tbuckley/cabot-search huggingface dataset:
AB0104 Develop and Evaluate a New Modified Mankin Score System with Special Attention to Subchondral Bone
Authors: Y. He, A. Gram, O. Simonsen, K.K. Petersen, M.A. Karsdal, A.-C. Bay-Jensen
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The MANKIN score is the most widely used histology evaluation on osteoarthritis (OA). It has been modified in number of studies by different research groups since it was first published 40 years ago. The MANKIN score investigate the degradation level of the articular cartilage by assessing four parameters including: cartilage structure, cellularity, proteoglycan depletion and tidemark integrity. However, it is well-established that the interaction between cartilage and subchondral bone, such as the new vessel invasion from subchondral bone into calcified cartilage and the accompanied nerve formation, play essential role in the onset and progression of OA. <h3>Objectives</h3> As to better assess the pathologic changes in joint during OA, we developed a new modified MANKIN scoring system with special attention to the subchondral bone. <h3>Methods</h3> Besides 4 categories of evaluation on cartilage, we also performed type X collagen immunohistochemical staining, tartrate-resistant acidic phosphatase (TRAP) staining, cartilage and subchondral bone thickness measurement, the number of vessels counting (CD34), Vascular Endothelial Growth Factor Receptor (VEGFR) immunostaining and nerve growth factor receptor (NGFR, P75staining) immunostaining in 2 areas (lateral femur condyle and lateral tibia plateau) of 11 OA patients undergoing knee replacement surgery at Frederikshavn hospital. Each new evaluation was analyzed the correlation with MANKIN score, of which with moderate correlation would be included into the new scoring table. Furthermore, statistical analysis was performed for inter-/intra- observers variability according to the criteria of new modified scoring system. <h3>Results</h3> After carful assessment of the different novel parameters, following were found to be associated with cartilage quality: 1) number of vessels (moderate correlation with MANKIN score, Spearman9s r=0.6), 2) number of positive cells expressing NGFR (moderate correlation with MANKIN score, Spearman9s r=0.4), and 3) the thickness of cartilage/subchondral bone (moderate correlation with MANKIN score, Spearman9s r=0.7). A final scoring scheme was put together (table 1) and tested in 11 patients. The inter-observer variability among two observers for the new score system showed reliability (Person9s r=0.80). Repeating scoring by one of two observers showed good reproducibility (Person9s r=0.73). <h3>Conclusions</h3> The new scoring system was constructed with valuable information to indicate the changes in subchondral bone and the severity of OA, which might be used as a rapid and reliable histology evaluation on both human OA and experiment induced OA animal models. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4224
A systematic review and meta-analysis of the influence of peritoneal dialysis catheter type on complication rate and catheter survival
Authors: Sander M. Hagen, Jeffrey A. Lafranca, Jan N.M. Ijzermans, Frank J.M.F. Dor
Journal: Kidney International (2013)

Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease. There are several configurations of PD catheter design that may impact catheter function, such as the shape of the intraperitoneal segment, the number of cuffs, and the subcutaneous configuration. This review and meta-analysis was carried out to determine whether there is a clinical advantage for one of the catheter types or configurations. Comprehensive searches were conducted in MEDLINE, Embase, and CENTRAL (the Cochrane Library 2012, issue 10). The methodology was in accordance with the Cochrane Handbook for Interventional Systematic Reviews and written based on the PRISMA statement. The initial search yielded 682 hits from which 13 randomized controlled trials were identified. Outcomes of interest were as follows: catheter survival, drainage dysfunction, migration, leakage, exit-site infections, peritonitis, and catheter removal. Comparing straight vs. swan neck and single vs. double-cuffed catheters, no differences were found when results were pooled. Comparison of straight vs. coiled-tip catheters demonstrated that survival was significantly different in favor of straight catheters (hazard ratio 2.05; confidence interval 1.10-3.79, P=0.02). For surgically inserted catheters, the removal rate and survival at 1 year after insertion were significantly in favor of straight catheters. Our meta-analysis clearly demonstrates benefits for catheters with a straight intraperitoneal segment.
Intra-Uterine Death
Authors: J. P. Greenhill
Journal: JAMA (1963)

<h3>To the Editor:</h3> —The injection of a substance into the amniotic cavity to terminate pregnancy is, of course, not new. In 1935, Boero (<i>1936 Year Book of Obstetrics and Gynecology</i>, p 53) advocated the injection of 40% formalin for interrupting pregnancy before fetal viability. In 1954, Stamm and De Watteville (<i>1954-55 Year Book of Obstetrics and Gynecology</i>, p 36) reported on the use of the Aburel method of interrupting gestation by withdrawing 100 cc of amniotic fluid and replacing it with an equal quantity of hypertonic saline solution. In 1958, Brosset (<i>1959-60 Year Book of Obstetrics and Gynecology</i>, p 61) recommended 50% glucose for induction of abortion and emptying of the uterus in cases of missed abortion. In 1960, Svane (<i>1961-62 Year Book of Obstetrics and Gynecology</i>, p 55) claimed good results from instilling saline extra-ovularly into the uterus by way of the cervical canal for interrupting pregnancy. In 1962,
Abstract 625: Transcription factor slug conferring resistance To EGFR tyrosine kinase inhibitor gefitinib
Authors: Tzu-Hua Chang, Jin-Yuan Shih, Meng-Feng Tsai, Chih-Hsin Yang, Pan-Chyr Yang
Journal: Cancer Research (2010)

Abstract Purpose: Somatic EGFR mutations of non-small cell lung cancer (NSCLC) are reported to be associated with clinical responsiveness to tyrosine kinase inhibitor gefitinib. Despite the dramatic responses to gefitinib, most patients ultimately have a relapse. The underlying mechanism of the drug resistance is not well clear. Recently, many studies have shown that epithelial to mesenchymal transition (EMT) is involved in resistance to gefitinib in EGFR. Zinc finger transcription factor slug is one of the EMT regulators. In this study, we will investigate whether the slug plays a role in the gefitinib resistance. Materials and Methods: PC9/IR (gefitinib-resistant cell line) was isolated from PC9 (gefitinib-sensitive cell line) after long-term treatment of gefitinib. To identify the factors involved in gefitinib resistance, we analyzed the expression levels of EMT regulators (Slug, Snail, Twist, Zeb-1) in PC9/IR and PC9 cells using quantitative real time PCR and western blot. To investigate the association of Slug and gefitinib-induced resistance, we also engineered to stably express Slug and short hairpin RNA targeting Slug transcript in PC9 and PC9/IR, respectively. Results: The findings showed that mRNA and protein levels of Slug obviously increased in PC9/IR comparing with PC9 and expression of other EMT regulators Snail, Twist, Zeb-1 were similar between these two cell lines. After gefitinib treatment, PC9/IR expressing shRNA against Slug underwent apoptosis and activation of the intrinsic apoptosis pathway. Ectopic expression of Slug protected PC9 cells from undergoing apoptosis in response to gefitinib treatment. Knockdown the expression of slug reversed gefitinib resistance of PC9/IR cells by restoring Bim expression. Conclusions: These results suggest that expression of slug may contribute to resistance to gefitinib in PC9/IR and may be a useful target for treatment of resistance to EGFR tyrosine kinase inhibitor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 625.
Giardiasis: clinical and therapeutic aspects.
Authors: S G Wright, A M Tomkins, D S Ridley
Journal: Gut (1977)

Malabsorption was present in 29 of 40 symptomatic patients with giardiasis. Twenty-three had impaired D-xylose absorption; in 20 vitamin B12 absorption was low, and 15 patients had steatorrhoea. More severe malabsorption was associated with more marked histological abnormalities. Metronidazole, 2-0 g as a single daily dose on three successive days, produced a parasitological cure rate of 91%. In contrast, the standard course of mepacrine, 100 mg thrice daily for 10 days, eradicated the parasite in only 63% of patients. Improvements in absorption and jejunal morphology followed anti-giardial treatment. Tetracycline in eight patients failed to eradicate the parasite, intestinal absorption was unaltered, and histological appearances of the jejunal mucosa often deteriorated.
Oncolytic Herpes Simplex Virus Vector G47Δ in Combination with Androgen Ablation for the Treatment of Human Prostate Adenocarcinoma
Authors: Hiroshi Fukuhara, Robert L. Martuza, Samuel D. Rabkin, Yoshikazu Ito, Tomoki Todo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The use of oncolytic herpes simplex virus type 1 is a promising stategy for cancer treatment. We constructed herpes simplex virus type 1 vector G47Δ by deleting the α47 gene and the promoter region of US11 from G207. We now report studies demonstrating the potential of G47Δ as a therapeutic modality for prostate cancer in combination with androgen ablation. Experimental Design: The cytopathic activities of G47Δ at low multiplicities of infection was tested in human prostate cancer cell lines LNCaP, PC-3, and DU145 in vitro. Two androgen-dependent mouse s.c. tumor models, murine TRAMP and human HONDA, were used to investigate the in vivo efficacy of G47Δ in combination with androgen ablation. Results: G47Δ at low multiplicities of infection showed more rapid tumor cell killing than G207 in LNCaP and DU145 in vitro and showed a 22-fold higher virus yield in a single-step growth experiment. In vivo, G47Δ treatment resulted in reduced tumor growth of established s.c. TRAMP and HONDA tumors and inhibited the growth of recurrent HONDA tumors that once regressed by androgen ablation therapy. In both TRAMP and HONDA tumor xenografts, the combination therapy of G47Δ with androgen ablation led to significantly enhanced inhibition of the tumor growth and prolonged survival. Conclusions: These results suggest that oncolytic virus therapy with G47Δ can be usefully combined with androgen ablation therapy for the treatment of prostate cancer.
Outcome of restorative proctocolectomy when the diagnosis is suggestive of Crohn's disease.
Authors: S P Grobler, K B Hosie, E Affie, H Thompson, M R Keighley
Journal: Gut (1993)

Twenty of 81 patients treated by restorative proctocolectomy for presumed ulcerative colitis had some features of Crohn9s disease: 10 were classified as definite Crohn9s disease and 10 as indeterminate colitis. These pathological features were first apparent during synchronous colectomy and pouch construction in 10 of 11 cases. In the remainder, histological features of possible Crohn9s disease were first identified during rectal excision (n = 6), preliminary subtotal colectomy (n = 2), and after pouch excision (= 2). Complications were marginally more common in patients with features of possible Crohn9s disease: pelvic sepsis 30% (Crohn9s disease 30%, indeterminate colitis 30%) v 20%, fistulas 45% (Crohn9s disease 30%, indeterminate colitis 60%) v 16%; ileal stenosis 40% (Crohn9s disease 40%, indeterminate colitis 40%) v 21%, pouchitis 50% (Crohn9s disease 50%, indeterminate colitis 50%) v 26%, and small bowel obstruction 25% (Crohn9s disease 30%, indeterminate colitis 30%) v 13%. Pouch excision or a persistent proximal stoma has been necessary in six patients with possible Crohn9s disease (30%) (Crohn9s disease 3 cases 30%, indeterminate colitis 3 cases 30%) compared with nine (15%) of the remainder. Median hospital stay, however, was the same and stool frequency in those with a functioning pouch were comparable. These results show that there is a higher complication rate if there are features of Crohn9s disease but that the medium term functional results are acceptable if the pouch can be retained.
STUDY ON GROWTH OF RICKETTSIAE
Authors: Zanvil A. Cohn, F. Marilyn Bozeman, Janis M. Campbell, James W. Humphries, Thomas K. Sawyer
Journal: The Journal of Experimental Medicine (1959)

A system has been described in which the penetration of Rickettsia tsutsugamushi (Karp strain) into tissue culture cells can be quantitated, and the factors affecting this process studied. The results indicated that rickettsial penetration in vitro depended largely on the viability of the organisms. Certain components of the fluid environment such as the divalent cations and protein were found to be of importance. The temperature dependence of the penetration process was found to vary with the nature of the suspending medium. A number of compounds related to L-glutamic acid enhanced penetration, whereas metabolic inhibitors depressed this process. Aureomycin at concentrations between 50 and 250 µg./ml. inhibited the penetration of rickettsiae while chloramphenicol at similar concentrations was ineffective. The results are discussed in terms of the biological and biochemical properties of this group of agents.
The use of Mohs micrographic surgery for determination of residual tumor in incompletely excised basal cell carcinoma
Authors: Harlan C. Bieley, Robert S. Kirsner, Blas A. Reyes, Larry D. Garland
Journal: Journal of the American Academy of Dermatology (1992)

Background: The presence of tumor involving surgical margins after excision of basal cell carcinoma (BCC) presents a therapeutic dilemma. Some authors advocate a conservative policy whereas others recommend immediate reexcision. Objective: Our purpose was to evaluate residual tumor utilizing Mohs micrographic surgery (MMS) of those BCCs with margin involvement after primary excision. Methods: We retrospectively reviewed 77 patients with 78 tumors who underwent MMS because of margin involvement after primary excision of BCC to detect the presence or absence of residual tumor. Results: Residual tumor was found in 55% of the cases as defined by the need for two or more stages of MMS to achieve a tumor-free plane. Conclusion: We suggest reexcision of all BCCs that are found to have marginal involvement after primary excision because of the large percentage of cases found to have residual tumor. Background: The presence of tumor involving surgical margins after excision of basal cell carcinoma (BCC) presents a therapeutic dilemma. Some authors advocate a conservative policy whereas others recommend immediate reexcision. Objective: Our purpose was to evaluate residual tumor utilizing Mohs micrographic surgery (MMS) of those BCCs with margin involvement after primary excision. Methods: We retrospectively reviewed 77 patients with 78 tumors who underwent MMS because of margin involvement after primary excision of BCC to detect the presence or absence of residual tumor. Results: Residual tumor was found in 55% of the cases as defined by the need for two or more stages of MMS to achieve a tumor-free plane. Conclusion: We suggest reexcision of all BCCs that are found to have marginal involvement after primary excision because of the large percentage of cases found to have residual tumor.
THE COMPOSITION OF PROCAINE BORATE (BOROCAINE)
Authors: GEORGE W. COLLINS
Journal: JAMA (1928)

ABSTRACT Copeland and Notton, working in the Laboratories of Pharmacology and Chemistry, Cambridge, England, have reported on the borates of various local anesthetics, under the title  Borocaines: A New Class of Local Anesthetics.1 The general claim is made that the borocaines are less toxic than the original hydrochlorides, from which they can be prepared, but often exert ten times the anesthetic action. The explanation offered is that the products are easily hydrolyzed and that procaine,2 the base, is more active than the ion (such as procainium) when, as in the case of the latter, the highly ionized procaine hydrochloride is used. This is not a new observation, but a confirmation of work of others.The only member of the series brought out on the open market is procaine borate; it is sold in this country by Sharp and Dohme, under license from the British Drug Houses, under the
Postoperative Radiotherapy is Associated with Better Survival in Non–Small Cell Lung Cancer with Involved N2 Lymph Nodes: Results of an Analysis of the National Cancer Data Base
Authors: John L. Mikell, Theresa W. Gillespie, William A. Hall, Dana C. Nickleach, Yuan Liu, Joseph Lipscomb, Suresh S. Ramalingam, Raj S. Rajpara, Seth D. Force, Felix G. Fernandez, Taofeek K. Owonikoko, Rathi N. Pillai, Fadlo R. Khuri, Walter J. Curran, Kristin A. Higgins
Journal: Journal of Thoracic Oncology (2014)
Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity
Authors: Gene D. LeSage, Luca Marucci, Domenico Alvaro, Shannon S. Glaser, Antonio Benedetti, Marco Marzioni, Tushar Patel, Heather Francis, Jo Lynne Phinizy, Gianfranco Alpini
Journal: Hepatology (2002)

Insulin stimulates canalicular bile flow by interaction with hepatocytes. Insulin regulates the function of a number of epithelia through activation and membrane translocation of Ca 2+ -dependent PKC isoforms. No information exists regarding insulin regulation of ductal bile secretion. The aim of the study was to determine the role and mechanisms of action of insulin in the regulation of cholangiocyte secretion in BDL rats. We determined the subcellular localization of insulin receptor in cholangiocytes. We measured the effect of insulin on (1) secretin-stimulated cAMP levels in cholangiocytes and duct expansion in intrahepatic bile duct units (IBDUs) in the absence or presence of BAPTA/AM, H7 or rottlerin and (2) bile flow. We evaluated (1) if insulin effects are associated with activation of PKC alpha and (2) if activation of PKC causes inhibition of secretin-stimulated cAMP levels and PKA activity. We found insulin receptors only in the apical domain of cholangiocytes. Insulin inhibited secretin-induced choleresis and secretin-stimulated cholangiocyte cAMP levels. Insulin inhibited secretin-induced secretion in IBDUs when applied at the basolateral membrane or microinjected into IBDU lumen. Insulin inhibitory effects on cholangiocyte secretion were blocked by BAPTA/AM and H7. Insulin induced activation of PKC alpha, which decreased secretin-stimulated cAMP and PKA activity. In conclusion, insulin inhibited secretin-induced ductal secretion of BDL rats through activation of PKC and inhibition of secretin-stimulated cAMP and PKA activity. In conclusion, insulin counter-regulates cholangiocyte secretory processes in the BDL model, which is characterized by cholangiocyte proliferation.
30-Day Pharmacokinetic Evaluation of IV versus Subcutaneous Administration of Immunoglobulin with and without Recombinant Human Hyaluronidase in Dogs
Authors: V.W. Leesch, B.A. Johnson, C.S. Cook, R.C. Yocum, R.I. Schiff, E.M. Muchitsch, W. Teschner
Journal: Journal of Allergy and Clinical Immunology (2009)
Abstract P3-02-03: The phosphatase function of the eyes absent (EYA) homolog is required for the induction of breast cancer cellular proliferation via cyclin D1
Authors: RG Pestell, K Wu, Z Li, L Tian, K Chen, J Wang, J Hu, Y Sun, X Li, A Ertel
Journal: Cancer Research (2013)

Abstract The Drosophila Eyes Absent Homologue 1 (EYA1) is a component of the retinal determination gene network (RDGN) and serves as an H2AX phosphatase. The cell fate determination gene network includes the dachshund (dac), twin-of-eyeless (toy), eye absent (eya), teashirt (tsh) and sine oculis (So). In Drosophila, mutations of the RDGN leads to failure of eye formation, whereas, forced expression induces ectopic eye formation. EYA functions as a transcriptional co-activator being recruited in the context of local chromatin, but lacking intrinsic DNA binding activity. EYA family members EYA 1-4 are defined by a 275 amino acid carboxyl-terminal motif that is conserved between species, referred to as the EYA domain (ED). The human homologs EYA 1-4 are highly conserved in their EYA domain and amino termini, with the exception of a small tyrosine rich residue region named EYA domain II. Altered expression or functional activity of the RDGN has been documented in a variety of malignancies. DACH1 expression is reduced in breast, prostate, endometrial and brain cancer. EYA2 is up regulated in ovarian cancer, promoting tumor growth. EYA1 and EYA2 enhanced survival in response to DNA damage producing agents in HEK293 cells. Eya2 was required for Six1/TGFb signals that govern a prometastatic phenotype and epithelial mesenchymal transition (EMT). Although EYA proteins are expressed in human breast cancer, the relationship to molecular genetic subtype, prognosis and the molecular mechanisms governing contact-independent growth are not known. The cyclin D1 gene encodes the regulatory subunits of a holoenzyme that phosphorylates and inactivates the pRb protein. Herein, comparison with normal breast demonstrated EYA1 is overexpressed with cyclin D1 in luminal B breast cancer subtype. EYA1 enhanced breast tumor growth in mice in vivo requiring the phosphatase domain. EYA1 enhanced cellular proliferation, inhibited apoptosis, and induced contact-independent growth and cyclin D1 abundance. The induction of cellular proliferation and cyclin D1 abundance, but not apoptosis, was dependent upon the EYA1 phosphatase domain. The EYA1-mediated transcriptional induction of cyclin D1 occurred via the AP-1 binding site at -953 and required the EYA1 phosphatase function. The AP-1 mutation did not affect SIX1-dependent activation of cyclin D1. EYA1 was recruited in the context of local chromatin to the cyclin D1 AP-1 site. The EYA1 phosphatase function determined the recruitment of CBP, RNA polymerase II and acetylation of H3K9 at the cyclin D1 gene AP-1 site regulatory region in the context of local chromatin. The EYA1 phosphatase regulates cell cycle control via transcriptional complex formation at the cyclin D1 promoter. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-02-03.