tbuckley/cabot-search huggingface dataset:
A phylogenetic approach to the identification of phosphoglucomutase genes
Authors: D. B. Whitehouse, J. Tomkins, J. U. Lovegrove, D. A. Hopkinson, W. O. McMillan
Journal: Molecular Biology and Evolution (1998)

The expanding molecular database provides unparalleled opportunities for characterizing genes and for studying groups of related genes. We use sequences drawn from the database to construct an evolutionary framework for examining the important glycolytic enzyme phosphoglucomutase (PGM). Phosphoglucomutase plays a pivotal role in the synthesis and utilization of glycogen and is present in all organisms. In humans, there are three well-described isozymes, PGMI, PGM2, and PGM3. PGM1 was cloned 5 years ago; however, repeated attempts using both immunological approaches and molecular probes designed from PGM1 have failed to isolate either PGM2 or PGM3. Using a phylogenetic strategy, we first identified 47 highly divergent prokaryotic and eukaryotic PGM-like sequences from the database. Although overall amino acid identity often fell below 20%, the relative order, position, and sequence of three structural motifs, the active site and the magnesium--and sugar-binding sites, were conserved in all 47 sequences. The phylogenetic history of these sequences was complex and marked by duplications and translocations; two instances of transkingdom horizontal gene transfer were identified. Nonetheless, the sequences fell within six well-defined evolutionary lineages, three of which contained only prokaryotes. Of the two prokaryotic/eukaryotic lineages, one contained bacterial, yeast, slimemold, invertebrate, and vertebrate homologs to human PGM1 and the second contained likely homologs to human PGM2. Indeed, an amino acid sequence, derived from a partial human cDNA, that fell within the second cross-kingdom lineage bears several characteristics expected for PGM2. A third lineage may contain homologs to human PGM3. On a general level, our phylogenetic-based approach shows promise for the further utilization of the extensive molecular database.
Nephrologist follow-up improves all-cause mortality of severe acute kidney injury survivors
Authors: Ziv Harel, Ron Wald, Joanne M Bargman, Muhammad Mamdani, Edward Etchells, Amit X Garg, Joel G Ray, Jin Luo, Ping Li, Robert R Quinn, Alan Forster, Jeff Perl, Chaim M Bell
Journal: Kidney International (2013)
Multihost Experimental Evolution of the Pathogen Ralstonia solanacearum Unveils Genes Involved in Adaptation to Plants
Authors: Alice Guidot, Wei Jiang, Jean-Baptiste Ferdy, Christophe Thébaud, Patrick Barberis, Jérôme Gouzy, Stéphane Genin
Journal: Molecular Biology and Evolution (2014)

Ralstonia solanacearum, the causal agent of a lethal bacterial wilt plant disease, infects an unusually wide range of hosts. These hosts can further be split into plants where R. solanacearum is known to cause disease (original hosts) and those where this bacterium can grow asymptomatically (distant hosts). Moreover, this pathogen is able to adapt to many plants as supported by field observations reporting emergence of strains with enlarged pathogenic properties. To investigate the genetic bases of host adaptation, we conducted evolution experiments by serial passages of a single clone of the pathogen on three original and two distant hosts over 300 bacterial generations and then analyzed the whole-genome of nine evolved clones. Phenotypic analysis of the evolved clones showed that the pathogen can increase its fitness on both original and distant hosts although the magnitude of fitness increase was greater on distant hosts. Only few genomic modifications were detected in evolved clones compared with the ancestor but parallel evolutionary changes in two genes were observed in independent evolved populations. Independent mutations in the regulatory gene efpR were selected for in three populations evolved on beans, a distant host. Reverse genetic approaches confirmed that these mutations were associated with fitness gain on bean plants. This work provides a first step toward understanding the within-host evolutionary dynamics of R. solanacearum during infection and identifying bacterial genes subjected to in planta selection. The discovery of EfpR as a determinant conditioning host adaptation of the pathogen illustrates how experimental evolution coupled with whole-genome sequencing is a potent tool to identify novel molecular players involved in central life-history traits.
Pharmacology and safety of glycerol phenylbutyrate in healthy adults and adults with cirrhosis
Authors: Brendan M. McGuire, Igor A. Zupanets, Mark E. Lowe, Xunjun Xiao, Vasyliy A. Syplyviy, Jon Monteleone, Sharron Gargosky, Klara Dickinson, Antonia Martinez, Masoud Mokhtarani, Bruce F. Scharschmidt
Journal: Hepatology (2010)

Phenylbutyric acid (PBA), which is approved for treatment of urea cycle disorders (UCDs) as sodium phenylbutyrate (NaPBA), mediates waste nitrogen excretion via combination of PBA-derived phenylacetic acid with glutamine to form phenylactylglutamine (PAGN) that is excreted in urine. Glycerol phenylbutyrate (GPB), a liquid triglyceride pro-drug of PBA, containing no sodium and having favorable palatability, is being studied for treatment of hepatic encephalopathy (HE). In vitro and clinical studies have been performed to assess GPB digestion, safety, and pharmacology in healthy adults and individuals with cirrhosis. GPB hydrolysis was measured in vitro by way of pH titration. Twenty-four healthy adults underwent single-dose administration of GPB and NaPBA and eight healthy adults and 24 cirrhotic subjects underwent single-day and multiple-day dosing of GPB, with metabolites measured in blood and urine. Simulations were performed to assess GPB dosing at higher levels. GPB was hydrolyzed by human pancreatic triglyceride lipase, pancreatic lipase-related protein 2, and carboxyl-ester lipase. Clinical safety was satisfactory. Compared with NaPBA, peak metabolite blood levels with GPB occurred later and were lower; urinary PAGN excretion was similar but took longer. Steady state was achieved within 4 days for both NaPBA and GPB; intact GPB was not detected in blood or urine. Cirrhotic subjects converted GPB to PAGN similarly to healthy adults. Simulations suggest that GPB can be administered safely to cirrhotic subjects at levels equivalent to the highest approved NaPBA dose for UCDs. Conclusion: GPB exhibits delayed release characteristics, presumably reflecting gradual PBA release by pancreatic lipases, and is well tolerated in adults with cirrhosis, suggesting that further clinical testing for HE is warranted. (Hepatology 2010;)
Abstract 1902: Sorafenib overcome irinotecan resistance in colorectal cancer
Authors: Thibault Mazard, Annick Causse, Wilhem Leconet, Eric Assenat, Marc Ychou, Maguy Del Rio, Pierre Martineau, Bruno Robert, Céline Gongora
Journal: Cancer Research (2012)

Abstract Despite recent advances in the treatment of colon cancer, tumor resistance is a frequent cause of chemotherapy failure. In the last decade, several studies have shown that cetuximab, an anti-EGFR monoclonal antibody, can overcome acquired resistance to irinotecan chemotherapy, but only in KRAS non mutant tumors. Thus, new treatment options are needed to improve survival in patients with irinotecan refractory and KRAS mutated colorectal cancer. In this study, we examined if treatment with sorafenib, a potent inhibitor of Raf kinase and VEGF receptor, could reverse the resistant phenotype in tumor, thereby enhancing the therapeutic efficacy of currently used irinotecan treatment. We used both in vitro and in vivo models to test the efficacy of sorafenib either as a single agent or in combination with irinotecan. We have first tested these different combinations on seven colorectal cancer cell lines displaying different molecular characteristics (mutated or not for KRAS, BRAF, p53 and PIK3CA). We have shown that sorafenib, as a single agent, showed antitumor properties and the effects were more pronounced when it was used in combination with the active metabolite of irinotecan, SN38. Then we have tested these treatments on SN38-resistant clones derived from the colon adenocarcinoma HCT-116 (KRAS mut) and SW48 (KRAS WT) cell lines, that show various levels (6 to 60 fold) of resistance to SN-38 as compared to the corresponding parental cells. Sorafenib has improved the anti-tumoral activity of SN-38 on all the SN38 resistant clones in vitro. Moreover, sorafenib sensitized tumor cells derived from both SN38-sensitive and -resistant HCT116 cells to irinotecan treatment in xenograft models. Signalling pathways involved in this effect have been identified on xenografts using the proteome profiler array. Altogether, our results show for the first time that sorafenib can inhibit resistance to irinotecan and suggest that sorafenib could be used to overcome resistance to irinotecan-based chemotherapies in colorectal cancer, particularly in KRAS mutated tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1902. doi:1538-7445.AM2012-1902
Lamellar ichthyosis with laminated membrane structures
Authors: A. PATRIZI, I. NERI, V. LERNIA, G. PASQUINELLI, L. BADIALI GIORGI
Journal: British Journal of Dermatology (1993)

We review the published classifications of autosomal recessive congenital ichthyosis. a nd report a new case of congenital ichthyosis which presents the characteristics of ichthyosis congenita type III.
Transjugular intrahepatic portosystemic shunt: Is it the ultimate solution for refractory ascites?
Authors: Florence Wong, Laurence Blendis
Journal: Hepatology (1995)

Background. Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. Methods. Fifty of 62 consecutive patients with cirrhosis and refractory ascites were treated with the stent shunt-an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (±SD) of 426 ± 333 days. Results. The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses. Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 ± 0.09 mg per deciliter (133 ± 8 μmol per liter) before placement of the stent shunt, 1.5 ± 1.6 mg per deciliter (133 ± 141 μmol per liter) one week after the procedure, and 0.9 ± 0.3 mg per deciliter (80 ± 27 μmol per liter) after six months ( P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients. During follow-up, an additional 29 patients died-10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patient’s being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 μmol per liter), and having a complete response. Conclusions. Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial. (N Engl J Med 1995; 332:1192-7. Copyright 1995. Massachusetts Medical Society. All rights reserved).
PLASMA PROSTACYCLIN LEVELS IN BEHÇET'S DISEASE
Authors: Nail Hizli, Gonul Sahin, Fethi Sahin, Emin Kansu, Suna Duru, Sukran Karacadag, Figen Batman, Semra Dundar, Turgut Zileli, Hasan Telatar
Journal: The Lancet (1985)
Implications of the Acquired Immunodeficiency Syndrome for Health Policy
Authors: EDWARD N. BRANDT
Journal: Annals of Internal Medicine (1985)

The acquired immunodeficiency syndrome (AIDS) has spread rapidly through the high-risk population and has created fear and anxiety. The health policy implications of such a disorder are difficult to assess because the disease was totally unknown until a few years ago and because it occurs primarily in homosexual men and intravenous drug users. The latter factor has raised sociopolitical issues not present in other epidemics. Detection and surveillance systems, capabilities for prompt and effective scientific response, central coordination of scientific efforts, public information mechanisms, role definitions, and guidelines for funding are needed. The scientific community must study this epidemic and the total societal response to it with a view towards being better prepared in the future.
Incomplete Financial Disclosures in a Viewpoint on Depression
Authors: Charles F. Reynolds
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Post-operative Venous Thrombosis
Authors: H. Dodd
Journal: BMJ (1963)

ently sticking to, other cells are not uncommonly seen, but rarely more than one or two to a cell and never in our experience in anything like the numbers in this case.Nor is the adhesion specific' to one kind of cell, as this was.Absence of satellitism from the capillary blood film classifies it as an " in vitro " pheno- menon (analogous perhaps to the L.E. cell), but, since it has not been seen in some thousands of blood films prepared in the course of routine work from similarly treated samples, it cannot be attributed to either the anticoagulant or the technique.We cannot relate this phenomenon to any functional abnor- mality of the blood nor to the patient's symptoms, but we think the appearance is singular enough to be worth reporting.
Narrative Review: Buprenorphine for Opioid-Dependent Patients in Office Practice
Authors: Lynn E. Sullivan, David A. Fiellin
Journal: Annals of Internal Medicine (2008)

The profile of opioid dependence in the United States is changing. Abuse of prescription opioids is more common than that of illicit opioids: Recent data indicate that approximately 1.6 million persons abuse or are dependent on prescription opioids, whereas 323 000 abuse or are dependent on heroin. Despite this prevalence, nearly 80% of opioid-dependent persons remain untreated. One option for expanding treatment is the use of buprenorphine and the buprenorphine–naloxone combination. Buprenorphine is a partial opioid agonist that can be prescribed by trained physicians and dispensed at pharmacies. This article addresses the clinical presentation of a patient with opioid dependence and describes the relatively new practice of office-based treatment with buprenorphine–naloxone. The different components of treatment; the role of the physician who provides this treatment; and the logistics of treating this growing, multifaceted patient population are also examined.
Abstract 335: Aspirin, di-aspirin and their toxicity to colorectal cancer
Authors: Chandra S. Kankipati, Christopher J. Perry, Iain D. Nicholl
Journal: Cancer Research (2014)

Abstract Introduction The lifetime risk for developing colorectal cancer (CRC) is approximately 7%. In the USA over 140,000 people a year develop CRC, with approximately 51,000 deaths/year. Epidemiological studies indicate that long-term aspirin usage reduces the incidence of CRC, and may be protective against other non-CRC related adenocarcinoma, including esophageal cancer. We have investigated the mechanism by which aspirin exhibits toxicity to CRC by synthesising novel analogues of aspirin in an effort to identify functionally significant moieties. We previously suggested that “di-aspirin” (bis-carboxyphenol succinate, BCS) and analogues thereof retain relatively specific toxicity to colorectal cancer cells cultured in vitro. The cellular functions of the Inhibitors of Apoptosis (IAPs) correlate with suppression of apoptotic cell death, tumor progression and metastases. Aspirin triggered apoptosis correlates with its capacity to decrease expression of Survivin, a member of the IAP family. Survivin exhibits dual functions; as an inhibitor of apoptosis and regulator of mitosis. We hypothesised that studying the alterations in the expression of IAPs would give an insight into the cytotoxic nature of the compounds. Experimental procedure A cell viability assay (MTT) was employed to investigate the cytotoxicity of the analogues in various CRC (SW480, HCT116 and LoVo) and non-CRC cell lines (A549, MCF7 and EA.hy926). Expression levels of IAPs (c-IAP1, cIAP2, XIAP, Livin and Survivin) were examined in the SW480 cell line by immunoblotting. Survivin expression was further examined by immunofluorescence analysis. Changes in Survivin expression in the CRC and non-CRC cell lines was also determined by immunoblotting. Summary of data Herein, we show that the “di-aspirin” analogues are relatively more toxic to colorectal cancer cells compared to non-colorectal cancer cell lines. In addition we suggest that these analogues can potently reduce the expression of Survivin in comparison to other IAPs. Conclusion We conclude that the analogues of aspirin used in the study promote cell death in CRC and non-CRC cell lines. We propose that the compounds induce apoptosis by decreasing the expression of Survivin. We also propose that the anti-proliferative activity of “di-aspirins” and their analogues have potential benefit in tackling human cancer. Citation Format: Chandra S. Kankipati, Christopher J. Perry, Iain D. Nicholl. Aspirin, di-aspirin and their toxicity to colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 335. doi:10.1158/1538-7445.AM2014-335
Expression pattern of intracellular leukocyte-associated proteins in primary mediastinal B cell lymphoma
Authors: T Marafioti, M Pozzobon, M-L Hansmann, P Gaulard, T F Barth, C Copie-Bergman, H Roberton, R Ventura, J I Martín-Subero, R D Gascoyne, S A Pileri, R Siebert, E D Hsi, Y Natkunam, P Möller, D Y Mason
Journal: Leukemia (2005)
Prospect for the National Health Service
Authors: John Lister
Journal: New England Journal of Medicine (1962)

The concept of a fully comprehensive health service in which every member of the population could participate without direct payment at the time of illness was both imaginative and ambitious, and its introduction conferred an unparalleled social benefit on all classes of society.Although it was introduced by a Socialist government the other political parties were equally committed to it, and successive governments and ministers of health have become increasingly aware of its emergence as a sacred political cow. They have recognized that, at all costs, its apparently free nature must be preserved and any minor charges in the form . . .
Refining the Treatment of Alcohol Withdrawal
Authors: Richard K. Fuller
Journal: JAMA (1994)

An important advance of the past quarter century has been the use of benzodiazepines to treat alcohol withdrawal. The life-threatening consequence of alcohol withdrawal, delirium tremens, which formerly was a common cause for hospital admission, at least to public hospitals, is an uncommon occurrence today. The landmark multihospital controlled trial conducted by Kaim et al<sup>1</sup>comparing chlordiazepoxide with placebo and three other drugs established the therapeutic efficacy of benzodiazepines for alcohol withdrawal. This fact is sometimes lost sight of as newer pharmacologic agents are introduced and evaluated for treatment of alcohol withdrawal. Because there are different drugs available to treat alcohol withdrawal, physicians may be confused as to which one and which dosage regimen should be used as first-line therapy. See also p 519. For example, clonidine is effective for treatment of alcohol withdrawal symptoms<sup>2</sup>but is not recommended as first-line therapy because it does not prevent seizures.
Multicentric Early Gastric Carcinoma Mimicking Type I: (10 Years after B-I-Surgery)
Authors: S. Miederer, R. Müller, K. Kutz, E. Wobser, K. Elster
Journal: Endoscopy (1977)

10 YEARS AFTER B-I-partial gastrectomy for a proven benign gastric ulcer a multicentric early gastric carcinoma type II b, c was detected by endoscopy and histology. This early carcinoma differed from published cases in respect of its macroscopic classification, localization and expansion. The carcinoma situated next to the anastomosis invaded the duodenal mucosa. It also invaded a polypoid fold caused by the previous surgery, thus imitating an early gastric carcinoma type I.
Electrodiagnosis in Neuromuscular Disorders
Authors: John R. Warmolts
Journal: Annals of Internal Medicine (1981)

Nerve conduction and stimulation studies and needle electromyography are useful in objectively verifying the presence of disease of nerve and muscle. How pathologic alterations in muscle and nerve produce the electrical abnormalities detected by these combined techniques is explored to guide the clinician in distinguishing whether a neuromuscular disorder involves the motor neuron, peripheral nerve axon or myelin, neuromuscular synapse, or muscle; whether the problem is focal or generalized; and whether there is evidence of ongoing disease or repair.