tbuckley/cabot-search huggingface dataset:
Evidence that Systemic Gentamicin Suppresses Premature Stop Mutations in Patients with Cystic Fibrosis
Authors: J. P. CLANCY, ZSUZSA BEBÖK, FADEL RUIZ, CHRIS KING, JULIE JONES, LYNN WALKER, HEATHER GREER, JEONG HONG, LISA WING, MAURIZIO MACALUSO, RAYMOND LYRENE, ERIC J. SORSCHER, DAVID M. BEDWELL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Here we report the effects of gentamicin treatment on cystic fibrosis transmembrane regulator (CFTR) production and function in CF airway cells and patients with CF with premature stop mutations. Using immunocytochemical and functional [6-methoxy-N- (3-sulfopropyl) quinolinium (SPQ)-based] techniques, ex vivo exposure of airway cells from stop mutation CF patients led to the identification of surface-localized CFTR in a dose-dependent fashion. Next, five patients with CF with stop mutations and five CF control subjects were treated with parenteral gentamicin for 1 wk, and underwent repeated in vivo measures of CFTR function (nasal potential difference [PD] measurements and sweat chloride [Cl−] testing). During the treatment period, the number of nasal PD readings in the direction of Cl− secretion was increased approximately 3-fold in the stop mutation patient group compared with controls (p < 0.001), and four of five stop mutation patients with CF had at least one reading during gentamicin treatment with a Cl− secretory response of more than − 5 mV (hyperpolarized). A response of this magnitude was not seen in any of the CF control subjects (p < 0.05). In an independent series of experiments designed to test the ability of repeat nasal PDs to detect wild-type CFTR function, evidence of Cl− secretion was seen in 88% of control (non-CF) nasal PDs, and 71% were more than − 5 mV hyperpolarized. Together, these results suggest that gentamicin treatment can suppress premature stop mutations in airway cells from patients with CF, and produce small increases in CFTR Cl− conductance (as measured by the nasal PD) in vivo.
In vitro complement activation by antinuclear antibodies in the epidermis from patients with systemic sclerosis
Authors: G. REIMER, G. LIEBEL, O. P. HORNSTEIN
Journal: British Journal of Dermatology (1984)

Skin biopsies from twenty-one systemic sclerosis patients with significant serum fluorescent antinuclear antibody (FANA) titres (more than 1:40) were examined by direct immunofluorescence (DIF) and by in vitro immunofluorescent complement (C) activation (C + DIF). Eight patients showed epidermal nuclear ANA deposits by DIF. In vitro complement activation was achieved in epidermal nuclei from all eight patients. In addition, one patient with diffuse scleroderma revealed a dense speckled, and two patients with the CREST syndrome a discrete speckled, epidermal nuclear staining pattern by C + DIF. The latter two patients showed high titres of anticentromere antibody in their sera. We consider that the C + DIF findings of these two patients with the CREST syndrome reflect binding of serum anticentromere antibodies to their antigens in vivo.
Risk factors for cholangiocarcinoma
Authors: Gia L. Tyson, Hashem B. El-Serag
Journal: Hepatology (2011)

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra- and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC.
Clinical characteristics and outcomes of patients with angina and heart failure in the <scp>CHARM</scp> (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme
Authors: Athar A. Badar, Ana C. Perez‐Moreno, Nathaniel M. Hawkins, Alan P.T. Brunton, Pardeep S. Jhund, Chih M. Wong, Scott D. Solomon, Christopher B. Granger, Salim Yusuf, Marc A. Pfeffer, Karl Swedberg, Roy S. Gardner, Mark C. Petrie, John J.V. McMurray
Journal: European Journal of Heart Failure (2015)
Limited stage I disease is not necessarily indicative of an excellent prognosis in childhood anaplastic large cell lymphoma
Authors: Andishe Attarbaschi, Georg Mann, Angelo Rosolen, Denise Williams, Anne Uyttebroeck, Ildiko Marky, Laurence Lamant, Keizo Horibe, Grazyna Wrobel, Auke Beishuizen, Wilhelm Wössmann, Alfred Reiter, Audrey Mauguen, Marie-Cecile Le Deley, Laurence Brugières
Journal: Blood (2011)
Prescriptive Authority for Psychologists
Authors: Robert E. McGrath
Journal: Annual Review of Clinical Psychology (2010)

The proposal that psychologists should pursue prescriptive authority was first put forth 25 years ago, and it has been an official goal of the American Psychological Association for 15 years. Since then some form of prescriptive authority has been approved by three states, the Territory of Guam, and three branches of the military. Psychologists are also eligible to prescribe in the Public Health Service and the Indian Health Service. The movement has generated strong opinions both in favor and in opposition. Supporters focus particularly on increasing access to appropriate care and changing the role of psychologists within the healthcare system, while opponents raise concerns about how prescriptive authority will change professional psychology and whether psychologists will prescribe safely. This review provides a summary of milestones in the movement to date, as well as the arguments that have been raised for and against prescriptive authority.
Regression From Prediabetes to Normal Glucose Regulation Is Associated With Reduction in Cardiovascular Risk: Results From the Diabetes Prevention Program Outcomes Study
Authors: Leigh Perreault, Marinella Temprosa, Kieren J. Mather, Ed Horton, Abbas Kitabchi, Mary Larkin, Maria G. Montez, Debra Thayer, Trevor J. Orchard, Richard F. Hamman, Ronald B. Goldberg
Journal: Diabetes Care (2014)

Restoration of normal glucose regulation (NGR) in people with prediabetes significantly decreases the risk of future diabetes. We sought to examine whether regression to NGR is also associated with a long-term decrease in cardiovascular disease (CVD) risk.
Salivary Proteomics for Oral Cancer Biomarker Discovery
Authors: Shen Hu, Martha Arellano, Pinmanee Boontheung, Jianghua Wang, Hui Zhou, Jiang Jiang, David Elashoff, Roger Wei, Joseph A. Loo, David T. Wong
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aims to explore the presence of informative protein biomarkers in the human saliva proteome and to evaluate their potential for detection of oral squamous cell carcinoma (OSCC). Experimental Design: Whole saliva samples were collected from patients (n = 64) with OSCC and matched healthy subjects (n = 64). The proteins in pooled whole saliva samples of patients with OSCC (n = 16) and matched healthy subjects (n = 16) were profiled using shotgun proteomics based on C4 reversed-phase liquid chromatography for prefractionation, capillary reversed-phase liquid chromatography with quadruple time-of-flight mass spectrometry, and Mascot sequence database searching. Immunoassays were used for validation of the candidate biomarkers on a new group of OSCC (n = 48) and matched healthy subjects (n = 48). Receiver operating characteristic analysis was exploited to evaluate the diagnostic value of discovered candidate biomarkers for OSCC. Results: Subtractive proteomics revealed several salivary proteins at differential levels between the OSCC patients and matched control subjects. Five candidate biomarkers were successfully validated using immunoassays on an independent set of OSCC patients and matched healthy subjects. The combination of these candidate biomarkers yielded a receiver operating characteristic value of 93%, sensitivity of 90%, and specificity of 83% in detecting OSCC. Conclusion: Patient-based saliva proteomics is a promising approach to searching for OSCC biomarkers. The discovery of these new targets may lead to a simple clinical tool for the noninvasive diagnosis of oral cancer. Long-term longitudinal studies with large populations of individuals with oral cancer and those who are at high risk of developing oral cancer are needed to validate these potential biomarkers.
Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.
Authors: Y Kabasakal, D M Elvins, E F Ring, N J McHugh
Journal: Annals of the Rheumatic Diseases (1996)

To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls.A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls.Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%).There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries.
Role of Cytochrome P450 Phenotyping in Cancer Treatment
Authors: E. Claire Dees, Paul B. Watkins
Journal: Journal of Clinical Oncology (2005)

It is remarkable that cancer chemotherapies, with generally narrow therapeutic windows and possibilities for life-threatening toxicities, are usually dosed according to body-surface area (BSA). The appropriateness of BSAbaseddosinghasbeenchallenged, 1 butitremainsingrained in clinical oncology practice. The continued use of BSA dosing is understandable, as it applies a precise calculation toanintuitivelyobviousnotionthattooptimizetreatment, larger patients should receive more drug than smaller patients. Moreover, there is no validated substitute for BSAbased dosing for most chemotherapy regimens. However, theemergingfieldofpharmacogeneticspromisestochange this situation. Interindividual variability in toxicity and therapeutic responseisfrequentlyobserved,leadingtopotentiallylethal consequences of cancer treatment. Variability in response may be due to a combination of tumor- and host-related factors. Variability in chemotherapy-associated toxicity is a host-related phenomenon that is largely a consequence of variability in absorption and distribution, and particularly of metabolism and clearance. There is a high degree of interindividualvariabilityinthesystemicclearanceofmany chemotherapeutic agents, primarily reflecting differences in rates of hepatic drug metabolism. The cytochrome P450 (CYP) system catalyzes the rate-limiting step in the overall metabolism and subsequent elimination of many drugs and is known to be involved in the metabolism of many anticancer drugs including ifosfamide, cyclophosphamide, etoposide, paclitaxel, docetaxel, vinblastine, vincristine, vinorelbine,andtamoxifen. 2,3 Thesearchforfunctionalpolymorphisms in the CYP genes, with the goal of using an
Contentment With Quality of Life Among Breast Cancer Survivors With and Without Contralateral Prophylactic Mastectomy
Authors: Ann M. Geiger, Carmen N. West, Larissa Nekhlyudov, Lisa J. Herrinton, In-Liu A. Liu, Andrea Altschuler, Sharon J. Rolnick, Emily L. Harris, Sarah M. Greene, Joann G. Elmore, Karen M. Emmons, Suzanne W. Fletcher
Journal: Journal of Clinical Oncology (2006)

Purpose To understand psychosocial outcomes after prophylactic removal of the contralateral breast in women with unilateral breast cancer. Methods We mailed surveys to women with contralateral prophylactic mastectomy after breast cancer diagnosis between 1979 and 1999 at six health care delivery systems, and to a smaller random sample of women with breast cancer without the procedure. Measures were modeled on instruments developed to assess contentment with quality of life, body image, sexual satisfaction, breast cancer concern, depression, and health perception. We examined associations between quality of life and the other domains using logistic regression. Results The response rate was 72.6%. Among 519 women who underwent contralateral prophylactic mastectomy, 86.5% were satisfied with their decision; 76.3% reported high contentment with quality of life compared with 75.4% of 61 women who did not undergo the procedure (P = .88). Among all case subjects, less contentment with quality of life was not associated with contralateral prophylactic mastectomy or demographic characteristics, but was associated with poor or fair general health perception (odds ratio [OR], 7.0; 95% CI, 3.4 to 14.1); possible depression (OR, 5.4; 95% CI, 3.1 to 9.2); dissatisfaction with appearance when dressed (OR, 3.5; 95% CI, 2.0 to 6.0); self-consciousness about appearance (OR, 2.0; 95% CI, 1.1 to 3.7); and avoiding thoughts about breast cancer (modest: OR, 2.2; 95% CI, 1.1 to 4.5; highest: OR, 1.7; 95% CI, 0.9 to 3.2). Conclusion Most women undergoing contralateral prophylactic mastectomy report satisfaction with their decision and experience psychosocial outcomes similar to breast cancer survivors without the procedure.
MONEY: A REHABILITATION INCENTIVE FOR MENTAL PATIENTS
Authors: PETER A. PEFFER
Journal: American Journal of Psychiatry (1953)

An attempt has been made to combine a culturally powerful incentive common to mental hospital environment and society with the motivational system of certain hospitalized psychiatric patients to effect a successful rehabilitation. This has taken the form of monetary reward for socially acceptable productive activity, which forms a bridge between hospital adjustment and "outside" adjustment. It allows the individual to set his own ultimate goals and rewards. It initiates and demands group activity for obtaining the reward. It makes the mental patient undertake normal behavior for normal rewards. At Perry Point Veterans Administration Hospital, the theory was translated to the practical application of a member-employee system under which certain psychiatric patients were discharged to work as hospital employees with monetary rewards and certain subsidiary benefits. Of 20 patients only 3 were readmitted to the hospital. Remarkable personal adjustment resulted with improvements in appearance, behavior, and self-esteem. It enabled a financial saving to the government of approximately $69,379.55 per year. It has given current occupational-therapy and manual-arts procedures a higher goal and purpose. It gives the placement officer a recent work history to facilitate his task with industrialists. It permits former mental patients to be hired on the same basis as normal individuals. It is proposed to develop the member-employee system to the point of grading hours and tasks to various levels of patient adjustment. It has proved to be a most effective intermediate extramural rehabilitation process.
Vascular Endothelial Growth Factor-Trap Suppresses Tumorigenicity of Multiple Pancreatic Cancer Cell Lines
Authors: Mitsuharu Fukasawa, Murray Korc
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Vascular endothelial growth factor A (VEGF-A) is a potent angiogenic agent that binds to two high affinity VEGF receptors (VEGFRs), a process facilitated by the low affinity neuropilin receptors. Although VEGF-A is overexpressed in pancreatic ductal adenocarcinoma, it is not known whether the in vivo growth of multiple pancreatic cancer cells can be efficiently blocked by VEGF-A sequestration. Experimental Design: Four human pancreatic cancer cell lines were grown s.c. in athymic nude mice. One cell line also was used to generate an orthotopic model of metastatic pancreatic cancer. The consequences of VEGF-A sequestration on tumor growth and metastasis were examined by injecting the mice with a soluble VEGFR chimer (VEGF-Trap) that binds VEGF-A with high affinity. Results: VEGF-Trap, initiated 2 days after tumor cell inoculation, suppressed the s.c. growth of four pancreatic cancer cell lines and markedly decreased tumor microvessel density. Analysis of RNA from tumors generated with T3M4 cells revealed that VEGF-Trap decreased the expression of VEGFR-1 and neuropilin-1 and -2. VEGF-Trap, initiated 3 weeks after tumor implantation, also attenuated intrapancreatic tumor growth and metastasis in an orthotopic model using PANC-1 cells. Conclusions: VEGF-Trap is a potent suppressor of pancreatic tumor growth and metastasis and also may act to attenuate neuropilin-1 and -2 and VEGFR-1 expression. Therefore, VEGF-Trap may represent an exceedingly useful therapeutic modality for pancreatic ductal adenocarcinoma.
Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
Authors: Olivier Rixe, Ronald M Bukowski, M Dror Michaelson, George Wilding, Gary R Hudes, Oliver Bolte, Robert J Motzer, Paul Bycott, Katherine F Liau, James Freddo, Peter C Trask, Sinil Kim, Brian I Rini
Journal: The Lancet Oncology (2007)
Contribution of Angiotensin II to Late Renal Injury after Acute Ischemia
Authors: MARIA ENRICA PAGTALUNAN, JEAN L. OLSON, TIMOTHY W. MEYER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 ± 0.30 ml/min treated, 2.16 ± 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 ± 9% treated, 42 ± 13% untreated), or limit expansion of the interstitial volume fraction (25 ± 3% treated, 25 ± 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 ± 17 mg/d treated, 229 ± 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 ± 9% treated, 45 ± 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies
Authors: Kristina E.M. Persson, Fiona J. McCallum, Linda Reiling, Nicole A. Lister, Janine Stubbs, Alan F. Cowman, Kevin Marsh, James G. Beeson
Journal: Journal of Clinical Investigation (2008)

Antibodies that inhibit Plasmodium falciparum invasion of erythrocytes are believed to be an important component of immunity against malaria. During blood-stage infection, P. falciparum can use different pathways for erythrocyte invasion by varying the expression and/or utilization of members of 2 invasion ligand families: the erythrocyte-binding antigens (EBAs) and reticulocyte-binding homologs (PfRhs). Invasion pathways can be broadly classified into 2 groups based on the use of sialic acid (SA) on the erythrocyte surface by parasite ligands. We found that inhibitory antibodies are acquired by malaria-exposed Kenyan children and adults against ligands of SA-dependent and SA-independent invasion pathways, and the ability of antibodies to inhibit erythrocyte invasion depended on the pathway used by P. falciparum isolates. Differential inhibition of P. falciparum lines that varied in their use of specific EBA and PfRh proteins pointed to these ligand families as major targets of inhibitory antibodies. Antibodies against recombinant EBA and PfRh proteins were acquired in an age-associated manner, and inhibitory antibodies against EBA175 appeared prominent among some individuals. These findings suggest that variation in invasion phenotype might have evolved as a mechanism that facilitates immune evasion by P. falciparum and that a broad inhibitory response against multiple ligands may be required for effective immunity.
Fulminant Clostridium difficile colitis
Authors: J M Jansen, J F Bartelsman
Journal: Gut (2007)

<i>Neisseria meningitidis</i> inhibits the alternative pathway (AP) of complement using diverse mechanisms, including expression of capsule (select serogroups), Neisserial surface protein A (NspA), factor H (fH) binding protein (fHbp), and lipooligosaccharide (LOS) sialylation. The contribution of the latter three molecules in AP regulation in encapsulated meningococci was studied using isogenic mutants. When LOS was unsialylated, deleting NspA alone from group A strain A2594 (low fHbp/high NspA) significantly increased AP-mediated C3 deposition. C3 deposition further increased ∼2-fold in a ΔfHbpΔNspA double mutant, indicating cooperative fHbp function. LOS sialylation of A2594 ΔfHbpΔNspA decreased the rate of C3 deposition, revealing AP inhibition by LOS sialic acid. Maximal C3 deposition on group B strain H44/76 (high fHbp/low NspA) occurred when all three molecules were absent; again, LOS sialylation attenuated the AP in the absence of both fHbp and NspA. When H44/76 LOS was unsialylated, both fHbp and NspA independently inhibited the AP. LOS sialylation enhanced binding of fH C-terminal domains 18–20 to C3 fragments deposited on bacteria. Interaction of meningococci with nonhuman complement is relevant for animal models and vaccine evaluation studies that use nonhuman complement. Consistent with their human-specific fH binding, neither fHbp nor NspA regulated the rat AP. However, LOS sialylation inhibited the rat AP and, as with human serum, enhanced binding of rat fH to surface-bound C3. These data highlight the cooperative roles of meningococcal NspA and fHbp in regulating the human AP and broaden the molecular basis for LOS sialylation in AP regulation on meningococci in more than one animal species.
History of anxiety disorders is associated with a decreased likelihood of angiographic coronary artery disease in women with chest pain: the WISE study
Authors: Thomas Rutledge, Steven E Reis, Marian Olson, Jane Owens, Sheryl F Kelsey, Carl J Pepine, Nathaniel Reichek, William J Rogers, C.Noel Bairey Merz, George Sopko, Carol E Cornell, Barry Sharaf, Karen A Matthews
Journal: Journal of the American College of Cardiology (2001)