tbuckley/cabot-search huggingface dataset:
Letter to the Editor
Authors: Carmen W. van den Berg, Karolina E. Taylor
Journal: Circulation Research (2005)

With interest we read the recent report by Bisoendial et al in Circulation Research regarding their observation that infusion of C reactive protein (CRP) into humans induces the release of inflammatory mediators and coagulation factors. 1 The CRP used in this study was generated in Escherichia coli, therefore there is a major possibility of the CRP being contaminated with bacterial products.Although the authors tried to remove endotoxin contamination using gel-filtration, in our opinion this is not a very rigorous method.The kinetics of Bisoendial et al observations suggests that endotoxin contamination and not CRP itself is responsible for their observations.This is especially clear considering the levels of CRP found in the plasma and the kinetics of IL-6 and IL-8 induction.The authors observe a continuous presence of CRP, which even increases after 24 hours, most likely attributable to the generation of CRP in the volunteer.If, as the authors suggest, their observation is caused by CRP itself, this would suggest that CRP can directly or indirectly increase its own synthesis; this would be a self-perpetuating effect and CRP levels would keep increasing until maximal achievable levels were obtained.However, IL-6 and IL-8 levels peak after 4 hours and are back to baseline levels at 8 hours.If CRP were responsible for the increased expression of these cytokines, levels would not peak, but because of the continuous and increasing levels of CRP, IL-6, and IL-8 levels would keep increasing similar to CRP.The kinetics of the increase in CRP, IL-6, and IL-8 levels can be completely explained by the presence of small amounts of endotoxin contamination.Endotoxin, because it would be removed from the circulation, would only cause a temporary increase in IL-6 and IL-8 whereas CRP would increase after 24 hours.We and others have shown that contamination of commercial E coli-derived CRP is responsible for numerous effects previously ascribed to CRP [2][3][4][5][6][7] and that endotoxin contamination is responsible for chemokine and cytokine secretion in vitro. 2,7It has been shown that contaminations of protein with minute amounts of endotoxin can increase cytokine secretion. 8In conclusion, we suggest that the events observed by Bisoendial et al are most likely caused by endotoxin contamination of their CRP preparation and that the results of this study have to be interpreted with great care.
Influence of lung volume on histamine-induced bronchoconstriction in guinea-pigs
Authors: A M Lorino, M Benichou, I Macquin-Mavier, M L Franco-Montoya, H Lorino, A Harf
Journal: European Respiratory Journal (1991)

The influence of lung volume on bronchopulmonary reactivity was investigated in 4 groups of 14 anaesthetized paralysed mechanically ventilated guinea-pigs: animals of group 1 served as control; in animals of group 2, the parasympathetic nervous system was blockaded with atropine; animals of group 3 were submitted to a bilateral cervical vagotomy; animals of group 4 were both vagotomized and pretreated with atropine. In each group, the animals were randomly divided into 2 subgroups: one was ventilated at zero end-expiratory pressure (ZEEP), the other with 0.2 kPa positive end-expiratory pressure (PEEP) resulting in a mean increase in lung volume of about 1 ml. Bronchopulmonary response to infused histamine was assessed by the respiratory conductance and compliance values measured during bronchoconstriction (respectively HGrs and HCrs). In the control group, animals exposed to PEEP were found significantly less reactive than those ventilated at ZEEP. In groups 2, 3 and 4, this difference was significantly reduced for HGrs and even abolished for HCrs. These results demonstrate that the effect of lung volume on moderate histamine-induced bronchoconstriction in guinea-pigs is not purely mechanical, but is partly vagally mediated. They also suggest that this vagally mediated inhibitory influence results from involvement of central reflexes evoked by stretch receptor stimulation.
Impact of Chemotherapy Dosing on Ovarian Cancer Survival According to Body Mass Index
Authors: Elisa V. Bandera, Valerie S. Lee, Lorna Rodriguez-Rodriguez, C. Bethan Powell, Lawrence H. Kushi
Journal: JAMA Oncology (2015)

Optimal chemotherapy dosing in obese patients remains uncertain, with variation in practice. Dose reduction strategies are often used to avoid chemotoxicity, but recent American Society of Clinical Oncology guidelines recommend full dose.To evaluate the impact of body mass index (BMI) on chemotherapy dosing and of dose reduction on ovarian cancer survival.Cohort study in Kaiser Permanente Northern California (KPNC) health care setting of patients with primary invasive epithelial ovarian cancers diagnosed from January 2000 through March 2013. Analyses focused on 806 patients receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent.Overall and ovarian cancer-specific mortality. Deaths were identified through the KPNC Mortality Linkage System, with median follow-up of 52.5 months. Hazard ratios (HRs) and 95% CIs were estimated from proportional hazards regression, accounting for prognostic variables including age at diagnosis, race, stage, grade, histologic type, chemotoxic effects, comorbidities, cancer antigen 125 levels, and BMI at diagnosis.The strongest predictor of dose reduction was a high BMI. Compared with normal-weight women, obese class III women received 38% and 45% lower doses in milligrams per kilogram of body weight of paclitaxel and carboplatin, respectively (P < .001 for each agent). They also received lower relative dose intensity (RDI) for each agent and the combined regimen, calculated as average RDI (ARDI). Mean ARDI was 73.7% for obese class III women and 88.2% for normal-weight women (P < .001). Lower ARDI (<70%) was associated with worse overall (HR, 1.62 [95% CI, 1.10-2.37]) and ovarian cancer-specific survival (HR, 1.69 [95% CI, 1.12-2.55]). Women who were obese at diagnosis appeared to have better survival. In multivariable-adjusted analyses considering joint effects by BMI and ARDI, compared with women with normal weight and no dose reduction, normal-weight women with dose reduction (ARDI < 85%) experienced worse survival (HR, 1.50 [95% CI, 1.02-2.21]). For each BMI category, those with ARDI less than 85% had worse survival than those without dose reduction. The improved survival among obese women was no longer apparent with dose reduction.Lower RDI was an independent predictor of ovarian cancer mortality. This finding was strongest among normal-weight women but seen at all levels of BMI. Our results suggest that body size should not be a major factor influencing dose reduction decisions in women with ovarian cancer.
Cervical HPV natural history among young Western Cape, South African women: The randomized control EVRI Trial
Authors: Staci L. Sudenga, B. Nelson Torres, Matthys H. Botha, Michele Zeier, Martha E. Abrahamsen, Richard H. Glashoff, Susan Engelbrecht, Maarten F. Schim Van der Loeff, Louvina E. Van der Laan, Siegfried Kipping, Douglas Taylor, Anna R. Giuliano
Journal: Journal of Infection (2015)
Incidence of Major Complications of Neurolytic Coeliac Plexus Block
Authors: David Denison Davies
Journal: Journal of the Royal Society of Medicine (1993)

The number of neurolytic coeliac plexus blocks carried out in England and Wales over a 5 year period (1986–1990) was ascertained. The number of cases of the major complications of permanent paraplegia and/or loss of anal and bladder sphincter function following on from such blocks, over the same period of time, was also ascertained. The information was obtained by means of a questionnaire which was sent to most of the pain clinics in England and Wales. There were 2730 neurolytic blocks carried out over the 5 year period. The number of cases of permanent paraplegia following on from the blocks was four. Of these four cases, three of them also had loss of anal and bladder sphincter function — loss of sphincter function never occurred in isolation. The incidence of major complications following neurolytic coeliac plexus block was thus one case per 683 blocks.
The role of number of lymph node passes and methods of pathological examination in the adequacy specimens of EBUS-TBNA in the verification of mediastinal lymphadenopathy
Authors: Grigorii Kudriashov, Igor Vasilyev, Nikolay Yakushenko, Nataliya Blum, Anna Lazareva, Peter Yablonsky
Journal: European Respiratory Journal (2013)

BACKGROUND: The role of EBUS-TBNA in the verification of isolated mediastinal lymphadenopathy (IML) is now being actively discussed. Some papers showed, the relationship of adequacy specimens of EBUS-TBNA and number of lymph node passes it is not significant (Ting Ye, 2011). The role of pathological examination of TBNA- specimens is unclear. AIM: To determine the role of number of lymph node passes and methods of pathological examination of TBNA- specimens in the verification of IML. METHODS: Prospective clinical trial of 72 consecutive patients with IML. MATERIAL: EBUS-TBNA of bifurcation lymph nodes was performed. Less than five passes through lymph node were made in Group (Gr.) 1 (22 patients/31%). Five and more passes were made in Gr. 2 (50 patients/69%). VTS biopsy of paratracheal lymph nodes as gold standard was performed. After procedure material were divided in 3 groups of pathological examination of specimens: Gr. “C” - only cytology (16/22%), Gr. “CB” - cytoblock (12/17%), Gr. “MIX” (44/61%). RESULTS: TBNA-specimens from 60 patients were accepted pathologically adequate (83.3%). In Gr. 1- 64%, Gr. 2 – 92%. (p 0.05). CONCLUSIONS: EBUS-TBNA have a high diagnostic accuracy in the verification of IML. Performance five and more passes of bifurcation lymph node and the creation of cytoblocks – are more preferable. But of course, additional trials are necessary.
Global Analysis of Palmitoylated Proteins in Toxoplasma gondii
Authors: Ian T. Foe, Matthew A. Child, Jaimeen D. Majmudar, Shruthi Krishnamurthy, Wouter A. van der Linden, Gary E. Ward, Brent R. Martin, Matthew Bogyo
Journal: Cell Host & Microbe (2015)

Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T. gondii, identifying a total of 282 proteins, including cytosolic, membrane-associated, and transmembrane proteins. From this large set of palmitoylated targets, we validate palmitoylation of proteins involved in motility (myosin light chain 1, myosin A), cell morphology (PhIL1), and host cell invasion (apical membrane antigen 1, AMA1). Further studies reveal that blocking AMA1 palmitoylation enhances the release of AMA1 and other invasion-related proteins from apical secretory organelles, suggesting a previously unrecognized role for AMA1. These findings suggest that palmitoylation is ubiquitous throughout the T. gondii proteome and reveal insights into the biology of this important human pathogen.
Outbreak of KPC-3-producing, and colistin-resistant, Klebsiella pneumoniae infections in two Sicilian hospitals
Authors: M.L. Mezzatesta, F. Gona, C. Caio, V. Petrolito, D. Sciortino, A. Sciacca, C. Santangelo, S. Stefani
Journal: Clinical Microbiology and Infection (2011)
Novel delivery approaches for cancer therapeutics
Authors: Ashim K. Mitra, Vibhuti Agrahari, Abhirup Mandal, Kishore Cholkar, Chandramouli Natarajan, Sujay Shah, Mary Joseph, Hoang M. Trinh, Ravi Vaishya, Xiaoyan Yang, Yi Hao, Varun Khurana, Dhananjay Pal
Journal: Journal of Controlled Release (2015)
High prevalence of hyperthyroidism in patients with poor prognosis non seminomatous germ cell tumors
Authors: S. Oosting-Lenstra, E. C. de Haas, T. P. Links, I. J. de Jong, H. J. Hoekstra, D. T. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2008)

16018 Background: Patients (pts) with metastatic non seminomatous germ cell tumors (NSGCT) with elevated beta human chorionic gonadotrophin (ß-HCG) can present with hyperthyroidism. This paraneoplastic phenomenon is due to a weak intrinsic thyroid stimulating activity of ß-HCG. The prevalence of hyperthyroidism in pts presenting with NSGCT is unknown. Methods: All consecutive metastatic NSGCT pts who presented at the UMCG between April 2001 and April 2007 were analyzed. Thyroid function was assessed by measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels. Hyperthyroidism was diagnosed when TSH was below normal (< 0.40 mE/L) combined with an elevated FT4 (>18.2 pmol/L). Information on disease status including International Germ Cell Cancer Classification (IGCCC), symptoms and clinical outcome was subtracted from the medical records. Results: 148 NSGCT pts were included in this analysis. Thyroid function tests 2 weeks before or within 1 week after starting chemotherapy were available for 144 pts. Prognosis was good in 86 (60%), intermediate in 37 (26%) and poor in 21 pts (14%) according to IGCCC. Five pts with hyperthyroidism (3.5%) were identified with TSH levels ranging from 0.002 to 0.21 mE/L and FT4 levels ranging from 21.3 to >75 pmol/L. Hyperthyroidism was present in 5/21 poor prognosis pts (24%) versus in none in the good and intermediate prognostic group (p<0.001). Of the pts with ß- HCG ≥ 50,000 IU/L, 50% had hyperthyroidism versus 0 % in patients with a ß-HCG < 50,000 IU/L (p<0.001). Pts presented with weight loss (n=5), fatigue (n=3), tachycardia (n=3), night sweats (n=2) and irregular pulse (n=1) as potential manifestations of hyperthyroidism. FT4 normalized < 26 days after starting chemotherapy in all pts. One pt received propranolol for tachycardias. Conclusions: Hyperthyroidism is frequently present in pts with NSGCT with poor prognosis including highly elevated ß-HCG. Since its symptoms overlap with those of extensive metastatic disease, it may not be recognized. To optimize supportive care at start of chemotherapy in poor prognosis pts, thyroid function should be known and symptomatic hyperthyroidism should be treated temporarily with beta blockade or antithyroidal medication. No significant financial relationships to disclose.
Posttranscriptional changes of serum albumin: Clinical and prognostic significance in hospitalized patients with cirrhosis
Authors: Marco Domenicali, Maurizio Baldassarre, Ferdinando A Giannone, Marina Naldi, Marianna Mastroroberto, Maurizio Biselli, Maristella Laggetta, Daniela Patrono, Carlo Bertucci, Mauro Bernardi, Paolo Caraceni
Journal: Hepatology (2014)

Beside the regulation of fluid distribution, human serum albumin (HSA) carries other activities, such as binding, transport, and detoxification of many molecules. In patients with cirrhosis, HSA exhibits posttranscriptional alterations that likely affect its functions. This study aimed at identifying the structural HSA alterations occurring in cirrhosis and determining their relationship with specific clinical complications and patient survival. One hundred sixty-eight patients with cirrhosis, 35 with stable conditions and 133 hospitalized for acute clinical complications, and 94 healthy controls were enrolled. Posttranscriptional HSA molecular changes were identified and quantified by using a high-performance liquid chromatography/electrospray ionization mass spectrometry technique. Clinical and biochemical parameters were also recorded and hospitalized patients were followed for up to 1 year. Seven HSA isoforms carrying one or more posttranscriptional changes were identified. Altered HSA isoforms were significantly more represented in patients than in healthy controls. Conversely, the native, unchanged HSA isoform was significantly reduced in cirrhosis. Native HSA and most altered isoforms correlated with both Child-Pugh and Model for End-Stage Liver Disease scores. In hospitalized patients, oxidized and N-terminal truncated isoforms were independently associated with ascites, renal impairment, and bacterial infection. Finally, the native HSA and cysteinylated/N-terminal truncated isoforms were predictors of 1-year survival, with greater prognostic accuracy than total serum albumin concentration. Conclusions: Extensive posttranscriptional changes of HSA, involving several molecular sites and increasing in parallel with disease severity, occur in patients with cirrhosis. Altered isoforms are independently associated with specific clinical complications, whereas the residual, native HSA isoform independently predicts patient survival. These findings support the concept of the "effective albumin concentration," which implies that the global HSA function is related not only to its serum concentration, but also to the preservation of its structural integrity. (Hepatology 2014;60:1850–1859)
Promoter methylation of p16<sup>INK4A</sup>, RASSF1A, and RAR2b genes in tumor DNA from patients with breast cancer (BC) in correlation with clinical recurrence.
Authors: S. Voyatzi, K. Desiris, D. A. Paikos, E. Stergiou, G. Geromichalos, K. Pazaitou, A. Kiziridou, P. Stravoravdi, G. Simbilidis
Journal: Journal of Clinical Oncology (2010)

1551 Background: Currently, no definite epigenetic markers exist to predict tumor recurrence after surgical resection in patients (pts) with BC. We studied the methylation pattern of 3 growth regulatory genes p16INK4A , RASSF1A and RAR2b in pts with BC to determine if this process is associated with an increased recurrence risk. Methods: Genomic DNA from paraffin-embedded tissue specimens extracted from 74 pts with Breast Lesions (BL), who underwent surgical excision between 2003- 2005. DNA methylation was determined by chemical modification of DNA and subsequent double “hot start” methylation-specific PCR (MSP), followed by capillary-array electrophoresis analysis. The median follow-up of pts was 54 months. Results: 52/74 pts had BC and 22 benign lesions. Methylation of p16INK4A was observed in 20/52 (38.4%) and in 2/22 (9%), of RASSF1A in 30/52 (57.7%) and in 10/22 (45.4%), of RAR 2b in 22/52 (42.3%) and in 14/22(63.6%) of pts respectively. Both p16INK4A and RASSF1A were methylated in 10/52 and 0/22, p16INK4A and RAR2b in 8/52 and 2/22, and RASSF1A and RAR 2b in 18/52 and 8/22 pts respectively. Methylation of at least one of the genes was observed in 44/52 (84.6%) and in 16/22 (72.7%) pts. All 3 genes were methylated in 6/52 (11.5%) and 0/22 pts respectively. During follow up 8/52 pts developed recurrence and 2/8 had methylated all 3 genes. No correlation with recurrence was observed when one and/or two of the 3 genes were methylated. Conclusions: Methylation of p16INK4A was observed more frequently in BC than in benign BL; methylation of RASSF1A and RAR2b did not reveal any difference among BC and benign BL; methylation of the 3 genes simultaneously was noted only in BC pts. The last finding may indicate a possible role of the triple methylated genes in the development of the recurrence. Larger studies are required to confirm if our finding point out an epigenetic marker, which could predict BC recurrence. No significant financial relationships to disclose.
Shock index as a prognostic value in risk stratification of patients with acute pulmonary embolism
Authors: Alaa E.Abd Elmoniem, Lamia Shaban, Maha Elkholy, Khalid Kotb, Salah Abo Saif
Journal: European Respiratory Journal (2013)

Background: Patients with acute pulmonary embolism (PE) presenting with haemodynamic instability have the worst prognosis. The Shock Index (SI) is a sensitive indicator of left ventricular dysfunction. Objective: To assess the value of shock index and echocardiographic abnormalities as predictors of in-hospital complications and mortality in patients with acute pulmonary embolism.Patients&methods: 81 patients who were diagnosed as acute pulmonary embolism were included in this study. Haemodynamic instability defined by shock index ≥1 (HR/systolic blood pressure).Detailed Doppler echocardiography (within 72h of admission)done for all patients. Results: Heart rate, systolic blood pressure and shock index >1 were significantly higher and more frequent in patients with in hospital mortality (P 1, right ventricular end diastolic diameter >3, interventricular septal flattening, peak systolic PAP >50 mmHg and E/A ratio  1 independent of right ventricular hypokinesia, RV/LV>1 and systolic PAP>50mmHg was associated with significant in-hospital mortality P  1 was associated with increased in-hospital mortality independently of other abnormal echocardiographic Doppler parameters and could be helpful in early diagnosis of patients with acute pulmonary embolism who are in need for meticulous observation.
Genetic analysis of two novel mucin-like genes in the disease-susceptibility locus for diffuse panbronchiolitis
Authors: Minako Hijikata, Ikumi Matsushita, Hideyuki Ito, Jun Ohashi, Sakae Homma, Yoshio Taguchi, Arata Azuma, Shoji Kudoh, Naoto Keicho
Journal: European Respiratory Journal (2011)

Background:  Diffuse panbronchiolitis (DPB), which is characterized by chronic inflammation in respiratory bronchioles and sinobronchial infection, is a complex genetic disease affecting East Asians. DPB is strongly associated with HLA-B54 in Japanese and HLA-A11 in Koreans. We hypothesized that a major susceptibility gene for DPB might be located between the HLA-A and HLA-B loci and recently cloned two novel mucin-like genes designated panbronchiolitis related mucin-like 1 and 2 (PBMUCL1 and PBMUCL2) in the candidate region. We found disease-associated genetic polymorphisms in the new genes.   Objectives:  The aim of the study is to compare the genetic polymorphisms of the genes between Japanese and European descent, because genetic predisposition to DPB has been assumed only in Asians.   Methods:  We genotyped polymorphisms in 50 DNA samples of European descent and compared their frequency and haplotype structure with 108 Japanese DPB patients and 98 Japanese controls. Expression of PBMUCL1 transcript was investigated in primary-cultured human bronchial epithelial (HBE) cells.   Results:  The haplotypes were different between European descent and Japanese. The mRNA expression pattern of the HBE cells with Asian-specific haplotype was analyzed.   Conclusions:  Further analysis of newly identified mucin-like genes may provide insights into the pathogenesis of the disease.
Implications for the Ajcc Staging Systems on Esophageal Squamous Cell Cancer Patients Receiving Multimodality Therapy
Authors: Motoo Nomura, Tetsuya Abe, Hiroya Taniguchi, Shigenori Kadowaki, Daisuke Takahari, Takashi Ura, Masashi Andoh, Yasumasa Niwa, Kei Muro
Journal: Annals of Oncology (2014)