytokines, rather than inhibition of platelet degranulation or COX-1 inhibition. In summary, we have identified a 2-signal requirement (Tlr9 and the Nalp3 inflammasome) for acetaminophen-induced hepatotoxicity and some potential therapeutic approaches.
Syncope: Causes, Clinical Evaluation, and Current Therapy
Authors: D G Benditt, S Remole, S Milstein, S Bailin
Journal: Annual Review of Medicine (1992)

Syncope is a common clinical problem comprising the sudden loss of both consciousness and postural tone, with a subsequent spontaneous and relatively prompt recovery. Often it is difficult to differentiate a true syncopal spell from other conditions, such as seizure disorders, or from some simple accidents. Even more difficult is the identification of the cause of syncopal episodes. Nonetheless, establishing a definitive diagnosis ia an important task given the high risk of recurrent symptoms. Careful use of noninvasive and invasive cardiovascular studies (including electrophysiologic testing and tilt-table testing) along with selected hematologic, biochemical, and neurologic studies provides, in the majority of cases, the most effective strategy for obtaining a specific diagnosis and for directing therapy.
Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003
Authors: S.G.O Johansson, Thomas Bieber, Ronald Dahl, Peter S Friedmann, Bobby Q Lanier, Richard F Lockey, Cassim Motala, Jose A Ortega Martell, Thomas A.E Platts-Mills, Johannes Ring
Journal: Journal of Allergy and Clinical Immunology (2004)
Functional Genetic Targeting of Embryonic Kidney Progenitor Cells Ex Vivo
Authors: Sanna Junttila, Ulla Saarela, Kimmo Halt, Aki Manninen, Heikki Pärssinen, M. Rita Lecca, André W. Brändli, Sunder Sims-Lucas, Ilya Skovorodkin, Seppo J. Vainio
Journal: Journal of the American Society of Nephrology (2014)

The embryonic mammalian metanephric mesenchyme (MM) is a unique tissue because it is competent to generate the nephrons in response to Wnt signaling. An ex vivo culture in which the MM is separated from the ureteric bud (UB), the natural inducer, can be used as a classic tubule induction model for studying nephrogenesis. However, technological restrictions currently prevent using this model to study the molecular genetic details before or during tubule induction. Using nephron segment-specific markers, we now show that tubule induction in the MM ex vivo also leads to the assembly of highly segmented nephrons. This induction capacity was reconstituted when MM tissue was dissociated into a cell suspension and then reaggregated (drMM) in the presence of human recombinant bone morphogenetic protein 7/human recombinant fibroblast growth factor 2 for 24 hours before induction. Growth factor-treated drMM also recovered the capacity for organogenesis when recombined with the UB. Cell tracking and time-lapse imaging of chimeric drMM cultures indicated that the nephron is not derived from a single progenitor cell. Furthermore, viral vector-mediated transduction of green fluorescent protein was much more efficient in dissociated MM cells than in intact mesenchyme, and the nephrogenic competence of transduced drMM progenitor cells was preserved. Moreover, drMM cells transduced with viral vectors mediating Lhx1 knockdown were excluded from the nephric tubules, whereas cells transduced with control vectors were incorporated. In summary, these techniques allow reproducible cellular and molecular examinations of the mechanisms behind nephrogenesis and kidney organogenesis in an ex vivo organ culture/organoid setting.
Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease
Authors: I Nilsson
Journal: Gut (2000)

<h3>BACKGROUND</h3> Bile tolerant helicobacter species such as <i>H hepaticus</i> and<i>H bilis</i> have frequently been reported to cause hepatitis in mice and other rodents. <h3>AIMS</h3> To investigate the possible pathogenic role of these and other helicobacter species in chronic liver disease in humans. <h3>METHODS</h3> Serum samples from 144 patients with various chronic liver diseases, 30 patients with primary sclerosing cholangitis (PSC), and 48 healthy blood donors were analysed for antibodies against <i>H hepaticus</i> murine strain CCUG 33637 and<i> H pylori</i> strain CCUG 17874. Cell surface proteins of <i>H hepaticus</i>were extracted by acid glycine buffer and used in an enzyme immunoassay (EIA) and immunoblot (IB). <h3>RESULTS</h3> 56 of 144 (39%) patients with chronic liver diseases and six of 30 (20%) with PSC showed increased antibody concentrations in the <i>H hepaticus</i> EIA; in the <i>H pylori</i> EIA the numbers were 58% and 13% respectively. Compared with the healthy blood donors the antibody reactivity against the two helicobacter species was not increased (46% and 48% respectively). Patient serum samples retested by the <i>H hepaticus</i> EIA after absorption with sonicated <i>H pylori</i>cells remained positive in 12 of 37 (33%) serum samples. Distinct antibody reactivity to 55–65 kDa proteins was observed by<i>H hepaticus</i> IB, after the absorption step, and was considered specific for <i>H hepaticus</i>. These 12 serum samples were from patients with chronic alcoholic liver disease. <h3>CONCLUSIONS</h3> Antibodies to<i>H hepaticus</i>, often cross reacting with<i>H pylori</i>, occur frequently in patients with chronic liver diseases, with no clear cut relation to specific diagnostic groups. The pathogenic significance of these findings is not known.
Cerebellum does more than recalibration of movements after perturbations
Authors: C. Gielen
Journal: Behavioral and Brain Sciences (1996)

We argue that the function of the cerebellum is more than just an error-detecting mechanism. Rather, the cerebellum plays an important role in all movements. The bias in (re)calibration is an unfortunate restrictive result of a very successful and important experiment, [SMITH, THACH]
Allopurinol improves endothelial function in sleep apnoea: a randomised controlled study
Authors: A. A. El Solh, R. Saliba, T. Bosinski, B. J. B. Grant, E. Berbary, N. Miller
Journal: European Respiratory Journal (2006)

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of &lt;90%. Allopurinol caused a significant increase in FMD compared to placebo (10.4±3.2 versus 7.4±2.8%, respectively). Plasma malondialdehyde levels were significantly reduced with allopurinol treatment (1.5±0.3 versus 1.2±0.3 μmol·L −1 ), consistent with reduced oxidative stress. Allopurinol improves endothelial dysfunction in patients with moderate-to-severe obstructive sleep apnoea. These observations suggest that xanthine oxidase contributes significantly to vasodilatory impairment.
Transcriptional Network Structure Has Little Effect on the Rate of Regulatory Evolution in Yeast
Authors: Artyom Kopp, Lauren M. McIntyre
Journal: Molecular Biology and Evolution (2010)

Studies in evolutionary developmental biology suggest that the structure of genetic pathways may bias the fixation of natural variation toward particular nodes in these pathways. In an attempt to test this trend genome wide, we integrated several previously published data sets to examine whether the position of genes in the whole-genome transcriptional network of Saccharomyces cerevisiae is associated with the amount of cis-regulatory expression divergence between S. cerevisiae and its sibling species Saccharomyces paradoxus. We find little evidence for an association between connectivity and divergence in the global network that combines data from multiple conditions. However, relationships between connectivity and divergence are apparent in some of the smaller subnetworks. Despite a slight tendency for genes with more transcriptional interactions to show greater divergence, these differences explain no more than a small fraction of variation in evolutionary rates. These results suggest that the systems biology focus on large interactomes may miss some critical details of local interactions. More detailed experimental analysis will be needed to define the genetic pathways that control specific phenotypic traits and quantify the rate of regulatory changes at different points in these pathways.
The effects of 5‐HT on cholinergic contraction in human airways in vitro
Authors: L.j. Dupont, J.l. Pype, M.g. Demedts, P. De Leyn, G. Deneffe, G.m. Verleden
Journal: European Respiratory Journal (1999)

Inhaled 5-hydroxytryptamine (5-HT) causes bronchoconstriction in asthmatics, and 5-HT plasma levels are elevated in asthma. Electrical field stimulation (EFS) of human airways, in vitro, evokes cholinergic contraction mediated by the release of acetylcholine (Ach) from postganglionic cholinergic nerves. The present study investigates whether selective 5-HT agonists and antagonists can modulate EFS-induced cholinergic contraction in human airways in vitro. Human airways, obtained from resections for bronchial carcinoma or organ transplant donors, were suspended under 2-g tension, between two platinum wire electrodes, in carbogenated Krebs solution at 37 degrees C and EFS was applied (1-32 Hz, 50 V, 0.5 ms, 15 s every 4 min) to elicit cholinergic contractions. 5-HT (10 microM-0.3 mM) produced frequency- and concentration-dependent facilitation of cholinergic contraction, but did not displace the concentration/response curve to Ach. Tropisetron (1 microM), a 5-HT3 and 5-HT4 antagonist, completely blocked the facilitatory effect of 5-HT (100 microM), whereas both ondansetron (1 microM) and GR 125478D (1 microM), a selective 5-HT3 and 5-HT4 antagonist, respectively, also attenuated the 5-HT-induced enhancement of cholinergic contraction. This facilitatory effect of 5-HT was partially mimicked by both selective 5-HT3 (2-methyl-5-HT) and 5-HT4 (RS 67333 and 5-methoxytryptamine) agonists. Fluoxetine (10 microM), a 5-HT uptake inhibitor, had no effect on the 5-HT (10-100 microm) induced potentiation of cholinergic contraction. These findings suggest that 5-HT facilitates cholinergic contraction in human airways in vitro through stimulation of both prejunctional 5-HT3 and 5-HT4 receptors. This may implicate a role of 5-HT in asthma.
A Randomized Trial of Aspirin to Prevent Colorectal Adenomas
Authors: John A. Baron, Bernard F. Cole, Robert S. Sandler, Robert W. Haile, Dennis Ahnen, Robert Bresalier, Gail McKeown-Eyssen, Robert W. Summers, Richard Rothstein, Carol A. Burke, Dale C. Snover, Timothy R. Church, John I. Allen, Michael Beach, Gerald J. Beck, John H. Bond, Tim Byers, E. Robert Greenberg, Jack S. Mandel, Norman Marcon, Leila A. Mott, Loretta Pearson, Fred Saibil, Rosalind U. van Stolk
Journal: New England Journal of Medicine (2003)

Laboratory and epidemiologic data suggest that aspirin has an antineoplastic effect in the large bowel.
The Ligamp TP53 Assay for Detection of Minimal Residual Disease in Head and Neck Squamous Cell Carcinoma Surgical Margins
Authors: M. Luana Poeta, Judith Manola, David Goldenberg, Arlene Forastiere, Joseph A. Califano, John A. Ridge, Jarrard Goodwin, Daniel Kenady, John Saunders, William Westra, David Sidransky, Wayne M. Koch
Journal: Clinical Cancer Research (2009)

PURPOSE: Detect tumor-related DNA using LigAmp in histologically clear margins and associate results with clinical outcome. EXPERIMENTAL DESIGN: Patients with head and neck cancer were registered for molecular analysis of surgical margins. Adequacy of resection was ensured using histologic margin analysis. Further margins were then harvested and DNA extracted. TP53 mutations in tumor were determined using Affymetrix p53 GeneChip. Margins were analyzed by Ligamp in comparison with standard curves for quantification of mutant DNA. Ligation used two oligonucleotides to isolate DNA targeting the mutation. Ligated DNA was amplified using real-time PCR. The quantity of mutation in the margin was determined as percent of mutant species relative to plasmid and relative to tumor. Cutpoints were identified and defined groups were evaluated for local failure-free, cancer-specific, and overall survival. Study margins were examined for presence of tumor by light microscopy. RESULTS: Tissue from 95 patients with common mutations was analyzed. Fifteen experienced local recurrence. Cutpoints of 0.15% for mutant species relative to plasmid and 0.5% for mutant species relative to tumor were chosen as most selective of recurrent cases. LigAmp had slightly better area under the receiver operator characteristic curve (P = 0.09) than light microscopy correctly predicting 9 of 15 recurrent tumors. There were 6 false negative cases and 26 false positive results. No statistically significant distinctions were observed in cancer-specific or overall survival in this limited cohort. CONCLUSIONS: Ligamp provides quantifiable, sensitive detection of mutant DNA in histologically normal margins. Detection of mutant species in margins may identify patients at risk of local recurrence. (Clin Cancer Res 2009;15(24):7658-65).
Foot orthotics in therapy and sport.: S Hunter, M G Dolan, J M Davis. (Pp 141; soft cover; pound31.00.) Leeds: Human Kinetics Europe Ltd, 1995. ISBN 0-87322-829-4.
Authors: N Padhiar
Journal: British Journal of Sports Medicine (2000)

This book lacks vigour and colour. The front cover looked promising but unfortunately the book does not live up to this promise. It is an out of date basic book which is disappointing, considering the biography and experience of …
Infection with <i>Burkholderia cepacia</i> in Cystic Fibrosis
Authors: CECILIA CHAPARRO, JANET MAURER, CARLOS GUTIERREZ, MEL KRAJDEN, CHARLIE CHAN, TIMOTHY WINTON, SHAFF KESHAVJEE, MASSINA SCAVUZZO, ELIZABETH TULLIS, MICHAEL HUTCHEON, STEVEN KESTEN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.
The Treatment of Cricopharyngeal Dysmotility with a Transmucosal Cricopharyngeal Myotomy Using the Potassium-Titanyl-Phosphate (KTP) Laser
Authors: D. J. Halvorson
Journal: Endoscopy (1998)

Cricopharyngeal dysfunction is a relatively uncommon disorder that is misunderstood by many physicians. Cricopharyngeal dysmotility is thought to indicate abnormal function in the upper esophageal or cricopharyngeal sphincter, the etiology of which is related to uncoordinated pharyngeal swallowing, achalasia, or a combination of these factors. Unfortunately, standard diagnostic tests do not consistently show that the cricopharyngeal sphincter malfunctions; so cricopharyngeal myotomy has been suggested as a diagnostic and therapeutic tool in the treatment of dysmotility. The current report reviews trends in the diagnosis and treatment of cricopharyngeal myotomy, including the results of cricopharyngeal myotomy using the potassium-titanyl-phosphate (KTP) laser. A transmucosal cricopharyngeal myotomy with the KTP laser may be a viable alternative for patients with cricopharyngeal dysmotility compared with conventional techniques.
Coronary heart disease case fatality in four countries. A community study. The Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen, FINMONICA, Newcastle, and Perth.
Authors: H Löwel, A Dobson, U Keil, B Herman, M S Hobbs, A Stewart, M Arstila, H Miettinen, H Mustaniemi, J Tuomilehto
Journal: Circulation (1993)

BACKGROUND Community-based registers participating in the MONICA Project of the World Health Organization show markedly different attack and death rates of coronary heart disease. This variation is a function of both the incidence and case fatality occurring within countries. The contribution of case fatality to the international variation in coronary heart disease mortality rates is not well understood. METHODS AND RESULTS The register data from eight study populations--Augsburg and Bremen in Germany, Auckland in New Zealand, Perth and Newcastle in Australia, and North Karelia, Kuopio, and Turku/Loimaa in Finland--were compared. All patients with definite myocardial infarction or coronary death aged 35 to 64 years occurring in the study populations in 1985 through 1989 are the basis for the case fatality calculations by different definitions: 28-day case fatality for all cases, for hospitalized cases, and for hospitalized 24-hour survivors; out-of-hospital case fatality; and 24-hour case fatality for hospitalized cases. Differences in case fatality were much smaller than differences in attack and mortality rates in these populations. About two thirds of deaths occurred before the patients reached a hospital. The 28-day case fatality ranged from 37% for men in Perth to 58% for women in Augsburg. Among those who reached the hospital alive, 28-day case fatality was 13% to 27% for men and 20% to 35% for women. In those who survived 24 hours from the onset of symptoms, 28-day case fatality was 8% to 17% for men and 12% to 26% for women. CONCLUSIONS Differences in case fatality were not associated with differences in coronary mortality rates between these populations. As most deaths occurred before reaching a hospital, opportunities for reducing case fatality through improved hospital care are limited. This emphasizes the primary role of prevention in reducing coronary death rates.
Transthoracic needle biopsy of thoracic tumours by a colour Doppler ultrasound puncture guiding device.
Authors: H C Wang, C J Yu, D B Chang, A Yuan, Y C Lee, P C Yang, S H Kuo, K T Luh
Journal: Thorax (1995)

BACKGROUND--Ultrasound guided transthoracic needle aspiration biopsy has recently been used to obtain specimens for histological diagnosis of pulmonary and mediastinal tumours. Conventional real time, grey scale puncture guiding devices cannot differentiate vascular structures, and clear visualisation of the needle shaft or tip within a desired target is not always possible. This study describes a new built-in colour Doppler ultrasound puncture guiding device and assesses the relative safety of transthoracic needle aspiration biopsy of thoracic tumours by grey scale or colour Doppler ultrasound guidance. METHODS--Thirty patients with radiographic evidence of pulmonary (22 patients) or mediastinal tumours (eight patients) underwent ultrasonographic evaluation and transthoracic needle aspiration biopsy by using the colour Doppler ultrasound puncture guiding device (Aloka UST 5045P-3.5). These tumours were initially examined by grey scale ultrasound, and colour Doppler imaging was then used to evaluate the number of blood vessels surrounding and within the target tumour and the possibility of visualisation of the needle shaft or needle tip during the aspiration biopsy procedure. RESULTS--The colour Doppler ultrasound guiding device was far superior to the grey scale device for identification of the number of vessels surrounding or within the target tumour (83% v 20%) and for visualisation of the needle shaft or needle tip (80% v 17%). CONCLUSIONS--By using the colour Doppler ultrasound puncture device, vascular structures surrounding or within the target tumour can be verified. Visualisation of the needle shaft or tip is also better. Biopsy routes can be selected to avoid puncturing vessels. This approach should be particularly helpful for guiding biopsies of mediastinal tumours, where puncturing the heart or great vessels is a potential complication.