tbuckley/cabot-search huggingface dataset:
Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype.
Authors: T W Post, M K Liszewski, E M Adams, I Tedja, E A Miller, J P Atkinson
Journal: The Journal of Experimental Medicine (1991)

Membrane cofactor protein (MCP) is a complement regulatory protein that is expressed on human cells and cell lines as two relatively broad species with Mr of 58,000-68,000 and 48,000-56,000. The structure of a previously reported cDNA clone indicated that MCP was a type 1 membrane glycoprotein and a member of the regulators of complement activation gene/protein cluster. However, it did not provide an explanation for the unusual phenotypic pattern of MCP. Therefore, in parallel with an analysis of the gene, additional cDNAs were cloned and characterized. Six different MCP cDNA classes were identified. All encode the same 5' untranslated signal peptide, four SCRs, transmembrane domain, and basic amino acid anchor. However, they differ in the length and composition of an extracellular serine/threonine/proline (STP)-rich area, a site of heavy O-glycosylation, and cytoplasmic tail. Analysis of the MCP gene demonstrated that the variation in cDNA structure was a result of alternative splicing. Peripheral blood cells and cell lines predominantly expressed four of the six isoforms. These varied by the presence or absence of an STP-rich segment of 15 amino acids (STPB) and by the use of one of two cytoplasmic domains. Analysis by polymerase chain reaction, Northern blots, and transfection indicated that the predominance of MCP cDNA isoforms with STPB correlated with the high molecular weight protein phenotype, while the predominance of isoforms without STPB correlated with the lower molecular weight phenotype. The expression in a single cell of four distinct protein species with variable STP-rich regions and cytoplasmic tails represents an interesting example of the use of alternative splicing to provide variability in a mammalian protein.
Centrosome abnormalities in human carcinomas of the gallbladder and intrahepatic and extrahepatic bile ducts
Authors: Kung-Kai Kuo, Norihiro Sato, Kazuhiro Mizumoto, Naoki Maehara, Hirotoshi Yonemasu, Chen-Guo Ker, Pai-Ching Sheen, Masao Tanaka
Journal: Hepatology (2000)

During mitosis, 2 centrosomes ensure accurate assembly of bipolar spindles and fidelity of the chromosomal segregation. The presence of more than 2 copies of centrosomes during mitosis can result in the formation of multipolar spindles, unbalanced chromosome segregation, and aneuploidy. Recent studies have provided evidence that centrosome hyperamplification plays a pivotal role in carcinogenesis. Using immunofluorescence analysis with gamma-tubulin and pericentrin antibodies, paraffin-embedded sections from 40 malignant biliary diseases including gallbladder cancers (GC; n = 13), intrahepatic cholangiocellular carcinoma (CCC; n = 19), and extrahepatic bile duct cancers (BDC; n = 8) were examined. Thirty-seven benign biliary diseases including chronic cholecystitis, gallbladder adenoma, hepatolithiasis, and choledochal cyst were included as benign controls. The frequencies of the centrosome abnormalities were 70% for GC, 58% for CCC, and 50% for BDC, respectively. The frequencies of centrosome abnormalities in malignant biliary diseases were significantly higher than in their benign counterparts (GC, CCC, BDC; P =.001,.002, and.001, respectively). The results of current study also indicated that biliary malignancy in the advanced stage (III-IV) displayed a higher frequency of centrosome abnormalities than in the early stage (I-II) (P <.001). We conclude that abnormalities in size, number, and shape of the centrosome are frequently observed in biliary tract malignancy. Centrosome abnormalities started to occur in the early stage of biliary malignancy and became very frequent in the advanced stage. This implies that centrosome abnormality might relate to the transition from early to advanced malignancy in biliary malignancy.
Surgical conversion of herpes simplex from an epidermal to a dermal disease
Authors: WALTER B. SHELLEY, MARGARET GRAY WOOD
Journal: British Journal of Dermatology (1979)

A new post-surgical form of recurrent herpes simplex is described. It appeared as an erythematous bulla at sites of recurrent herpes from which the prior epidermal lesion had been transversely excised. Histologically, it was characterized by a lesion-free epidermis, a large subepidermal bulla, and a marked inflammatory response in the uppermost dermis, complete with diagnostic multinucleate giant cells. It is postulated that epidermal surgery leaves the area immune to future direct herpetic involvement of the epidermis because it denervates the epidermis. The possibility is raised that such dermal forms of herpes may also occur in the natural course of the disease.
Prostaglandins and menstrual disorders.
Authors: M G Elder
Journal: BMJ (1983)

investigating patients with inconsistent hypokalaemia or mild hypokalaemia taking thiazide diuretics, and in these circumstances the more reasonable approach is to attempt control with a regimen which includes a potassium retaining diuretic.Where either the raised blood pressure or the low serum potassium concentration cannot be adequately controlled more intensive investigation for primary aldosteronism in a special centre will be needed.With these guidelines the occasional patient with surgically correctable primary aldosteronism will be missed, but the cost of such an error in terms of patient morbidity or mortality will be extremely small.
Preservation of high-energy phosphates by verapamil in reperfused myocardium.
Authors: R Lange, J Ingwall, S L Hale, K J Alker, E Braunwald, R A Kloner
Journal: Circulation (1984)

To determine whether verapamil prevents depletion of adenine nucleotides during and after severe myocardial ischemia, dogs were subjected to 15 min occlusions of the left anterior descending coronary artery followed by 240 min of reperfusion. One hour before occlusion, dogs were randomly assigned to a treatment group (n = 10) to which an infusion of intravenous verapamil was given until the onset of reperfusion or to an untreated saline group (n = 9). Verapamil reduced mean aortic pressure and heart rate. After 15 min of ischemia, endocardial adenosine triphosphate (ATP) level, determined by needle biopsy, decreased in the untreated group from 34.7 +/- 2.0 to 24.4 +/- 2.7 nmol X mg protein-1 (p less than .005 vs preocclusion) and in the verapamil group from 32.8 +/- 1.5 to 30.3 +/- 1.5 nmol X mg protein-1 (NS vs preocclusion). Dogs receiving verapamil had significantly higher ATP levels than untreated animals after 90 and 240 min of reperfusion. In untreated animals the sum of inosine and hypoxanthine levels increased during occlusion from very low levels to 4.6 +/- 1.1 nmol X mg protein-1 in the epicardium and to 6.8 +/- 1.5 nmol X mg protein-1 in the endocardium (p less than .05 compared with preocclusion values). In verapamil-treated dogs inosine and hypoxanthine levels increased to only 1.2 +/- 0.3 (epicardium) and 1.9 +/- 0.6 nmol X mg protein-1 (endocardium) (both NS compared with preocclusion values). After 90 min of reperfusion the sum of ATP, adenosine diphosphate, adenosine monophosphate, inosine, and hypoxanthine levels was decreased in the endocardium by 10.2 nmol X mg protein-1 in the untreated group, but no change was observed in verapamil-treated animals. We conclude that breakdown of ATP to inosine and hypoxanthine during severe ischemia is reduced by verapamil, resulting in higher ATP concentrations during occlusion and reperfusion and decreased washout of the diffusible purines inosine and hypoxanthine during reperfusion.
Differential impact of carolina rinse and university of wisconsin solutions on microcirculation, leukocyte adhesion, kupffer cell activity and biliary excretion after liver transplantation
Authors: Stefan Post, Pablo Palma, Markus Rentsch, Alberto P. Gonzalez, Michael D. Menger
Journal: Hepatology (1993)

This quantitative in vivo fluorescence microscopy study investigated the relative impact of an optimized rinse solution (warm Carolina rinse) and that of an established storage solution (University of Wisconsin solution) on various pathomechanisms of hepatic reperfusion injury after cold storage. Syngeneic orthotopic, arterialized liver transplantation was performed in male Lewis rats after 24 hr of cold ischemia (n = 24). The four experimental groups differed according to the type of preservation/rinse solution used: University of Wisconsin solution/albumin rinse (group 1), autologous blood (just external cooling)/albumin rinse (group 2), blood/Carolina rinse (group 3) and University of Wisconsin solution/Carolina rinse (group 4). Hepatic microvascular perfusion, leukocyte accumulation and phagocytic activity of Kupffer cells were assessed by means of intravital fluorescence microscopy 30 to 90 min after reperfusion. Disturbances of microvascular perfusion were most pronounced in group 2, markedly reduced by University of Wisconsin solution (group 1) and Carolina rinse (group 3) and minimized by combined use of University of Wisconsin solution and Carolina rinse in group 4. Intrahepatic leukocyte-endothelium interaction in sinusoids and postsinusoidal venules was found to depend on the application of Carolina rinse before reperfusion rather than the use of University of Wisconsin solution during cold storage. Activation of phagocytosis by Kupffer cells was most pronounced in group 1, intermediate in groups 2 and 3 and not noticeable in group 4. Hepatocellular excretory function as assessed on the basis of total bile flow and excretion of bile acids during the first 90 min after reperfusion was found to be improved by application of Carolina rinse, both after storage in blood or in University of Wisconsin solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Busulfan Treatment During Pregnancy
Authors: Derek W. Williams
Journal: JAMA (1967)

<h3>To the Editor:—</h3> "Busulfan Treatment of Leukemia During Pregnancy" is of special interest both to obstetricians and hematologists. However, the authors' conclusions concerning a lack of fetal toxicity should be accepted with some reservations. As was pointed out in my article, "Busulfan in Early Pregnancy" (<i>Obstet Gynec</i><b>27</b>:738, 1966), many of these children are of low birth weight. In the cases documented to this time, at least 50% of the children weighed less than 2,500 gm although of term gestation. This is suggestive of an effect on fetal metabolism in utero although the role of the leukemic process itself cannot be resolved. The possible gonadal effect is an important consideration in light of animal studies.<sup>1</sup>As the authors point out, these children have not attained puberty. It is also true, however, that there has been no good follow-up on these children.
Self management is the future
Authors: D Hambidge
Journal: BMJ (2002)

EDITOR—I assume that I am one of the few medical practitioners in this country who self manages his own oral anticoagulation and would like to comment on the paper by Fitzmaurice and Machin on patients undertaking self management of oral anticoagulation.1

Firstly, the suggestion that patient demand for self management is partly fuelled by a national media advertising campaign for CoaguChek is disingenuous. I wonder how much of an NHS hospital trust haematology department budget is derived from patients attending their warfarin clinic?

Secondly, routine performance in anticoagulation clinics in …
Abstract B42: Heat Shock Protein 27 (HSP27, HSPB1) is up-regulated by MET kinase inhibition and limits the effectiveness of inhibitors
Authors: Daniele Musiani, Alberto Ramirez Rivera, John David Konda, Simona Pavan, Erica Torchiaro, Martina Olivero, Maria Flavia Di Renzo
Journal: Clinical Cancer Research (2012)

Abstract The receptor for the hepatocyte growth factor (HGF) is encoded by the MET oncogene and its activation results in cell growth, survival, motility and invasiveness. Deregulated HGF/MET signaling is observed in many tumors and both HGF and MET are attractive candidates for targeted therapies. Unexpectedly, we found that in ovarian cancer cells the activation of the MET receptor downmodulated the expression of the small heat shock protein 27 (HSP27), which functions as a molecular chaperone and as an antiapoptotic protein. In MET addicted gastric carcinoma cells, where MET is constitutively active, MET kinase inhibition by JNJ-38877605 up-regulated HSP27 expression. More importantly, in these gastric carcinoma cells suppression of HSP27 was alone able to induce cell death and increased cell susceptibility to MET inhibition. HSP27 suppression did not affect MET stability and phosphorylation, but increased activation of caspase 3, which is a known HSP27 client protein. Regulation of HSP27 expression by MET signaling occurred at transcriptional level, as confirmed by the use of HSP27 promoter in a reporter assay. It was not due to the engagement of HSF1, the master key transcription factor regulating HSPs expression, but depended on MEK activation and resulting HIF 1alpha stabilization. MEK inhibition and HIF 1 alpha silencing resulted in the induction of HSP27, suggesting a direct or indirect transcriptional repression. Altogether data show that MET activation down-regulates and MET inhibition up-regulates HSP27 expression, and that HSP27 increased expression protects cells from death induced by MET inhibitors. Therefore, in therapies with MET targeting agents, HSP27 increase might impair the effectiveness of MET inhibitors. As it is known that HSP27 protects cells for chemotherapeutics, data suggest that HSP27 might strongly affect combinatorial treatments.
US commission calls for protection of privacy in whole genome sequencing
Authors: J. H. Tanne
Journal: BMJ (2012)

Whole genome sequencing has enormous promise for improving health by gathering data from thousands of people and identifying mutations that cause disease, but privacy of individuals needs to be protected, a new report concludes.1

The report was produced by the Presidential Commission for the Study of Bioethical Issues, which held four public hearings and took information from 18 federal agencies about their systems for safeguarding genetic and whole genome sequence data. The commission, which is chaired by Amy Gutmann, president of the University of Pennsylvania, offered recommendations for ensuring privacy and security as the field of genomics advances.

While society …
Toxic Reaction to Prolonged High-Dose Fluorouracil
Authors: Robert H. Schosser
Journal: JAMA (1986)

<h3>To the Editor.—</h3> Based on the information and photograph presented by Drs Feldman and Ajani<sup>1</sup>in their PHOTO/ESSAY, I am unable to accept their conclusion that this represents a "toxic reaction to fluorouracil." A hyperkeratotic erythematous eruption involving the feet in a "moccasin distribution" and the palmar aspect of the hands is much more likely to be dermatophytosis or pityriasis rubra pilaris. No evidence was presented that would eliminate the possibility of a fungal etiology for these lesions. The biopsy results as stated do not rule out either dermatophytosis or pityriasis rubra pilaris. The photographed foot the authors present does not resemble bleomycin-associated Raynaud's phenomenon or the "peculiar acral erythema" described by Burgdorff et al.<sup>2</sup>
Polycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins
Authors: Yonghong Huan, Janet van Adelsberg
Journal: Journal of Clinical Investigation (1999)

Autosomal dominant polycystic kidney disease (ADPKD) is a common human genetic disease characterized by cyst formation in kidney tubules and other ductular epithelia. Cells lining the cysts have abnormalities in cell proliferation and cell polarity. The majority of ADPKD cases are caused by mutations in the PKD1 gene, which codes for polycystin-1, a large integral membrane protein of unknown function that is expressed on the plasma membrane of renal tubular epithelial cells in fetal kidneys. Because signaling from cell-cell and cell-matrix adhesion complexes regulates cell proliferation and polarity, we speculated that polycystin-1 might interact with these complexes. We show here that polycystin-1 colocalized with the cell adhesion molecules E-cadherin and alpha-, beta-, and gamma-catenin. Polycystin-1 coprecipitated with these proteins and comigrated with them on sucrose density gradients, but it did not colocalize, coprecipitate, or comigrate with focal adhesion kinase, a component of the focal adhesion. We conclude that polycystin-1 is in a complex containing E-cadherin and alpha-, beta-, and gamma-catenin. These observations raise the question of whether the defects in cell proliferation and cell polarity observed in ADPKD are mediated by E-cadherin or the catenins.
PERICOLITIS SINISTRA WITH ABSCESS FORMATION: RECOVERY
Authors: R. Donaldson
Journal: BMJ (1907)

pebble, which I cast in passing upon your monument of fame.But, should it be the means of preventing one unnecessary or pernicious nephrectomy, or preserve to one poor wretch the internal secretion of his testicles, neither your bequest nor my labours will have been expended quite in vain.
Treatment of Oxyuriasis
Authors: Z. Farid
Journal: BMJ (1963)

JOURNLtechniques and the training of nurses in those techniques.To avoid a multiplication of methods with ensuing con- fusion it would seem highly advisable that some effort is made for centres with the greatest practical experience to get together and agree a standard method.We feel that the method depicted in the article is open to reasonable but serious criticism, and are unhappy that it may be accepted as a recommended and standard procedure.-Weare, etc.,
77 IMAGING MASS SPECTROMETRY PROVIDES FINGERPRINTS FOR DISTINGUISHING HEPATOCELLULAR CARCINOMA FROM CIRRHOSIS AND SUGGESTS AN UBIQUITIN RECYCLING DEFECT IN HEPATOCELLULAR CARCINOMA
Authors: J. Le Faouder, S. Laouirem, M. Chapelle, J. Belghiti, F. Degos, V. Paradis, J.-M. Camadro, P. Bedossa
Journal: Journal of Hepatology (2011)
Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte
Authors: Bertrand Coiffier, Catherine Thieblemont, Eric Van Den Neste, Gérard Lepeu, Isabelle Plantier, Sylvie Castaigne, Sophie Lefort, Gérald Marit, Margaret Macro, Catherine Sebban, Karim Belhadj, Dominique Bordessoule, Christophe Fermé, Hervé Tilly
Journal: Blood (2010)
Detection of complement components on unlysed erythrocytes from acid hemolysis and thrombin test reactions in paroxysmal nocturnal hemoglobinuria.
Authors: D E Jenkins, W N Christenson, R L Engle
Journal: Journal of Clinical Investigation (1966)

paper: PNH, paroxysmal nocturnal hemoglobinuria; PNHE, erythrocytes from patients with PNH; AH- PNHE, residual, unlysed PNH erythrocytes surviving the acid hemolysis reaction; Thr-PNHE, residual, un- lysed PNH erythrocytes surviving thrombin test hemolysis; EAC' hemolysis, in vitro hemolytic reaction in- volving erythrocytes (E), antibody (A), and complement (C') ; C'1, C'2, C'3, and C'4, the first, second, third, and fourth components of complement; fi1m-globulin, hu- man C'4; 8,c-globulin, a subcomponent of human C'3.
Cutaneous involvement by post‐polycythemia vera myelofibrosis
Authors: Alessandro Pecci, Giorgio Croci, Carlo L. Balduini, Emanuela Boveri
Journal: American Journal of Hematology (2013)

A 69-year-old man presented with multiple skin lesions scattered across his thorax and abdomen that had appeared 3 months earlier. He had a 20-year history of polycythemia vera with homozygosity for JAK2 V617F and was treated with hydroxyurea and aspirin since diagnosis. Skin lesions were macular to papulo-nodular, reddish to purple, up to 3 cm in diameter (Image 1A), and hard on palpation. The patient denied they were itchy or painful. Apart from that, physical examination was notable only for mild hepatosplenomegaly. Blood cell count showed leukocytosis (WBC 14.3 × 109/L) with hemoglobin concentration and platelet count within normal limits. Peripheral blood smear was characterized by red cell anisopoikilocytosis with dacryocytosis, and leukoerythroblastic picture with 2% micromegakaryocytes and 1% blasts. Ultrasonografy showed that spleen major diameter was 13.5 cm. A punch biopsy of a thoracic skin nodule demonstrated a dermal perivascular and periadnexal infiltrate with mild interstitial fibrosis (Image 1B, HE, 20×) composed by glycophorin C+ erythroblasts (Image 1C, 60×) immature MPO+ granulopoietic elements (Image 1D, 40×), and dysmorphic LAT+ megakaryocytes (Image 1E, 60×), without CD34+ or CD117+ blasts. A diagnosis of post-polycythemia vera myelofibrosis was established on the concurrent bone marrow biopsy (Image 1F,G) 1 and the trilineage hemopoiesis observed on the cutaneous biopsy was consistent with a neoplastic skin involvement by the disease. Cutaneous involvement has been reported in a few patients with myelofibrosis 2-4 and was associated with progressive disease and very poor prognosis 3. Our patient was asymptomatic and, apart from development of the skin lesions, had no signs of progressive disease, and we, therefore, did not modify his treatment. After a 15 months follow-up, his clinical and hematological picture is stable and the skin lesions show no modifications in size or number. This suggests that cutaneous involvement by myelofibrosis should not be always regarded as a manifestation of the terminal phase of the disease. The observation in adult patients of extramedullary trilineage hemopoiesis, even in absence of blasts, should always rise the suspect of a neoplastic proliferation, which is usually expression of a underlying myeloid proliferation, especially chronic myeloproliferative diseases 5: thus, as in our case, it is important to integrate the extramedullary findings with clinical picture and results of bone marrow biopsy.
Growth factor-induced survival pathways in activated human HSC: long-term dynamics and PI 3-K-independednt modulation of BAD phosphorylation
Authors: Alessandra Gentilini, Raffaella M.S. DeFranco, Benedetta Lottini, Marta Meucci, Marco Foschi, Paolo Gentilini, Massimo Pinzani
Journal: Journal of Hepatology (2002)
P520Percutaneous coronary intervention for chronic total occlusions of coronary arteries: procedural characteristics and long-term clinical outcomes
Authors: V Jeremic, S Stojkovic, M Dobric, V Vukcevic, D Orlic, I Cvorovic, Z Vasiljevic-Pokrajcic
Journal: Cardiovascular Research (2014)

Purpose: Despite the fact that techniques for recanalization of chronic total occlusions (CTO) are improved, the benefit of successful recanalization of the artery remains unclear. The aim of our study is to determine the success rate of percutaneous procedures and to evaluate the event free long-term survival in patients with CTO who underwent percutaneous coronary intervention (PCI).

Methods: Our study included 283 consecutive patients with chronic total occlusions who underwent percutaneous coronary intervention on CTO at Clinic for Cardiology, between Jan 1st 2009 and Dec 31st 2010. Data were obtained retrospectively from Cath lab database at Clinic for Cardiology. Follow up data were obtained by direct phone contact.

Results: Overall procedural success was achieved in 62.3% interventions. Independent predictors for procedural failure were presence of vessel tortuosity (P=0.007), vessel wall calcifications (P=0.000), blunt stump (P=0.000) and unstable angina pectoris as negative predictor (P=0.009). Overall MACE rates were similar in the procedural success and procedural failure groups (10% vs. 12.8%, p=0.455). There was no significant difference in the event free survival rate between success and failure group (89.8% vs. 87.2%, Log-Rank =0.468, p=0.494).

Conclusions: Our study demonstrated that success rate of PCI in patients with CTO is acceptable and safe. Nevertheless, successful recanalization of CTO was not associated with an improved event free survival.