tbuckley/cabot-search huggingface dataset:
Sparing effect of hemiplegia on tophaceous gout.
Authors: J J Glynn, M L Clayton
Journal: Annals of the Rheumatic Diseases (1976)

Sparing effect of hemiplegia on tophaceous gout.The sparing effect of hemiplegia on the development of tophaceous gout is described.The useless upper limb had no tophaceous deposits and the partially paralysed lower limb had only limited urate deposits.Disuse was presumably the major contributor to the limited deposition of urates on the paralysed side.
PTPH1 Dephosphorylates and Cooperates with p38γ MAPK to Increase Ras Oncogenesis through PDZ-Mediated Interaction
Authors: Song-Wang Hou, Hui-Ying Zhi, Nicole Pohl, Mathew Loesch, Xiao-Mei Qi, Rong-Shan Li, Zainab Basir, Guan Chen
Journal: Cancer Research (2010)

Protein phosphatases are believed to coordinate with kinases to execute biological functions, but examples of such integrated activities, however, are still missing. In this report, we have identified protein tyrosine phosphatase H1 (PTPH1) as a specific phosphatase for p38gamma mitogen-activated protein kinase (MAPK) and shown their cooperative oncogenic activity through direct binding. p38gamma, a Ras effector known to act independent of its phosphorylation, was first shown to require its unique PDZ-binding motif to increase Ras transformation. Yeast two-hybrid screening and in vitro and in vivo analyses further identified PTPH1 as a specific p38gamma phosphatase through PDZ-mediated binding. Additional experiments showed that PTPH1 itself plays a role in Ras-dependent malignant growth in vitro and/or in mice by a mechanism depending on its p38gamma-binding activity. Moreover, Ras increases both p38gamma and PTPH1 protein expression and there is a coupling of increased p38gamma and PTPH1 protein expression in primary colon cancer tissues. These results reveal a coordinative oncogenic activity of a MAPK with its specific phosphatase and suggest that PDZ-mediated p38gamma/PTPH1 complex may be a novel target for Ras-dependent malignancies.
3-Phosphoinositide-Dependent Protein Kinase-1/Akt Signaling Represents a Major Cyclooxygenase-2-Independent Target for Celecoxib in Prostate Cancer Cells
Authors: Samuel K. Kulp, Ya-Ting Yang, Chin-Chun Hung, Kuen-Feng Chen, Ju-Ping Lai, Ping-Hui Tseng, Joseph W. Fowble, Patrick J. Ward, Ching-Shih Chen
Journal: Cancer Research (2004)

Abstract Regarding the involvement of cyclooxygenase-2 (COX-2)-independent pathways in celecoxib-mediated antineoplastic effects, the following two issues remain outstanding: identity of the non-COX-2 targets and relative contributions of COX-2-dependent versus -independent mechanisms. We use a close celecoxib analog deficient in COX-2-inhibitory activity, DMC {4-[5-(2,5-dimethylphenyl)-3(trifluoromethyl)-1H-pyrazol-1-yl]benzene-sulfonamide}, to examine the premise that Akt signaling represents a major non-COX-2 target. Celecoxib and DMC block Akt activation in PC-3 cells through the inhibition of phosphoinositide-dependent kinase-1 (PDK-1) with IC50 of 48 and 38 μm, respectively. The consequent effect on Akt activation is more pronounced (IC50 values of 28 and 20 μm, respectively), which might be attributed to the concomitant dephosphorylation by protein phosphatase 2A. In serum-supplemented medium, celecoxib and DMC cause G1 arrest, and at higher concentrations, they induce apoptosis with relative potency comparable with that in blocking Akt activation. Moreover, the effect of daily oral celecoxib and DMC at 100 and 200 mg/kg on established PC-3 xenograft tumors is assessed. Celecoxib at both doses and DMC at 100 mg/kg had marginal impacts. However, a correlation exists between the in vitro potency of DMC and its ability at 200 mg/kg to inhibit xenograft tumor growth through the inhibition of Akt activation. Analysis of the tumor samples indicates that a differential reduction in the phospho-Akt/Akt ratio was noted in celecoxib- and DMC-treated groups vis-à-vis the control group. Together, these data underscore the role of 3-phosphoinositide-dependent protein kinase-1/Akt signaling in celecoxib-mediated in vitro antiproliferative effects in prostate cancer cells.
Osteoarthritis at the base of the thumb
Authors: R. E. Anakwe, S. D. Middleton
Journal: BMJ (2011)

#### Summary points

Patients with osteoarthritis of the thumb carpometacarpal joint, or base of the thumb, commonly present to primary care practitioners and orthopaedic surgeons because of pain and disability. The prevalence of this condition increases with age and is greatest in postmenopausal women. There is broad agreement regarding the prevalence of base of the thumb osteoarthritis. The largest longitudinal cohort study found a 15% prevalence in adults in Finland,1 and a smaller British study of postmenopausal women found a prevalence of 33%.2 This is likely to increase as populations age and people stay active for longer. Presentation and diagnosis may be delayed because patients try to adapt by adjusting their hand position, using splints, and adopting preferential hand use to limit disability. For most patients the primary treatment is non-operative and can be delivered effectively by primary care doctors, physiotherapists, and occupational therapists. Patients with symptoms that persist despite conservative treatment require referral to a specialist and possibly surgery.3

Various studies have looked at osteoarthritis at the base of the thumb, including large epidemiological and patient cohort studies; biomechanical research; and smaller …
Plasma clearance of intravenously injected aspartate aminotransferase isozymes: Evidence for preferential uptake by sinusoidal liver cells
Authors: Yukio Kamimoto, Seikoh Horiuchi, Sumio Tanase, Yoshimasa Morino
Journal: Hepatology (1985)

Both cytosolic (c–AAT) and mitochondrial (m–AAT) isozymes of aspartate aminotransferase (EC 2.6.1.1) appear in serum in some diseases including hepatobiliary dysfunction. The present study aimed at elucidation of the mechanism by which AAT isozymes are cleared from blood. Intravenous injection into rats of m–AAT and c–AAT purified from rat liver exhibited a biphasic clearance curve with an overall half–life of 42 min and 4.7 hr, respectively. The tissue distribution of the radioactivity following intravenous administration of 125 I–labeled isozymes revealed that the liver is a major organ involved in plasma clearance of these isozymes. This conclusion was also supported by the significant retardation in plasma clearance of m–AAT in hepatectomized as well as CCI 4 –intoxicated rats. Furthermore, clearance rate of each AAT isozyme in an isolated perfused liver exhibited a single exponential process with the uptake rate for m–AAT being much faster than that for c–AAT. Separation of hepatocytes and sinusoidal liver cells from the rat intravenously injected with 125 I–labeled AAT isozymes revealed that sinusoidal cells were responsible for the plasma clearances. In vitro uptake study showed that both isozymes were exclusively taken up by sinusoidal liver cells. The uptake rate for m–AAT was considerably greater than that for c–AAT. Endocytotic index for uptake by sinusoidal cells was 16 times with c–AAT and 34 times with m–AAT as compared with that for inulin or dextran which are taken up by fluid–phase endocytosis, suggesting involvement of adsorptive endocytosis in the uptake of the isozymes.
Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice
Authors: Kathryn Rogers, Kevin M Felsenstein, Lori Hrdlicka, Zhiming Tu, Faris Albayya, Winnie Lee, Sarah Hopp, Mary-Jo Miller, Darcie Spaulding, Zhiyong Yang, Hilliary Hodgdon, Scott Nolan, Melody Wen, Don Costa, Jean-Francois Blain, Emily Freeman, Bart De Strooper, Veerle Vulsteke, Louise Scrocchi, Henrik Zetterberg, Erik Portelius, Birgit Hutter-Paier, Daniel Havas, Michael Ahlijanian, Dorothy Flood, Liza Leventhal, Gideon Shapiro, Holger Patzke, Richard Chesworth, Gerhard Koenig
Journal: Molecular Neurodegeneration (2012)

A hallmark of Alzheimer's disease is the presence of senile plaques in human brain primarily containing the amyloid peptides Aβ42 and Aβ40. Many drug discovery efforts have focused on decreasing the production of Aβ42 through γ-secretase inhibition. However, identification of γ-secretase inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these side effects has been modulation of γ-secretase to shift Aβ production to favor shorter, less amyloidogenic peptides than Aβ42, without affecting the overall cleavage efficiency of the enzyme. This approach, frequently called γ-secretase modulation, appears more promising and has lead to the development of new therapeutic candidates for disease modification in Alzheimer's disease.Here we describe EVP-0015962, a novel small molecule γ-secretase modulator. EVP-0015962 decreased Aβ42 in H4 cells (IC50 = 67 nM) and increased the shorter Aβ38 by 1.7 fold at the IC50 for lowering of Aβ42. AβTotal, as well as other carboxyl-terminal fragments of amyloid precursor protein, were not changed. EVP-0015962 did not cause the accumulation of other γ-secretase substrates, such as the Notch and ephrin A4 receptors, whereas a γ-secretase inhibitor reduced processing of both. A single oral dose of EVP-0015962 (30 mg/kg) decreased Aβ42 and did not alter AβTotal peptide levels in a dose-dependent manner in Tg2576 mouse brain at an age when overt Aβ deposition was not present. In Tg2576 mice, chronic treatment with EVP-0015962 (20 or 60 mg/kg/day in a food formulation) reduced Aβ aggregates, amyloid plaques, inflammatory markers, and cognitive deficits.EVP-0015962 is orally bioavailable, detected in brain, and a potent, selective γ-secretase modulator in vitro and in vivo. Chronic treatment with EVP-0015962 was well tolerated in mice and lowered the production of Aβ42, attenuated memory deficits, and reduced Aβ plaque formation and inflammation in Tg2576 transgenic animals. In summary, these data suggest that γ-secretase modulation with EVP-0015962 represents a viable therapeutic alternative for disease modification in Alzheimer's disease.
THE HUMAN VISUAL CORTEX
Authors: Kalanit Grill-Spector, Rafael Malach
Journal: Annual Review of Neuroscience (2004)

The discovery and analysis of cortical visual areas is a major accomplishment of visual neuroscience. In the past decade the use of noninvasive functional imaging, particularly functional magnetic resonance imaging (fMRI), has dramatically increased our detailed knowledge of the functional organization of the human visual cortex and its relation to visual perception. The fMRI method offers a major advantage over other techniques applied in neuroscience by providing a large-scale neuroanatomical perspective that stems from its ability to image the entire brain essentially at once. This bird's eye view has the potential to reveal large-scale principles within the very complex plethora of visual areas. Thus, it could arrange the entire constellation of human visual areas in a unified functional organizational framework. Here we review recent findings and methods employed to uncover the functional properties of the human visual cortex focusing on two themes: functional specialization and hierarchical processing.
FRI0078 The effect of socioeconomic class and immigrant status on disease activity in rheumatoid arthritis. data from barfot, a multicenter study of early ra.
Authors: M. K. Söderlin, S. Bergman, M. L. Andersson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There are no studies reporting the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. <h3>Objectives</h3> We wanted to study the effect of immigration and socioeconomic class on outcome in RA in Sweden. <h3>Methods</h3> Between 1992 and 2005, 2,800 adult patients were included in the BARFOT early RA study in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), drug treatment and European League Against Rheumatism (EULAR) response criteria were applied up to 8 years. The patients completed in 2010 a questionnaire enquiring about demographics and lifestyle factors <h3>Results</h3> A total of 139/1430 (9.5%) of the patients were immigrants. Immigrants had higher baseline mean HAQ (immigrants 1.2 vs. non-immigrants 0.97, p=0.001), DAS28 (5.6 vs. 5.2, p=0.0001), visual analog scale (VAS) pain (56 mm vs. 45 mm, p=0.0001), VAS global health (53 mm vs. 44 mm, p=0.0001) and tender joint count (TJC) (10 vs. 8, p=0.0001), these differences persisting up to 2 years of follow-up and for HAQ up to 8 years of follow-up. Immigrant status did not have effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have impact on treatment or outcome. <h3>Conclusions</h3> Immigrants scored worse in pain, function and TJC up to 2 years of follow-up, but did not differ in objective measures of inflammation or EULAR outcome as compared to non-immigrants. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class did not have impact on treatment or outcome and this could be due to the relatively egalitarian society in Sweden. <h3>Disclosure of Interest</h3> M. Söderlin Consultant for: Pfizer, Speakers bureau: Abbott, MSD, BMS, Pfizer, S. Bergman: None Declared, M. Andersson: None Declared
Criminal Offending in Schizophrenia Over a 25-Year Period Marked by Deinstitutionalization and Increasing Prevalence of Comorbid Substance Use Disorders
Authors: Cameron Wallace, Paul E Mullen, Philip Burgess
Journal: American Journal of Psychiatry (2004)

This study examined the pattern of criminal convictions in persons with schizophrenia over a 25-year period marked by both radical deinstitutionalization and increasing rates of substance abuse problems among persons with schizophrenia in the community.The criminal records of 2,861 patients (1,689 of whom were male) who had a first admission for schizophrenia in the Australian state of Victoria in 1975, 1980, 1985, 1990, and 1995 were compared for the period from 1975 to 2000 with those of an equal number of community comparison subjects matched for age, gender, and neighborhood of residence.Relative to the comparison subjects, the patients with schizophrenia accumulated a greater total number of criminal convictions (8,791 versus 1,119) and were significantly more likely to have been convicted of a criminal offense (21.6% versus 7.8%) and of an offense involving violence (8.2% versus 1.8%). The proportion of patients who had a conviction increased from 14.8% of the 1975 cohort to 25.0% of the 1995 cohort, but a proportionately similar increase from 5.1% to 9.6% occurred among the comparison subjects. Rates of known substance abuse problems among the schizophrenia patients increased from 8.3% in 1975 to 26.1% in 1995. Significantly higher rates of criminal conviction were found for patients with substances abuse problems than for those without substance abuse problems (68.1% versus 11.7%).A significant association was demonstrated between having schizophrenia and a higher rate of criminal convictions, particularly for violent offenses. However, the rate of increase in the frequency of convictions over the 25-year study period was similar among schizophrenia patients and comparison subjects, despite a change from predominantly institutional to community care and a dramatic escalation in the frequency of substance abuse problems among persons with schizophrenia. The results do not support theories that attempt to explain the mediation of offending behaviors in schizophrenia by single factors, such as substance abuse, active symptoms, or characteristics of systems of care, but suggest that offending reflects a range of factors that are operative before, during, and after periods of active illness.
Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype
Authors: Edward K Lobenhofer, J Todd Auman, Pamela E Blackshear, Gary A Boorman, Pierre R Bushel, Michael L Cunningham, Jennifer M Fostel, Kevin Gerrish, Alexandra N Heinloth, Richard D Irwin, David E Malarkey, B Alex Merrick, Stella O Sieber, Charles J Tucker, Sandra M Ward, Ralph E Wilson, Patrick Hurban, Raymond W Tennant, Richard S Paules
Journal: Genome biology (2008)

This report details the standardized experimental design and the different data streams that were collected (histopathology, clinical chemistry, hematology and gene expression from the target tissue (liver) and a bio-available tissue (blood)) after treatment with eight known hepatotoxicants (at multiple time points and doses with multiple biological replicates). The results of the study demonstrate the classification of histopathological differences, likely reflecting differences in mechanisms of cell-specific toxicity, using either liver tissue or blood transcriptomic data.
Transurethral Resection of Muscle-Invasive Bladder Cancer: 10-Year Outcome
Authors: Harry W. Herr
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the 10-year outcome of patients with muscle-invasive bladder cancer treated by transurethral resection (TUR) alone. PATIENTS AND METHODS: Of 432 newly evaluated patients with muscle-invasive bladder cancer, 151 were treated by standard radical cystectomy or by definitive TUR, if restaging TUR of the primary tumor site showed no (T0) or only non–muscle-invasive (T1) residual tumor. Patients were followed-up every 3 to 6 months thereafter for a minimum of 10 years and up to 20 years. Primary end points of the study were disease-specific survival, survival with a bladder, frequency of recurrent invasive tumors in the bladder, and survival after salvage cystectomy. RESULTS: The 10-year disease-specific survival was 76% of 99 patients who received TUR as definitive therapy (57% with bladder preserved) compared with 71% of 52 patients who had immediate cystectomy (P = .3). Of the 99 patients treated with TUR, 82% of 73 who had T0 on restaging TUR survived versus 57% of the 26 patients who had residual T1 tumor on restaging TUR (P = .003). Thirty-four patients (34%) relapsed in the bladder with a new muscle-invasive tumor, 18 (53%) were successfully treated with salvage therapy via cystectomy, and 16 patients (16%) died of disease. CONCLUSION: Radical TUR for muscle-invasive bladder cancer is a successful bladder-sparing therapeutic strategy in selected patients who have no residual tumor on a repeat vigorous resection of the primary tumor site.
Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27
Authors: Harry D. Bear, Stewart Anderson, Roy E. Smith, Charles E. Geyer, Eleftherios P. Mamounas, Bernard Fisher, Ann M. Brown, Andre Robidoux, Richard Margolese, Morton S. Kahlenberg, Soonmyung Paik, Atilla Soran, D. Lawrence Wickerham, Norman Wolmark
Journal: Journal of Clinical Oncology (2006)

This study was designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS).Women with operable breast cancer (N = 2,411) were randomly assigned to receive preoperative AC followed by surgery, AC followed by T and surgery, or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9 months.Addition of T to AC did not significantly impact DFS or OS. There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events (P = .0034). Preoperative T, but not postoperative T, significantly improved DFS in patients who had a clinical partial response after AC (hazard ratio [HR] = 0.71; 95% CI, 0.55 to 0.91; P = .007). Pathologic complete response, which was doubled by addition of preoperative T, was a significant predictor of OS regardless of treatment (HR = 0.33; 95% CI, 0.23 to 0.47; P < .0001). Pathologic nodal status after chemotherapy was a significant predictor of OS (P < .0001).The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS, slightly improved DFS, and decreased the incidence of local recurrences. The sample size of this study was not sufficient to yield significance for the moderate DFS improvement. Concurrent use of tamoxifen may have limited the impact of adding T.
Microscopic (collagenous and lymphocytic) colitis triggered by food allergy
Authors: M Weidenhiller
Journal: Gut (2005)

<h3>Abstract</h3> Systematic analysis of calorie restriction (CR) mechanisms and pathways in cancer biology has not been carried out, leaving therapeutic benefits unclear. Using a systems biology approach and metadata analysis, we studied gene expression changes in the response of normal mouse duodenum mucosa (DM) to short-term (2-weeks) 25% CR as a biological model. We found a high similarity of gene expression profiles in human and mouse DM tissues. Surprisingly, 26% of the 467 CR responding differential expressed genes (DEGs) in mice consist of cancer-associated genes—most never studied in CR contexts. The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways (MRP) that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest a misbalance in telomere maintenance and activation of metabolic pathways playing dual (anti-cancer and pro-oncogenic) roles. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor immune evasion controls. Thus, CR induces MRP suppressing multiple immune mechanics and activating oncogenic pathways, potentially driving pre-malignant and cancer states. These findings change the paradigm regarding the anti-cancer role of CR and may initiate specific treatment target development.
Renal Failure After Open Heart Surgery
Authors: J. GANESH BHAT
Journal: Annals of Internal Medicine (1976)

One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis.