tbuckley/cabot-search huggingface dataset:
Zoledronic Acid and Angiogenesis
Authors: Gianluigi Ferretti, Alessandra Fabi, Paolo Carlini, Paola Papaldo, Alessandra Felici, Silverio Tomao, Francesco Cognetti
Journal: Clinical Cancer Research (2007)

To the Editors: In a recent issue of Clinical Cancer Research , Santini and co-workers ([1][1]) assert that zoledronic acid (ZA) may inhibit several antiangiogenic-related cascades and its metronomic administration could represent a new potential therapy targeting the endothelial-tumor-stroma
Blockade of sarcolemmal TRPV2 accumulation inhibits progression of dilated cardiomyopathy
Authors: Yuko Iwata, Hitomi Ohtake, Osamu Suzuki, Junichiro Matsuda, Kazuo Komamura, Shigeo Wakabayashi
Journal: Cardiovascular Research (2013)

Dilated cardiomyopathy (DCM) is a severe disorder defined by ventricular dilation and contractile dysfunction. Abnormal Ca(2+) handling is hypothesized to play a critical pathological role in DCM progression. The transient receptor potential vanilloid 2 (TRPV2) has been previously suggested as a candidate pathway for enhanced Ca(2+) entry. Here, we examined the sarcolemmal accumulation of TRPV2 in various heart-failure model animals and DCM patients, and assessed whether presently available inhibitory tools against TRPV2 ameliorate DCM symptoms.Immunological and cell physiological analyses revealed that TRPV2 is highly concentrated and activated in the ventricular sarcolemma of DCM patients and three animal models-δ-sarcoglycan-deficient hamsters (J2N-k), transgenic mice over-expressing sialytransferase (4C30), and doxorubicin (DOX)-induced DCM mice. Over-expression of the amino-terminal (NT) domain of TRPV2 could block the plasma membrane accumulation and influx of Ca(2+) via TRPV2. Transgenic (Tg) or adenoviral expression of the NT domain in DCM animals caused effective removal of sarcolemmal TRPV2 along with reduction in the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) and reactive oxygen species (ROS) production, which were activated in DCM; further, it prevented ventricular dilation and fibrosis, ameliorated contractile dysfunction in DCM, and improved survival of the affected animals. The TRPV2 inhibitor tranilast markedly suppressed DCM progression.Sarcolemmal TRPV2 accumulation appears to have considerable pathological impact on DCM progression, and blockade of this channel may be a promising therapeutic strategy for treating advanced heart failure.
Prevention of Major Depression
Authors: Ricardo F. Muñoz, Pim Cuijpers, Filip Smit, Alinne Z. Barrera, Yan Leykin
Journal: Annual Review of Clinical Psychology (2010)

Before the 1980s, no randomized controlled trials had been carried out to test whether major depressive episodes could be prevented. In the past 30 years, several trials have reported success in reducing the incidence (the number of new cases) of major depressive episodes. These studies suggest that major depression can be prevented. Given the large burden of disease caused by major depression, it is time for substantial systematic efforts to replicate these studies, carry out multisite trials, and widely disseminate prevention interventions found to be effective. The present review examines the conceptual and practical differences between treatment and prevention trials and the importance of identifying groups at high short-term risk for major depressive episodes to make prevention trials feasible. We also list the randomized controlled prevention trials that have been carried out to date and discuss the need for prevention interventions that go beyond the limits of traditional face-to-face interventions.
Stab Wounds Penetrating the Left Atrium
Authors: M. Paul
Journal: Thorax (1961)

A stab wound penetrating the left atrium (excluding the left auricle) would have to penetrate through other chambers of the heart or through the great arteries at their origin from the heart to reach the left atrium from the front of the chest. Such wounds would be fatal, the patient dying from profuse haemorrhage within a few minutes. A stab wound through the back of the chest could reach the left atrium in the narrow sulcus between the root of the left lung in front and the oesophagus and descending thoracic aorta behind, but placing a wound at this site without at the same time severing the vessels in the root of the left lung or the descending thoracic aorta would be an exceptional event, and the survival of a patient after a stab wound penetrating the left atrium would be dependent on it. The present case of survival after a stab wound penetrating the left atrium appears to be the only one of its kind in the literature. It is reported not only on account of the rarity of its occurrence but also because of the unusual methods used to arrest the haemorrhage. Our experience in this case stimulated us to investigate by experimental surgery on animals the possibility of arresting haemorrhage from stab wounds of the heart without sutures, and these experiments confirmed the feasibility of this being done, even with stab wounds penetrating the ventricles of the heart.
Attempt to classify patients with arthritis of the hip suitable for prosthetic replacement, and their femoral heads.
Authors: P D Byers, B A Roper, B Glennie
Journal: Annals of the Rheumatic Diseases (1975)

Using clinical, radiological, and morbid anatomical data about patients with arthritis of the hip and their femoral heads resected during total hip replacement, an attempt has been made first, to classify patients and femoral heads by a cluster analysis technique, and secondly and more realistically, to use existing clinical and radiological classification as a basis for seeking discriminating features in the data from the femoral head. Both types of analysis failed to give results, and led to a conclusion that arthritis of the hip is a spectrum of disease. This may not pose problems to the clinician, but it does to the investigator studying the pathogenesis of osteoarthrosis. This problem is briefly discussed.
Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats
Authors: A Giacometti
Journal: Gut (2003)

Background: Postoperative morbidity in patients with obstructive jaundice remains high because of increased susceptibility to endotoxin and the inflammatory cascade. Aims: An experimental study was designed to investigate the efficacy of protegrin peptide IB-367, an antimicrobial positively charged peptide, in neutralising Escherichia coli 0111:B4 lipopolysaccharide (LPS) in bile duct ligated rats. Methods: Adult male Wistar rats were injected intraperitoneally with 2 mg/kg E coli 0111:B4 LPS one week after sham operation or bile duct ligation (BDL). Six groups were studied: sham with placebo, sham with 120 mg/kg tazobactam-piperacillin (TZP), sham with 1 mg/kg IB-367, BDL with placebo, BDL with 120 mg/kg TZP, and BDL with 1 mg/kg IB-367. Results: Main outcome measures were: endotoxin and tumour necrosis factor α (TNF-α) concentrations in plasma, evidence of bacterial translocation in blood and peritoneum, and lethality. After LPS, TNF-α plasma levels were significantly higher in BDL rats compared with sham operated animals. IB-367 caused a significant reduction in plasma endotoxin and TNF-α concentrations compared with placebo and TZP treated groups. In contrast, both TZP and IB-367 significantly reduced bacterial growth compared with saline treatment. Finally, LPS induced 60% and 55% lethality in BDL placebo and TZP treated rats and no lethality in sham operated rats, while only IB-367 significantly reduced lethality to 10%. Conclusions: By virtue of its dual antimicrobial and antiendotoxin properties, IB-367 could be an interesting compound to inhibit bacterial translocation and endotoxin release in obstructive jaundice.
The Renal Lesions of Alport Syndrome
Authors: Laurence Heidet, Marie-Claire Gubler
Journal: Journal of the American Society of Nephrology (2009)

Alport syndrome is a hereditary, progressive, hematuric nephropathy characterized by glomerular basement membrane abnormalities with frequent hearing defects and ocular anomalies. The disease is associated with mutations in genes encoding the α3, α4, or α5 chains of type IV collagen, <i>COL4A3</i>, or <i>COL4A4</i> in the autosomal forms of the disease, <i>COL4A5</i> in the more frequent X-linked variety. Ultrastructural changes in the glomerular basement membrane and frequent abnormal expression of type IV collagen chains in renal and skin basement membranes are crucial elements for the diagnosis of Alport syndrome, determination of the mode of inheritance, and genetic counseling. Animal models have provided invaluable tools to study the mechanisms leading to progressive deterioration of the glomerular basement membrane and ultimately to renal failure, and to evaluate benefits of potential targeted therapies.
The genome of the polar eukaryotic microalga Coccomyxa subellipsoidea reveals traits of cold adaptation
Authors: Guillaume Blanc, Irina Agarkova, Jane Grimwood, Alan Kuo, Andrew Brueggeman, David D Dunigan, James Gurnon, Istvan Ladunga, Erika Lindquist, Susan Lucas, Jasmyn Pangilinan, Thomas Pröschold, Asaf Salamov, Jeremy Schmutz, Donald Weeks, Takashi Yamada, Alexandre Lomsadze, Mark Borodovsky, Jean-Michel Claverie, Igor V Grigoriev, James L Van Etten
Journal: Genome biology (2012)

Little is known about the mechanisms of adaptation of life to the extreme environmental conditions encountered in polar regions. Here we present the genome sequence of a unicellular green alga from the division chlorophyta, Coccomyxa subellipsoidea C-169, which we will hereafter refer to as C-169. This is the first eukaryotic microorganism from a polar environment to have its genome sequenced.The 48.8 Mb genome contained in 20 chromosomes exhibits significant synteny conservation with the chromosomes of its relatives Chlorella variabilis and Chlamydomonas reinhardtii. The order of the genes is highly reshuffled within synteny blocks, suggesting that intra-chromosomal rearrangements were more prevalent than inter-chromosomal rearrangements. Remarkably, Zepp retrotransposons occur in clusters of nested elements with strictly one cluster per chromosome probably residing at the centromere. Several protein families overrepresented in C. subellipsoidae include proteins involved in lipid metabolism, transporters, cellulose synthases and short alcohol dehydrogenases. Conversely, C-169 lacks proteins that exist in all other sequenced chlorophytes, including components of the glycosyl phosphatidyl inositol anchoring system, pyruvate phosphate dikinase and the photosystem 1 reaction center subunit N (PsaN).We suggest that some of these gene losses and gains could have contributed to adaptation to low temperatures. Comparison of these genomic features with the adaptive strategies of psychrophilic microbes suggests that prokaryotes and eukaryotes followed comparable evolutionary routes to adapt to cold environments.
Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era
Authors: Jari M. Tapanainen, Kai S. Lindgren, Timo H. Mäkikallio, Olli Vuolteenaho, Juhani Leppäluoto, Heikki V. Huikuri
Journal: Journal of the American College of Cardiology (2004)
High-Density Lipoprotein Promotes Endothelial Cell Migration and Reendothelialization via Scavenger Receptor-B Type I
Authors: Divya Seetharam, Chieko Mineo, Andrew K. Gormley, Linda L. Gibson, Wanpen Vongpatanasin, Ken L. Chambliss, Lisa D. Hahner, Melissa L. Cummings, Richard L. Kitchens, Yves L. Marcel, Daniel J. Rader, Philip W. Shaul
Journal: Circulation Research (2005)

Vascular disease risk is inversely related to circulating levels of high-density lipoprotein (HDL) cholesterol. However, the mechanisms by which HDL provides vascular protection are unclear. The disruption of endothelial monolayer integrity is an important contributing factor in multiple vascular disorders, and vascular lesion severity is tempered by enhanced endothelial repair. Here, we show that HDL stimulates endothelial cell migration in vitro in a nitric oxide-independent manner via scavenger receptor B type I (SR-BI)-mediated activation of Rac GTPase. This process does not require HDL cargo molecules, and it is dependent on the activation of Src kinases, phosphatidylinositol 3-kinase, and p44/42 mitogen-activated protein kinases. Rapid initial stimulation of lamellipodia formation by HDL via SR-BI, Src kinases, and Rac is also demonstrable. Paralleling the in vitro findings, carotid artery reendothelialization after perivascular electric injury is blunted in apolipoprotein A-I(-/-) mice, and reconstitution of apolipoprotein A-I expression rescues normal reendothelialization. Furthermore, reendothelialization is impaired in SR-BI(-/-) mice. Thus, HDL stimulates endothelial cell migration via SR-BI-initiated signaling, and these mechanisms promote endothelial monolayer integrity in vivo.
Statistical Evaluation of the Rodin–Ohno Hypothesis: Sense/Antisense Coding of Ancestral Class I and II Aminoacyl-tRNA Synthetases
Authors: Srinivas Niranj Chandrasekaran, Galip Gürkan Yardimci, Ozgün Erdogan, Jeffrey Roach, Charles W. Carter
Journal: Molecular Biology and Evolution (2013)

We tested the idea that ancestral class I and II aminoacyl-tRNA synthetases arose on opposite strands of the same gene. We assembled excerpted 94-residue Urgenes for class I tryptophanyl-tRNA synthetase (TrpRS) and class II Histidyl-tRNA synthetase (HisRS) from a diverse group of species, by identifying and catenating three blocks coding for secondary structures that position the most highly conserved, active-site residues. The codon middle-base pairing frequency was 0.35 ± 0.0002 in all-by-all sense/antisense alignments for 211 TrpRS and 207 HisRS sequences, compared with frequencies between 0.22 ± 0.0009 and 0.27 ± 0.0005 for eight different representations of the null hypothesis. Clustering algorithms demonstrate further that profiles of middle-base pairing in the synthetase antisense alignments are correlated along the sequences from one species-pair to another, whereas this is not the case for similar operations on sets representing the null hypothesis. Most probable reconstructed sequences for ancestral nodes of maximum likelihood trees show that middle-base pairing frequency increases to approximately 0.42 ± 0.002 as bacterial trees approach their roots; ancestral nodes from trees including archaeal sequences show a less pronounced increase. Thus, contemporary and reconstructed sequences all validate important bioinformatic predictions based on descent from opposite strands of the same ancestral gene. They further provide novel evidence for the hypothesis that bacteria lie closer than archaea to the origin of translation. Moreover, the inverse polarity of genetic coding, together with a priori α-helix propensities suggest that in-frame coding on opposite strands leads to similar secondary structures with opposite polarity, as observed in TrpRS and HisRS crystal structures.
Multiple low-dose streptozotocin-induced diabetes in the mouse. Evidence for stimulation of a cytotoxic cellular immune response against an insulin-producing beta cell line.
Authors: R C McEvoy, J Andersson, S Sandler, C Hellerström
Journal: Journal of Clinical Investigation (1984)

Mice were examined for the presence of splenocytes specifically cytotoxic for a rat insulinoma cell line (RIN) during the induction of diabetes by streptozotocin (SZ) in multiple low doses (Multi-Strep). Cytotoxicity was quantitated by the release of 51Cr from damaged cells. A low but statistically significant level of cytolysis (5%) by splenocytes was first detectable on day 8 after the first dose of SZ. The cytotoxicity reached a maximum of approximately 9% on day 10 and slowly decreased thereafter, becoming undetectable 42 d after SZ was first given. The time course of the in vitro cytotoxic response correlated with the degree of insulitis demonstrable in the pancreata of the Multi-Strep mice. The degree of cytotoxicity after Multi-Strep was related to the number of effector splenocytes to which the target RIN cells were exposed and was comparable to that detectable after immunization by intraperitoneal injection of RIN cells in normal mice. The cytotoxicity was specific for insulin-producing cells; syngeneic, allogeneic, and xenogeneic lymphocytes and lymphoblasts, 3T3 cells, and a human keratinocyte cell line were not specifically lysed by the splenocytes of the Multi-Strep mice. This phenomenon was limited to the Multi-Strep mice. Splenocytes from mice made diabetic by a single, high dose of SZ exhibited a very low level of cytotoxicity against the RIN cells. The cytotoxic response was also quantitated in splenocytes from control and Multi-Strep mice (10 d after the first dose of SZ) before and after culture with mitomycin-treated RIN cells in the presence of T cell growth factor (TCGF). The cytotoxicity of the Multi-Strep splenocytes was enhanced more than fivefold after such culture, suggesting the proliferation of an effector cell that could be stimulated and supported in vitro by TCGF. These results support the hypothesis that cell-mediated anti-beta cell autoimmunity may play a role in the destruction of the beta cells in this animal model. The stimulation of this response by TCGF may provide a tool by which enough cytotoxic effector cells could be obtained to establish their possible direct pathogenetic role in the induction of insulin-dependent diabetes. In addition, such cells will be a valuable tool to define the specific beta-cell antigens that may direct the highly selective cell-mediated destruction of these cells in experimental models and, perhaps, in human insulin-dependent diabetes mellitus.
Despeciated Bovine Serum: Substitute for Human Plasma
Authors: F. R. Edwards
Journal: BMJ (1944)

After various modifications in treatment the routine use of pamaquin was abandoned.The most generally useful course of drugs in uncomplicated cases was found to be quinine gr. 10 t.d.s. by mouth for two or three days, and mepacrine 0.1 g. t.d.s. for six days, the two drugs being with advantage ".overlapped " for 24 hours.The patient's usual dose of a suppressive drug was resumed as soon as the course was finished, and an adequate period of convalescence was regarded as of the greatest importance.Our thanks are due to Col. 0.
Rheumatoid factors in 129XB recombinant inbred strains. Igh-1-linked control of allotypic and isotypic specificities.
Authors: J Van Snick, J P Coutelier, E Van Roost, J L Guénet
Journal: The Journal of Experimental Medicine (1984)

To examine the role of autologous IgG in the induction of murine rheumatoid factors (RF) we have analyzed the allotypic specificity of anti-IgG2a RF in recombinant inbred strains derived from 129/Sv (Igh-1a) and C57BL/6 (Igh-1b) mice. In five of six Igh-1a strains, anti-IgG2a RF reacted with IgG2aa but failed to react with IgG2ab. In contrast, isotype-specific RF, which reacted equally well with a and b allotypes of IgG2a, represented the major RF species in one Igh-1a and all five Igh-1b strains tested. An additional form of RF specific for IgG2ab and not reactive with IgG2aa was detected in one Igh-1b strain. RF specific for a give allotype was thus only found in the presence of that allotype, which strongly suggests the involvement of autologous IgG in the induction of mouse RF synthesis. The specificity of RF was apparently further controlled by genes linked to but different from the Igh-C locus, as indicated by the absence of IgG2aa-specific RF in one of the 6 Igh-1a strains tested. Because this strain, 129XBG, has been shown to express idiotypic markers characteristic of Igh-1b mice, it is likely that the genes, which in the presence of a given allotype induce the production of isotype rather than allotype-specific RF, are identical to those that control the expression of idiotypes. Evidence was also obtained to indicate that Igh-1-linked genes influence the isotypic specificity and the isotype of RF itself: IgA anti-IgG2a predominated in Igh-1a strains and IgM anti-IgG1 in Igh-1b strains. Interestingly enough, total IgA and IgG2a levels also were higher in Igh-1a than in Igh-1b strains.
Ventilator-associated pneumonia due to colistin susceptible-only microorganisms
Authors: F. G. Rios, C. M. Luna, B. Maskin, A. Saenz. Valiente, M. Lloria, S. Gando, C. Sosa, S. Baquero, C. Llerena, C. Petrati, C. Apezteguia
Journal: European Respiratory Journal (2007)

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.
Stimulation of Myocardial Na <sup>+</sup> -Independent Cl <sup>−</sup> -HCO <sub>3</sub> <sup>−</sup> Exchanger by Angiotensin II Is Mediated by Endogenous Endothelin
Authors: Maria C. Camilión de Hurtado, Bernardo V. Alvarez, Irene L. Ennis, Horacio E. Cingolani
Journal: Circulation Research (2000)

Abstract —Experiments were performed in isolated cat papillary muscles loaded with the pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in the esterified form to study the effect of endothelin-1 (ET-1) on the activity of the Na + -independent Cl − -HCO 3 − exchanger. Exposure to ET-1 (10 nmol/L) raised pH i by 0.13±0.03 U ( P &lt;0.05) in papillary muscles superfused with nominally HCO 3 − -free solution, whereas no significant change was detected under CO 2 /HCO 3 − -buffered medium. However, if ET-1 was applied to muscles pretreated with the anion exchanger inhibitor 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid, pH i increased by 0.09±0.02 U ( P &lt;0.05) in the presence of CO 2 /HCO 3 − buffer. The rate of pH i recovery from trimethylamine hydrochloride–induced intracellular alkaline load was enhanced so that net HCO 3 efflux increased about three times in the presence of ET-1 (2.74±0.25 versus 9.66±1.29 mmol · L −1 · min −1 at pH i 7.55, P &lt;0.05). This effect was canceled by previous exposure to either 50 nmol/L PD 142,893 (nonselective endothelin receptor blocker) or 300 nmol/L BQ 123 (selective blocker of ET A receptors). BQ 123 also abolished angiotensin II–induced activation of the Na + independent Cl − -HCO 3 − exchanger. These results show that ET-1 increases the activity of the Na + -independent Cl − -HCO 3 − exchanger in cardiac tissue through the ET A receptors. Furthermore, our data suggest that the previously described angiotensin II–induced stimulation of the anion exchanger activity is mediated by endogenous ET-1.