tbuckley/cabot-search huggingface dataset:
HIV protease inhibitors provide neuroprotection through inhibition of mitochondrial apoptosis in mice
Authors: Toshio Hisatomi, Toru Nakazawa, Kousuke Noda, Lama Almulki, Shinsuke Miyahara, Shintaro Nakao, Yasuhiro Ito, Haicheng She, Riichiro Kohno, Norman Michaud, Tatsuro Ishibashi, Ali Hafezi-Moghadam, Andrew D. Badley, Guido Kroemer, Joan W. Miller
Journal: Journal of Clinical Investigation (2008)

Neuroprotection can be achieved by preventing apoptotic death of postmitotic cells. Apoptotic death can occur by either a caspase-dependent mechanism, involving cytochrome c, apoptosis protease-activating factor–1 (Apaf-1), and caspase-9, or a caspase-independent mechanism, involving apoptosis-inducing factor (AIF). HIV protease inhibitors (PIs) avert apoptosis in part by preventing mitochondrial outer membrane permeabilization (MOMP), but the precise mechanism by which they work is not known. Here, we evaluated the impact of the PIs in a mouse model of retinal detachment (RD) in vivo and in murine primary retinal cell cultures in vitro. Oral administration of the PIs nelfinavir and ritonavir significantly inhibited photoreceptor apoptosis, while preventing the translocation of AIF from mitochondria to the nucleus as well as the activation of caspase-9. RD-induced photoreceptor apoptosis was similarly inhibited in mice carrying hypomorphic mutations of the genes encoding AIF or Apaf-1. Nelfinavir attenuated apoptosis as well as mitochondrial release of AIF and cytochrome c, and subsequent activation of caspase-9 in vitro, in photoreceptor cultures exposed to starvation or monocyte chemoattractant protein–1–stimulated (MCP-1–stimulated) macrophages. Our results suggest that the MOMP inhibition by PIs involved interruption of both caspase-dependent and caspase-independent apoptosis pathways and that PIs may be clinically useful for the treatment of diseases caused by excessive apoptosis.
Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus
Authors: Atsushi Enomoto, Naoya Asai, Takashi Namba, Yun Wang, Takuya Kato, Motoki Tanaka, Hitoshi Tatsumi, Shinichiro Taya, Daisuke Tsuboi, Keisuke Kuroda, Naoko Kaneko, Kazunobu Sawamoto, Rieko Miyamoto, Mayumi Jijiwa, Yoshiki Murakumo, Masahiro Sokabe, Tatsunori Seki, Kozo Kaibuchi, Masahide Takahashi
Journal: Neuron (2009)
4‐Hydroxynonenal: A membrane lipid oxidation product of medicinal interest
Authors: G. Poli, R.J. Schaur, W.G. Siems, G. Leonarduzzi
Journal: Medicinal Research Reviews (2007)

Abstract A comprehensive focus on 4‐hydroxynonenal (HNE) as candidate molecule in a variety of pathophysiological conditions occurring in humans is here provided. Despite an active, now well characterized, metabolism in most cells and tissues, HNE can be easily detected and quantified by means of several methods, although with different sensitivity. Measurements of HNE and/or stable metabolites in biological fluids are already applied as lipid peroxidation/oxidative stress markers in a huge number of human disease processes, often sustained by inflammatory reactions. A primary involvement of this aldehydic product of membrane lipid oxidation in inflammation‐related events, as well as in regulation of cell proliferation and growth, in necrotic or apoptotic cell death, appears supported by its marked ability to modulate several major pathways of cell signaling and, consequently, gene expression. The actual knowledge of HNE reactivity, metabolism, signaling and modulatory effect in the various human organs should provide a solid background to the investigation of the aldehyde's contribution to the pathogenesis of human major chronic diseases and would likely promote advanced and oriented applications not only in diagnosis and prevention but also in molecular treatment of human diseases. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 4, 569–631, 2008
Nature and extent of histological changes induced by argon laser photocoagulation in canine gastric mucosa.
Authors: D F Kelly, S G Bown, P R Salmon, B M Calder, H Pearson, B M Weaver
Journal: Gut (1980)

The tissue changes in canine gastric mucosa caused by exposure to an argon laser beam vary from mild mucosal oedema to complete cell destruction. Intermediate degrees of damage cause an inflammatory cell response with the formation of granulation tissue, particularly in the submucosa. The rate of healing is similar to that after other forms of injury to the gastric mucosa. Cell destruction at the surface of the mucosa starts with energies greater than 8 Joules on any one spot, and occurs at greater depths as the energy is increased but, unless cells are actually destroyed, the extent of histological damage is limited to a zone 1 mm lateral to, or below, the area exposed to the laser beam. Haemostasis is achieved by thermal contraction of bleeding vessels and of the surrounding tissue, thrombosis only occurring as a secondary effect.
Population Genetics of Speciation in Nonmodel Organisms: I. Ancestral Polymorphism in Mangroves
Authors: Renchao Zhou, Kai Zeng, Wei Wu, Xiaoshu Chen, Ziheng Yang, Suhua Shi, Chung-I Wu
Journal: Molecular Biology and Evolution (2007)

The level of DNA polymorphism in the ancestral species at the time of speciation can be estimated using DNA sequences from many loci sampled from 2 or more extant species. The comparison between ancestral and extant polymorphism can be informative about the population genetics of speciation. In this study, we collected and analyzed DNA sequences of ∼60 genes from 4 species of Sonneratia, a common genus of mangroves on the Indo-Pacific coasts. We found that the 3 ancestral species were comparable to each other in terms of level of polymorphism. However, the ancestral species at the time of speciation were substantially more polymorphic than the extant geographical populations. This ancestral polymorphism is in fact larger than, or at least equal to, the level of polymorphism of the entire species across extant geographical populations. The observations are not fully compatible with speciation by strict allopatry. We suggest that, at the time of speciation, the ancestral species consisted of interconnected but strongly divided geographical populations. This population structure would give rise to high level of polymorphism across species range. This approach of studying the speciation history by genomic means should be applicable to nonmodel organisms.
Pretreatment with Statin Attenuates the Cardiotoxicity of Doxorubicin in Mice
Authors: Alexander Riad, Sandra Bien, Dirk Westermann, Peter M. Becher, Komal Loya, Ulf Landmesser, Heyo K. Kroemer, Heinz P. Schultheiss, Carsten Tschöpe
Journal: Cancer Research (2009)

Abstract Cardiotoxicity, which may result from intense cardiac oxidative stress and inflammation, is the main limiting factor of the anticancer therapy using doxorubicin. Because statins might exert beneficial pleiotropic cardiovascular effects, among other things, by anti-inflammatory and antioxidative mechanisms, we investigated whether or not fluvastatin pretreatment can attenuate doxorubicin-induced cardiotoxicity. Five days after a single injection of doxorubicin (20 mg/kg; i.p.), left ventricular (LV) function was measured in fluvastatin-treated (DoxStatin; 100 mg/kg/day, p.o.) and saline-treated (doxorubicin) mice (n = 8 per group) by a micro conductance catheter. Untreated mice served as controls (placebo; n = 8 per group). After measurement of cardiac function, LV tissues were analyzed by molecular biological and immunohistologic methods. Injection resulted in significantly impaired LV function (LV pressure, −29%; dp/dtmax, −45%; cardiac output, −68%; P &amp;lt; 0.05) when compared with placebo. This was associated with a significant increase in cardiac oxidative stress, inflammation and apoptotic mechanisms, as indicated by significant increased cardiac lipid peroxidation activity, protein expression of nitrotyrosine, tumor necrosis factor α and Bax (P &amp;lt; 0.05). In contrast, DoxStatin mice showed improved LV function (LV pressure, +24%; dp/dtmax, +87%; cardiac output, +87%; P &amp;lt; 0.05) when compared with untreated doxorubicin mice. This was associated with reduced cardiac expression of nitrotyrosine, enhanced expression of the mitochondrial located antioxidative SOD 2, attenuated mitochondrial apoptotic pathways, and reduced cardiac inflammatory response. Statin pretreatment attenuates doxorubicin-induced cardiotoxicity via antioxidative and anti-inflammatory effects. [Cancer Res 2009;69(2):695–9]
Interstitial Lung Abnormalities and Reduced Exercise Capacity
Authors: Tracy J. Doyle, George R. Washko, Isis E. Fernandez, Mizuki Nishino, Yuka Okajima, Tsuneo Yamashiro, Miguel J. Divo, Bartolome R. Celli, Frank C. Sciurba, Edwin K. Silverman, Hiroto Hatabu, Ivan O. Rosas, Gary M. Hunninghake
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The relationship between interstitial lung abnormalities (ILA) and exercise capacity has not been comprehensively evaluated.To assess the validity of the 6-minute walk test in subjects with ILA, and to examine the association between ILA and 6-minute walk distance (6MWD).Spearman correlation coefficients were used to assess the strength of the relationships between 6MWD and relevant measures of dyspnea, health-related quality of life, and pulmonary function in a cohort of 2,416 people who smoke from the COPDGene study. Unadjusted and adjusted linear and logistic regression models were used to assess the strength of the association between ILA and 6MWD.In all subjects, and in those with ILA, 6MWD in COPDGene was associated with relevant clinical and physiologic measures. The mean 6MWD in COPDGene subjects with ILA was 386 m (SD, 128 m), and 82% and 19% of subjects with ILA had 6MWDs less than or equal to 500 and 250 m, respectively. ILA was associated with a reduced 6MWD in univariate (-30 m; 95% confidence interval, -50 to -10; P = 0.004) and multivariate models (-19 m; 95% confidence interval, -33 to -5; P = 0.008). Compared with subjects without ILA, subjects with ILA had an 80% and 77% increase in their odds to have a walk distance limited to less than or equal to 500 and 250 m, respectively. Although these findings were dependent on ILA subtype, they were not limited to those with COPD.Our study demonstrates that ILA is associated with measurable decrements in the 6MWD of people who smoke. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
Langerhans cells in autosomal dominant ichthyosis vulgaris
Authors: G.P. FORD, P.S. FRIEDMANN, J. ROSS
Journal: British Journal of Dermatology (1983)

Five patients with autosomal dominant ichthyosis vulgaris (ADI) were studied to see whether the abnormal keratinization was associated with disturbances of the appearance or the distribution of epidermal Langerhans cells (LCs). The LCs were identified by ATPase staining and electron microscopy. They were present in normal numbers, were of normal morphology and were in their usual mid‐epidermal position. These observations do not support the hypothesis that LCs are involved directly in the process of keratinization.
Effects of murine recombinant interleukin 1 on intact homologous articular cartilage: a quantitative and autoradiographic study.
Authors: W B van den Berg, F A van de Loo, W A Zwarts, I G Otterness
Journal: Annals of the Rheumatic Diseases (1988)

Murine recombinant interleukin 1 (IL1) was tested for its ability to affect intact murine articular cartilage. IL1 caused enhanced proteoglycan degradation and severe inhibition of chondrocyte synthetic function at a concentration of 3 U/ml (100 pg/ml). Inhibition of proteoglycan synthesis appeared to be delayed in onset but occurred consistently after 24 hours. Pulse chase experiments made it clear that proteoglycan degradation and inhibition of proteoglycan synthesis are two distinct actions of IL1. No indications were obtained for selective degradation of either newly synthesised or processed proteoglycan. Moreover, chondrocyte synthetic activity appeared to be inhibited uniformly throughout the cartilage matrix, i.e., no evidence was found for selective suppression of cells in certain regions. IL1 uptake measurement in the cartilage, using [125I]IL1, yielded a partition coefficient far below 1, and autoradiography demonstrated a faint but even distribution within the cartilage matrix. The coordinated induction of enhanced breakdown of proteoglycan and inhibition of proteoglycan synthesis, with such low concentrations of IL1 reaching the chondrocytes, underlines the impressive destructive potential of IL1.
Efficacy of Ablative High-Dose-per-Fraction Radiation for Implanted Human Renal Cell Cancer in a Nude Mouse Model
Authors: Lance Walsh, Jennifer L. Stanfield, L. Chinsoo Cho, Cheng-hui Chang, Kenneth Forster, Wareef Kabbani, Jeffrey A. Cadeddu, Jer-Tsong Hsieh, Hak Choy, Robert Timmerman, Yair Lotan
Journal: European Urology (2006)
Cortisone in Rheumatism
Authors: W. G. Waugh
Journal: BMJ (1952)

MBEDIsH-all these add up to more than a speck of dust.It is, however, with the significance of the complications rather than their severity that I am concerned.Very often a study of the side-effects of certain forms of therapy reveals a lot about the mechanism of the disease uhder consideration.I have not myself introduced any form of drastic treatment in disease, but I have witnessed the effects of some heroic, not to say peculiar, forms of therapy in leprosy and rheumatism.A recession of lesions in leprosy-cure of a kind- followed such treatment as intravenous tinned milk, intravenous sodium salicylate, intravenous dyes and chemicals of uncertain
THE SOLUBLE SPECIFIC SUBSTANCE OF PNEUMOCOCCUS
Authors: M. Heidelberger, O. T. Avery
Journal: The Journal of Experimental Medicine (1923)

1. A method is given for the concentration and purification of the soluble specific substance of the pneumococcus. 2. The material obtained by this method is shown to consist mainly of a carbohydrate which appears to be a polysaccharide built up of glucose molecules. 3. Whether the soluble specific substance is actually the polysaccharide, or occurs merely associated with it, is still undecided, although the evidence points in the direction of the former possibility.
PMO-047 Diversion colitis treatment with rapidly fermentable fibre-suppositories
Authors: W Roediger, R Le Leu, T Jones
Journal: Gut (2012)

<h3>Introduction</h3> Diversion colitis, a nutritional deficiency disease of short chain fatty acids (SCFAs) in the defunctioned rectum, responds to butyrate enemas but these are impracticable due to unpleasant malodour. Treatment with rapidly fermentable fibre to SCFAs as suppositories, seemed a preferable option and was tested. <h3>Methods</h3> “Hi-maize 260” which is naturally high in resistant starch and is optimally fermented to n-butyrate in the colon<sup>1</sup> was formulated into 2.0 g suppositories with a binding agent of cocoa butter. Patients were selected on symptoms (blood stained discharge, or anorectal discomfort) for treatment. Suppositories were used on alternative nights for 14 days. Colonoscopic examination of the rectum was performed before and 6 days after completion of treatment. <h3>Results</h3> “Hi-maize 260” produces a concentration of 20.3 mmol of butyrate in the colon. The diverted rectum of three patients showed severe macroscopic proctitis and mucosal appearances returned to normal after 2 weeks treatment. Long term recovery was not assessed as two patients had the diversion reversed. <h3>Conclusion</h3> Dietary fibre suppositories are a convenient treatment for diversion colitis. The healing capacity of fermentable fibre should enable distinction between diversion colitis and ulcerative colitis or Crohn9s Disease in a diverted rectum where further reconnection or proctectomy might be contemplated. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Le Leu RK,</b><i>et al.</i> Effect of high amylose maize starches on colonic fermentation and apoptotic response to DNA-damage in the colon of rats. <i>Nutr Metab</i> 2009;<b>6</b>:11–20.
Priorities for respiratory research in the UK
Authors: S. T Holgate
Journal: Thorax (2006)

Respiratory diseases are placing an increasing burden on the UK health system

In the past, respiratory research has proved itself effective in vanquishing major killers such as tuberculosis, transforming the lives of patients with asthma and developing life-saving non-invasive ventilation for those with chronic respiratory failure. Now, new problems affect our patients with respiratory diseases and present an enormous burden of ill health that we are currently ill equipped to deal with. The second edition of the Burden of lung disease was published by the British Thoracic Society in June 20061; it documents that respiratory diseases now kill one in five people in the UK, with the standardised mortality ratio for respiratory diseases showing a threefold difference across social classes. More people die from respiratory disease than from ischaemic heart disease. Respiratory diseases are the most common cause of long-term illness in children, result in the highest levels of consultations with general practitioners and are the second most common reason for emergency hospital admission. Examples of the severity of the situation from UK statistics are as follows:





Although research has undoubtedly contributed to a greater understanding of disease mechanisms, epidemiology, diagnosis and treatment when compared with other specialities, progress has been slow. In …
Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury
Authors: Li Li, Liping Huang, Hong Ye, Steven P. Song, Amandeep Bajwa, Sang Ju Lee, Emily K. Moser, Katarzyna Jaworska, Gilbert R. Kinsey, Yuan J. Day, Joel Linden, Peter I. Lobo, Diane L. Rosin, Mark D. Okusa
Journal: Journal of Clinical Investigation (2012)

DC-mediated NKT cell activation is critical in initiating the immune response following kidney ischemia/reperfusion injury (IRI), which mimics human acute kidney injury (AKI). Adenosine is an important antiinflammatory molecule in tissue inflammation, and adenosine 2A receptor (A₂AR) agonists protect kidneys from IRI through their actions on leukocytes. In this study, we showed that mice with A₂AR-deficient DCs are more susceptible to kidney IRI and are not protected from injury by A₂AR agonists. In addition, administration of DCs treated ex vivo with an A₂AR agonist protected the kidneys of WT mice from IRI by suppressing NKT production of IFN-γ and by regulating DC costimulatory molecules that are important for NKT cell activation. A₂AR agonists had no effect on DC antigen presentation or on Tregs. We conclude that ex vivo A₂AR-induced tolerized DCs suppress NKT cell activation in vivo and provide a unique and potent cell-based strategy to attenuate organ IRI.
A Clinical Lecture on Puerperal Inguinal Parametritis; or the Common Kind of Pelvic Cellulitis: Delivered at the London Hospital
Authors: G. E. Herman
Journal: BMJ (1900)

GENTLEMEN,-My subject to-day is the common kind of pelvic cellulitis, or puerperal inguinal parametritis.WHY PUERPERAL CELLULITIS IS OFTEN INGUINAL.Cellulitis after delivery is usually inguinal, because during pregnancy the cellular tissue at the side of the uterus becomes looser, and the peritoneum is raised above the brim of the pelvis, so that at the end of pregnancy there is loose cellular tissue extending from the side of the uterus to the groin.Hence inflammation of pelvic cellular tissue after delivery tends to spread up to the groin.Apart from pregnancy the cellular tissue is not so loose, the peritoneum is not raised up towards the groin, and so cellulitis is seldom inguinal.Puer- peral inguinal cellulitis is commoner than any other kind.HISTORICAL.
Genomic Evidence for Large, Long-Lived Ancestors to Placental Mammals
Authors: J. Romiguier, V. Ranwez, E.J.P. Douzery, N. Galtier
Journal: Molecular Biology and Evolution (2012)

It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters and evolved into modern forms after dinosaurs went extinct, 65 Ma.The small size of most Mesozoic mammalian fossils essentially supports this view.Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages.Here, we use full-genome data to estimate the longevity and body mass of early placental mammals.Analyzing 36 fully sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics, namely GC-content evolution and nonsynonymous over synonymous rate ratio.Linking these molecular evolutionary processes to life-history traits in modern species, we estimate that early placental mammals had a life span above 25 years and a body mass above 1 kg.This is similar to current primates, cetartiodactyls, or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution.Our results imply that long-lived mammals existed in the Cretaceous era and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis.
Safety and Efficacy of Switching From Either Unfractionated Heparin or Enoxaparin to Bivalirudin in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes Managed With an Invasive Strategy
Authors: Harvey D. White, Derek P. Chew, James W. Hoekstra, Chadwick D. Miller, Charles V. Pollack, Frederick Feit, A. Michael Lincoff, Michel Bertrand, Stuart Pocock, James Ware, E. Magnus Ohman, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2008)
The Extracellular Domain of CD83 Inhibits Dendritic Cell–mediated T Cell Stimulation and Binds to a Ligand on Dendritic Cells
Authors: Matthias Lechmann, Daniëlle J.E.B. Krooshoop, Diana Dudziak, Elisabeth Kremmer, Christine Kuhnt, Carl G. Figdor, Gerold Schuler, Alexander Steinkasserer
Journal: The Journal of Experimental Medicine (2001)

CD83 is an immunoglobulin (Ig) superfamily member that is upregulated during the maturation of dendritic cells (DCs). It has been widely used as a marker for mature DCs, but its function is still unknown. To approach its potential functional role, we have expressed the extracellular Ig domain of human CD83 (hCD83ext) as a soluble protein. Using this tool we could show that immature as well as mature DCs bind to CD83. Since CD83 binds a ligand also expressed on immature DCs, which do not express CD83, indicates that binding is not a homophilic interaction. In addition we demonstrate that hCD83ext interferes with DC maturation downmodulating the expression of CD80 and CD83, while no phenotypical effects were observed on T cells. Finally, we show that hCD83ext inhibits DC-dependent allogeneic and peptide-specific T cell proliferation in a concentration dependent manner in vitro. This is the first report regarding functional aspects of CD83 and the binding of CD83 to DCs.