tbuckley/cabot-search huggingface dataset:
Gene Capture from across the Grass Family in the Allohexaploid Elymus repens (L.) Gould (Poaceae, Triticeae) as Evidenced by ITS, GBSSI, and Molecular Cytogenetics
Authors: Václav Mahelka, David Kopecký
Journal: Molecular Biology and Evolution (2010)

Four accessions of hexaploid Elymus repens from its native Central European distribution area were analyzed using sequencing of multicopy (internal transcribed spacer, ITS) and single-copy (granule-bound starch synthase I, GBSSI) DNA in concert with genomic and fluorescent in situ hybridization (GISH and FISH) to disentangle its allopolyploid origin. Despite extensive ITS homogenization, nrDNA in E. repens allowed us to identify at least four distinct lineages. Apart from Pseudoroegneria and Hordeum, representing the major genome constituents, the presence of further unexpected alien genetic material, originating from species outside the Triticeae and close to Panicum (Paniceae) and Bromus (Bromeae), was revealed. GBSSI sequences provided information complementary to the ITS. Apart from Pseudoroegneria and Hordeum, two additional gene variants from within the Triticeae were discovered: One was Taeniatherum-like, but the other did not have a close relationship with any of the diploids sampled. GISH results were largely congruent with the sequence-based markers. GISH clearly confirmed Pseudoroegneria and Hordeum as major genome constituents and further showed the presence of a small chromosome segment corresponding to Panicum. It resided in the Hordeum subgenome and probably represents an old acquisition of a Hordeum progenitor. Spotty hybridization signals across all chromosomes after GISH with Taeniatherum and Bromus probes suggested that gene acquisition from these species is more likely due to common ancestry of the grasses or early introgression than to recent hybridization or allopolyploid origin of E. repens. Physical mapping of rDNA loci using FISH revealed that all rDNA loci except one minor were located on Pseudoroegneria-derived chromosomes, which suggests the loss of all Hordeum-derived loci but one. Because homogenization mechanisms seem to operate effectively among Pseudoroegneria-like copies in this species, incomplete ITS homogenization in our samples is probably due to an interstitial position of an individual minor rDNA locus located within the Hordeum-derived subgenome.
An anchored restriction-mapping approach applied to the genetic analysis of the Anopheles gambiae malaria vector complex 1.
Authors: K. D. Mathiopoulos, J. D. Powell, T. F. McCutchan
Journal: Molecular Biology and Evolution (1995)

We introduce here a simple approach for rapidly determining restriction maps for a number of regions of a genome; this involves "anchoring" a map with a rare restriction site (in this case the seldom-cutting EagI) followed by partial digestion of a frequent-cutting enzyme (e.g., Sau 3A). We applied this technology to five species of the Anopheles gambiae complex. In a single Southern blot we obtained about a 15-kb restriction map each for the mtDNA, rRNA gene, and a scnDNA region for each of five species. Phylogenetic analyses of these regions yield trees at odds with the more traditional chromosome inversion-based trees. The value of the approach for systematic purposes is the ease with which several large, independent regions of the genome can be quickly assayed for molecular variation.
The mechanical characteristics of hypertrophied rabbit cardiac muscle in the absence of congestive heart failure: the contractile and series elastic elements.
Authors: B B Hamrell, N R Alpert
Journal: Circulation Research (1977)

Right ventricular papillary muscles from normal rabbits and rabbits with sustained pulmonary artery constriction (67% decrease in external diameter) were studied at several resting muscle lengths and at an early instant in the isometric twitch. Instantaneous force-velocity data were obtained at 30-38% of time to peak tension (TPT) and at 96%, 98%, and 100% of the resting muscle length at which active twitch tension was maximal. Unloaded shortening velocity (Vmax) was estimated with a linearized form of the Hill hyperbolic formula, and was depressed in hypertrophy to 36% less than normal. We found that Vmax did not change with muscle length in the normal or hypertrophied muscles; therefore there was a length- and time-independent depression of contractile element shortening capacity that was consistent with previous work from this laboratory which demonstrated a depression of myosin and actomyosin ATPase activity in hypertrophy.
Off-Pump versus On-Pump Coronary-Artery Bypass Grafting in Elderly Patients
Authors: Anno Diegeler, Jochen Börgermann, Utz Kappert, Martin Breuer, Andreas Böning, Adrian Ursulescu, Ardawan Rastan, David Holzhey, Hendrik Treede, Friedrich-Christian Rieß, Philippe Veeckmann, Amjad Asfoor, Wilko Reents, Michael Zacher, Michael Hilker
Journal: New England Journal of Medicine (2013)

The benefits of coronary-artery bypass grafting (CABG) without cardiopulmonary bypass in the elderly are still undetermined.We randomly assigned patients 75 years of age or older who were scheduled for elective first-time CABG to undergo the procedure either without cardiopulmonary bypass (off-pump CABG) or with it (on-pump CABG). The primary end point was a composite of death, stroke, myocardial infarction, repeat revascularization, or new renal-replacement therapy at 30 days and at 12 months after surgery.A total of 2539 patients underwent randomization. At 30 days after surgery, there was no significant difference between patients who underwent off-pump surgery and those who underwent on-pump surgery in terms of the composite outcome (7.8% vs. 8.2%; odds ratio, 0.95; 95% confidence interval [CI], 0.71 to 1.28; P=0.74) or four of the components (death, stroke, myocardial infarction, or new renal-replacement therapy). Repeat revascularization occurred more frequently after off-pump CABG than after on-pump CABG (1.3% vs. 0.4%; odds ratio, 2.42; 95% CI, 1.03 to 5.72; P=0.04). At 12 months, there was no significant between-group difference in the composite end point (13.1% vs. 14.0%; hazard ratio, 0.93; 95% CI, 0.76 to 1.16; P=0.48) or in any of the individual components. Similar results were obtained in a per-protocol analysis that excluded the 177 patients who crossed over from the assigned treatment to the other treatment.In patients 75 years of age or older, there was no significant difference between on-pump and off-pump CABG with regard to the composite outcome of death, stroke, myocardial infarction, repeat revascularization, or new renal-replacement therapy within 30 days and within 12 months after surgery. (Funded by Maquet; GOPCABE ClinicalTrials.gov number, NCT00719667.).
Glanzmann's thrombasthenia in two pregnant females
Authors: Murat Dede, A. Ugur Ural, Mufit Yenen, Zeki Mesten, Iskender Baser
Journal: American Journal of Hematology (2006)

To the Editor: Renal damage after stem cell transplantation (SCT) may manifest as acute renal failure, renal tubular acidosis, and proteinuria [1].Post-SCT nephrotic syndrome (NS) has histological association with membranous nephropathy.It usually accompanies acute/chronic graft versus host disease (aGVHD/cGVHD) [2], and represents kidney damage mediated by donor lymphocytes.By natural history, GVHD severity usually decreases with time.However, therapeutic induction of GVHD by donor lymphocyte infusion (DLI) may be needed to enhance the graft versus leukemia (GVL) effect.The clinical spectrum of DLI-related GVHD is often different from that after initial SCT [3].Very little is known about the manifestation, histology, and optimal treatment for DLI related glomerulonephritis [4].A 27-year-old man with chronic myeloid leukemia (CML) received SCT from an unrelated donor.He was engrafted with grade I aGVHD with no cGVHD.Cyclosporine (CsA) was tailed-off at 1 year.However, molecular and cytogenetic relapse of CML occurred at 36 months.Two doses of DLI (3.5 Â 10 5 lymphocytes/kg) produced complete molecular remission, accompanied Fig. 1.Electron microscopy shows discrete electron-dense deposits in the subepithelial region (original magnification 33,900).
Adenovirus-Mediated Overexpression of Diacylglycerol Kinase-ζ Inhibits Endothelin-1–Induced Cardiomyocyte Hypertrophy
Authors: Hiroki Takahashi, Yasuchika Takeishi, Tim Seidler, Takanori Arimoto, Hideyuki Akiyama, Yasukazu Hozumi, Yo Koyama, Tetsuro Shishido, Yuichi Tsunoda, Takeshi Niizeki, Naoki Nozaki, Jun-ichi Abe, Gerd Hasenfuss, Kaoru Goto, Isao Kubota
Journal: Circulation (2005)

Diacylglycerol (DAG) is a lipid second messenger that transiently accumulates in cells stimulated by endothelin-1 (ET-1) and other Galphaq protein-coupled receptor agonists. Diacylglycerol kinase (DGK) is thought to be an enzyme that controls the cellular levels of DAG by converting it to phosphatidic acid; however, the functional role of DGK has not been examined in cardiomyocytes. Because DGK inactivates DAG, a strong activator of protein kinase C (PKC), we hypothesized that DGK inhibited ET-1-induced activation of a DAG-PKC signaling cascade and subsequent cardiomyocyte hypertrophy.Real-time reverse transcription-polymerase chain reaction demonstrated a significant increase of DGK-zeta mRNA by ET-1 in cardiomyocytes. To determine the functional role of DGK-zeta, we overexpressed DGK-zeta in cardiomyocytes using a recombinant adenovirus encoding rat DGK-zeta (Ad-DGKzeta). ET-1-induced translocation of PKC-epsilon was blocked by Ad-DGKzeta (P<0.01). Ad-DGKzeta also inhibited ET-1-induced activation of extracellular signal-regulated kinase (P<0.01). Luciferase reporter assay revealed that ET-1-mediated increase of activator protein-1 (AP1) DNA-binding activity was significantly inhibited by DGK-zeta (P<0.01). In cardiomyocytes transfected with DGK-zeta, ET-1 failed to cause gene induction of atrial natriuretic factor, increases in [3H]-leucine uptake, and increases in cardiomyocyte surface area.We demonstrated for the first time that DGK-zeta blocked ET-1-induced activation of the PKC-epsilon-ERK-AP1 signaling pathway, atrial natriuretic factor gene induction, and resultant cardiomyocyte hypertrophy. DGK-zeta might act as a negative regulator of hypertrophic program in response to ET-1, possibly by controlling cellular DAG levels.
Linking Cost Sharing to Value: An Unrivaled Yet Unrealized Public Health Opportunity
Authors: R. Scott Braithwaite, Allison B. Rosen
Journal: Annals of Internal Medicine (2007)

As the financial burden of cost sharing continues to rise, patients increasingly avoid necessary care, thereby contributing to the high morbidity and mortality of the U.S. population compared with that of other developed countries. The rationale for cost sharing is often based on the moral hazard argument, which states that individuals may overuse care if they do not share in its costs. We evaluate this argument in detail, using it to distinguish between appropriate and inappropriate settings for cost sharing. Cost sharing may be appropriate when health services are of low value (low ratio of benefits to costs), whereas it is inappropriate when health services are of high value (high ratio of benefits to costs). In practice, cost sharing is rarely linked to value, and therefore much of the cost sharing that currently occurs is inappropriate and harmful. Cost-effectiveness analysis is an objective method to estimate the value of health services and may be a way to systematically evaluate whether cost-sharing policies are appropriate. Systematic efforts to discourage inappropriate cost sharing may improve public health.
Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension
Authors: Ventzislav Petkov, Wilhelm Mosgoeller, Rolf Ziesche, Markus Raderer, Leopold Stiebellehner, Karin Vonbank, Georg-Christian Funk, Gerhard Hamilton, Clemens Novotny, Bernhard Burian, Lutz-Henning Block
Journal: Journal of Clinical Investigation (2003)

Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension.
FOLFOX4 plus cetuximab administered weekly or every second week in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer: a randomized phase II CECOG study
Authors: T. Brodowicz, T.E. Ciuleanu, D. Radosavljevic, E. Shacham-Shmueli, D. Vrbanec, S. Plate, Z. Mrsic-Krmpotic, M. Dank, G. Purkalne, D. Messinger, C.C. Zielinski
Journal: Annals of Oncology (2013)

BackgroundThis randomized phase II study investigated first-line chemotherapy plus cetuximab administered every second week in KRAS wild-type metastatic colorectal cancer.Patients and methodsPatients received FOLFOX4 plus either standard weekly cetuximab (arm 1) or cetuximab (500 mg/m2) every second week (arm 2), until disease progression or unacceptable toxicity. Primary end point was the objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were also investigated. The study was not powered to establish non-inferiority, but aimed at the estimation of treatment differences.ResultsOf 152 randomized eligible patients, 75 were treated in arm 1 and 77 in arm 2; ORRs [53% versus 62%, odds ratio 1.40, 95% confidence interval (CI) 0.74–2.66], PFS [median 9.5 versus 9.2 months, hazard ratio (HR) 0.92, 95% CI 0.63–1.34], OS (median 25.8 versus 23.0 months, HR 0.86, 95% CI 0.56–1.30) and DCR (87%) were comparable. HRs adjusted for baseline factors were 1.01 and 0.99 for PFS and OS, respectively. Frequencies of grade 3/4 adverse events in arms 1 versus 2 were similar: most common were neutropenia (28% versus 34%) and rash (15% versus 17%).ConclusionsActivity and safety of FOLFOX4 plus either cetuximab administered weekly or every second week were similar.
The LIM and SH3 domain protein family: structural proteins or signal transducers or both?
Authors: Thomas GP Grunewald, Elke Butt
Journal: Molecular Cancer (2008)

LIM and SH3 Protein 1 (LASP-1) was initially identified from a cDNA library of metastatic axillary lymph nodes (MLN) more than a decade ago. It was found to be overexpressed in human breast and ovarian cancer and became the first member of a newly defined LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. LASP2, a novel LASP1-related gene was first identified and characterized in silico. Subsequently it proved to be a splice variant of the Nebulin gene and therefore was also termed LIM/nebulette. LASP-1 and -2 are highly conserved in their LIM, nebulin-like and SH3 domains but differ significantly at their linker regions. Both proteins are ubiquitously expressed and involved in cytoskeletal architecture, especially in the organization of focal adhesions. Here we present the first systematic review to summarize all relevant data concerning their domain organization, expression profiles, regulating factors and function. We compile evidence that both, LASP-1 and LASP-2, are important during early embryo- and fetogenesis and are highly expressed in the central nervous system of the adult. However, only LASP-1 seems to participate significantly in neuronal differentiation and plays an important functional role in migration and proliferation of certain cancer cells while the role of LASP-2 is more structural. The increased expression of LASP-1 in breast tumours correlates with high rates of nodal-metastasis and refers to a possible relevance as a prognostic marker.
Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium.
Authors: G N Tseng
Journal: Circulation Research (1988)

Restitution of the conventional L-type calcium current (ICa) was studied in dog or guinea pig ventricular myocytes to understand its time course and regulation. Whole-cell ICa free of other overlapping currents was recorded with a suction pipette. The intracellular environment was varied by intracellular dialysis. The properties of ICa were similar in dog and guinea pig ventricular myocytes, except that the amplitude of ICa was larger in the latter (2.2 +/- 0.5 nA in guinea pig cells and 0.9 +/- 0.2 nA in dog cells, n = 8 for both). In both types of cells during restitution a holding voltage (Vh) negative to -50 mV induced a transient increase in ICa above the control level (ICa overshoot). This overshoot was inhibited by substituting barium for calcium, lowering [Ca]0, increasing intracellular calcium buffering capacity, ryanodine (1-2 microM), or caffeine (10 mM). The overshoot peaked 30-100 msec after repolarization from the conditioning depolarization and gradually declined over the following 2-3 seconds. During the overshoot, although the amplitude of ICa was larger its half-time of decay was longer than the control. The maximum overshoot occurred following a conditioning step to plateau voltages and it was decreased by prolonging the conditioning step from 50 to 100 or 500 msec. It is concluded that intracellular calcium regulates restitution of the L-type calcium channels in mammalian ventricular myocytes and that the sarcoplasmic reticulum is involved in this process.
Tinzaparin and vitamin K antagonist (VKA) use in patients with cancer associated venous thromboembolism (VTE): A cohort study
Authors: Elise Noel-Savina, Olivier Sanchez, Renaud Descourt, Michel Andre, Guy Meyer, Christophe Leroyer, Francis Couturaud
Journal: European Respiratory Journal (2014)

Introduction:  Low Molecular Weight Heparins are the mainstay of anticoagulation during the first 3 to 6 months of treatment of VTE in cancer patients. After 6 months,the optimal anticoagulant strategy remains uncertain.  Objectives:  The primary objective was to determine the risk of recurrent VTE and bleeding during and after 6 months of follow-up. Secondary objectives were to identify the risk factor.  Methods:  Multicenter retrospective cohort study (Jan 2004 to Mar 2011) including patients with cancer who received tinzaparin during at least 3 months for VTE. Outcomes were the recurrent VTE, bleeding and death.  Results:  250 patients were included. At 6 months, recurrent VTE occurred in 26 patients (10.4%, 22 on tinzaparin, 2 on VKA) and major bleeding in 14 patients (5.6% all on tinzaparin). Stopping anticoagulation in patients considered at low risk by physicians (i.e.; prior cancer surgery) was the only factor increased recurrent VTE (OR 7.2 95%CI, 2.0-25.7; p=0.002). After 6 months, recurrent VTE occurred in 20 patients (8%) and major bleeding in 4 patients (1.6%). Stopping anticoagulation in relation with major bleeding or metastatic cancer increased risk of recurrent VTE (OR 2.3, 95%CI, 0.9-5.4; p=0.07; and OR 1.8 95%CI, 1.0-3.3; p=0.07; respectively). No factor increased the risk of major bleeding.The overall mortality was 42.8%.  Conclusions:  During the first 6 months, the recurrent VTE was related to early discontinuation of anticoagulation in patients considered at low risk of recurrence by physicians. After 6 month, the risks of recurrent VTE were similar with either VKA or tinzaparin and were mainly related to metastatic cancer and major bleeding.
Report on the Value of Sodium Silicofluoride as an Antiseptic
Authors: T. J. Bokenham
Journal: BMJ (1890)

delirious in the night.Profuse yellow expectoration.Temperature 99.60, pulse 100, morning; temperature 100.4°, pulse 100, evening.March 24th (sixth day) had a good night.Moist rdales on right side, with comparative dulness half way up.Temperature 99.80, pulse 100, morning; temperature 100.40, pulse 92, evening.She was soon up, but continued weak for a while.CASE Ir.-Miss B. S., aged 25.Had pain in the chest on April 1st.On April 3rd some cough.Friction heard on left side.April 4th friction on left front.Moist rdles on left, behind.These signs TIMM-EI EM EM IM 9EME;MJME M EIMEM EIM EIM FMEIM EME E M E_ E ME 977./0 ~i3 70 v~37.9 } o.--9continued.The temperature, which was 105.4°onApril 6th, fell to 99.4°on April 7th, and she steadily improved.The chart shows the course of temperature and pulse.CasE Iv.-M.S., aged 9, began on March 17th with high fever, and went to bed at once.Broncho-pneumonia was developed, and ran a regular course.The chart shows the temperature and pulse.
Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor.
Authors: R Bertini, M Bianchi, P Ghezzi
Journal: The Journal of Experimental Medicine (1988)

To clarify the possible role of TNF and IL-1 in endotoxic shock, the lethality of rTNF (human and murine) and IL-1 in adrenalectomized mice was studied. Adrenalectomy, which has long been known to increase the susceptibility to endotoxin, rendered mice susceptible to TNF and IL-1 in terms of mortality. The lethality of endotoxin, TNF, or IL-1 was totally prevented by pretreatment with dexamethasone (minimal effective dose, 0.3 mg/Kg) but not by ibuprofen (10 mg/Kg).
Familial Risk of Preeclampsia in Newfoundland
Authors: Lesa M. Dawson, Patrick S. Parfrey, Donna Hefferton, Elizabeth L. Dicks, M. Jim Cooper, David Young, Philip A. Marsden
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. This study sought to quantify the familial risk of preeclampsia (proteinuric hypertension) in Newfoundland and to identify characteristics in probands that predict increased familial risk. Reviewed were 5173 obstetric charts from 10 hospitals, representing 99% of deliveries on the island of Newfoundland for a 1-yr period from April 1996 to March 1997; pregnancy-induced hypertension was diagnosed according to strict criteria. Family obstetric histories were obtained from identified probands with preeclampsia, and sisters and mothers of probands were interviewed. In addition, the obstetric charts from sisters and mothers were reviewed to identify preeclampsia. The incidence of preeclampsia in the population was 5.6% (n = 292), and in primiparous women it was 7.9%. Factors independently associated with increased risk of preeclampsia included primiparous delivery, multiple gestation, pregestational and gestational diabetes, maternal age of more than 35 yr, and region of the province. Of 330 sisters identified, 217 had 445 pregnancies, with 331 charts located for review. The incidence of preeclampsia (based on chart review) in 163 primiparous sisters was 20.2%. The relative risk of preeclampsia in primiparous sisters of probands with preeclampsia compared with primiparous women in the population was 2.6 (95% confidence interval, 1.8 to 3.6). Factors in probands independently associated with a higher risk of preeclampsia in sisters included at least 2+ proteinuria and region of the province. This population-based study, which used unbiased ascertainment and strict diagnostic criteria, demonstrated a significantly higher risk of preeclampsia in sisters of probands with preeclampsia, particularly when probands were defined by severity of preeclampsia and by geographic region.