tbuckley/cabot-search huggingface dataset:
Phylogenetic analysis of the 5-aminolevulinate synthase gene [published erratum appears in Mol Biol Evol 1999 Jun;16(6):following 883]
Authors: R. Duncan, M. A. Faggart, A. J. Roger, N. W. Cornell
Journal: Molecular Biology and Evolution (1999)

The evolution of 5-aminolevulinate synthase (ALS) was studied by acquiring sequence data and generating phylogenetic trees. Gene sequences were already available for a variety of vertebrates (which have both a housekeeping and an erythroid form of the gene), fungi, alpha-proteobacteria, and one protist and one protostome. In order to generate representative trees, ALS sequence data were acquired from various deuterostomes and protostomes. The species and tissues selected for study were beluga whale liver, hagfish blood, sea urchin gonadal tissue, cuttlefish hepatopancreas, horseshoe crab hepatopancreas, and bloodworm blood. The new sequences and those previously published were examined for the presence of heme-regulatory motifs (HRMs) and iron-responsive elements (IREs). The HRMs are present in almost all eukaryotic species, which suggests their fundamental role in the regulation of ALS. The IREs are present in all vertebrate erythroid forms of ALS, which indicates that in those animals, expression of the erythroid form of the enzyme and, hence, hemoglobin production can be influenced by the intracellular content of iron. The new sequences were aligned with previously reported ALS sequences, and phylogenetic analyses were performed. The resulting trees provided evidence regarding the timing of the gene duplication event that led to the two forms of the ALS gene in vertebrates. It appears that the housekeeping and erythroid forms of ALS probably arose before the divergence of hagfish from the deuterostome line leading to the vertebrates. The data also add to the evidence indicating that alpha-proteobacteria are the nearest contemporary relatives of mitochondria.
THE EFFECT OF OXIDATION OF FILTRATES OF A CHICKEN SARCOMA (CHICKEN TUMOR I—ROUS)
Authors: J. Howard Mueller
Journal: The Journal of Experimental Medicine (1928)

1. The rapid autoinactivation at 37° of candle filtrates of the Rous Foul Sarcoma I is due in large part to oxidation. 2. Such oxidation may be prevented by a dilution of 1-2000 cysteine hydrochloride brought to pH 7.4 with NaOH. 3. The variability of infectiousness of candle filtrates is due in part at least to oxidative changes which take place during their preparation; and more active extracts may be obtained by preventing these by means of cysteine. 4. For elaborate experiments it is possible to preserve filtrates in the ice box with cysteine and vaseline until test inoculations have established their infectivity.
Acute Myocardial Infarction and Renal Dysfunction: A High-Risk Combination
Authors: R. Scott Wright, Guy S. Reeder, Charles A. Herzog, Robert C. Albright, Brent A. Williams, David L. Dvorak, Wayne L. Miller, Joseph G. Murphy, Stephen L. Kopecky, Allan S. Jaffe
Journal: Annals of Internal Medicine (2002)

Background: Survival is poor in patients with acute myocardial infarction (MI) who also have severe renal disease. Less is known about the outcome of acute MI in patients with mild to moderate renal insufficiency. Objective: To compare outcomes after acute MI in patients with varying levels of renal disease and in patients without renal failure. Design: Retrospective cohort study. Setting: Academic medical center. Patients: 3106 total patients admitted with acute MI and end-stage renal disease (n = 44), severe renal insufficiency (creatinine clearance < 0.59 mL/s [<35 mL/min]) (n = 391), moderate renal dysfunction (creatinine clearance ≥ 0.59 mL/s [<35 mL/min] but ≤ 0.84 mL/s [≤ 50 mL/min]) (n = 491), mild chronic renal insufficiency (creatinine clearance > 0.84 mL/s [>50 mL/min] but ≤ 1.25 mL/s [≤ 75 mL/min]) (n = 860), or no renal disease (n = 1320). Measurements: Clinical characteristics, treatment strategies, and short- and long-term survival were compared after patients were stratified by creatinine clearance. Results: In-hospital mortality rates were 2% in patients with normal renal function, 6% in those with mild renal failure, 14% in those with moderate renal failure, 21% in those with severe renal failure, and 30% in those with end-stage renal disease (P < 0.001). Compared with patients without renal disease, similar adjusted trends were present for postdischarge death in patients with end-stage renal disease (hazard ratio, 5.4 [95% CI, 3.0 to 9.7]; P < 0.001), severe renal insufficiency (hazard ratio, 1.9 [CI, 1.2 to 3.0]; P = 0.006), moderate renal dysfunction (hazard ratio, 2.2 [CI, 1.5 to 3.3]; P < 0.001), and mild chronic renal insufficiency (hazard ratio, 2.4 [CI, 1.7 to 3.3]; P < 0.001). Patients with renal failure received adjunctive and reperfusion therapies less frequently than those with normal renal function (P < 0.001). Postdischarge death was less likely in patients who received acute reperfusion therapy (odds ratio, 0.7 [CI, 0.6 to 0.9]), aspirin (odds ratio, 0.7 [CI, 0.5 to 0.8]), and β-blocker therapy (odds ratio, 0.7 [CI, 0.6 to 0.9]). Conclusion: Patients with renal failure are at increased risk for death after acute MI and receive less aggressive treatment than patients with normal renal function.
Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways
Authors: Rodrigue Romon, Eric Adriaenssens, Chann Lagadec, Emmanuelle Germain, Hubert Hondermarck, Xuefen Le Bourhis
Journal: Molecular Cancer (2010)

Abstract Background Although several anti-angiogenic therapies have been approved in the treatment of cancer, the survival benefits of such therapies are relatively modest. Discovering new molecules and/or better understating signaling pathways of angiogenesis is therefore essential for therapeutic improvements. The objective of the present study was to determine the involvement of nerve growth factor (NGF) in breast cancer angiogenesis and the underlying molecular mechanisms. Results We showed that both recombinant NGF and NGF produced by breast cancer cells stimulated angiogenesis in Matrigel plugs in immunodeficient mice. NGF strongly increased invasion, cord formation and the monolayer permeability of endothelial cells. Moreover, NGF-stimulated invasion was under the control of its tyrosine kinase receptor (TrkA) and downstream signaling pathways such as PI3K and ERK, leading to the activation of matrix metalloprotease 2 and nitric oxide synthase. Interestingly, NGF increased the secretion of VEGF in both endothelial and breast cancer cells. Inhibition of VEGF, with a neutralizing antibody, reduced about half of NGF-induced endothelial cell invasion and angiogenesis in vivo . Conclusions Our findings provided direct evidence that NGF could be an important stimulator for breast cancer angiogenesis. Thus, NGF, as well as the activated signaling pathways, should be regarded as potential new targets for anti-angiogenic therapy against breast cancer.
Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts
Authors: J. van der Velden, L.J. Klein, R. Zaremba, N.M. Boontje, M.A.J.M. Huybregts, W. Stooker, L. Eijsman, J.W. de Jong, C.A. Visser, F.C. Visser, G.J.M. Stienen
Journal: Circulation (2001)

During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca(2+), P(i), and pH.Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P(i) to 0.33+/-0.02 of the control force (pH 7.1, 0 mmol/L P(i)) at 30 mmol/L P(i) and increased with pH from 0.64+/-0.03 at pH 6.2 to 1.27+/-0.02 at pH 7.4. Force dependency on P(i) and pH did not differ between donor and failing hearts. Incubation of myocytes in a P(i)-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca(2+)]. Ca(2+) sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca(2+) responsiveness of force and myosin light chain 2 phosphorylation.Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca(2+) responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its P(i) and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [P(i)] at submaximal [Ca(2+)] may even be less than in donor hearts because of the increased Ca(2+) responsiveness.
High-Dose Chemotherapy for Resistant Germ Cell Tumors: Recent Advances and Future Directions
Authors: R. J. Motzer, G. J. Bosl
Journal: JNCI Journal of the National Cancer Institute (1992)

A review of the published literature shows that treatment with high-dose carboplatin and etoposide with autologous bone marrow transplantation results in durable complete responses (3-42 months, continuous at time of report) in about 10%-20% of heavily pretreated patients with cisplatin-resistant germ cell tumors and represents a curative therapy in patients who would otherwise die of their disease. In a recent follow-up study of 40 patients with refractory germ cell tumors, 15% (six) were alive and free of disease more than 24 months after treatment with high-dose carboplatin and etoposide with autologous bone marrow transplantation. The several studies that incorporated an oxazaphosphorine (usually cyclo-phosphamide) in the regimen strongly suggest that the addition of this third drug to high doses of carboplatin and etoposide results in a higher proportion of complete responses (35%, 23% durable) than carboplatin and etoposide alone (26%, 12% durable). Early intervention with high-dose chemotherapy and autologous bone marrow transplantation appears to reduce hematologic toxicity. Its role in the treatment of less heavily pretreated patients will depend on the definition of "cisplatin-resistant", which may encompass those who failed to respond to the drug or those who are judged not likely to respond. Studies to improve treatment efficacy and to lessen the burden of supportive care during hematopoietic reconstitution are ongoing and include the use of peripheral blood-derived stem cells. [J Natl Cancer Inst 84:1703–1709, 1992]
A step forward in the evidence-based treatment of opportunist mycobacteria
Authors: P ORMEROD
Journal: Thorax (2001)

Renal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na<sup>+</sup>,K<sup>+</sup>-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na<sup>+</sup>,K<sup>+</sup>-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na<sup>+</sup>,K<sup>+</sup>-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na<sup>+</sup>,K<sup>+</sup>-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion–induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na<sup>+</sup>,K<sup>+</sup>-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na<sup>+</sup>,K<sup>+</sup>-ATPase to the energy state of renal epithelial cells.
Physical Activity Intervention Studies
Authors: Bess H. Marcus, David M. Williams, Patricia M. Dubbert, James F. Sallis, Abby C. King, Antronette K. Yancey, Barry A. Franklin, David Buchner, Stephen R. Daniels, Randal P. Claytor
Journal: Circulation (2006)

In this review, our first purpose is to provide an overview of existing physical activity intervention research, focusing on subpopulations and intervention modalities. Our reviews within each area are not exhaustive or quantitative, as each area has been reviewed in more depth in numerous other reports. Instead, our goal is to provide a single document that provides a qualitative overview of intervention research that emphasizes selected topics of particular importance for improving the population-wide impact of interventions. Therefore, in synthesizing this vast literature, we begin with existing reviews of physical activity research in each area and incorporate in our discussions recent reports of well-designed individual physical activity intervention studies that expand the existing research base and/or target new areas of research. Our second purpose is to offer new ideas and recommendations to improve the state of the science within each area and, where possible, to propose ideas to help bridge the gaps between these existing categories of research.
The Question of Method in Ethics Consultation
Authors: George J. Agich
Journal: The American Journal of Bioethics (2001)

This paper offers an exposition of what the question of method in ethics consultation involves under two conditions: when ethics consultation is regarded as a practice and when the question of method is treated systematically. It discusses the concept of the practice and the importance of rules in constituting the actions, cognition, and perceptions of practitioners. The main body of the paper focuses on three elements of the question of method: canon, discipline, and history, which are treated heuristically to outline what the question of method in ethics consultation fully involves.
CONTROLLED TRIAL OF ADJUVANT CHEMOTHERAPY WITH MELPHALAN FOR BREAST CANCER
Authors: R.D. Rubens, R.K. Knight, I.S. Fentiman, A. Howell, D. Crowther, W.D. George, J.L. Hayward, R.D. Bulbrook, M. Chaudary, H. Bush, R.A. Sellwood, J.M.T. Howat
Journal: The Lancet (1983)
Time-Course Genetic Analysis of Albuminuria in Dahl Salt-Sensitive Rats on Low-Salt Diet
Authors: Michael R. Garrett, Howard Dene, John P. Rapp
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The Dahl salt-sensitive hypertensive (S) rat develops albuminuria early in life even on a low-salt diet. In contrast, the spontaneously hypertensive rat (SHR) is highly resistant to developing albuminuria despite elevated BP. An F1 hybrid of S and SHR showed a low urinary albumin excretion (UAE) and low urinary protein excretion (UPE) similar to SHR, i.e., SHR was dominant. A genetic analysis was carried out on a large population (n = 276) obtained by backcrossing F1 rats to the recessive S strain; the population was fed a low-salt diet. Genome scans done at 8, 12, and 16 wk of age yielded ten quantitative trait loci (QTL) for UAE and/or UPE with variable time-course patterns on nine rat chromosomes (RNO), i.e., RNO1, RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, RNO13, and RNO19. There were two UPE QTL on RNO6. At most of the UAE and/or UPE QTL, the S allele was associated with increased excretion, except for one of the QTL on RNO6 and the QTL on RNO11, where the S allele caused decreased excretion. Only the UAE and UPE QTL on RNO10 co-localized with a BP QTL. The S allele on RNO10 caused higher BP and higher UAE. Two additional BP QTL were detected on RNO1 and RNO6. Most of the UAE and UPE QTL co-localized with QTL for kidney lesions characteristic of S rats. Multiple interactions were observed for UAE, many of which involved RNO2. In summary, UAE is highly polygenic and the majority of the QTL altering UAE do not co-localize with QTL for BP as evaluated by tail-cuff measurements of BP. E-mail: [email protected]
Vascular Endothelial Growth Factor Increases the Mitogenic Response to Fibroblast Growth Factor-2 in Vascular Smooth Muscle Cells In Vivo via Expression of <i>fms-</i> Like Tyrosine Kinase-1
Authors: Leslie L. Couper, Shane R. Bryant, Jens Eldrup-Jørgensen, Carl E. Bredenberg, Volkhard Lindner
Journal: Circulation Research (1997)

Abstract Vascular endothelial growth factor (VEGF) has traditionally been considered an endothelial cell–specific factor inducing angiogenesis and vascular permeability in vivo. In the present study, expression of VEGF and its receptors, fetal liver kinase-1 (flk-1) and fms -like tyrosine kinase-1 (flt-1), was examined in rat carotid arteries after balloon injury. Although VEGF and flk-1 were not detectable, high levels of flt-1 mRNA and protein were expressed by smooth muscle cells (SMCs) in the neointima, as demonstrated by en face in situ hybridization and Western blotting. Intimal SMC proliferation in chronically denuded rat carotid arteries was unaffected by intraluminal infusion of VEGF, whereas fibroblast growth factor (FGF)-2 increased the number of replicating SMCs 4-fold. Pretreatment with VEGF doubled the mitogenic response to infused FGF-2 by increasing SMC replication in deeper layers of the intima. VEGF increased the permeability of chronically denuded vessels to plasma proteins but had no effect on the uptake of locally infused biotinylated FGF-2. These findings demonstrate that vascular SMCs express functional flt-1 receptors after arterial injury and that VEGF has synergistic effects with FGF-2 on SMC proliferation. These effects are likely to be mediated by a VEGF-mediated increase in permeability as well as a direct interaction between the VEGF and FGF signaling pathways.
High prevalence of familial sarcoidosis in an Irish population.
Authors: N J Brennan, P Crean, J P Long, M X Fitzgerald
Journal: Thorax (1984)

Previous studies in the Republic of Ireland have demonstrated a high national prevalence of sarcoidosis. Observations in our sarcoid clinic suggested a high prevalence of the disease among siblings and prompted a survey to quantify this phenomenon. The study group comprised 114 index patients with biopsy proved sarcoidosis and a total sibling pool of 534 individuals. Eleven of the index patients (9.6%) were found to have at least one sibling with sarcoidosis. Of the 13 siblings thus identified, eight had biopsy proof of the disease, while the remaining five showed highly suggestive clinical and radiological evidence of sarcoidosis. There was no significant difference in the mode of presentation between the sibling pairs or between familial and non-familial cases and there was an equal distribution of like sex and unlike sex pairs. In only two instances was the temporal profile of onset of the disease suggestive of intrafamilial spread of a transmissible agent. The high prevalence of sarcoidosis among siblings reported here (2.4%) suggests that genetic factors significantly predispose to the development of sarcoidosis and that family members of affected patients should be screened for this disease.
Postoperative Biomarkers Predict Acute Kidney Injury and Poor Outcomes after Adult Cardiac Surgery
Authors: Chirag R. Parikh, Steven G. Coca, Heather Thiessen-Philbrook, Michael G. Shlipak, Jay L. Koyner, Zhu Wang, Charles L. Edelstein, Prasad Devarajan, Uptal D. Patel, Michael Zappitelli, Catherine D. Krawczeski, Cary S. Passik, Madhav Swaminathan, Amit X. Garg
Journal: Journal of the American Society of Nephrology (2011)

Acute kidney injury (AKI) is a frequent complication of cardiac surgery and increases morbidity and mortality. The identification of reliable biomarkers that allow earlier diagnosis of AKI in the postoperative period may increase the success of therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 1219 adults undergoing cardiac surgery to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse patient outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. After multivariable adjustment, the highest quintiles of urine IL-18 and plasma NGAL associated with 6.8-fold and 5-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine and plasma NGAL levels associated with longer length of hospital stay, longer intensive care unit stay, and higher risk for dialysis or death. The clinical prediction model for AKI had an area under the receiver-operating characteristic curve (AUC) of 0.69. Urine IL-18 and plasma NGAL significantly improved the AUC to 0.76 and 0.75, respectively. Urine IL-18 and plasma NGAL significantly improved risk prediction over the clinical models alone as measured by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). In conclusion, urine IL-18, urine NGAL, and plasma NGAL associate with subsequent AKI and poor outcomes among adults undergoing cardiac surgery. (Clinical Trials.gov number, NCT00774137).
Chemotherapy-Induced Hyperpigmentation of the Tongue
Authors: Marcelo Blaya, Nakhle Saba
Journal: New England Journal of Medicine (2011)

After undergoing breast lumpectomy and biopsy of the sentinel lymph nodes, a 42-year-old woman with invasive ductal carcinoma began adjuvant chemotherapy. After the second cycle, asymptomatic hyperpigmented macules and patches were noted on the patient's tongue.
Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics
Authors: Rebecca J. Howard, James R. Trudell, R. Adron Harris
Journal: Pharmacological Reviews (2014)

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.
Posterior dislocation of the hip while playing basketball
Authors: T D Tennent, A F Chambler, D J Rossouw
Journal: British Journal of Sports Medicine (1998)

Injuries in basketball are usually to the ankles and knees. Dislocation of the hip is usually associated with severe trauma--for example, road traffic accidents. A case is reported here in which a 22 year old club basketball player slipped on landing from a jump shot, forcing him into a side splits position from which he sustained a posterior dislocation of the hip resulting in a sciatic nerve palsy.