tbuckley/cabot-search huggingface dataset:
Reduced leucocyte zinc in liver disease.
Authors: P W Keeling, R B Jones, P J Hilton, R P Thompson
Journal: Gut (1980)

The zinc content of peripheral blood leucocytes has been measured in normal controls and in three groups of patients with liver disease. A significant reduction in leucocyte zinc, but not erythrocyte zinc, was observed in patients with primary biliary cirrhosis, alcoholic cirrhosis, and active chronic hepatitis. It is suggested that the nucleated tissues of some patients with liver disease are therefore zinc deficient, and that leucocyte zinc may prove of value in the assessment of the zinc status of such patients.
Effects of dietary-induced hyperparathyroidism on the parathyroid hormone-receptor-adenylate cyclase system of canine kidney. Evidence for postreceptor mechanism of desensitization.
Authors: J Tamayo, E Bellorin-Font, K J Martin
Journal: Journal of Clinical Investigation (1983)

The present studies were designed to examine the consequences of chronic mild elevations of endogenous parathyroid hormone (PTH) in vivo on the PTH receptor-adenylate cyclase system of canine kidney cortex. Hyperparathyroidism was induced in normal dogs by feeding a diet low in calcium, high in phosphorus to the animals for a period of 6-9 wk. This maneuver resulted in a two to threefold increase in the plasma levels of carboxy-terminal immunoreactive PTH. This degree of hyperparathyroidism is similar to that seen in patients with hyperparathyroidism and normal renal function. After 6-9 wk on the diet the animals were killed and basolateral renal cortical membranes prepared for the study of the PTH receptor-adenylate cyclase system in vitro. The dietary hyperparathyroidism resulted in desensitization of the PTH-responsive adenylate cyclase (Vmax 3,648 +/- 654 pmol cyclic (c)AMP/mg protein per 30 min in hyperparathyroid animals vs. 5,303 +/- 348 in normal controls). The Kact (concentration of PTH required for half-maximal enzyme activation) was unchanged. However, PTH receptor binding (125I-norleucyl8-norleucyl18-tyrosinyl34, 125I[Nle8, Nle18, Tyr34] bPTH (1-34) NH2 as radioligand) was not different in the two groups of animals. Thus, dietary hyperparathyroidism resulted in an uncoupling of the PTH receptor-adenylate cyclase system. This defect was not corrected by guanyl nucleotides in vitro, and the effects of guanyl nucleotides on PTH binding and enzyme activation appeared normal. NaF-stimulated enzyme activity was reduced in the hyperparathyroid animals (8,285 +/- 607 pmol cAMP/mg protein per 30 min vs. 10,851 +/- 247 in controls). These data indicate that desensitization of the PTH-responsive adenylate cyclase system of canine kidney as a result of mild chronic elevations of endogenous PTH is due to a postreceptor defect, demonstrable by NaF activation, not corrected by guanyl nucleotides, leading to abnormal PTH-receptor adenylate cyclase coupling.
Inspiratory Muscle Weakness in Chronic Heart Failure: Role of Nutrition and Electrolyte Status and Systemic Myopathy
Authors: Colm McParland, Elizabeth F. Resch, Bharath Krishnan, Yimei Wang, Bibiana Cujec, Charles G. Gallagher
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Inspiratory muscle weakness has been demonstrated in ambulatory, stable chronic heart failure (CHF) and may contribute to dyspnea during daily living. However, the mechanisms underlying this weakness are unknown. Malnutrition and electrolyte depletion are recognized complications of CHF that may impair skeletal muscle function, and limb muscle weakness and myopathic changes have also been demonstrated in CHF. We examined whether nutrition and electrolyte status contribute to the reduced skeletal muscle strength and whether inspiratory muscle weakness in CHF is part of general skeletal muscle weakness. We measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength, maximum hand-grip strength as an index of limb muscle strength, anthropometric indices, serum albumin, and total lymphocyte count as indices of nutritional status, and serum electrolytes in 15 stable patients with chronic cardiac pump failure who had no evidence of primary lung disease, and in 15 age-and-sex-matched healthy controls. As compared with the matched controls, the CHF patients had reduced inspiratory muscle strength (p < 0.0025), but their expiratory and limb muscle strength were not significantly reduced. CHF patients were not malnourished; they were heavier than matched controls because of increased body fat (p < 0.05). Serum sodium was significantly lower in the CHF patients than in the controls (p < 0.01), but was within the normal range in both groups. Inspiratory muscle strength in the CHF patients was not correlated with nutrition, electrolyte status, or limb muscle strength. These findings indicate that patients with stable CHF have inspiratory muscle weakness that is not due to readily measurable nutritional or electrolyte abnormalities, and which occurs without limb or expiratory muscle weakness, suggesting that the inspiratory muscle weakness is not simply due to generalized skeletal muscle weakness.
Oxidation increases mucin polymer cross-links to stiffen airway mucus gels
Authors: Shaopeng Yuan, Martin Hollinger, Marrah E. Lachowicz-Scroggins, Sheena C. Kerr, Eleanor M. Dunican, Brian M. Daniel, Sudakshina Ghosh, Serpel C. Erzurum, Belinda Willard, Stanley L. Hazen, Xiaozhu Huang, Stephen D. Carrington, Stefan Oscarson, John V. Fahy
Journal: Science Translational Medicine (2015)

A thiol-modified carbohydrate compound treats pathologic mucus gel formation in inflamed airways.
Prognostic Value of Bone Sialoprotein Expression in Clinically Localized Human Prostate Cancer
Authors: D. Waltregny, A. Bellahcene, V. Castronovo, W. Dewe, J. de Leval, I. Van Riet, L. W. Fisher, M. Young, P. Fernandez
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk. Methods: Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. Results: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% C1 = 2.3%–20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P:lt; .05) among patients with moderately differentiated tumors or with pathologically confined tumors. Conclusions: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas. [J Nall Cancer Inst 1998;90:1000–8]
L-arginine administration prevents glomerular hyperfiltration and decreases proteinuria in diabetic rats.
Authors: A A Reyes, I E Karl, J Kissane, S Klahr
Journal: Journal of the American Society of Nephrology (1993)

The effect(s) of L-arginine administration on the renal function of rats with untreated diabetes mellitus was examined. Rats received streptozotocin (N = 11) or vehicle (N = 12): Group 1 (normal rats, N = 6) drank tap water; Group 2 (normal rats, N = 6) drank tap water containing 1% L-arginine; Group 3 (diabetic rats, N = 5) drank tap water; and Group 4 (diabetic rats, N = 6) drank tap water with 1% L-arginine. Rats were fed a standard rat chow diet (22.8% protein, 142% L-arginine) with free access to food and water for 14 wk. Diabetic rats gained less weight, had significantly lower plasma levels of albumin and L-arginine, and had greater values for 24-h urine volumes and urine excretion of glucose, protein, urea, creatinine, nitrate, and nitrite than control rats. Diabetic rats given L-arginine (Group 4) had significantly lower protein and cGMP excretion in the urine than did rats of Group 3. The administration of L-arginine did not affect the plasma levels of glucose or L-arginine in Groups 2 or 4 compared with those of their respective controls. Group 3 had significantly higher values for GFR than did the other three groups of rats, but values for effective RPF, mean arterial pressure, hematocrit, and renal vascular resistance were not significantly different between Groups 3 and 4. There was no significant difference in glomerular morphology among the four groups of rats as determined by light microscopy, and both groups of diabetic rats exhibited the Armanni-Ebstein lesion in their tubules.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of the self-evaluation scoring questionnaire and chest digital radiography in lung cancer screening: A three-year follow-up study
Authors: Bojiang Chen, Youjuan Wang, Dan Liu, Weimin Li
Journal: European Respiratory Journal (2011)

Background:  To assess whether the Self-evaluation Scoring Questionnaire for High-risk Individuals of Lung Cancer combined with chest digital radiography (DR) examinations could detect early lung cancer effectively.   Methods:  Subjects with scores over 116 points were regarded as high-risk individuals and underwent DR scans a year from 2007 to 2009. Noncalcified nodules with a diameter over 30 mm, along with enlarged pulmonary hilus and atelectasis, were considered to be positive and subjected to further special examinations. Efficacy of screening protocol was estimated by the 3-year9s results.   Results:  Among 1,537 subjects, 13, 11 and 7 ones were diagnosed with lung cancer in the first, second and third year respectively, indicating the detection rate of 2.02% (31/1,537). In addition, 77.42% (24/31) of the patients were in stage I.   Conclusions:  The questionnaire combined with DR scans is a effective approach to detect early stage of lung cancer.
Anti-TIF1γ antibodies (anti-p155) in adult patients with dermatomyositis: comparison of different diagnostic assays
Authors: Moises Labrador-Horrillo, Maria Angeles Martínez, Albert Selva-O'Callaghan, Ernesto Trallero-Araguás, Eva Balada, Miquel Vilardell-Tarrés, Candido Juarez
Journal: Annals of the Rheumatic Diseases (2012)

A new myositis-specific autoantibody (anti-p155) directed against transcriptional intermediary factor 1 γ (TIF1γ) has been described as a good marker of cancer-associated myositis (CAM).To analyse the feasibility of detecting this autoantibody in patient serum samples using new assays with commercially available recombinant TIF1γ.The study included 90 Spanish patients with dermatomyositis (DM), classified as clinically amyopathic DM, CAM, or DM without cancer. Anti-TIF1γ antibodies were detected by ELISA and immunoblot techniques and compared with anti-p155 antibody detection by protein immunoprecipitation assays with radiolabelled HeLa cells. The κ coefficient was used to compare the agreement between the different tests.Serum samples from 23 (25.6%) and 20 (22.2%) patients with DM recognised TIF1γ by ELISA and immunoblot, respectively. ELISA (κ=0.91) and immunoblot (κ=0.88) showed excellent agreement with immunoprecipitation analysis (anti-p155). Good concordance (κ=0.91) was also seen between ELISA and immunoblot.Excellent agreement was found between anti-p155 detected by immunoprecipitation and anti-TIF1γ detected by ELISA or immunoblot. These data indicate that identification of this autoantibody can be reliably performed in a standard laboratory setting, with potential application in clinical practice for cancer screening in adult patients with DM.
PTU-132 Hepatology E-consultation: The Way Forward? A Review Of Our Initial Experience And Cost Analysis
Authors: S Moreea, PB Southern, J Connolly, VJ Appleby
Journal: Gut (2014)

<h3>Introduction</h3> Outpatient visits to secondary care are costly to Primary Care (PC), time consuming for patients and not always appropriate. Our Trust having been a pioneer in nephrology e-Consultation (eC), we started a hepatology eC service in March 2012. This allows patients’ records to be shared between PC and secondary care (SC) without the need for a detailed referral letter. Our aims were to analyse our initial experience and perform a cost analysis of hepatology eC. <h3>Methods</h3> Retrospective analysis of eC between Mar 12- Oct 13 using SystmOne. Tariffs used for cost analysis: new patient (NP) referral £181, follow up (FU) £103, <b>eC £24.</b> <h3>Results</h3> In 18 months there were 81 eC (31M/50F mean age 52/56 y), each taking 10–15 min to complete. The median response time was 2 days (43% within 1 day). Referral reasons: isolated raised bilirubin/ALT/ALP/GGT: 44/81 (54%), mixed raised LFT’s: 16/81 (20%), abnormal radiology 10%, hyperferritinaemia 9%, HBV/HCV 4%, general advice 2%. There was one inappropriate referral. In 18 cases, SC referral was recommended (22%), with 10/18 being referred and seen. The mean number of FU appointments was 3. Total cost to PC was £8,114: eC £1,944 and £6,170 for subsequent referrals. A minimum cost saving of £14,890 was made (81 NP (£14,661) and assuming one FU for each (£8,343)). <h3>Conclusion</h3> eC is a rapid, cost-effective method of providing hepatology advice. Hidden costs including consultant time, clinic costs etc are difficult to quantify. We would, however, recommend eC as the way forward with a more appropriate tariff. <h3>Disclosure of Interest</h3> None Declared.
Transgenic expression of the human amphiregulin gene induces a psoriasis-like phenotype.
Authors: P W Cook, M Piepkorn, C H Clegg, G D Plowman, J M DeMay, J R Brown, M R Pittelkow
Journal: Journal of Clinical Investigation (1997)

Amphiregulin (AR) is a heparin-binding, heparin-inhibited member of the epidermal growth factor (EGF) family and an autocrine growth factor for human keratinocytes. Previous studies have shown that AR expression is increased in psoriatic epidermis. To test the hypothesis that aberrant AR expression is central to the development of psoriatic lesions, we constructed a transgene (K14-ARGE) encoding a human keratin 14 promoter-driven AR gene. Our results indicate that transgene integration and subsequent expression of AR in basal keratinocytes correlated with a psoriasis-like skin phenotype. Afflicted mice demonstrated shortened life spans, prominent scaling and erythematous skin with alopecia, and occasional papillomatous epidermal growths. Histologic examination revealed extensive areas of marked hyperkeratosis with focal parakeratosis, acanthosis, dermal and epidermal lymphocytic and neutrophilic infiltration, and dilated blood vessels within the papillary dermis. Our results reveal that AR exerts activity in the skin that is distinct from that of transgenic transforming growth factor-alpha or other cytokines, and induces skin pathology with striking similarities to psoriasis. Our observations also link the keratinocyte EGF receptor-ligand system to psoriatic inflammation, and suggest that aberrant expression of AR in the epidermis may represent a critical step in the development or propagation of psoriatic lesions.
Left recurrent laryngeal nerve palsy associated with silicosis
Authors: D. Lardinois, M. Gugger, M.c Balmer, H.b. Ris
Journal: European Respiratory Journal (1999)

Left recurrent laryngeal nerve palsy usually results from invasion or compression of the nerve caused by diseases localized within the aortopulmonary window. This study reports the case of a 76-yr-old male with vocal cord paralysis due to lymph node involvement by silicosis. This rare entity was identified by video-mediastinoscopy, which revealed a granulomatous and fibrosed recurrent lymph node encasing the nerve. The nerve was dissected and released from scar tissues. Progressive clinical improvement was observed followed by total and durable recovery of the voice after 15 weeks follow-up.
Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization
Authors: Nobutaka Kobayashi, Seiji Miyoshi, Takahide Mikami, Hiroshi Koyama, Masato Kitazawa, Michiko Takeoka, Kenji Sano, Jun Amano, Zenzo Isogai, Shumpei Niida, Kayoko Oguri, Minoru Okayama, John A. McDonald, Koji Kimata, Shun'ichiro Taniguchi, Naoki Itano
Journal: Cancer Research (2010)

Despite the importance of stromal cells in tumor progression, our overall understanding of the molecular signals that regulate the complex cellular interactions within tumor stroma is limited. Here, we provide multiple lines of evidence that tumor-associated macrophages (TAM) preferentially traffic to stromal areas formed within tumors in a manner dependent on a hyaluronan (HA)-rich tumor microenvironment. To address the role of stroma-derived HA in macrophage recruitment, we disrupted the HA synthase 2 (Has2) gene in stromal fibroblasts using conditional gene targeting. The Has2 null fibroblasts showed severe impairment in recruiting macrophages when inoculated with tumor cells into nude mice, which shows the contribution of stroma-derived HA in intratumoral macrophage mobilization. Furthermore, a deficiency in stromal HA attenuated tumor angiogenesis and lymphangiogenesis concomitantly with impaired macrophage recruitment. Taken together, our results suggest that stromal HA serves as a microenvironmental signal for the recruitment of TAMs, which are key regulatory cells involved in tumor neovascularization.
The platelet activating factor receptor: a new anti-infective target in respiratory disease?: Figure 1
Authors: Jonathan Grigg
Journal: Thorax (2012)

There is increasing evidence that vulnerability to pneumococcal pneumonia is mediated by the expression of adhesion receptors for bacteria on lower airway cells. A key bacterial adhesion receptor is the platelet-activating factor receptor (PAFR). In vitro and animal studies have shown that upregulation of PAFR increases vulnerability to infection and blocking PAFR and knockdown of PAFR attenuates infection. Blocking PAFR may therefore be a novel therapeutic strategy in acute and chronic airway infection.
The Inflammasome-Mediated Caspase-1 Activation Controls Adipocyte Differentiation and Insulin Sensitivity
Authors: Rinke Stienstra, Leo A.B. Joosten, Tim Koenen, Berry van Tits, Janna A. van Diepen, Sjoerd A.A. van den Berg, Patrick C.N. Rensen, Peter J. Voshol, Giamilla Fantuzzi, Anneke Hijmans, Sander Kersten, Michael Müller, Wim B. van den Berg, Nico van Rooijen, Martin Wabitsch, Bart-Jan Kullberg, Jos W.M. van der Meer, Thirumala Kanneganti, Cees J. Tack, Mihai G. Netea
Journal: Cell Metabolism (2010)
IGSF4 is a novel TCR ζ-chain–interacting protein that enhances TCR-mediated signaling
Authors: Hye-Ran Kim, Byeong-Hun Jeon, Hyun-Su Lee, Sin-Hyeog Im, Masatake Araki, Kimi Araki, Ken-ichi Yamamura, Suck-Chei Choi, Do-Sim Park, Chang-Duk Jun
Journal: The Journal of Experimental Medicine (2011)

Immunoglobulin superfamily member 4 (IGSF4) is a known ligand of CRTAM, a receptor expressed in activated NKT and CD8+ T cells, but its function in T cell immunity has not been elucidated. In this study, we show that IGSF4 directly interacts with the T cell receptor (TCR) ζ-chain and enhances TCR signaling by enhancing ζ-chain phosphorylation. Ectopic overexpression of IGSF4 enhances TCR-mediated T cell activation. In contrast, IGSF4 knockdown shows a dramatic decrease in markers associated with T cell activation compared with those in control small interfering RNA. The transmembrane domain is essential for TCR ζ-chain association and clustering to the immunological synapse, and the ectodomain is associated with T cell interaction with antigen-presenting cells (APCs). IGSF4-deficient mice have impaired TCR-mediated thymocyte selection and maturation. Furthermore, these mice reveal attenuated effector T cell functions accompanied by defective TCR signaling. Collectively, the results indicate that IGSF4 plays a central role in T cell functioning by dual independent mechanisms, control of TCR signaling and control of T cell–APC interaction.
Correlation of the Osteoarthritis Susceptibility Variants That Map to Chromosome 20q13 With an Expression Quantitative Trait Locus Operating on <i>NCOA3</i> and With Functional Variation at the Polymorphism rs116855380
Authors: Fiona Gee, Michael D. Rushton, John Loughlin, Louise N. Reynard
Journal: Arthritis & Rheumatology (2015)

Objective To functionally characterize the osteoarthritis (OA) susceptibility variants that map to a region of high linkage disequilibrium (LD) on chromosome 20q13 marked by the single‐nucleotide polymorphism (SNP) rs6094710 and encompassing NCOA3 and SULF2 . Methods Nucleic acids were extracted from the cartilage of OA patients. Overall and allelic expression of NCOA3 and SULF2 were measured by quantitative reverse transcription–polymerase chain reaction and pyrosequencing, respectively. The functional effect of SNPs within the 20q13 locus was assessed in vitro using luciferase reporter constructs and electrophoretic mobility shift assays (EMSAs). The in vivo effect of nuclear receptor coactivator 3 (NCOA3) protein depletion on primary human OA articular cartilage chondrocytes was assessed using RNA interference. Results Expression of NCOA3 correlated with the genotype at rs6094710 ( P = 0.006), and the gene demonstrated allelic expression imbalance (AEI) in individuals heterozygous for the SNP (mean AEI 1.21; P &lt; 0.0001). In both instances, expression of the OA‐associated allele was reduced. In addition, there was reduced enhancer activity of the OA‐associated allele of rs116855380, a SNP in perfect LD with rs6094710 in luciferase assays ( P &lt; 0.001). EMSAs demonstrated a protein complex binding with reduced affinity to this allele. Depletion of NCOA3 led to significant changes (all P &lt; 0.05) in the expression of genes involved in cartilage homeostasis. Conclusion NCOA3 is subject to a cis ‐acting expression quantitative trait locus in articular cartilage, which correlates with the OA association signal and with the OA‐associated allele of the functional SNP rs116855380, a SNP that is located only 10.3 kb upstream of NCOA3 . These findings elucidate the effect of the association of the 20q13 region on OA cartilage and provide compelling evidence of a potentially causal candidate SNP.