tbuckley/cabot-search huggingface dataset:
Muscular fat as a cardio-metabolic modulator in COPD
Authors: Isabelle Vivodtzev, Luc Montcharmont, Renaud Tamisier, Clémence Minet, Jean-Christian Borel, Patrick Lévy, Gilbert Ferretti, Jean-Louis Pépin
Journal: European Respiratory Journal (2014)

Background: Loss of peripheral skeletal muscle mass and excessive fat accumulation have been associated with cardiometabolic morbidity and mortality in COPD. We aimed at identifying the role of skeletal muscle fat infiltration on cardiometabolic surrogate risk factors in COPD.  Methods: 78 COPD (64 ± 9 years) were prospectively included and assessed using metabolic and inflammatory biological parameters as well as subclinical markers of cardiovascular risk (arterial stiffness and endothelial function). Tertiles of body mass index (BMI) (Low [15lBMI≤23], middle [23lBMI≤28] and high [28lBMI≤36] kg/m2) were used for comparison in mid-thigh quadriceps muscle volume and percent of muscle fat infiltration (MFI=intramuscular fat volume/[intramuscular fat volume+ muscle volume]) measured by CT scan (automatic segmentation :-190 to -30; -30 to +30 and +30 to +70 Hounsfield Units for fat, intramuscular fat and muscle, respectively, in a 4-cm height).  Results: The highest BMI COPD tertile showed higher intramuscular fat volume that corresponded to 52 [43; 60]% of total muscle volume vs. 47 [38; 55]% and 34 [29; 38]% in middle and low BMI groups, respectively, p l0.0001. A high muscle volume was associated with lower NT-pro BNP and fibrinogen and with higher thiols in the whole group of patients reflecting less inflammation and oxidative stress. On the contrary, MFI was negatively associated with antioxidant capacity (thiols/proteins ratio: r = -0.50, p = 0.009) and SaO2 (r = -0.45, p = 0.01) in the high BMI group but also with endothelial function (r = -0.40, p = 0.04) in low BMI COPD.  Conclusion: Not only in obese patients but also in lean COPD patients skeletal muscle fat infiltration may contribute to increase cardiometabolic risk factors.
Alterations in ORMDL expression in experimental esthma
Authors: Michaela Schedel, Anthony Joetham, Michael Kabesch, Erwin Gelfand
Journal: European Respiratory Journal (2012)

INTRODUCTION:  A susceptibility locus on 17q21, including  ORMDL3 , has been identified in childhood asthma. We determined if expression of  ORMDL3  and the other members of the highly conserved  ORMDL  family ( ORMDL1-2 ) are altered in the lungs and tissues of mice with experimental asthma.   METHODS:  Intraperitoneal sensitization of C57BL/6 and Balb/c mice to ovalbumin (OVA) was carried out on days 1 and 14. Sensitized and naive mice received aerosol challenges on days 24-26.  ORMDL1-3  expression levels were analyzed in different tissues (brain, gut, heart, kidney, liver, lung, skeletal muscle, spleen, thymus) and isolated cells (lymph nodes, blood). Kinetic studies of  ORMDL  expression in lung, spleen, and thymus were performed 24h, 48h, and 72h after the last challenge. Gene expression data are described as relative fold-changes.   RESULTS:  ORMDL1-3  expression in all tissues was shown at comparable levels for both mouse strains and mRNA levels were altered only in lung and lymphoid tissues (spleen, thymus) with a peak 48h after the last challenge. In lungs of non-sensitized/challenged (n=11) vs. sensitized/challenged (n=11) C57BL/6 mice, significant decreases were observed for  ORMDL1  (1.0 vs. 0.47, p=2.09E-07),  ORMDL2  (1.0 vs. 0.56, p=1.12E-07), and  ORMDL3  (1.0 vs. 0.50, p=2.72E-05). In parallel, significantly lower levels of  ORMDL2  (1.0 vs. 0.72, p=0.01), and  ORMDL3  (1.0 vs. 0.77, p=3.14E-05) were detected in spleen. In Balb/c mice similar significant effects were detectable, albeit to a lower degree. In contrast,  ORMDL  mRNA expression in the thymus trended upwards in sensitized and challenged mice of both strains.   CONCLUSION:  These data demonstrate the involvement of all members of the  ORMDL  family in experimental asthma.
ENURESIS IN THE NAVY
Authors: Alexander Levine
Journal: American Journal of Psychiatry (2006)

One hundred and fifty cases of enuresis among recruits at the Norfolk Naval Training Station were studied. It was found that enuresis is not a clinical entity in itself but a manifestation of a deep seated personality disturbance. In addition to the enuresis, symptomatology of a neurotic nature was often present, such as somnambulism, nightmares, severe nail-biting and nervousness. The recruit as a rule, attributed his condition to kidney involvement and rarely sought medical attention. The bed-wetter is usually immature, maladjusted, emotionally unstable and insecure. A study of the family background revealed the presence of numerous psychiatric abnormalities among the other siblings and the parents. There was a high incidence of enuresis and home disruption was a common finding. The parents had no insight into their offsprings' manifestations and used crude methods in order to effect a cure. It is felt that the most common etiological factor in the causation of enuresis in the cases studied is the lack ...
Screening for hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children is not possible when employing clinical and static biochemical parameters
Authors: Ekkehard Zöllner, Carl Lombard, Ushma Galal, Stephen Hough, Elvis Irusen, Eugene Weinberg
Journal: European Respiratory Journal (2013)

Background:  It is impractical to test asthmatic children for HPAS with dynamic adrenal function tests.   Objective:  To determine which parameter is the most useful screening test for HPAS.   Methods:  143 asthmatic children were recruited. Height velocity (HV), weight velocity (WV), height standard deviation score (SDS), weight SDS, change in systolic blood pressure from supine to standing were recorded. Early morning urinary free cortisol (UFC), morning serum cortisol (C), adrenocorticotropin hormone (ACTH) and dehydroepiandrosterone sulphate (DHEAS) were collected. UFC was expressed as a ratio of Cr excretion and as a ratio of body surface area. A metyrapone (MTP) test was performed if the 08:00 hr C was >83nmol/l. Spearman correlation coefficients (r) were calculated between the post-MTP ACTH, 11-deoxycortisol (11DOC), 11DOC+C, and each variable. Diagnostic statistics were calculated.   Results:  All screening variables were weakly correlated with the three PMTP outcomes. Only DHEAS and UFC (nmol/m 2 ) were statistically significant – DHEAS for PMTP ACTH and 11DOC (r = 0.20, p 0.025 & r = 0.21, p 0.017); UFC (nmol/m 2 ) for PMTP 11DOC and 11DOC+C (r=0.19, p 0.033 & r = 0.20, p 0.022). The area under ROC curve for DHEAS in the 5-9 year age group was 0.69 (CI: 0.47-0.92). At DHEAS cut-off of 0.2 µmol/l: sensitivity = 0.88, specificity = 0.61, positive predictive value = 0.37, negative predictive value = 0.95, accuracy = 0.67, positive likelihood ratio = 2.26, negative likelihood ratio = 0.20.   Conclusions:  No parameter is useful as a universal screening test.DHEAS may be suitable to exclude HPAS before adrenarche.
What Is the Appropriate Approach to Treating Women With Incurable Cervical Cancer?
Authors: Lois Ramondetta
Journal: Journal of the National Comprehensive Cancer Network (2013)

Women should not die of cervical cancer...but they do. Most cases of cervical cancer are preventable and, if caught early, highly curable. Despite this, cervical cancer is the second most common cause of cancer death in women worldwide. Unfortunately, cure is less likely when the disease is diagnosed at an advanced stage. Treatment of locally advanced disease often has serious lifelong side effects, including cystitis, proctitis, intestinal strictures, fistulas, vaginal agglutination/sexual dysfunction, and chronic pain. Unresectable recurrent disease may be associated with all these symptoms, in addition to disturbing malodorous discharge and bleeding and a life expectancy of less than 6 to 10 months. Supportive/palliative care interventions are needed at diagnosis and recurrence. Honest, conflict-free conversations about potential for response and expectations are needed for women with recurrent disease to help preserve and improve quality of life and avoid treatments that offer no benefit. Aims of trial design should include not only molecular targeting but also supportive care objectives, such as reducing pain, anxiety, depression, cachexia, and fatigue. A β-adrenergic blockade could potentially be part of these intervention trials. This article addresses the following questions and issues: whether therapeutic treatment of incurable cervical cancer is ever appropriate, the common symptoms of recurrent cervical cancer, the quantifying benefits of treatment, decision aids in treatment planning, doctor-patient candor, and integrating psychosocial factors into treatment.
The effect of hypnotics on sleep quality in hypercapnic patients receiving long-term nocturnal noninvasive ventilation
Authors: Tomomasa Tsuboi, Toru Oga, Shuichi Yano, Takefumi Saito, Shohei Takada, Tetsuro Ohdaira, Kensuke Sumi, Kazuo Chin
Journal: European Respiratory Journal (2014)

Background: Hypnotics are usually avoided in patients with chronic hypercapnic respiratory failure. Among hypercapnitic patients receiving long-term nocturnal noninvasive ventilation (NIV), many complain about insomnia. It should be important to evaluate the safety and efficacy of hypnotics in hypercapnic patients receiving long-term NIV.  Methods: Twenty six patients who received long-term NIV were studied prospectively (Multicenter, Randomized, Placebo-Control, Double blinded, Cross-over study; UMI05989). After more than five days9 washout periods, patients received first polysomnography under nocturnal ten hours9 NIV, taking whether zolpidem (5mg) or placebo. After next one week without hypnotics, they received second polysomnography taking an inverse medication. Sleep stage, transcutaneous PCO 2  (PtcCO 2 ), and Leeds Sleep Evaluation Questionnaire (LSEQ) in the morning were measured and analyzed.  Results: 26 patients consist of 12 restrictive thoracic disease, 6 COPD, 8 miscellaneous diseases. Their mean daytime PaCO 2  was 55.1 mmHg. Total sleep time (440 vs 374 min; p=0.0012), stage-2 sleep (205 vs 162 min; p=0.0002), stage-3/4 sleep (72 vs 50 min; p=0.0012) all significantly increased when patients9 taking zolpidem. There was no significant difference between zolpidem and placebo in PtcCO 2  at stage-1, -2, -3/4, REM sleep, and awake, respectively. In LSEQ, getting to sleep was significantly quicker (p=0.04) and quality of sleep tended to be more restful (p=0.06) when patients9 taking zolpidem.  Conclusion: Zolpidem may be safe and improve sleep quality in hypercapnic patients receiving long-term NIV.
Nephrotoxicity of acyclovir and ganciclovir in rats
Authors: M de F Dos Santos, O F Dos Santos, M A Boim, C V Razvickas, L A de Moura, H Ajzen, N Schor
Journal: Journal of the American Society of Nephrology (1997)

Whole-kidney function and glomerular hemodynamics were evaluated after acute (50 mg/kg, iv, in bolus) and short-term chronic (50 mg mg/kg, ip, 5 days) acyclovir (ACV) and short-term chronic ganciclovir (Gan; 30 mg/kg, ip, 5 days) treatment in envolemic Munich-Wistar rats. The evaluation of whole-kidney function of the ACV groups showed a significant reduction in total GFR (0.96 +/- 0.10 to 0.28 +/- 0.02 mL/min in the acute group, P < 0.05, and 1.04 +/- 0.09 to 0.33 +/- 0.04 mL/min in the chronic group, P < 0.05) with a marked increase in total renal vascular resistance (TRVR) (33 +/- 5 to 122 +/- 26 mm Hg.min/mL in the acute group and 28 +/- 3 to 74 +/- 18 mm Hg.min/mL in the chronic group, P < 0.05) and a reduction in RPF (2.29 +/- 0.25 to 0.81 +/- 0.15 mL/min in the acute group and 2.57 +/- 0.36 to 1.30 +/- 0.40 mL/min in the chronic group, P < 0.05). Conversely, urinary flow (V') was unchanged (3.6 +/- 0.4 to 3.6 +/- 0.2 microL/min in the acute group) or elevated (3.7 +/- 0.6 to 6.6 +/- 1.4 microL/min in the chronic group, P < 0.05). The evaluation of glomerular hemodynamics after ACV treatment showed a reduction in single-nephron GFR (SNGFR) (46.4 +/- 5.3 to 26.2 +/- 3.4 nL/min in the acute group and 38.7 +/- 5.7 to 21.1 +/- 5.7 nL/min in the chronic group, P < 0.05), a significant elevation in total arteriolar resistance (RT) (2.90 +/- 0.44 to 4.94 +/- 0.77 x 10(10) dyn.s.cm-5 in the acute group and 3.72 +/- 0.45 to 9.00 +/- 2.40 x 10(10) dyn.s.cm-5 in the chronic group, P < 0.05) and a severe reduction in glomerular plasma flow rate (QA) (152.6 +/- 29.5 to 103.8 +/- 27.8 nL/min in the acute group and 149.1 +/- 29.8 to 68.5 +/- 10.0 nL/min in the chronic group, P < 0.05). However, the glomerular ultrafiltration coefficient, Kf, was changed only in the chronic group (0.1002 +/- 0.0165 to 0.0499 +/- 0.0090 nL/(s.mm Hg), P < 0.05). After Gan treatment, no changes were observed in GFR (1.04 +/- 0.09 to 0.96 +/- 0.08 mL/min, with the maintenance of RPF (2.57 +/- 0.36 to 2.66 +/- 0.34 mL/min) and a nonsignificant reduction in TRVR (28 +/- 3 to 20 +/- 3 mm Hg.min/mL. The short-term Gan treatment also showed a different pattern in glomerular hemodynamics by inducing an elevation in SNGFR (38.7 +/- 5.7 to 50.3 +/- 2.8 nL/min, P < 0.05) with no changes in QA (150 +/- 30 to 135 +/- 22 nL/min) and a mild vasodilation, RT (3.7 +/- 0.5 to 2.7 +/- 0.3 x 10(10) dyn.s.cm-5, P < 0.05) associated with an increment in Kf (0.1002 +/- 0.0165 to 0.2400 +/- 0.0700 nL/(s.mm Hg), P < 0.05). Thus, ACV induced acute renal failure by reducing GFR and SNGFR by an increase in TRVR and RT with a reduction in RPF and QA. Also, after short-term treatment with ACV, a reduction in Kf led to a reduction of SNGFR. On the other hand, Gan treatment did not induce acute renal failure by the adopted techniques.
Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4+ and CD8+ T Cell Activation to Localized Viral Infection
Authors: Jyh Liang Hor, Paul G. Whitney, Ali Zaid, Andrew G. Brooks, William R. Heath, Scott N. Mueller
Journal: Immunity (2015)

Highlights•Activation of T cell subsets after peripheral virus infection is temporally regulated•CD4+ T cells, but not CD8+ T cells, are activated early by migratory DCs•CD8+ T cell activation is delayed until LN-resident XCR1+ DCs can prime•XCR1+ DCs are critical for the delivery of T cell helpSummaryThe dynamics of when and where CD4+ T cells provide help for CD8+ T cell priming and which dendritic cells (DCs) activate CD4+ T cells in vivo after localized infection are poorly understood. By using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node (LN) to concurrently visualize pathogen-specific CD4+ and CD8+ T cells, we found that early priming of CD4+ T cells involved clustering with migratory skin DCs. CD8+ T cells did not interact with migratory DCs and their activation was delayed, requiring later clustering interactions with LN-resident XCR1+ DCs. CD4+ T cells interacted with these late CD8+ T cell clusters on resident XCR1+ DCs. Together, these data reveal asynchronous T cell activation by distinct DC subsets and highlight the key role of XCR1+ DCs as the central platform for cytotoxic T lymphocyte activation and the delivery of CD4+ T cell help.Graphical abstract
Expression of Thy 1 Antigen in Normal and Neoplastic Mammary Cells of Mice 2
Authors: Ronald W. Gillette
Journal: JNCI Journal of the National Cancer Institute (1977)

The expression of Thy 1.2 (theta C3H) antigen was measured on the membranes of normal and neoplastic RIII and C3H mammary cells. Competitive inhibition assays revealed that the average membrane content of Thy 1.2 in mammary tissues was about equal to that of lymph node cells. Higher percentages of Thy 1.2-positive cells than mammary tumor virus (MuMTV)-positive cells were observed by immunofluorescence, which suggested that not all the Thy 1.2-positive cells recovered from tumors were also MuMTV-positive. Established tissue culture cell lines C3H and RIII MT expressed lower levels of Thy 1.2 than did cells from mammary tumors. Treatment with the synthetic gluco-corticoid dexamethasone increased the average Thy 1.2 expression in cultured mammary tumor cells as well as the levels of RNA-directed DNA polymerase. Since the percentages of Thy 1.2-positive cells also were greater in steroid-treated cultures, while fewer cells were needed to absorb a standard amount of anti-Thy 1.2 activity, it was concluded that dexamethasone enhanced membrane Thy 1.2 expression as well as MuMTV production by the cultured cells.
Antilymphoma Activity of &lt;sc&gt;L&lt;/sc&gt;-Asparaginase &lt;italic&gt;In Vivo:&lt;/italic&gt; Clearance Rates of Enzyme Preparations From Guinea Pig Serum and Yeast in Relation to Their Effect on Tumor Growth
Authors: J D Broome
Journal: JNCI Journal of the National Cancer Institute (1965)

Following evidence that L-asparaginase in guinea pig serum possesses antilymphoma properties, purified L-asparaginase was obtained from yeast and tested on the growth of the guinea pig serum-sensitive Lymphoma 6C3HED in C3H mice. No inhibition of the tumor resulted. A probable explanation was found in the extremely rapid rate of clearance of this enzyme in the mouse. Whereas guinea pig serum L-asparaginase persisted in the blood in considerable amount for 3 or more days after intravenous injection, the yeast enzyme was almost completely cleared in less than 1 hour. Ultracentrifugal studies suggested that the yeast L-asparaginase was in the form of molecular aggregates, of a kind likely to be taken up by the reticuloendothelial system with great avidity.
Patients' knowledge and prejudices about chronic obstructive pulmonary disease
Authors: Ljudmila Nagorni-Obradovic, Dragica Pesut
Journal: European Respiratory Journal (2012)

Background:  Proper patients9 (Pts) knowledge on a chronic disease is an important issue in successful disease management.   Aim : To estimate Pts9 knowledge and prejudices about chronic obstructive pulmonary disease (COPD).   Methods : Observational, questionnaire based study included 68 pts (mean age 63 yr, M/F=41/27) treated for COPD at University hospital in Belgrade, Serbia, from June to December 2011. Pts completed the 9-item questionnaire voluntarily and anonymously.   Results : A total of 50 (73.5%) pts underestimate recommended respiratory rehabilitation and have not used it; 28 (41.2%) pts prefer teophyllin compared to the other therapy; 41(60.2%) pts have not get vaccinated against influenza to reduce exacerbation of the disease; 33 (48.5%) pts used more frequently short-acting β 2  agonists instead advised therapy scheme; 29 (42.6%) pts had correct technique of using inhalation therapy; 22 (32.4%) pts overreact in using antibiotics during exacerbation; 53 (77.9%) Pts do not seek help for symptoms of depression in COPD; 20 (29.1%) pts cut down therapy themselves; 36 (52.9%) Pts are active smokers and one third of them do not recognize tobacco smoking as risk factor for pulmonary disease.   Conclusion : COPD Pts9 knowledge about the disease should be improved to achieve their better adherence to treatment, quality of life and more successful disease management.
Formation of immunoglobulin light chain amyloid oligomers in primary cutaneous nodular amyloidosis
Authors: A.L. Clos, C.A. Lasagna-Reeves, D.L. Castillo-Carranza, U. Sengupta, G.R. Jackson, B. Kelly, T.M. Beachkofsky, R. Kayed
Journal: British Journal of Dermatology (2011)

Primary cutaneous nodular amyloidosis (PCNA) is thought to be a plasma cell dyscrasia. The amyloid deposits are found in the dermis and subcutis, and they contain clonal immunoglobulin light chains, produced by a local proliferation of plasma cells. New insights into amyloid diseases have revealed that the pathology is due more to the presence of small, misfolded protein species termed oligomers than to the deposition of fibrillar material.To demonstrate the presence of amyloid oligomers in PCNA and to provide evidence that cutaneous amyloid diseases share a common pathogenic pathway similar to other amyloid diseases.Immunohistochemical staining with conformation-specific and sequence-specific antibodies was used to localize different amyloid species of light chain immunoglobulins in a case of PCNA. Additionally, in vitro characterization of immunoglobulin oligomers and fibrils was performed to determine, through toxicity studies in a human keratinocyte cell line, which amyloidogenic form of the immunoglobulin is toxic in PCNA.Amyloid oligomers were identified in PCNA. Oligomers were mainly formed by lambda light chain immunoglobulins, and kappa light chain oligomers were detected in lesser amounts. Amyloid species were detected intra- and extracellularly. In addition, amyloid oligomers and fibrils, derived from unknown protein sources, were detected. This finding suggests that immunoglobulin amyloids can act as seeds capable of inducing the aggregation of heterogeneous proteins in the skin. Furthermore, cytotoxicity studies demonstrated that immunoglobulin oligomers, but not monomers or fibrils, are toxic to human keratinocytes.These data indicate that PCNA has common pathways with other amyloid diseases with respect to protein misfolding and pathogenesis. Immunoglobulin oligomers may prove to be targets for the treatment of PCNA.
MicroRNAome genome: A treasure for cancer diagnosis and therapy
Authors: Ioana Berindan‐Neagoe, Paloma del C. Monroig, Barbara Pasculli, George A. Calin
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract The interplay between abnormalities in genes coding for proteins and noncoding microRNAs (miRNAs) has been among the most exciting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as miRNAs, produced from what was once considered “genomic trash,” have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development, and differentiation at the transcriptional, posttranscriptional, and/or translational level. In this review article, miRNAs are presented as ubiquitous players involved in all cancer hallmarks. The authors also describe the most used methods to detect their expression, which have revealed the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment response is discussed. Along with this, the authors explore current strategies in designing miRNA‐targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, a new wave in molecular oncology translational research is introduced: the study of long noncoding RNAs. CA Cancer J Clin 2014;64:311–336. © 2014 American Cancer Society.