tbuckley/cabot-search huggingface dataset:
Possible evolutionary relationship between mammalian alanine:glyoxylate aminotransferase 1 and the 42-kD subunit of cyanobacterial soluble hydrogenase.
Authors: P A de Zoysa, C J Danpure
Journal: Molecular Biology and Evolution (1993)

Using the sequence comparison programs TFASTA / FASTA ( Pearson and Lipman 1988) to search the GenBank/EMBL DNA data bases, we have discovered that there is considerable amino acid sequence identity between mammalian alanine: glyoxylate aminotransferase 1 (AGT; E.C.2.6.1.44) and the 42-kD tritium-exchange subunit of cyanobacterial soluble hydrogenase (TES; E.C. 1.12.-.-/ 1.18.-.-) . Over a 36 l-amino-acid region (residues 24-384) of human liver AGT (Takada et al. 1990) and a 355amino-acid region (residues 6-360) of Anabaena cylindrica TES (Ewart et al. 1990)) 110 amino acids were found to be identical, and 90 were found to be similar (using the criteria advocated by Barker and Dayhoff 1972) (see fig. 1). When gaps are counted as mismatches, the level of sequence identity is 30. I%, and similarity is 54.8%. Similar results were obtained when comparisons were made between TES from Anabaena or Synechococcus (Van der Oost et al. 1989) and the AGT sequences obtained from rat ( Oda et al. 1987 ), marmoset, and rabbit (Purdue et al. 1992). Eightytwo (23.7%) amino acids are absolutely conserved in all six proteins (i.e., two TESS and four AGTs) (see fig. 1). In some regions there is considerably greater match between Anabaena TES and human AGT. For example, TES residues 66-98 and AGT residues 85-117 show 17/33 (51.5%) identity and 27/33 (81.8%) similarity. Two regions (TES 137-148/AGT 153-164, and TES 164-175/AGT 179-190) show 7 / 12 ( 58.3% ) amino acid identity and 12/ 12 ( 100% ) similarity. Whether these regions represent equivalent functional domains has yet to be determined. AGT, like all aminotransferases, requires pyridoxal phosphate as a cofactor. The binding site for this cofactor has been suggested to be Lys-209 (Oda et al. 1987). There is no evidence that hydrogenases require pyridoxal phosphate. Therefore, it is surprising to find that, not only is this Lys absolutely conserved in both TES sequences, in addition to all four AGT sequences, but the four preceding amino acids are conserved as well. However, this SerGlySerGlnLys sequence is not found in other aminotransferases (Mehta et al. 1989), and, therefore, its functional significance is unclear. As far as is currently known, there are no similarities in the catalytic or functional properties of mammalian AGT and cyanobacterial soluble hydrogenase. Nevertheless, they show considerably more sequence identity to each other than does either AGT to other aminotransferases or TES to other hydrogenases, indicating that, although AGT and TES might be functionally disparate, they are homologous proteins and that they may have evolved independently from other aminotransferases or hydrogenases. Whether mammalian AGTs and cyanobacterial soluble hydrogenases actually do share any functional/catalytic properties awaits investigation.
Churg-Strauss vasculitis syndrome and leukotriene receptor antagonists
Authors: J Ng
Journal: Annals of the Rheumatic Diseases (2005)

This case illustrates the usefulness of a therapeutic trial of colchicine monitored objectively by frequent acute phase protein measurements in patients with undiagnosed periodic fever syndromes.It also raises the possibility that a low threshold for analysing the FMF gene might disclose a wider spectrum of associated disease.
A Metabolic Study of Patients with Lung Cancer and Hyponatremia of Malignancy
Authors: John P. Chute, Elizabeth Taylor, John Williams, Frederic Kaye, David Venzon, Bruce E. Johnson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: One-third of patients with lung cancer and hyponatremia have no evidence of ectopic arginine vasopressin (AVP) production and the cause of their hyponatremia is not conclusively established. We sought to distinguish patients with hyponatremia caused by elevated AVP versus those with ectopic atrial natriuretic peptide (ANP) via this detailed metabolic study. Experimental Design: We enrolled 24 patients recently diagnosed with lung cancer in a metabolic study in which patients were placed on sodium and fluid restriction for 4 days. Serum electrolytes, osmolality, urine electrolytes and osmolality, plasma AVP, ANP, aldosterone, urinary cyclic AMP and cyclic guanosine 3′,5′-monophosphate were measured daily and tumor tissue was obtained to measure ectopic hormone production. We attempted to characterize the pathophysiology of hyponatremia caused by ectopic ANP production in patients with small cell lung cancer (SCLC) and to determine its effect on the aldosterone axis. Results: Seven of the nine patients with SCLC presented with hyponatremia and three had elevated ANP levels at presentation without elevation of AVP. All three patients who presented with hyponatremia and elevated ANP showed a decline in serum sodium following fluid restriction, whereas two patients with SCLC and elevated AVP had normalized serum sodium levels. The combination of hyponatremia and elevated ANP was associated with a persistent natriuresis and inappropriately low aldosterone levels despite sodium restriction, suggesting ANP suppression of the aldosterone axis. Conclusions: Management of patients with hyponatremia and SCLC should be guided by the knowledge that some patients with SCLC have ectopic production of ANP as the cause of their hyponatremia.
Critical factors in the translation of improved antimicrobial strategies for medical implants and devices
Authors: David W. Grainger, Henny C. van der Mei, Paul C. Jutte, Jan J.A.M. van den Dungen, Marcus J. Schultz, Bernard F.A.M. van der Laan, Sebastian A.J. Zaat, Henk J. Busscher
Journal: Biomaterials (2013)
Genetically Abnormal Circulating Cells in Lung Cancer Patients: An Antigen-Independent Fluorescence <i>In situ</i> Hybridization–Based Case-Control Study
Authors: Ruth L. Katz, Weigong He, Abha Khanna, Ricardo L. Fernandez, Tanweer M. Zaidi, Matthew Krebs, Nancy P. Caraway, Hua-Zhong Zhang, Feng Jiang, Margaret R. Spitz, David P. Blowers, Carlos A. Jimenez, Reza J. Mehran, Stephen G. Swisher, Jack A. Roth, Jeffrey S. Morris, Carol J. Etzel, Randa El-Zein
Journal: Clinical Cancer Research (2010)

We performed a study to determine if a fluorescence in situ hybridization (FISH)-based assay using isolated peripheral blood mononuclear cells (PBMCs) with DNA probes targeting specific sites on chromosomes known to have abnormalities in non-small cell lung cancer (NSCLC) cases could detect circulating genetically abnormal cells (CACs).We evaluated 59 NSCLC cases with stage I through IV disease and 24 controls. PBMCs and matched tumors were hybridized with 2 two-color [3p22.1/CEP3 and 10q22.3 (SP-A)/CEP10) and 2 four-color [CEP3, CEP7, CEP17, and 9p21.3 (URO); and EGFR, c-MYC, 6p11-q11, and 5p15.2 (LAV)] FISH probes. Percentages of cytogenetically abnormal cells (CACs) in peripheral blood and in matched tumor specimens were quantified by using an automated fluorescent scanner. Numbers of CACs were calculated based on the percentage of CACs (defined as PBMCs with genetic abnormalities) per milliliter of blood and expressed per microliter of blood.Patients with NSCLC had significantly higher numbers of CACs than controls. Mean number of CACs ranged from 7.23 +/- 1.32/microL for deletions of 10q22.3/CEP10 to 45.52 +/- 7.49/microL for deletions of 3p22.1/CEP3. Numbers of CACs with deletions of 3p22.1, 10q22.3, and 9p21.3, and gains of URO, increased significantly from early to advanced stage of disease.We have developed a sensitive and quantitative antigen-independent FISH-based test for detecting CACs in peripheral blood of patients with NSCLC, which showed a significant correlation with the presence of cancer. If this pilot study can be validated in a larger study, CACs may have a role in the management of patients with NSCLC.
Seizures in patients with systemic lupus erythematosus: data from LUMINA, a multiethnic cohort (LUMINA LIV)
Authors: R M Andrade, G S Alarcon, L A Gonzalez, M Fernandez, M Apte, L M Vila, G McGwin, J D Reveille
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To examine the predictors of time-to-seizure occurrence and their impact on damage accrual and mortality in LUMINA, a multiethnic (Hispanic, African American and Caucasian) cohort of patients with systemic lupus erythematosus. <h3>Methods:</h3> Seizures were defined as per the American College of Rheumatology (ARC) nomenclature and case definitions for neuropsychiatric lupus syndromes. Factors associated with time-to-seizure occurrence occurring at or after diagnosis (TD) of systemic lupus erythematosus were examined by univariable and multivariable Cox proportional hazard regression analyses. The impact of seizures on damage accrual and mortality was also examined by multivariable analyses after adjusting for variables known to affect these outcomes. <h3>Results:</h3> A total of 600 patients were included in these analyses. Of them, 40 (6.7%) developed seizures at or after TD; by multivariable analyses, disease activity and younger age were independent predictors of a shorter time-to-seizure occurrence (HR = 1.10 and 1.04; 95% CI 1.04 to 1.15 and 1.00 to 1.08, p = 0.0004 and 0.0304, respectively) whereas mucocutaneous involvement (HR = 0.34, 95% CI 0.16 to 0.41, p = 0.0039) and hydroxychloroquine use (HR = 0.35, 95% CI 0.15 to 0.80, p = 0.0131) were independent predictors of a longer time-to-seizure occurrence. Seizures were an independent contributor to damage accrual but not to mortality. <h3>Conclusions:</h3> Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual. Younger age and disease activity are independent predictors of a shorter time-to-seizure occurrence; antimalarials appear to have a protective role in seizure occurrence.
Response of <i>BRAF</i>-Mutant Melanoma to BRAF Inhibition Is Mediated by a Network of Transcriptional Regulators of Glycolysis
Authors: Tiffany J. Parmenter, Margarete Kleinschmidt, Kathryn M. Kinross, Simon T. Bond, Jason Li, Mohan R. Kaadige, Aparna Rao, Karen E. Sheppard, Willy Hugo, Gulietta M. Pupo, Richard B. Pearson, Sean L. McGee, Georgina V. Long, Richard A. Scolyer, Helen Rizos, Roger S. Lo, Carleen Cullinane, Donald E. Ayer, Antoni Ribas, Ricky W. Johnstone, Rodney J. Hicks, Grant A. McArthur
Journal: Cancer Discovery (2014)

Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis downstream of BRAF(V600), is critical for responses to BRAF inhibition, and is modulated by BRAF inhibition in clinical melanoma specimens. Furthermore, we show that concurrent inhibition of BRAF and glycolysis induces cell death in BRAF inhibitor (BRAFi)-resistant melanoma cells. Thus, we provide a proof-of-principle for treatment of melanoma with combinations of BRAFis and glycolysis inhibitors.BRAF is suppress glycolysis and provide strong clinical benefi t in BRAF V600 melanoma. We show that BRAF inhibition suppresses glycolysis via a network of transcription factors that are critical for complete BRAFi responses. Furthermore, we provide evidence for the clinical potential of therapies that combine BRAFis with glycolysis inhibitors.
The myth of pulmonary Raynaud's phenomenon: the contribution of pulmonary arterial vasospasm in patients with systemic sclerosis related pulmonary arterial hypertension
Authors: D Mukerjee
Journal: Annals of the Rheumatic Diseases (2004)

To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation.In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10-15 degrees C for two minutes if tolerated) and central (direct cold water at 4 degrees C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery.19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm(-5); CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4 degrees C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge.Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.
Primary CNS Lymphoma in Children and Adolescents: A Descriptive Analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG)
Authors: Oussama Abla, Sheila Weitzman, Jean-Yves Blay, Brian Patrick O'Neill, Lauren E. Abrey, Edward Neuwelt, Nancy D. Doolittle, Joachim Baehring, Kamnesh Pradhan, S. Eric Martin, Michael Guerrera, Shafqat Shah, Hervé Ghesquieres, Michael Silver, Rebecca A. Betensky, Tracy Batchelor
Journal: Clinical Cancer Research (2011)

To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL).A retrospective series of children and adolescents with PCNSL was assembled from 10 cancer centers in 3 countries.Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or greater. Frontline therapy consisted of chemotherapy only in 20 patients (69%), while 9 (31%) had chemotherapy plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (complete remission 69%, partial remission 17%). The 2-year progression-free survival (PFS) and overall survival (OS) rates were 61% and 86%, respectively; the 3-year OS was 82%. Univariate analyses were conducted for age (≤ 14 vs. >14 years), PS (0 or 1 vs. >1), deep brain lesions, MTX dose, primary treatment with chemotherapy alone, intrathecal chemotherapy, and high-dose therapy. Primary treatment with chemotherapy alone was associated with better overall response rates with an odds ratio (OR) of 0.125 (P = 0.02). There was a marginally significant relationship between higher doses of MTX and response (OR = 1.5, P = 0.06). ECOG-PS of 0 to 1 was the only factor associated with better outcome with hazard ratios of 0.136 (P = 0.017) and 0.073 (P = 0.033) for PFS and OS, respectively.This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents seems to be better than in adults. PS of 0 to 1 is associated with better survival.
In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice
Authors: Paula Rı́o, José Carlos Segovia, Helmut Hanenberg, JoséAntonio Casado, Jesús Martı́nez, Kerstin Göttsche, Ngan Ching Cheng, Henri J. Van de Vrugt, Fré Arwert, Hans Joenje, Juan A. Bueren
Journal: Blood (2002)
Pituitary apoplexy after combined test of anterior pituitary function.
Authors: A J Chapman, G Williams, A D Hockley, D R London
Journal: BMJ (1985)

bicarbonate concentration, which indicated a non-ketoacidotic coma.We believe this to have been due to metolazone.Controversy over the use of thiazide diuretics in hypertension continues because of their adverse metabolic effects.Consequently, the use of this group of drugs for hypertension may diminish.The use of metolazone, however, may increase in refractory oedema or sodium retention (due to congestive heart failure, hepatic cirrhosis, and renal disease) as a loop diuretic has a synergistic effect when given with a thiazide.2 5Adrenergic blocking drugs have been associated with carbo- hydrate intolerance-and propranolol particularly with recurrent non-ketotic hyperosmolar diabetic coma3-but in our patient metoprolol was continued without ill effect.Fonesca and Phear found that b adrenergic blockers are not of great importance in the pathogenesis of the hyperosmolar non-ketotic state.'Few reports of disturbance of carbohydrate metabolism with metolazone exist, and the Committee on Safety of Medicines (personal communication) has only one report each of diabetes mellitus, abnormality of electrolyte concentrations, and glycosuria.Metolazone has, however, been shown to influence diabetic control adversely.4The mechanism of this adverse reaction is not known and is common to all diuretic benzothiadiazines, including some without diuretic activity such as diazoxide.It may entail both a decrease in the secretion of insulin and an extrapancreatic effect on the liver.5This case emphasises that despite its different chemical structure metolazone, like chlorthalidone, may be associated with the hyper- osmolar non-ketotic diabetic syndrome.Clinicians using this drug in refractory sodium retention should be alert to this possibility as well as that of massive natriuresis, so that early detection may prevent the development of coma with its attendant high mortality.1 Fonesca V, Phear DN.Hyperosmolar non-ketotic diabetic syndrome precipitated by treatment with diuretics.Br MedJa 1982;284:36-7.
Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice
Authors: Hyun-Woo Jeong, Un Sil Jeon, Bon-Kyoung Koo, Wan-Young Kim, Sun-Kyoung Im, Juhee Shin, Yunje Cho, Jin Kim, Young-Yun Kong
Journal: Journal of Clinical Investigation (2009)

The heterogeneous cellular composition of the mammalian renal collecting duct enables regulation of fluid, electrolytes, and acid-base homeostasis, but the molecular mechanism of its development has yet to be elucidated. The Notch signaling pathway is involved in cell fate determination and has been implicated in proximal-distal patterning in the mammalian kidney. To investigate the role of Notch signaling in renal collecting duct development, we generated mice in which Mind bomb-1 (Mib1), an E3 ubiquitin ligase required for the initiation of Notch signaling, was specifically inactivated in the ureteric bud of the developing kidney. Mice lacking Mib1 in the renal collecting duct displayed increased urinary production, decreased urinary osmolality, progressive hydronephrosis, sodium wasting, and a severe urinary concentrating defect manifested as nephrogenic diabetes insipidus. Histological analysis revealed a diminished number of principal cells and corresponding increase in the number of intercalated cells. Transgenic overexpression of Notch intracellular domain reversed the altered cellular composition of mutant renal collecting duct, with principal cells occupying the entire region. Our data demonstrate that Notch signaling is required for the development of the mammalian renal collecting duct and principal cell differentiation and indicate that pathway dysregulation may contribute to distal renal tubular disorders.
On Open Fallopian Tube
Authors: J. M. Duncan
Journal: BMJ (1881)

THE uterine end of the Fallopian tube is regarded almost exclusively as a closed, or amerelypoteritial, tube or canal.It is spoken of as large enough to permit-a bristle to be pushed through it; but.this is done with diffi- culty, and, for practical purposes, it is no doubt generally closed, for fluids accumttlate'ih 'the uterine cavity under considerable pressure; Iand the use of,intra-uterinei injections, whether after delivery or at other ,times, is feasible, because the injected fluids,' as a rule, do not find an open passage In the' tubes.The closure 'of the tube is not by such, apposition of its walls as is seen when a piece, of gut is pressed flat bet.weentwo parallel surfaces, :but is stricture-like, or such as is pro- duced by an, active sphincter.. The'cervix uteri has a canal, wbich is .gpnSrallyneither closed, nor
Desquamative interstitial pneumonia in a Danish cohort, treatment response and outcome
Authors: Charlotte Hyldgaard, Elisabeth Bendstrup, Ole Hilberg
Journal: European Respiratory Journal (2014)

Introduction

Desquamative interstitial pneumonia (DIP) is a rare form of idiopathic interstitial pneumonia with accumulation of macrophages in the alveolar spaces.

Objectives

The aim of this study was to characterize disease severity and treatment response in a Danish DIP cohort.

Methods

The study population was 20 patients diagnosed with DIP at Aarhus University Hospital between April 03 and April 09. Patients were followed until November 09. Details on referral, examinations, pulmonary function and medication were recorded in the Central Denmark ILD Registry.

Results

Patients were followed for 3.5 years on average. Mean age was 49 years, FEV1 was 66%, FVC 70% and DLco 58% of predicted. Mean BMI was 28. Eighty percent of the patients were smokers with an average of 31 pack years. Bronchoscopy was performed in 65% and thoracoscopic biopsy in 75% of the patients.

Twelve patients had steroid pulse therapy and eight of these patients also received oral prednisolone during the course of follow up. Four patients received oral prednisolone only, and four patients had no active treatment. Mortality was 5% (n=1) and the cause of death was gradual disease progression and pulmonary hypertension. At first visit, four patients had severe disease (DLco 60%).

Based on pulmonary function tests at first visit and after one year, eight patients improved, eight patients were stable and four patients progressed.

Conclusion

Although the mortality was low in this DIP cohort, severely impaired pulmonary function was common with improvement seen in only 40 % of patients after one year.
White matter microstructural recovery with abstinence and decline with relapse in alcohol dependence interacts with normal ageing: a controlled longitudinal DTI study
Authors: Adolf Pfefferbaum, Margaret J Rosenbloom, Weiwei Chu, Stephanie A Sassoon, Torsten Rohlfing, Kilian M Pohl, Natalie M Zahr, Edith V Sullivan
Journal: The Lancet Psychiatry (2014)