tbuckley/cabot-search huggingface dataset:
Polycystin-1 Induces Resistance to Apoptosis through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
Authors: Manila Boca, Gianfranco Distefano, Feng Qian, Anil K. Bhunia, Gregory G. Germino, Alessandra Boletta
Journal: Journal of the American Society of Nephrology (2006)

Polycystin-1 (PC-1), the PKD1 gene product, is a large receptor whose expression in renal epithelial cells results in resistance to apoptosis and tubulogenesis, a model consistent with the phenotype observed in patients. This study links PC-1 expression to a signaling pathway that is known to be both antiapoptotic and important for normal tubulogenesis. This study found that PC-1 expression results in phosphorylation of Akt and downstream effectors and that phosphatidylinositol 3-kinase (PI3-K) inhibitors prevent this process. In addition, it is shown that dominant negative Akt can revert PC-1-induced protection from apoptosis. Furthermore, it was observed that increased PI3-K beta activity in PC-1-expressing MDCK cells seems to be dependent on both tyrosine-kinase activity and heterotrimeric G proteins. It also was found that PC-1-induced tubulogenesis is inhibited by PI3-K inhibitors. Taken together, these data suggest that the PI3-K/Akt cascade may be a central modulator of PC-1 function and that its deregulation might be important in autosomal dominant polycystic kidney disease.
Acidosis and coma after hemodialysis.
Authors: R Taylor, J Bower, M M Salem
Journal: Journal of the American Society of Nephrology (1997)

Ethylene glycol poisoning is a rare yet potentially fatal illness seen most commonly in association with ingestion by alcoholics or in suicide attempts. It is characterized by an elevated anion gap metabolic acidosis, osmolal gap, calcium oxalate crystals in the urine, and a well-defined clinical picture. Prompt treatment is crucial because effective intervention can prevent the neurologic, cardiac, pulmonary, and renal sequelae associated with ethylene glycol poisoning. Hemodialysis offers rapid clearance of ethylene glycol and its toxic metabolites. In this article, the case of a hemodialysis patient who suffered contamination of the dialysate solution with ethylene glycol, leading to altered mental status, coma, and severe anion gap metabolic acidosis, is reported. Despite prolonged dialysis and correction of the acidosis, the patient remained comatose and subsequently died.
P161 CD14CD16 MONOCYTES FROM PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS DRIVE MEMORY T CELL PROLIFERATION AND POLARISE THEM TO A STEROID RESISTANT TH17 PHENOTYPE
Authors: A. Dhanda, B. Liu, R. Nussenblatt, A.D. Dick, R.W. Lee, P.L. Collins
Journal: Journal of Hepatology (2014)
Evaluation of pathologic criteria for acute renal allograft rejection
Authors: R B Colvin, A H Cohen, C Saiontz, S Bonsib, M Buick, B Burke, S Carter, T Cavallo, M Haas, A Lindblad, J C Manivel, C C Nast, D Salomon, C Weaver, M Weiss
Journal: Journal of the American Society of Nephrology (1997)

This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in > or =5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type III: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist's diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of > or =1 tubule with tubulitis and > or =5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P < 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P > 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection.
Hormone Whodunit: Clues for Solving the Case of Intratumor Androgen Production
Authors: Karen E. Knudsen
Journal: Clinical Cancer Research (2014)

One of the key mechanisms by which prostate cancer cells evade hormone therapy is through intratumor testosterone production. New evidence points toward androstenedione as a potential precursor of intratumor androgen production and furthers nomination of AKR1C3 as a therapeutic target in advanced disease.
DIETARY FACTORS IN HUMAN COLORECTAL CANCER
Authors: Martin Lipkin, Bandaru Reddy, Harold Newmark, Sergio A. Lamprecht
Journal: Annual Review of Nutrition (1999)

▪ Abstract Colorectal cancer is a significant cause of mortality in Western societies. The progression of the disease from normal colonic epithelium to the acquisition of the malignant phenotype is accompanied by numerous genetic and epigenetic alterations. Compelling experimental and epidemiological evidence indicates that diet and nutrition are key factors in the modulation of colorectal cancer. A salient case in point is the recent observation that a dietary regimen based on a Western-style diet provokes in the rodent colon the appearance of preneoplastic lesions in the absence of any genotoxic insult. This review mainly describes dietary factors that inhibit the development and progression of colorectal cancer. Much is unknown about the precise mechanisms of action of chemically disparate nutrients and how they interfere with the development and progression of this disease. Current knowledge about this important issue is summarized. We believe that continuing scrutiny and precise assessment of the benefits (and potential risks) of nutrients in the treatment and prevention of colorectal cancer will prove significant to controlling this devastating disease.
HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis
Authors: S Laivoranta-Nyman
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. <b>Methods:</b> 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. <b>Results:</b> The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes—(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502—were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. <b>Conclusions:</b> When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.
Clinical, Molecular, and Prognostic Significance of WHO Type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and Various Other 3q Abnormalities in Acute Myeloid Leukemia
Authors: Sanne Lugthart, Stefan Gröschel, H. Berna Beverloo, Sabine Kayser, Peter J.M. Valk, Shama Lydia van Zelderen-Bhola, Gert Jan Ossenkoppele, Edo Vellenga, Eva van den Berg-de Ruiter, Urs Schanz, Gregor Verhoef, Peter Vandenberghe, Augustin Ferrant, Claus-Henning Köhne, Michael Pfreundschuh, Heinz A. Horst, Elisabeth Koller, Marie von Lilienfeld-Toal, Martin Bentz, Arnold Ganser, Brigitte Schlegelberger, Martine Jotterand, Jürgen Krauter, Thomas Pabst, Matthias Theobald, Richard F. Schlenk, Ruud Delwel, Konstanze Döhner, Bob Löwenberg, Hartmut Döhner
Journal: Journal of Clinical Oncology (2010)

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) [inv(3)/t(3;3)] is recognized as a distinctive entity in the WHO classification. Risk assignment and clinical and genetic characterization of AML with chromosome 3q abnormalities other than inv(3)/t(3;3) remain largely unresolved.Cytogenetics, molecular genetics, therapy response, and outcome analysis were performed in 6,515 newly diagnosed adult AML patients. Patients were treated on Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research (HOVON/SAKK; n = 3,501) and German-Austrian Acute Myeloid Leukemia Study Group (AMLSG; n = 3,014) protocols. EVI1 and MDS1/EVI1 expression was determined by real-time quantitative polymerase chain reaction.3q abnormalities were detected in 4.4% of AML patients (288 of 6,515). Four distinct groups were defined: A: inv(3)/t(3;3), 32%; B: balanced t(3q26), 18%; C: balanced t(3q21), 7%; and D: other 3q abnormalities, 43%. Monosomy 7 was the most common additional aberration in groups (A), 66%; (B), 31%; and (D), 37%. N-RAS mutations and dissociate EVI1 versus MDS1/EVI1 overexpression were associated with inv(3)/t(3;3). Patients with inv(3)/t(3;3) and balanced t(3q21) at diagnosis presented with higher WBC and platelet counts. In multivariable analysis, only inv(3)/t(3;3), but not t(3q26) and t(3q21), predicted reduced relapse-free survival (hazard ratio [HR], 1.99; P < .001) and overall survival (HR, 1.4; P = .006). This adverse prognostic impact of inv(3)/t(3;3) was enhanced by additional monosomy 7. Group D 3q aberrant AML also had a poor outcome related to the coexistence of complex and/or monosomal karyotypes and cryptic inv(3)/t(3;3).Various categories of 3q abnormalities in AML can be distinguished according to their clinical, hematologic, and genetic features. AML with inv(3)/t(3;3) represents a distinctive subgroup with unfavorable prognosis.
Relation between myocardial damage and noradrenergic activities in the central and peripheral nervous systems in patients with subarachnoid hemorrhage
Authors: Shinichiro Yamamoto, Takashi Masuda, Narihisa Matsuyama, Kiyotaka Sato, Koh-ichiro Okuhara, Chiharu Noda, Kazuko Murakami, Takashi Ohwada
Journal: Journal of the American College of Cardiology (1996)
Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-Cell Malignancies Can Be Effectively Treated With Autologous T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor
Authors: James N. Kochenderfer, Mark E. Dudley, Sadik H. Kassim, Robert P.T. Somerville, Robert O. Carpenter, Maryalice Stetler-Stevenson, James C. Yang, Giao Q. Phan, Marybeth S. Hughes, Richard M. Sherry, Mark Raffeld, Steven Feldman, Lily Lu, Yong F. Li, Lien T. Ngo, Andre Goy, Tatyana Feldman, David E. Spaner, Michael L. Wang, Clara C. Chen, Sarah M. Kranick, Avindra Nath, Debbie-Ann N. Nathan, Kathleen E. Morton, Mary Ann Toomey, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2014)

T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies.
Spending in Scotland goes up while activity goes down
Authors: Bryan Christie
Journal: BMJ (2005)

A report looking at the performance of the NHS in Scotland has found that it is difficult to assess whether the service is providing value for money.

The report from Audit Scotland says that expenditure in Scotland is higher than in the rest of the United Kingdom and a sample of European countries, including Denmark, the Netherlands, and Finland. Extra investment has helped to fund improvements in the quality and availability of treatment, yet Scotland continues to have some of the highest premature death rates in the developed world.

The report …
Scanning electron microscopy of pulmonary alveolar capillary vessels
Authors: I. G. S. Alexander, B. C. Ritchie, J. E. Maloney
Journal: Thorax (1973)

The pattern of subepithelial vessels in pulmonary alveoli of rabbits has been studied using scanning electron microscopy. Alveolar capillaries form a network of interconnecting vascular rings, most of which surround the periphery of type II cells of the alveolar epithelium. Individual capillaries contributing to the formation of adjacent rings follow a corrugated course with angulations located on the sites of junction with other capillaries completing the rings; the capillaries are covered by type I epithelial cells which also extend into and form the alveolar lining at the peripheral area of the interstices of the capillary network. Single type II cells form the alveolar lining at the centre of vascular rings. The pattern of pulmonary alveolar capillaries revealed by scanning electron microscopy is thus similar to that postulated by Weibel (1963) on the basis of transmission microscopic studies.
Transcriptional silencing of Polo-like kinase 2<i>(SNK/PLK2)</i>is a frequent event in B-cell malignancies
Authors: Nelofer Syed, Paul Smith, Alexandra Sullivan, Lindsay C. Spender, Martin Dyer, Lorraine Karran, Jenny O'Nions, Martin Allday, Ingrid Hoffmann, Dorothy Crawford, Beverley Griffin, Paul J. Farrell, Tim Crook
Journal: Blood (2005)
Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management
Authors: R A Kyle, B G M Durie, S V Rajkumar, O Landgren, J Blade, G Merlini, N Kröger, H Einsele, D H Vesole, M Dimopoulos, J San Miguel, H Avet-Loiseau, R Hajek, W M Chen, K C Anderson, H Ludwig, P Sonneveld, S Pavlovsky, A Palumbo, P G Richardson, B Barlogie, P Greipp, R Vescio, I Turesson, J Westin, M Boccadoro
Journal: Leukemia (2010)
A meta-analysis comparing the efficacy of five 5-HT3-receptor antagonists (5-HT3-RAs) for acute chemotherapy induced emesis
Authors: K. Jordan, A. Hinke, A. Grothey, H. J. Schmoll
Journal: Journal of Clinical Oncology (2004)

8048 Background: 5-HT3-RAs are the most important components of antiemetic therapy. Five different 5-HT3-RAs are currently available: granisetron (GRA), tropisetron (TRO), ondansetron (OND) dolasetron (DOL) and very recently palonosetron (PALO). None of the puplished reviews demonstrated superiority of one 5-HT3-Ras over another yet, however several new studies have since been published which could given more conclusive informations. Methods: More than 50 studies (> 20.000 pts) were included in the meta-analysis comparing: GRA vs OND, GRA vs TRO, OND vs TRO, OND vs DOL and OND vs PALO. Efficacy was classified as complete acute response (no vomiting and only mild nausea in the first 24h). Studies were divided into cisplatin-based and non-cisplatin-based chemotherapy. For each indivudual study odds ratio was calculated. Combined odds ratios for cisplatin-based and non-cisplatin-based studies were generated according to the methods developed by the Peto group. Sub-analysis were performed comparing different doses of OND and GRA. Furthermore a sub-analysis of 5-HT3-Ras with or without steroids were carried out. Results: Comparison of GRA and OND revealed equivalent efficacy. Sub-analysis comparing 3 mg GRA vs 8 mg OND showed a possible superiority of GRA for non-cisplatin based studies (p<0,05). Pooled analysis of cisplatinum and non-cisplatinum based chemotherapy showed a significant advantage of GRA over TRO overall (p=0.042). There is no clear advantage of OND over TRO or DOL. Conclusions: This is the first meta-analysis of all available randomized trials between 1992–2003 to compare all available 5-HT3-Ras. There is no apparent difference in efficacy of OND, GRA and DOL with the exception of 8 mg OND vs 3 mg GRA. However a comparing study of 1 mg GRA with 8 mg OND is still lacking. GRA may have advantage over TRO in terms of improved efficacy during the first 24 h after chemotherapy. The influence of different doses and steroids as well as the comparison of OND with PALO will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-LaRoche Hoffmann-LaRoche
Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
Authors: Brunangelo Falini, Cristina Mecucci, Enrico Tiacci, Myriam Alcalay, Roberto Rosati, Laura Pasqualucci, Roberta La Starza, Daniela Diverio, Emanuela Colombo, Antonella Santucci, Barbara Bigerna, Roberta Pacini, Alessandra Pucciarini, Arcangelo Liso, Marco Vignetti, Paola Fazi, Natalia Meani, Valentina Pettirossi, Giuseppe Saglio, Franco Mandelli, Francesco Lo-Coco, Pier-Giuseppe Pelicci, Massimo F. Martelli
Journal: New England Journal of Medicine (2005)

Nucleophosmin (NPM), a nucleocytoplasmic shuttling protein with prominent nucleolar localization, regulates the ARF-p53 tumor-suppressor pathway. Translocations involving the NPM gene cause cytoplasmic dislocation of the NPM protein.We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow-biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML). We then correlated the presence of cytoplasmic NPM with clinical and biologic features of the disease.Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML. It was associated with a wide spectrum of morphologic subtypes of the disease, a normal karyotype, and responsiveness to induction chemotherapy, but not with recurrent genetic abnormalities. There was a high frequency of FLT3 internal tandem duplications and absence of CD34 and CD133 in AML specimens with a normal karyotype and cytoplasmic dislocation of NPM, but not in those in which the protein was restricted to the nucleus. AML specimens with cytoplasmic NPM carried mutations of the NPM gene that were predicted to alter the protein at its C-terminal; this mutant gene caused cytoplasmic localization of NPM in transfected cells.Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.
Phosphatidylinositol 3-kinase-dependent activation of trypsinogen modulates the severity of acute pancreatitis
Authors: Vijay P. Singh, Ashok K. Saluja, Lakshmi Bhagat, Gijs J.D. van Acker, Albert M. Song, Stephen P. Soltoff, Lewis C. Cantley, Michael L. Steer
Journal: Journal of Clinical Investigation (2001)

Intra-acinar cell activation of digestive enzyme zymogens including trypsinogen is generally believed to be an early and critical event in acute pancreatitis. We have found that the phosphatidylinositol 3-kinase inhibitor wortmannin can reduce the intrapancreatic activation of trypsinogen that occurs during two dissimilar experimental models of rodent acute pancreatitis, secretagogue- and duct injection-induced pancreatitis. The severity of both models was also reduced by wortmannin administration. In contrast, the NF-kappa B activation that occurs during the early stages of secretagogue-induced pancreatitis is not altered by administration of wortmannin. Ex vivo, caerulein-induced trypsinogen activation is inhibited by wortmannin and LY294002. However, the cytoskeletal changes induced by caerulein were not affected by wortmannin. Concentrations of caerulein that induced ex vivo trypsinogen activation do not significantly increase phosphatidylinositol-3,4-bisphosphate or phosphatidylinositol 3,4,5-trisphosphate levels or induce phosphorylation of Akt/PKB, suggesting that class I phosphatidylinositol 3-kinases are not involved. The concentration of wortmannin that inhibits trypsinogen activation causes a 75% decrease in phosphatidylinositol 3-phosphate, which is implicated in vesicle trafficking and fusion. We conclude that a wortmannin-inhibitable phosphatidylinositol 3-kinase is necessary for intrapancreatic activation of trypsinogen and regulating the severity of acute pancreatitis. Our observations suggest that phosphatidylinositol 3-kinase inhibition might be of benefit in preventing acute pancreatitis.
Preoperative integrated PET-CT scanning reduces the number of futile thoracotomies for lung cancer
Authors: N. Navani
Journal: Thorax (2009)

In this Danish trial, patients being assessed for surgery of early stage non-small cell lung cancer (NSCLC) were randomised to either conventional staging and PET-CT scanning or conventional staging alone. The number of futile thoracotomies in each arm is a measure of staging accuracy and was used as the primary outcome. A …