tbuckley/cabot-search huggingface dataset:
Expression of a Novel PDGF Isoform, PDGF-C, in Normal and Diseased Rat Kidney
Authors: Frank Eitner, Tammo Ostendorf, Claudia Van Roeyen, Masashi Kitahara, Xuri Li, Karin Aase, Hermann-Josef Gro[Combining Diaeresis]ne, Ulf Eriksson, Ju[Combining Diaeresis]rgen Floege
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Platelet-derived growth factor-C (PDGF-C) is a new member of the PDGF family. Its expression in normal and diseased kidney is unknown. Rabbit antisera were generated against human full-length, core domain, and mouse PDGF-C, and their specificity was confirmed by Western blot analyses. Renal PDGF-C expression was analyzed by immunohistochemistry in normal rats (n = 8), mesangioproliferative anti-Thy 1.1 nephritis (n = 4 each at days 1, 4, 6, and 85), passive Heymann nephritis (PHN, n = 4), puromycin nephrosis (PAN, n = 2), Milan normotensive rats (MN, n = 2), and obese Zucker rats (n = 3). PDGF-C expression was also studied in anti-Thy 1.1 rats treated with PDGF-B aptamer antagonists (n = 5) or irrelevant control aptamers (n = 5). PDGF-C was constitutively expressed in arterial smooth muscle cells and collecting duct epithelial cells. Mesangial PDGF-C was markedly upregulated in anti-Thy 1.1 nephritis in parallel with the peak mesangial cell proliferation. Furthermore, PDGF-CC acted as a potent growth factor for mesangial cells in vitro. Inhibition of PDGF-B via specific aptamers reduced the injury in anti-Thy 1.1 nephritis but did not affect the glomerular PDGF-C overexpression or the mitogenicity of PDGF-CC in vitro. In PHN, PAN, and obese Zucker rats, glomeruli remained negative for PDGF-C despite severe glomerular injury. PDGF-C localized to podocytes at sites of focal and segmental sclerosis in MN. Interstitial PDGF-C expression was increased at sites of fibrosing injury in obese Zucker rats. The use of the different antisera resulted in virtually identical findings. It is concluded that PDGF-C is a novel mesangial cell mitogen that is constitutively expressed in the kidney and specifically upregulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells. PDGF-C may therefore be involved in the pathogenesis of renal scarring.
Tbx3 Represses E-Cadherin Expression and Enhances Melanoma Invasiveness
Authors: Mercedes Rodriguez, Ewa Aladowicz, Luisa Lanfrancone, Colin R. Goding
Journal: Cancer Research (2008)

Abstract The T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21CIP1 expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels. [Cancer Res 2008;68(19):7872–81]
Frequency of Hyperprolinemia in Alcoholic Liver Cirrhosis: Relationship to Blood Lactate
Authors: Spencer Shaw, Theresa M. Worner, Charles S. Lieber
Journal: Hepatology (1984)

In alcohol-induced liver injury, hyperprolinemia has been proposed as a marker of fibrogenesis probably secondary to hyperlactacidemia. However, some studies of plasma proline in alcoholics with cirrhosis have reported normal rather than increased levels. In order to evaluate the frequency of hyperprolinemia in alcoholic liver disease and its relationship to blood lactate, we measured plasma proline levels in 145 subjects including 91 alcoholics with a spectrum of liver disease as well as 22 nonalcoholics with liver injury unrelated to alcohol. We also studied baboons fed alcohol as 50% of total calories for 1 to 4 years. Among alcoholics only 21/91 had elevated proline values. Elevations were most frequent among patients with severe hepatic decompensation (3/8), in patients with alcoholic hepatitis on liver biopsy (5/17), and in those with acute alcohol-related withdrawal, with alcohol still present in the blood (4/9). Patients with liver disease unrelated to alcohol but severe in nature also has elevations in proline (3/3). Only 4/28 patients with cirrhosis due to alcohol had elevated values, and none of the baboons fed alcohol had hyperprolinemia whether withdrawn from alcohol or not. Hyperlactacidemia was associated with hyperprolinemia, but so were depressed serum albumin values and prolongations of the prothrombin time, suggesting a general association with severe liver disease. These results reveal that hyperprolinemia occurs infrequently in patients with alcohol-induced cirrhosis and therefore does not appear to be a sensitive marker of hepatic fibrosis in these patients.
Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach.
Authors: P D Oldham
Journal: Thorax (1979)

Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach Sir,-Drs Sobol and Sobol (editorial, February 1979) effectively demolish the logic of using 80% of pre- dicted as the lower limit of normality in pulmonary function tests.(Perhaps I have led a sheltered life, but
Role of the SIKVAV Site of Laminin in Promotion of Angiogenesis and Tumor Growth: An In Vivo Matrigel Model
Authors: M. C. Kibbey, D. S. Grant, H. K. Kleinman
Journal: JNCI Journal of the National Cancer Institute (1992)

Angiogenesis (vascularization) has a critical role in tumor growth and metastasis, and peptides containing the SIKVAV amino acid sequence (Ser-Ile-Lys-Val-Ala-Val) have been shown to stimulate many angiogenic activities in vitro. The use of model systems to identify agents that stimulate or inhibit angiogenesis may lead to the development of new antitumor strategies.Our purpose was to use an in vivo murine model system to study the angiogenic activity of a synthetic peptide derived from the laminin A protein chain and containing the SIKVAV amino acid sequence. We also examined the ability of the peptide to enhance tumor growth in vivo.The SIKVAV-containing peptide was mixed with Matrigel, a reconstituted basement membrane extract used to assay stimulation of angiogenesis. The mixture was subcutaneously injected into C57BL/6 mice. At various times after injection, the Matrigel plug was excised, and angiogenic activity was assessed by histologic examination and immunohistochemical staining with an antibody to the von Willebrand factor (vWF), an endothelium-specific antigen. In other experiments, the mixture of peptide and Matrigel was co-injected with B16F10 murine melanoma cells into C57BL/6 mice, and the resultant tumors were assessed for size and vascularization.When co-injected with Matrigel at doses as low as 10 micrograms, the SIKVAV-containing peptide stimulated angiogenesis fourfold greater than that seen in controls, and maximum angiogenic activity was observed 2 weeks after injection. This peptide was angiogenic in a dose-dependent manner up to a 100-micrograms dose. When co-injected with Matrigel and B16F10 melanoma cells, the peptide enhanced tumor growth by approximately 2.5-fold, and tumor vascularization was significantly increased (P = .027) over that observed after injection with melanoma cells and Matrigel alone.These data demonstrate that the laminin-derived SIKVAV-containing peptide is angiogenic in a new in vivo model system and can enhance tumor vascularization and growth.
TCT-899 Risk of Respiratory Failure After Minimally Invasive Transapical Aortic Valve Implantation
Authors: Martin Haensig, David Holzhey, Michael Borger, Sven Lehmann, Axel Linke, Joerg Seeburger, Gerhard Schuler, Friedrich Mohr
Journal: Journal of the American College of Cardiology (2012)
P3 Are inflammatory cytokine levels altered by treatment of pulmonary arterial hypertension?
Authors: G. Hagan, M. Southwood, C. Treacy, K. Sheares, N. Morrell, J. Pepke-Zaba
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Markers of immune activation and inflammation are raised in pulmonary arterial hypertension; the degree of elevation of levels of pro-inflammatory cytokines in idiopathic pulmonary arterial hypertension has recently been shown to predict long term survival (Soon <i>et al</i>, Circulation, 2010). Much less is known of the role of cytokines in disease monitoring. We assessed levels of serum cytokines in patients at initial assessment prior to commencement of targeted therapy for pulmonary hypertension, and when the patient returned to the hospital for follow-up. We also examined if changes in serum cytokines correlated with changes in 6-min walk test (6MWT). <h3>Methods</h3> 19 patients with a diagnosis of Group I PAH or Group IV chronic thromboembolic pulmonary hypertension in a distribution inaccessible to surgery were included. Patients with inflammatory conditions other than an associated connective tissue disease or a musculoskeletal condition that would interfere with the 6MWT were excluded. 11 healthy volunteers acted as a control group. Serum levels of interleukin (IL) 1ß, 2, 4, 6, 8, 10, 12p70 and tumour necrosis factor α (TNFα) were measured using a multiplex analyser. A Wilcoxon matched pairs test was used to compare differences between baseline and follow-up samples. <h3>Results</h3> Patient and control demographics are presented in the Abstract P3 table 1. Levels of IL 2,6,8,10 and TNFα were elevated in the patient group compared to controls. Average time to repeat patient sampling was 4.7±1.8 months. There were no significant differences between the levels of any cytokines between baseline and follow-up in the patients and no overall correlation existed between change in 6MWT and change in any cytokine. When patients who had improved their 6MWT on follow-up were analysed as a separate group, there was a significant (p=0.0068) drop in IL6 levels on follow-up. <h3>Conclusions</h3> Several cytokines were elevated in these patients with pulmonary hypertension. The role of cytokines in disease monitoring requires further study and there seems to be little relation with serum cytokines, except IL6, and a change in a patient9s clinical state as measured by 6MWT. Replication of results from this pilot study and examination of longitudinal trends in cytokine levels are warranted.
Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFα inhibitors and rituximab
Authors: Joachim Listing, Jörn Kekow, Bernhard Manger, Gerd-Rüdiger Burmester, Dagmar Pattloch, Angela Zink, Anja Strangfeld
Journal: Annals of the Rheumatic Diseases (2013)

To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival.Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking.During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28 > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97).Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.
Changes in Altitude Cause Unintended Insulin Delivery From Insulin Pumps
Authors: Bruce R. King, Peter W. Goss, Megan A. Paterson, Patricia A. Crock, Donald G. Anderson
Journal: Diabetes Care (2011)

Children and adults with type 1 diabetes who receive insulin pump therapy have reported hypoglycemia during air travel. We studied the effects of atmospheric pressure on insulin pump delivery.Ten insulin pumps were connected to capillary tubes. The effects of changes in ambient pressure on insulin delivery, bubble formation, bubble size, and cartridge plunger movement were analyzed.During a flight (200 mmHg pressure decrease), excess insulin delivery of 0.623% of the cartridge volume occurred (P < 0.001, Student t test). In hypobaric chamber studies, bubbles developed in the insulin when the pressure decreased and displaced the insulin out of the cartridge. Pre-existing bubbles changed in size consistent with Boyle law. Cartridge plunger movement did not occur in normal flight conditions but did occur when catastrophic plane depressurization was mimicked.Atmospheric pressure reduction causes predictable, unintended insulin delivery in pumps by bubble formation and expansion of existing bubbles.
Adjuvant Treatment of High-Risk, Radically Resected Gastric Cancer Patients With 5-Fluorouracil, Leucovorin, Cisplatin, and Epidoxorubicin in a Randomized Controlled Trial
Authors: S. Cascinu, R. Labianca, C. Barone, A. Santoro, C. Carnaghi, A. Cassano, G. D. Beretta, V. Catalano, O. Bertetto, S. Barni, L. Frontini, E. Aitini, S. Rota, V. Torri, I. Floriani
Journal: JNCI Journal of the National Cancer Institute (2007)

Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients. From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m 2 ), LV (250 mg/m 2 ), epidoxorubicin (35 mg/m 2 ), 5-FU (500 mg/m 2 ), and glutathione (1.5 g/m 2 ) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m 2 daily) and LV (20 mg/m 2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan–Meier estimates. All statistical tests were two-sided. The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm. Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.
Moving in Three-Dimensional Space: Frames of Reference, Vectors, and Coordinate Systems
Authors: J F Soechting, M Flanders
Journal: Annual Review of Neuroscience (1992)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Is Adult ADHD a Childhood-Onset Neurodevelopmental Disorder? Evidence From a Four-Decade Longitudinal Cohort Study
Authors: Terrie E. Moffitt, Renate Houts, Philip Asherson, Daniel W. Belsky, David L. Corcoran, Maggie Hammerle, HonaLee Harrington, Sean Hogan, Madeline H. Meier, Guilherme V. Polanczyk, Richie Poulton, Sandhya Ramrakha, Karen Sugden, Benjamin Williams, Luis Augusto Rohde, Avshalom Caspi
Journal: American Journal of Psychiatry (2015)

Objective: Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective longitudinal study has described the childhoods of the adult ADHD population. The authors report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort. Method: Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, genome-wide association study-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological test results, and administrative records. Adult ADHD diagnoses used DSM-5 criteria, apart from onset age and cross-setting corroboration, which were study outcome measures. Results: As expected, childhood ADHD had a prevalence of 6% (predominantly male) and was associated with childhood comorbid disorders, neurocognitive deficits, polygenic risk, and residual adult life impairment. Also as expected, adult ADHD had a prevalence of 3% (gender balanced) and was associated with adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood ADHD and adult ADHD groups comprised virtually nonoverlapping sets; 90% of adult ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD. Conclusions: The findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder’s place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD.
Late-breaking abstract: Short-term, conditional TGFá expression produces airway smooth muscle thickening and hyperresponsiveness in mice deficient in early growth response one
Authors: Kimberley Wang, Timothy Le Cras, Alexander Larcombe, Graeme Zosky, Alan James, Peter Noble
Journal: European Respiratory Journal (2014)

Introduction: Expression of transforming growth factor alpha (TGFa) and its receptor, epidermal growth factor receptor, is increased in the airways of asthmatic patients. Mouse models show that prolonged TGFa expression promotes chronic lung disease particularly in early growth response-1 (Egr-1) deficient mice.

Aim: To examine the role of short-term TGFa expression in airway disease including airway smooth muscle (ASM) thickening and airway responsiveness to methacholine (MCh).

Method: TGFa was conditionally expressed in the airway epithelium of transgenic mice (Clara cell secretory protein-rtTA(+/-)/\[tetO\](7)-TGFa(+/-)) following 1W or 10d exposure to doxycycline in chow (Dox). Egr-1 deficient mice on Dox were compared with a control group that were wild type for Egr-1 and did not receive Dox. Airway and lung mechanics were assessed by the forced oscillation technique and lungs fixed for subsequent airway morphometry.

Results: Mice exposed to Dox for 10d (n=8) produced thickening of the ASM layer compared with control (n=13) and an increase in airway responsiveness to MCh. Airway resistance was positively correlated to ASM layer thickness before (r=0.55, n=14) and after MCh (r=0.58, n=13). Shorter periods of Dox exposure (1W, n=7) had no effect on ASM layer thickness or airway responsiveness. Dox had no effect on tissue damping and lung elastance before or after MCh.

Conclusion: Dox induced-TGFa expression in Egr-1 deficient mice, after 10d, produces thickening of the ASM layer, increased airway responsiveness, without a change in baseline lung mechanics. TGFa signalling may contribute to airway disease independent of inflammation.
VIRAL LOAD AND CD4+ CELL COUNT AS RISK FACTORS FOR PROLONGED QTC INTERVAL IN HIV-INFECTED SUBJECTS: A COHORT-NESTED CASE-CONTROL STUDY IN AN OUTPATIENT POPULATION
Authors: Ashraf Y. QaQa, Hamid S. Shaaban, Vincent A. DeBari, Susan Phung, Jihad Slim, George Perez, Fayez Shamoon
Journal: Journal of the American College of Cardiology (2010)
Survivor’s Tale
Authors: Gretel Young Hickman
Journal: JAMA (2005)

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