tbuckley/cabot-search huggingface dataset:
Clinical Dysfunction and Psychosocial Interventions: The Interplay of Research, Methods, and Conceptualization of Challenges
Authors: Alan E. Kazdin
Journal: Annual Review of Clinical Psychology (2015)

I describe the development and course of my research in studying clinical dysfunction among children, adolescents, and adults. This is an autobiographical account that highlights programs of research, career moves, and experiences along the way that were particularly influential. Research on specific topics and the methods to study them were inherently fascinating but invariably led me to broader issues well beyond what I was studying. The research alerted me to how and why current methods, assumptions, and research practices might be constraining and perhaps slightly misguided. My research and specific findings in a given area were not necessarily part of any particular breakthrough but rather helped me see how more, different, and better work was needed. Collaborations with a diverse set of colleagues and models from other disciplines than psychology helped me conceptualize the goals of research on a given topic (e.g., developing evidence-based treatments, reducing the burden of mental illness, promoting a sustainable environment to mitigate climate change) and propose a shift from current practices as a means to obtain them.
Adaptation of canine femoral head articular cartilage to long distance running exercise in young beagles.
Authors: M J Lammi, T P Hakkinen, J J Parkkinen, M M Hyttinen, M Jortikka, H J Helminen, M I Tammi
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVE--To study the effects of long term (one year), long distance (up to 40 km/day) running on the metabolism of articular cartilage the biosynthesis of proteoglycans was examined by in vitro labelling of anterior (weight bearing) and posterior (less weight bearing) areas of the femoral head from young beagles. METHODS--Total sulphate incorporation rates were determined and distribution of the incorporated sulphate was localised by quantitative autoradiography. Concentration and extractability of the proteoglycans were determined, and proteoglycan structures were investigated by gel filtration chromatography, agarose gel electrophoresis, and chemical determinations. RESULTS--In the less weight bearing area the amount of extractable proteoglycans was decreased (p &lt; or = 0.02), simultaneously with an increased concentration of residual glycosaminoglycans in the tissue after 4 M GuCl extraction (p &lt; or = 0.05). In control animals proteoglycan synthesis was most active in the deep zone of the cartilage, whereas exercise increased synthesis in the intermediate zone. There was a tendency to a lower keratan: chondroitin sulphate ratio in the running dogs. No macroscopical or microscopical signs of articular degeneration or injury were visible in any of the animals. CONCLUSION--The articular cartilage of the femoral head showed a great capacity to adapt to the increased mechanical loading. The reduced proteoglycan extractability in the less weight bearing area changed it similar to the weight bearing area, suggesting that the low extractability of proteoglycans reflects the long term loading history of articular cartilage. The congruency of the femoral head with acetabulum seems to protect the cartilage from the untoward alterations that occur in the femoral condyles subjected to a similar running programme.
Identification of novel immunohistochemical tumor markers for primary hepatocellular carcinoma; clathrin heavy chain and formiminotransferase cyclodeaminase
Authors: Masanori Seimiya, Takeshi Tomonaga, Kazuyuki Matsushita, Masahiko Sunaga, Masamichi Oh‐ishi, Yoshio Kodera, Tadakazu Maeda, Shigetsugu Takano, Akira Togawa, Hideyuki Yoshitomi, Masayuki Otsuka, Masakazu Yamamoto, Masayuki Nakano, Masaru Miyazaki, Fumio Nomura
Journal: Hepatology (2008)

Early diagnosis of hepatocellular carcinoma (HCC) greatly improves its prognosis. However, the distinction between benign and malignant tumors is often difficult, and novel immunohistochemical markers are necessary. Using agarose two-dimensional fluorescence difference gel electrophoresis, we analyzed HCC tissues from 10 patients. The fluorescence volumes of 48 spots increased and 79 spots decreased in tumor tissues compared with adjacent nontumor tissue, and 83 proteins were identified by mass spectrometry. Immunoblot confirmed that the expression of clathrin heavy chain (CHC) and Ku86 significantly increased, whereas formiminotransferase cyclodeaminase (FTCD), rhodanese, and vinculin decreased in tumor. The protein expression in tumor and nontumor tissues was further evaluated by immunostaining. Interestingly, CHC and FTCD expression was strikingly different between tumor and nontumor tissues. The sensitivity and specificity of individual markers or a combination for the detection of HCC were 51.8% and 95.6% for CHC, 61.4% and 98.5% for FTCD, and 80.7% and 94.1% for CHC+FTCD, respectively. Strikingly, the sensitivity and specificity increased to 86.7% and 95.6% when glypican-3, another potential biomarker for HCC, was used with FTCD. Moreover, CHC and FTCD were useful to distinguish early HCC from benign tumors such as regenerative nodule or focal nodular hyperplasia, because the sensitivity and specificity of the markers are 41.2% and 77.8% for CHC, 44.4% and 80.0% for FTCD, which is comparable with those of glypican-3 (33.3% and 100%). The sensitivity significantly increased by combination of these markers, 72.2% for CHC+FTCD, and 61.1% for CHC+glypican-3 and FTCD+glypican-3, as 44.4% of glypican-3 negative early HCC were able to be detected by either CHC or FTCD staining. Conclusion: Immunostaining of CHC and FTCD could make substantial contributions to the early diagnosis of HCC. (HEPATOLOGY 2008.)
A Large Cohort Study of Long-Term Daily Use of Adult-Strength Aspirin and Cancer Incidence
Authors: E. J. Jacobs, M. J. Thun, E. B. Bain, C. Rodriguez, S. J. Henley, E. E. Calle
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundEpidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers, including prostate and breast cancers. Recent results from the Women's Health Study randomized trial indicate that long-term use of low-dose aspirin (100 mg every other day) does not substantially reduce cancer risk. However, the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain.
microRNA-10b: A New Marker or the Marker of Pancreatic Ductal Adenocarcinoma?
Authors: Tetsuro Setoyama, Xinna Zhang, Shoji Natsugoe, George A. Calin
Journal: Clinical Cancer Research (2011)

Abstract microRNA-10b (miR-10b) expression in pancreatic ductal adenocarcinoma (PDAC), as identified by in situ hybridization, is highly correlated with cancer diagnosis, therapy response, and prognosis. If these findings are further confirmed in prospective studies, miR-10b could be used to improve the management of PDAC and decrease the mortality rate of this deadly cancer. Clin Cancer Res; 17(17); 5527–9. ©2011 AACR.
Critical Role of Mast Cell Chymase in Mouse Abdominal Aortic Aneurysm Formation
Authors: Jiusong Sun, Jie Zhang, Jes S. Lindholt, Galina K. Sukhova, Jian Liu, Aina He, Magnus Åbrink, Gunnar Pejler, Richard L. Stevens, Robert W. Thompson, Terri L. Ennis, Michael F. Gurish, Peter Libby, Guo-Ping Shi
Journal: Circulation (2009)

Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown.Human AAA lesions had high numbers of chymase-immunoreactive mast cells. Serum chymase level correlated with AAA growth rate (P=0.009) in a prospective clinical study. In experimental AAA produced by aortic elastase perfusion in wild-type (WT) mice or those deficient in the chymase ortholog mouse mast cell protease-4 (mMCP-4) or deficient in mMCP-5 (Mcpt4(-/-), Mcpt5(-/-)), Mcpt4(-/-) but not Mcpt5(-/-) had reduced AAA formation 14 days after elastase perfusion. Even 8 weeks after perfusion, aortic expansion in Mcpt4(-/-) mice fell by 50% compared with that of the WT mice (P=0.0003). AAA lesions in Mcpt4(-/-) mice had fewer inflammatory cells and less apoptosis, angiogenesis, and elastin fragmentation than those of WT mice. Although Kit(W-sh/W-sh) mice had protection from AAA formation, reconstitution with mast cells from WT mice, but not those from Mcpt4(-/-) mice, partially restored the AAA phenotype. Mechanistic studies suggested that mMCP-4 regulates expression and activation of cysteine protease cathepsins, elastin degradation, angiogenesis, and vascular cell apoptosis.High chymase-positive mast cell content in human AAA lesions, greatly reduced AAA formation in Mcpt4(-/-) mice, and significant correlation of serum chymase levels with human AAA expansion rate suggests participation of mast cell chymase in the progression of human and mouse AAA.
Dexrazoxane Prevention of Anthracycline Cardiomyopathy
Authors: Rudolf Steiner, Kurt Hellmann
Journal: Journal of Clinical Oncology (2013)

dexamethasone (61% v 52%) on days 2 and 3.Although true, we are not sure of its relevance when the more detailed measure of average nausea, which was our primary outcome, and peak nausea were each significantly improved by the addition of dexamethasone on days 2 and 3. Rather than using a simple dichotomous measure of yes or no to assess nausea rates, we used average nausea on the basis of 11 assessment points, each on a 7-point scale.The peak nausea variable in our analyses was the highest nausea reported at any of these 11 reporting points.Celio and Aapro 2 raise an important point regarding aprepitant for control of vomiting.In our discussion of vomiting in the online-only Appendix, 1 we noted that although aprepitant was not more effective than prochlorperazine in controlling DN when both were combined with palonosetron and dexamethasone, this lack of a statistically significant difference could be moderated with what might be a clinically relevant benefit for patients receiving aprepitant.That is, patients receiving aprepitant had a nearly statistically significant lower incidence of DV than patients receiving prochlorperazine (8% v 14%), and also had significantly less DN if DV did occur.Concerning the assessment of Celio and Aapro that our "data indicate that prochlorperazine may play a specific role in DN when acute emesis is well controlled," we concur, provided that the word "delayed" is substituted for the word "acute."However, we think a better way to conceptualize our findings is to say that aprepitant may be more helpful than prochlorperazine in approximately 14% of patients, either by providing more effective control of DV or by helping to control nausea when DV does occur.Given that we found no benefit of palonosetron compared with granisetron in any of our analyses and, for 86% of patients, there was no benefit of aprepitant compared with prochlorperazine, we suggest that the widespread use of palonosetron be reconsidered, and a more targeted approach be used for aprepitant.We are also pleased with the positive comments on our article by Ishiguro et al. 4 They raise important issues not addressed in our article 1 concerning the substantially greater costs of the newer antiemetics compared with the older generic ones, and concerning the financial support and design of large antiemetic trials.Their points are well taken.
Transcriptional Repression and Inhibition of Nuclear Translocation of Androgen Receptor by Diallyl Trisulfide in Human Prostate Cancer Cells
Authors: Silvia D. Stan, Shivendra V. Singh
Journal: Clinical Cancer Research (2009)

The present study was undertaken to determine the effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic, on androgen receptor (AR) protein expression and function using prostate cancer cells.The protein levels of AR and prostate-specific antigen (PSA) were determined by immunoblotting. The effect of DATS treatment on AR mRNA level and AR promoter activity was determined by quantitative reverse transcription-PCR and luciferase reporter assay, respectively. Expression of AR protein in poorly differentiated carcinoma and normal prostate of transgenic adenocarcinoma of mouse prostate (TRAMP) mice was determined by immunohistochemistry. Confocal microscopy was done to determine nuclear translocation of AR. Cell viability was determined by trypan blue dye exclusion assay.Exposure of prostate cancer cells (LNCaP, C4-2, and TRAMP-C1) to DATS resulted in a concentration-dependent decrease in protein level of AR, which was accompanied by suppression of intracellular and secreted levels of PSA. Structure-activity studies revealed critical roles for allyl groups and the oligosulfide chain length in DATS-mediated down-modulation of AR protein. Quantitative reverse transcription-PCR showed a dose-dependent decrease in AR mRNA level, which correlated with inhibition of AR promoter activity. DATS treatment inhibited synthetic androgen (R1881)-stimulated nuclear translocation of AR in LNCaP/C4-2 cells and proliferation of LNCaP cells. Oral gavage of 2 mg/day DATS (three times per week for 13 weeks) markedly suppressed AR protein level in poorly differentiated prostate cancer in TRAMP mice.The present study shows, for the first time, that DATS treatment suppresses AR function in prostate cancer cells.
Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with residual disease following cytotoxic therapy
Authors: C.L. Mitchell, J.P.B. O'Connor, A. Jackson, G.J.M. Parker, C. Roberts, Y. Watson, S. Cheung, K. Davies, G.A. Buonaccorsi, A.R. Clamp, J. Hasan, L. Byrd, A. Backen, C. Dive, G.C. Jayson
Journal: Annals of Oncology (2010)
Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses
Authors: K Robinson, R Kenefeck, E L Pidgeon, S Shakib, S Patel, R J Polson, A M Zaitoun, J C Atherton
Journal: Gut (2008)

<h3>Background and aims:</h3> <i>Helicobacter pylori</i> infection is the major cause of peptic ulceration and gastric adenocarcinoma. To address the hypothesis that the human acquired immune response to <i>H pylori</i> influences pathogenesis, we characterised the gastric T helper (Th) and regulatory T cell (Treg) response of infected patients. <h3>Methods:</h3> The human gastric CD4<sup>+</sup> T cell response of 28 donors who were infected with <i>H pylori</i> and 44 who were not infected was analysed using flow cytometry. The T cell associated mucosal cytokine response was analysed by real-time polymerase chain reaction assay of samples from 38 infected and 22 uninfected donors. Recombinant interleukin 10 (IL10) was added to co-cultures of <i>H pylori</i> and AGS cells and its suppressive effects upon inflammatory responses were measured. <h3>Results:</h3> We found that the <i>H pylori</i>-specific response consists of both T helper 1 and 2 subsets with high levels of IL10-secreting Tregs. People with peptic ulcer disease had a 2.4-fold reduced CD4<sup>+</sup>CD25<sup>hi</sup>IL10<sup>+</sup> Treg response (p = 0.05) but increased Th1 and Th2 responses (Th1: 3.2-fold, p = 0.038; Th2: 6.1-fold, p = 0.029) compared to those without ulcers. In vitro studies showed that IL10 inhibited IL8 expression and activation of nuclear factor kappa B induced by <i>H pylori</i> in gastric epithelial cells, and enhanced <i>H pylori</i> growth in a bacterial-cell co-culture model. <h3>Conclusions:</h3> Together our data suggest that <i>H pylori</i> induces a regulatory T cell response, possibly contributing to its peaceful coexistence with the human host, and that ulcers occur when this regulatory response is inadequate.
SOX4 Expression in Bladder Carcinoma: Clinical Aspects and <i>In vitro</i> Functional Characterization
Authors: Mads Aaboe, Karin Birkenkamp-Demtroder, Carsten Wiuf, Flemming Brandt Sørensen, Thomas Thykjaer, Guido Sauter, Klaus Møller-Ernst Jensen, Lars Dyrskjøt, Torben Ørntoft
Journal: Cancer Research (2006)

Abstract The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the SOX4 protein and, thus, did an evaluation of SOX4 protein expression in 2,360 bladder tumors using a tissue microarray with clinical annotation. We found a correlation (P &amp;lt; 0.05) between strong SOX4 expression and increased patient survival. When overexpressed in the bladder cell line HU609, SOX4 strongly impaired cell viability and promoted apoptosis. To characterize downstream target genes and SOX4-induced pathways, we used a time-course global expression study of the overexpressed SOX4. Analysis of the microarray data showed 130 novel SOX4-related genes, some involved in signal transduction (MAP2K5), angiogenesis (NRP2), and cell cycle arrest (PIK3R3) and others with unknown functions (CGI-62). Among the genes regulated by SOX4, 25 contained at least one SOX4-binding motif in the promoter sequence, suggesting a direct binding of SOX4. The gene set identified in vitro was analyzed in the clinical bladder material and a small subset of the genes showed a high correlation to SOX4 expression. The present data suggest a role of SOX4 in the bladder cancer disease. (Cancer Res 2006; 66(7): 3434-42)
EGFR Mutations and Lung Cancer
Authors: Gilda da Cunha Santos, Frances A. Shepherd, Ming Sound Tsao
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Epidermal growth factor receptor (EGFR) is a transmembrane protein with cytoplasmic kinase activity that transduces important growth factor signaling from the extracellular milieu to the cell. Given that more than 60% of non-small cell lung carcinomas (NSCLCs) express EGFR, EGFR has become an important therapeutic target for the treatment of these tumors. Inhibitors that target the kinase domain of EGFR have been developed and are clinically active. More importantly, such tyrosine kinase inhibitors (TKIs) are especially effective in patients whose tumors harbor activating mutations in the tyrosine kinase domain of the EGFR gene. More recent trials have suggested that for advanced NSCLC patients with EGFR mutant tumors, initial therapy with a TKI instead of chemotherapy may be the best choice of treatment. Therefore, mutation testing is mandatory to identify these patients, given that selection based only on clinico-pathologic characteristics is inadequate. We review the role of EGFR mutations in the diagnosis and management of NSCLC.
Surgical Reduction of Tumour Bulk in Management of Abdominal Burkitt's Lymphoma
Authors: I. T. Magrath, S. Lwanga, W. Carswell, N. Harrison
Journal: BMJ (1974)

The results of a retrospective study of the value of reductive surgery in the treatment of abdominal Burkitt9s lymphoma are reported. Nine patients had almost complete removal of the tumour, 16 had little over half of the tumour removed, and 43 underwent biopsy only. All patients subsequently received chemotherapy. There was a highly significant difference in the proportion of patients achieving a sustained durable remission (P &gt; 0·0001) and a significant difference in survival (P &gt; 0·05) between the group having almost complete removal and the partial resection group. Partial resection gave no advantage over no surgery. We believe that whenever possible complete removal of the abdominal tumour should be attempted regardless of the presence of extra-abdominal tumour; but unless at least 90% of the tumour can be removed there is no advantage in partial resection in terms of response to subsequent chemotherapy. In particular the removal of one of two involved ovaries can no longer be recommended. The implications of these results are related to cancer treatment strategy.
Risk Factors Identified in Childhood and Decreased Carotid Artery Elasticity in Adulthood
Authors: Markus Juonala, Mikko J. Järvisalo, Noora Mäki-Torkko, Mika Kähönen, Jorma S.A. Viikari, Olli T. Raitakari
Journal: Circulation (2005)

Background— Exposure to risk factors in childhood may have long-term influences on vascular function. We examined the relationship between risk factors identified in childhood and arterial elasticity assessed in adulthood. Methods and Results— Carotid artery compliance (CAC), Young’s elastic modulus (YEM), and stiffness index (SI), 3 measures of large-artery elasticity, were assessed with noninvasive ultrasound in 2255 healthy white adults aged 24 to 39 years participating in a population-based cohort study and who had risk factor data available since childhood. In multivariate models, childhood obesity (skinfold thickness) predicted decreased CAC ( P &lt;0.001), increased YEM ( P &lt;0.01), and increased SI ( P &lt;0.01) in adulthood. Childhood blood pressure was inversely associated with CAC ( P &lt;0.001) and directly associated with YEM ( P &lt;0.001). The number of risk factors identified in childhood, which included high LDL cholesterol (at or above 80th percentile), elevated blood pressure, skinfold thickness, low HDL cholesterol (at or below 20th percentile), and smoking, was related inversely with CAC ( P &lt;0.001) and directly with YEM ( P &lt;0.001). These associations remained highly significant after adjustment for the number of risk factors identified in adulthood ( P =0.005 for CAC and P &lt;0.001 for YEM). Conclusions— Cardiovascular risk factors identified in childhood and adolescence predict decreased carotid artery elasticity in adulthood. These data suggest that risk factors operating in early life may have sustained deleterious effects on arterial elasticity.
Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins
Authors: Fang Huang, Yasuyuki Kitaura, IhnKyung Jang, Mayumi Naramura, Hemanta H. Kole, Liping Liu, Haiyan Qin, Mark S. Schlissel, Hua Gu
Journal: Immunity (2006)
Effect of a participatory intervention with women's groups on birth outcomes and maternal depression in Jharkhand and Orissa, India: a cluster-randomised controlled trial
Authors: Prasanta Tripathy, Nirmala Nair, Sarah Barnett, Rajendra Mahapatra, Josephine Borghi, Shibanand Rath, Suchitra Rath, Rajkumar Gope, Dipnath Mahto, Rajesh Sinha, Rashmi Lakshminarayana, Vikram Patel, Christina Pagel, Audrey Prost, Anthony Costello
Journal: The Lancet (2010)
40-<i>O</i>-(2-Hydroxyethyl)-rapamycin Attenuates Pulmonary Arterial Hypertension and Neointimal Formation in Rats
Authors: TOSHIHIKO NISHIMURA, JOHN L. FAUL, GERALD J. BERRY, ISIDRE VEVE, RONALD G. PEARL, PETER N. KAO
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Pneumonectomized rats develop pulmonary hypertension (PH) and pulmonary vascular neointimal formation 4 wk after monocrotaline (MCT) administration. Male Sprague-Dawley rats were injected with MCT (60 mg/kg) on Day 7 after left pneumonectomy. Three groups (n = 5) received 40-O-(2-hydroxyethyl)-rapamycin (RAD, 2.5 mg/kg/d, by gavage): Group PMR5–35 from Day 5 to Day 35, Group PMR5–14 from Day 5 to Day 14, and Group PMR15–35 from Day 15 to Day 35. By Day 35, rats that received vehicle had higher mean pulmonary arterial pressures (Ppa = 41 ± 3 mm Hg) (p < 0.001), right ventricular systolic pressures (Prv,s = 45 ± 2 mm Hg) (p < 0.01), and right ventricle/(left ventricle plus septum) (0.55 ± 0.05) (p = 0.028) than rats in Groups PMR5–35 (Ppa = 25 ± 3 mm Hg, Prv,s = 32 ± 7 mm Hg, RV/LV&S = 0.42 ± 0.06) and PMR5–14 (Ppa = 29 ± 4 mm Hg, Prv,s = 30 ± 5 mm Hg, RV/LV&S = 0.43 ± 0.07). Pulmonary arterial neointimal formation (quantified by a vascular occlusion score) was more severe in vehicle-treated rats (1.93 ± 0.03) than in Groups PMR5–14 (1.56 ± 0.27) and PMR5–35 (1.57 ± 0.1) (p < 0.01). RAD attenuates the development of MCT-induced pulmonary arterial hypertension in the pneumonectomized rat.