tbuckley/cabot-search huggingface dataset:
Does Social Support Buffer Functional Decline in Elderly Patients With Unipolar Depression?
Authors: Judith C. Hays, David C. Steffens, Elizabeth P. Flint, Hayden B. Bosworth, Linda K. George
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study tested whether social support protects against functional decline, either generally or selectively, in the most severely depressed elderly patients undergoing treatment for major depressive disorder. METHOD: In a prospective cohort study design, 113 patients with incident and prevalent unipolar depression were followed for 12 months while they were undergoing naturalistic treatment. Outcome measures included performance on basic and instrumental activities of daily living; predictor variables included Hamilton Depression Rating Scale scores and four domains of informal social support. The analysis employed multivariable ordinary least squares regression models. RESULTS: Improved scores on instrumental activities of daily living and stable scores on basic activities of daily living characterized the subjects. In adjusted analyses, instrumental social support provided marginal protection against worsening performance on instrumental activities of daily living, which were primarily a function of baseline depression severity. Large social networks, more frequent social interaction, and the perceived adequacy of social support played a modest buffering role against declines in performance on basic activities of daily living among the most depressed elderly patients. CONCLUSIONS: Instrumental support was generally protective against worsening performance on instrumental abilities of daily living among elderly patients with recurrent unipolar depression. Subjective and structural dimensions of social support protected the most severely depressed elderly patients against the loss of basic maintenance abilities.
THE LIFE-CYCLE OF THE ORGANISM OF SYPHILIS
Authors: J. E. R. McDONAGH
Journal: British Journal of Dermatology (1912)

Journal Article THE LIFE‐CYCLE OF THE ORGANISM OF SYPHILIS Get access J. E. R. McDONAGH, F.R.C.S. J. E. R. McDONAGH, F.R.C.S. Surgeon, Out‐patients', London Lock HospitalsChief Assistant, Skin‐Department, St. Bartholomew's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 24, Issue 11, 1 November 1912, Pages 381–391, https://doi.org/10.1111/j.1365-2133.1912.tb16705.x Published: 01 November 1912
Comparative genomics using Fugu reveals insights into regulatory subfunctionalization
Authors: Adam Woolfe, Greg Elgar
Journal: Genome biology (2007)

A major mechanism for the preservation of gene duplicates in the genome is thought to be mediated via loss or modification of cis-regulatory subfunctions between paralogs following duplication (a process known as regulatory subfunctionalization). Despite a number of gene expression studies that support this mechanism, no comprehensive analysis of regulatory subfunctionalization has been undertaken at the level of the distal cis-regulatory modules involved. We have exploited fish-mammal genomic alignments to identify and compare more than 800 conserved non-coding elements (CNEs) that associate with genes that have undergone fish-specific duplication and retention. Using the abundance of duplicated genes within the Fugu genome, we selected seven pairs of teleost-specific paralogs involved in early vertebrate development, each containing clusters of CNEs in their vicinity. CNEs present around each Fugu duplicated gene were identified using multiple alignments of orthologous regions between single-copy mammalian orthologs (representing the ancestral locus) and each fish duplicated region in turn. Comparative analysis reveals a pattern of element retention and loss between paralogs indicative of subfunctionalization, the extent of which differs between duplicate pairs. In addition to complete loss of specific regulatory elements, a number of CNEs have been retained in both regions but may be responsible for more subtle levels of subfunctionalization through sequence divergence. Comparative analysis of conserved elements between duplicated genes provides a powerful approach for studying regulatory subfunctionalization at the level of the regulatory elements involved.
Raised monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebrospinal fluid of patients with neuropsychiatric lupus
Authors: N Iikuni
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> An imbalance in cytokine homoeostasis is thought to have a key role in the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE), and recently, a role for chemokines has been noted. <b>Objective:</b> To compare concentrations of monocyte chemotactic protein-1 (MCP-1)/CCL2 in cerebral spinal fluid (CSF) of patients with SLE, and with and without neuropsychiatric symptoms. <b>Methods:</b> CSF was obtained from 185 patients with SLE: 96 with NPSLE and 89 patients with SLE without neuropsychiatric symptoms (non-NPSLE patients). MCP-1/CCL2 concentrations were measured with an ELISA. <b>Results:</b> The average concentration of CSF MCP-1/CCL2 in patients with NPSLE was 1959 pg/ml, and in non-NPSLE patients 712 pg/ml. The average MCP-1/CCL2 concentration was significantly higher in the NPSLE group than in the non-NPSLE group (p&lt;0.001). In one representative patient with NPSLE, MCP-1/CCL2 levels in the CSF decreased in parallel with a decline in neuropsychiatric symptoms. <b>Conclusions:</b> CSF MCP-1/CCL2 levels are higher in patients with NPSLE than in non-NPSLE patients. MCP-1/CCL2 may have an important role in the expression of NPSLE. These results indicate that CSF MCP-1/CCL2 reflects an inflammatory activity in the brain, suggesting that it might be used as a diagnostic tool and a monitor for therapeutic responses in patients with NPSLE.
Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Authors: Massimo Di Maio, Paolo Chiodini, Vassilis Georgoulias, Dora Hatzidaki, Koji Takeda, Floris M. Wachters, Vittorio Gebbia, Egbert F. Smit, Alessandro Morabito, Ciro Gallo, Francesco Perrone, Cesare Gridelli
Journal: Journal of Clinical Oncology (2009)

Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non-small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival.We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial.Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034).Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.
Follicular molluscum contagiosum
Authors: F.A. IVE
Journal: British Journal of Dermatology (1985)

Four cases are reported in which atypical molluscum contagiosum lesions were found, arising from follicular epithelium. All the patients were adults and two had a history of atopic dermatitis. Histology showed intradermal nodules containing typical molluscum cells but lacking normal direct communication to the skin surface. This is the first description of true follicular involvement in molluscum contagiosum.
Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome
Authors: Jason S. Groshong, Melissa J. Spencer, Bula J. Bhattacharyya, Elena Kudryashova, Bhupinder P.S. Vohra, Roberto Zayas, Robert L. Wollmann, Richard J. Miller, Christopher M. Gomez
Journal: Journal of Clinical Investigation (2007)

The slow-channel myasthenic syndrome (SCS) is a hereditary disorder of the acetylcholine receptor (AChR) of the neuromuscular junction (NMJ) that leads to prolonged AChR channel opening, Ca(2+) overload, and degeneration of the NMJ. We used an SCS transgenic mouse model to investigate the role of the calcium-activated protease calpain in the pathogenesis of synaptic dysfunction in SCS. Cleavage of a fluorogenic calpain substrate was increased at the NMJ of dissociated muscle fibers. Inhibition of calpain using a calpastatin (CS) transgene improved strength and neuromuscular transmission. CS caused a 2-fold increase in the frequency of miniature endplate currents (MEPCs) and an increase in NMJ size, but MEPC amplitudes remained reduced. Persistent degeneration of the NMJ was associated with localized activation of the non-calpain protease caspase-3. This study suggests that calpain may act presynaptically to impair NMJ function in SCS but further reveals a role for other cysteine proteases whose inhibition may be of additional therapeutic benefit in SCS and other excitotoxic disorders.
The cytochrome P-450 inhibitor cobalt chloride prevents inhibition of renal Na,K-ATPase and redistribution of apical NHE-3 during acute hypertension.
Authors: Y B Zhang, C E Magyar, N H Holstein-Rathlou, A A McDonough
Journal: Journal of the American Society of Nephrology (1998)

Acute systolic arterial hypertension provokes a rapid decrease in proximal tubule sodium reabsorption and diuresis associated with inhibition of renal cortex Na,K-ATPase activity and redistribution of apical membrane Na/H exchanger (NHE-3) to heavier density membranes containing markers of intermicrovillar cleft and endosomes. Because cytochrome P-450-dependent arachidonate metabolites participate in the regulation of renal sodium transport and BP, this study tested the hypothesis that these renal responses to acute hypertension would be prevented if cytochrome P-450 metabolism were inhibited by cobalt chloride (CoCl2). Four groups of rats (n = 4 to 5) were studied: (1) sham-operated; (2) 50 mg of CoCl2/kg subcutaneously for 2 d; (3) acute hypertension by constricting arteries for 5 min; and (4) acute hypertension after CoCl2 treatment as in group 3. Renal cortex was analyzed after sorbitol density gradient fractionation. CoCl2 treatment alone did not significantly affect the rate of urine output, endogenous lithium clearance (an inverse measure of proximal tubule sodium reabsorption), maximal activity of Na,K-ATPase, or subcellular distribution of NHE-3-containing membranes. In non-CoCl2-treated animals, acute hypertension provoked a three- to fourfold increase in urine output and endogenous lithium clearance, 33% inhibition of renal cortex Na,K-ATPase activity, and redistribution of NHE-3 out of the apical membrane peak. In CoCl2-treated animals, acute urine output and endogenous lithium clearance increased only twofold during acute hypertension, there was no inhibition of Na,K-ATPase activity, and there was no redistribution of NHE-3 immunoreactivity to higher density membranes. These findings demonstrate that CoCl2 treatment both attenuates the inhibition of proximal tubule sodium reabsorption and diuresis and abolishes Na,K-ATPase inhibition and NHE-3 redistribution during acute hypertension, evidence that these responses may be mediated by cytochrome P-450 arachidonate metabolites.
Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data
Authors: J. Toppari, M. Kaleva, H.E. Virtanen
Journal: Human Reproduction Update (2001)

Cryptorchidism and hypospadias share possible risk factors, such as intrauterine growth retardation. According to the data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS), apparently increasing trends in the incidence of hypospadias were found in Sweden during the 1960s, and in Norway, Denmark, England and Hungary during the 1970s. In Norway and Denmark, the increase continued in the 1980s, while in the USA it has continued from the 1970s to the 1990s. Finland has shown a lower reported rate of hypospadias than other Nordic countries. However, it is difficult to make comparisons between countries because of variable inclusion criteria. Furthermore, the reliability of the data depends on correct ascertainment and reporting of the cases. The ICBDMS has also collected data on cryptorchidism, but these appear to be unreliable because of a discrepancy with the data from cohort studies. According to two comparable English studies, the incidence of cryptorchidism in full-term boys approximately doubled between the 1950s and the 1980s. Regionally there are large differences: e.g. in Finland the incidence of cryptorchidism is clearly lower than in Denmark. Regional and temporal trends may help to identify environmental factors that might be associated with these disorders.
The European Union standards for tuberculosis care: do they need an update?
Authors: Marieke J. van der Werf, Andreas Sandgren, Lia D'Ambrosio, Francesco Blasi, Giovanni Battista Migliori
Journal: European Respiratory Journal (2014)

Differences between ESTC and new ISTC discussed to inform clinicians and public health officers on best TB management http://ow.ly/tgbztThe International Standards for Tuberculosis Care (ISTC), published for the first time in 2006 [1], introduced a new way of looking at clinical and public health guidelines for tuberculosis (TB).The European Respiratory Journal published an editorial explaining the ISTC, promoting the rapid uptake of the standards [2].While guidelines represent a long, comprehensive document containing all the details the physician might need for managing TB, the standards are a simple set of 21 principles that guide day-to-day clinical decisions [3,4].In other words, guidelines are usually available in a physician's library while the standards are kept on their desk in the office.The ISTC prescribe a widely accepted level of TB care which guides all healthcare providers and clinicians, both public and private, in achieving optimal standards in managing patients who have, or are suspected of having, active TB [1][2][3][4].The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed a European Union (EU) adaptation of the ISTC document, known as the European Union Standards for Tuberculosis Care (ESTC) [4].These standards are tailored to the specific context of the EU/European Economic Area (EEA) as follows [4,5].1) Although the majority of EU/EEA member states have a low incidence of TB, it is a heterogeneous setting with some countries having a high or intermediate level of TB, with varying levels of multidrug-resistant (MDR)-TB and TB-HIV co-infection, and some countries bordering non-EU countries with a higher TB and MDR-TB burden.2) TB services are fully integrated and merged within the health system in the majority of EU/EEA member states.This presents peculiarities in allocating responsibilities for the delivery of TB care.3) The EU/EEA member states have a long established tradition of TB control that has evolved over the past decades.Implementation of new tools and high standards of diagnosis and care is aimed for in the EU/EEA member states.
Suppression of leukemia expressing wild-type or ITD-mutant FLT3 receptor by a fully human anti-FLT3 neutralizing antibody
Authors: Yiwen Li, Hongli Li, Mei-Nai Wang, Dan Lu, Rajiv Bassi, Yan Wu, Haifan Zhang, Paul Balderes, Dale L. Ludwig, Bronislaw Pytowski, Paul Kussie, Obdulio Piloto, Donald Small, Peter Bohlen, Larry Witte, Zhenping Zhu, Daniel J. Hicklin
Journal: Blood (2004)
Transpulmonary artery distance in patients with coal workers' pneumoconiosis
Authors: R. L. Sadler
Journal: Thorax (1972)

Correlation has been established between the size of the main pulmonary arteries, as seen on the postero-anterior radiograph, and the pulmonary artery pressure. In this study the distance between the bifurcations of the right and left pulmonary arteries, referred to as the transpulmonary artery distance (TPD), has been used as a measure of the size of these vessels. In 293 patients with simple pneumoconiosis TPD was significantly correlated with height but not with stem-height, age, weight or forced expiratory volume. The mean TPD of patients with simple pneumoconiosis with or without chronic bronchitis was similar. Among 367 patients with complicated pneumoconiosis those with early fibrosis (A shadows) had a mean TPD similar to that found in simple pneumoconiosis, but those patients with extensive fibrosis (B or C shadows) had significantly greater values. The pathological changes of pulmonary hypertension in complicated pneumoconiosis are reflected in these measurements.
Ceramide induces interleukin 6 gene expression in human fibroblasts.
Authors: S J Laulederkind, A Bielawska, R Raghow, Y A Hannun, L R Ballou
Journal: The Journal of Experimental Medicine (1995)

We previously reported that ceramide, the immediate product of sphingomyelin hydrolysis, increases in response to interleukin (IL)-1 beta and plays a role in modulating IL-1 beta-mediated prostaglandin E2 production and cyclooxygenase gene expression in human fibroblasts (Ballou, L. R., C. P. Chao, M. A. Holness, S. C. Barker, and R. Raghow. 1992. J. Biol. Chem. 267:20044-20050). Here we describe the effects of ceramide in another IL-1 beta-mediated process in these cells, the induction of IL-6 production. We found that submicromolar concentrations of C2-ceramide induced IL-6 gene expression and protein production as effectively as IL-1 beta. Both D-erythro-C2-ceramide (a cell-permeable analogue of natural ceramide) and D-threo-C2-ceramide were potent inducers of IL-6 production, while neither L isomer of ceramide was effective. Compared with IL-1 beta-induced IL-6 production, cells treated with ceramide or exogenous sphingomyelinase induced 82 and 50% of maximal IL-1 beta-induced IL-6 levels by 6 h, respectively; by 24 h all three treatments induced similar levels of IL-6 production. Ceramide-induced IL-6 messenger RNA could be detected within 1 h of treatment and reached maximal levels by 24 h. These findings suggest that ceramide may play a role in the regulation of IL-6 gene expression.
High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome–positive chronic phase chronic myeloid leukemia
Authors: Hagop Kantarjian, Moshe Talpaz, Susan O'Brien, Guillermo Garcia-Manero, Srdan Verstovsek, Francis Giles, Mary Beth Rios, Jianqin Shan, Laurie Letvak, Deborah Thomas, Stefan Faderl, Alessandra Ferrajoli, Jorge Cortes
Journal: Blood (2003)
Reversibility of Lung Collapse and Hypoxemia in Early Acute Respiratory Distress Syndrome
Authors: João B. Borges, Valdelis N. Okamoto, Gustavo F. J. Matos, Maria P. R. Caramez, Paula R. Arantes, Fabio Barros, Ciro E. Souza, Josué A. Victorino, Robert M. Kacmarek, Carmen S. V. Barbas, Carlos R. R. Carvalho, Marcelo B. P. Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: The hypothesis that lung collapse is detrimental during the acute respiratory distress syndrome is still debatable. One of the difficulties is the lack of an efficient maneuver to minimize it.Objectives: To test if a bedside recruitment strategy, capable of reversing hypoxemia and collapse in > 95% of lung units, is clinically applicable in early acute respiratory distress syndrome.Methods: Prospective assessment of a stepwise maximum-recruitment strategy using multislice computed tomography and continuous blood-gas hemodynamic monitoring.Measurements and Main Results: Twenty-six patients received sequential increments in inspiratory airway pressures, in 5 cm H2O steps, until the detection of PaO2 + PaCO2 ⩾ 400 mm Hg. Whenever this primary target was not met, despite inspiratory pressures reaching 60 cm H2O, the maneuver was considered incomplete. If there was hemodynamic deterioration or barotrauma, the maneuver was to be interrupted. Late assessment of recruitment efficacy was performed by computed tomography (9 patients) or by online continuous monitoring in the intensive care unit (15 patients) up to 6 h. It was possible to open the lung and to keep the lung open in the majority (24/26) of patients, at the expense of transient hemodynamic effects and hypercapnia but without major clinical consequences. No barotrauma directly associated with the maneuver was detected. There was a strong and inverse relationship between arterial oxygenation and percentage of collapsed lung mass (R = − 0.91; p < 0.0001).Conclusions: It is often possible to reverse hypoxemia and fully recruit the lung in early acute respiratory distress syndrome. Due to transient side effects, the required maneuver still awaits further evaluation before routine clinical application.
Efficient Blockade of Akt signaling is a determinant factor to overcome resistance to Matuzumab
Authors: Debora D Meira, Vitor H Almeida, Jânio S Mororó, Mauricio S Caetano, Isabel P Nóbrega, Delano Batista, Cinthya Sternberg, Carlos G Ferreira
Journal: Molecular Cancer (2011)

Abstract Background Clinical studies have shown antineoplastic effectiveness of monoclonal antibodies (MAbs) against EGFR for different indications. Several MAbs directed to EGFR were developed recently, such as matuzumab, but there is still lack of information on preclinical data on its combination with chemo-radiation. Thus, the present study intended to examine the molecular pathways triggered by matuzumab alone or associated to chemo-radiotherapy in gynecological cell lines and its impact on cell growth and signaling. Results Combination of matuzumab with radiation and cisplatin did not enhance its cytostatic effects on A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in clonogenic assays, when compared to controls. The lack of effect was mediated by persistent signaling through EGFR due to its impaired degradation. In spite of the fact that matuzumab inhibited phosphorylation of EGFR, it had no effect upon cell viability. To analyze which downstream molecules would be involved in the EGFR signaling in the presence of matuzumab, we have tested it in combination with either PD98059 (MAPK inhibitor), or LY294002 (PI3K inhibitor). Matuzumab exhibited a synergic effect with LY294002, leading to a reduction of Akt phosphorylation that was followed by a decrease in A431 and Caski cells survival. The combination of PD98059 and matuzumab did not show the same effect suggesting that PI3K is an important effector of EGFR signaling in matuzumab-treated cells. Nonetheless, matuzumab induced ADCC in Caski cells, but not in the C33A cell line, suggesting that its potential therapeutic effects in vitro are indeed dependent on EGFR expression. Conclusions Matuzumab combined with chemoradiation did not induce cytotoxic effects on gynecological cancer cell lines in vitro, most likely due to impaired EGFR degradation. However, a combination of matuzumab and PI3K inhibitor synergistically inhibited pAkt and cell survival, suggesting that the use of PI3K/Akt inhibitors could overcome intrinsic resistance to matuzumab in vitro. Altogether, data presented here can pave the way to a rational design of clinical strategies in patients with resistant profile to anti-EGFR inhibitors based on combination therapy.