tbuckley/cabot-search huggingface dataset:
Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis.
Authors: K Henriksson, K Uvnas-Moberg, C E Nord, C Johansson, R Gullberg
Journal: Annals of the Rheumatic Diseases (1986)

The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood.
G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells
Authors: Venugopalan Cheriyath, Keith B. Glaser, Jeffrey F. Waring, Rachid Baz, Mohamad A. Hussein, Ernest C. Borden
Journal: Journal of Clinical Investigation (2007)

The effectiveness of IFN-alpha2b for human multiple myeloma has been variable. TRAIL has been proposed to mediate IFN-alpha2b apoptosis in myeloma. In this study we assessed the effects of IFN-alpha2b signaling on the apoptotic activity of TRAIL and human myeloma cell survival. While TRAIL was one of the most potently induced proapoptotic genes in myeloma cells following IFN-alpha2b treatment, less than 20% of myeloma cells underwent apoptosis. Thus, we hypothesized that an IFN-stimulated gene (ISG) with prosurvival activity might suppress TRAIL-mediated apoptosis. Consistent with this, IFN-alpha2b stabilized mitochondria and inhibited caspase-3 activation, which antagonized TRAIL-mediated apoptosis and cytotoxicity after 24 hours of cotreatment in cell lines and in fresh myeloma cells, an effect not evident after 72 hours. Induced expression of G1P3, an ISG with largely unknown function, was correlated with the antiapoptotic activity of IFN-alpha2b. Ectopically expressed G1P3 localized to mitochondria and antagonized TRAIL-mediated mitochondrial potential loss, cytochrome c release, and apoptosis, suggesting specificity of G1P3 for the intrinsic apoptosis pathway. Furthermore, RNAi-mediated downregulation of G1P3 restored IFN-alpha2b-induced apoptosis. Our data identify the direct role of a mitochondria-localized prosurvival ISG in antagonizing the effect of TRAIL. Curtailing G1P3-mediated antiapoptotic signals could improve therapies for myeloma or other malignancies.
Epidemiologic Correlates of Cervical Neoplasia and Risk of Human Papillomavirus Infection in Asymptomatic Women in Brazil
Authors: L. L. Villa, E. L. F. Franco
Journal: JNCI Journal of the National Cancer Institute (1989)

To investigate whether the epidemiologic correlates of cervical cancer are predictors of infection with genital human papillomavirus (HPV), we performed a prevalence survey in two metropolitan areas of Brazil, Recife and São Paulo. The data records of four randomly selected HPV-negative women were matched on the basis of age, clinic, and admission period with those of each of 136 patients with positive HPV DNA hybridizations. Anal intercourse [prevalence rate ratio (PRR) = 1.7] and current pregnancy (PRR = 2.3) were the only variables associated with HPV 6/11 infection (P less than .10). Only the frequency of gynecologic consultations was associated (negatively) with risk of HPV 16/18 infection (P = .0175). Our data failed to provide evidence for the existence of shared risk factors for genital HPV infection and cervical cancer. The frequency of mixed HPV infections was 13 times higher than expected, a finding suggestive of the existence of additional determinants of HPV infection not akin to the general behavioral characteristics of women that are probed in the study.
Discovery and identification of potential biomarkers of papillary thyroid carcinoma
Authors: Yuxia Fan, Linan Shi, Qiuliang Liu, Rui Dong, Qian Zhang, Shaobo Yang, Yingzhong Fan, Heying Yang, Peng Wu, Jiekai Yu, Shu Zheng, Fuquan Yang, Jiaxiang Wang
Journal: Molecular Cancer (2009)

Thyroid carcinoma is the most common endocrine malignancy and a common cancer among the malignancies of head and neck. Noninvasive and convenient biomarkers for diagnosis of papillary thyroid carcinoma (PTC) as early as possible remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers for PTC specifically.Two hundred and twenty four (224) serum samples with 108 PTC and 116 controls were randomly divided into a training set and a blind testing set. Serum proteomic profiles were analyzed using SELDI-TOF-MS. Candidate biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays.A total of 3 peaks (m/z with 9190, 6631 and 8697 Da) were screened out by support vector machine (SVM) to construct the classification model with high discriminatory power in the training set. The sensitivity and specificity of the model were 95.15% and 93.97% respectively in the blind testing set. The candidate biomarker with m/z of 9190 Da was found to be up-regulated in PTC patients, and was identified as haptoglobin alpha-1 chain. Another two candidate biomarkers (6631, 8697 Da) were found down-regulated in PTC and identified as apolipoprotein C-I and apolipoprotein C-III, respectively. In addition, the level of haptoglobin alpha-1 chain (9190 Da) progressively increased with the clinical stage I, II, III and IV, and the expression of apolipoprotein C-I and apolipoprotein C-III (6631, 8697 Da) gradually decreased in higher stages.We have identified a set of biomarkers that could discriminate PTC from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved successful.
Seborrhoeic dermatitis is not caused by an altered immune response to<i>Malassezia</i>yeast
Authors: None Parry, None Sharpe
Journal: British Journal of Dermatology (1998)

The immune response of patients with seborrhoeic dermatitis and healthy age‐ and sex‐matched controls was examined to test the hypothesis that an inadequate or inappropriate immune response to Malassezia yeast leads to seborrhoeic dermatitis. Antibody responses were examined using enzyme‐linked immunosorbent assays (ELISAs) and Western blots and lymphocyte responses using lymphocyte proliferation assays. The level of IgG and IgM specific for whole yeast cells or extracted proteins of two isolates of M. furfur was tested in ELISA. A wide range of antibody levels was found but the patient and control groups were indistinguishable (n = 19), and the groups could not be distinguished by the pattern of Malassezia proteins recognized by their sera in Western blots. The average affinity of the subjects' antibodies specific for Malassezia cells or proteins was measured using ammonium thiocyanate dissociation. Most of the sera had moderate affinities corresponding to 50% dissociation at thiocyanate concentrations of 0.5–1.0 mol/L. There was no difference between patients and matched controls. The proliferation of the patients' lymphocytes in response to a number of M. furfur cell preparations was measured: whole cells, cytoplasmic proteins, cell walls, soluble molecules extracted from the cell walls using sonication, and a commercial preparation. There was a wide range of responses between individuals, but there was no difference between the three groups: patients with seborrhoeic dermatitis (n = 16), healthy controls (n = 16) and a group suffering from other inflammatory skin conditions (n = 15). The results do not support the hypothesis that an inadequate immune response to Malassezia yeast could lead to seborrhoeic dermatitis. Other possible pathological mechanisms include toxin production or lipase activity.
Polymorphisms of <i>FAS</i> and <i>FAS</i> Ligand Genes Involved in the Death Pathway and Risk and Progression of Squamous Cell Carcinoma of the Head and Neck
Authors: Zhengdong Zhang, Li-E Wang, Erich M. Sturgis, Adel K. El-Naggar, Waun K. Hong, Christopher I. Amos, Margaret R. Spitz, Qingyi Wei
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Alteration of the FAS/FAS ligand (FASLG) pathway regulating cell death may lead to cancer development, but the effects of functional promoter polymorphisms of the FAS and FASLG genes on risk of squamous cell carcinoma of the head and neck (SCCHN) are unknown. Design: We genotyped the FAS −1377 G&amp;gt;A, FAS −670 A&amp;gt;G, FASLG −844 C&amp;gt;T, and FASLG IVS2nt −124 A&amp;gt;G polymorphisms in 721 case patients with SCCHN and 1,234 cancer-free non–Hispanic White control subjects frequency-matched by age and sex. Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Compared with the FAS −1377 GG and −670 AA genotypes, the FAS −1377 AA and −670 (GG + AG) genotypes were associated with an increased risk of SCCHN (OR, 2.23; 95% CI, 1.07-4.64 and OR, 1.24; 95% CI, 1.01-1.52, respectively), whereas no risk of SCCHN was associated with any of the FASLG genotypes. When we used the combined FAS −1377 (GG + AG)/−670 AA genotypes as the reference, we found that the individuals carrying the FAS −1377 AA/−670 (GG + AG) had the highest risk (OR, 2.69; 95% CI, 1.24-5.83), whereas individuals carrying genotypes other than FAS −1377 (GG + AG)/−670 AA had a higher risk of SCCHN (OR, 1.24; 95% CI, 1.01-1.52). Furthermore, the elevated risk was particularly evident for pharyngeal cancer with the larger tumors without regional lymph metastasis (OR, 1.77; 95% CI, 1.07-2.94). Conclusions: The FAS (but not FASLG) polymorphisms seem to contribute to risk of developing SCCHN, particularly the pharyngeal cancer in non–Hispanic Whites. However, potential selection bias warrants future population-based studies to verify the findings.
Description of plantar pressure distribution in athletes
Authors: F Esparza, J Abellàn, P Ibañez, J M Sànchez Ayuso
Journal: British Journal of Sports Medicine (2011)

Background Lower extremities injuries caused by non-body contact are highly prevalent in sports. Repetitive high loads on the foot could cause these injuries. Plantar pressure refers to the pressure measured on the plantar surface of the foot. Objective To measure the plantar pressure in soccer and basketball players. Design Descriptive study. Setting Soccer and basketball players enrolled in elite division leagues. Participants Players were selected from the teams of the Federation of Soccer and Basketball of Murcia. Interventions Plantar pressure was assessed with Biofoot/IBV system. This system provides a digital footprint with the pressure distribution according to a colour code. Main outcome Footprint was divided into nine areas: 1. Lateral heel, 2. Medial heel, 3. Lateral arch, 4. Medial arch, 5. Medial forefoot, 6. Central forefoot, 7. Lateral forefoot, 8. Hallux, and 9. Lateral toes. Each placer was assessed to detect the peak pressure area. Results 72 male athletes were assessed, 40 soccer players (mean (SD) age 23.95 (3.62)) and 32 basketball players (mean (SD) age 25.97 (5.52)). 16 of the 40 soccer players (40%) presented the highest pressure in area 6 (central forefoot), in 10 of them (25%) peak pressure was detected in area 8 (hallux), and 8 players (20%) presented the highest pressure in area 5 (medial forefoot). Similarly, in 16 of the 32 basketball players (50%) the peak pressure was detected in area 6, and 8 players (25%) presented the highest pressure in area 8. The value of Peak pressure was equal in both groups. Conclusion Both soccer and basketball players show similar plantar pressure distribution. Soccer players present more frequently the peak pressure in the medial forefoot. Further studies should compare the plantar pressure of different sport-related movements.
Screening Methods for Early Detection of Hepatocellular Carcinoma
Authors: Kenichi Kobayashi, Tatsuho Sugimoto, Hiroshi Makino, Mikio Kumagai, Masashi Unoura, Nobuyoshi Tanaka, Yasuhiro Kato, Nobu Hattori
Journal: Hepatology (1985)

The value of various screening methods in the detection of early hepatocellular carcinoma was investigated in 95 patients with cirrhosis. Infusion hepatic angiography and computed tomography with angiography were performed yearly, ultrasound every 3 months, and determination of serum alpha-fetoprotein levels every 2 months. "Space-occupying lesions" suspicious for hepatocellular carcinoma were found in 13 of the 95 cases (13.7%). Detection rates of "space-occupying lesions" were 77% for infusion hepatic angiography, 77% for computed tomography with angiography and 54% for ultrasonography, respectively. In 8 of the 13 cases, "space-occupying lesions" were subsequently confirmed as hepatocellular carcinoma by operative findings or clinical course. Serum alpha-fetoprotein levels were negative in 3 of the 8 hepatocellular carcinoma-confirmed cases, and 3 of the remaining 5 cases demonstrated levels above 400 ng per ml at the time of diagnosis. A radical resection of hepatocellular carcinoma was successfully performed in two cases. Although it was difficult to differentiate hepatocellular carcinoma from other lesions in the case of "space-occupying lesions" smaller than 2 cm in diameter, the results suggest that regularly scheduled screening may be useful to detect early hepatocellular carcinoma.
Improving prognosis following a first variceal haemorrhage over four decades
Authors: P A McCormick, C O'Keefe
Journal: Gut (2001)

<h3>BACKGROUND</h3> Variceal bleeding is a frequent cause of death in patients with cirrhosis and portal hypertension. Over the past 40 years a number of new techniques have been introduced to control active variceal haemorrhage. Many randomised controlled trials were performed to evaluate these new therapies. While most have demonstrated efficacy in controlling haemorrhage few showed improved survival. <h3>AIM</h3> The aim of this study was to investigate whether the prognosis for cirrhotic patients following a first variceal haemorrhage has improved over the past four decades. <h3>PATIENTS AND METHODS</h3> A total of 1475 patients included in the control or untreated arms of randomised controlled prophylactic trials for the primary prevention of variceal haemorrhage between 1960 and 2000. Twenty eight eligible randomised controlled studies were included. Over the 40 year period of observation there was a reduction in bleeding related mortality over time from approximately 65% to approximately 40% (p=0.024). <h3>CONCLUSION</h3> This study suggests that there has been a significant reduction in bleeding related mortality in patients with cirrhosis and portal hypertension over the past 40 years.
Cost effectiveness of pneumococcal vaccination among Dutch infants: economic analysis of the seven valent pneumococcal conjugated vaccine and forecast for the 10 valent and 13 valent vaccines
Authors: M. H. Rozenbaum, E. A. M. Sanders, A. J. van Hoek, A. G. S. C. Jansen, A. van der Ende, G. van den Dobbelsteen, G. D. Rodenburg, E. Hak, M. J. Postma
Journal: BMJ (2010)

<b>Objectives</b> To update cost effectiveness estimates for the four dose (3+1) schedule of the seven valent pneumococcal conjugated vaccine (PCV-7) in the Netherlands and to explore the impact on cost effectiveness of reduced dose schedules and implementation of 10 valent and 13 valent pneumococcal vaccines (PCV-10 and PCV-13). <b>Design</b> Economic evaluation comparing PCV-7, PCV-10, and PCV-13 with no vaccination using a decision tree analytic model built from data in previous studies. <b>Setting</b> The Netherlands. <b>Population</b> A cohort of 180 000 newborns followed until 5 years of age. <b>Main outcome measures</b> Costs; gains in life years and quality adjusted life years (QALYs); and incremental cost effectiveness ratios. <b>Results</b> Under base case assumptions—that is, assuming a five year protective period of the vaccine and no assumed net indirect effects (herd protection minus serotype replacement) among children aged over 5 years—vaccination with PVC-7 in a four dose (3+1) schedule was estimated to prevent 71 and 5778 cases of invasive and non-invasive pneumococcal disease, respectively, in children aged up to 5 years. This corresponds with a total net gain of 173 life years or 277 QALYs. The incremental cost effectiveness ratio of PCV-7 was estimated at €113 891 (£98 300; $145 000) per QALY, well over the ratio of €50 000 per QALY required for PCV-7 to be regarded as potentially cost effective. A three dose (2+1) schedule of PCV-7 reduced the incremental cost effectiveness ratio to €82 975 per QALY. For various assumptions and including 10% of the maximum net indirect effects among individuals aged 5 years and over, PCV-10 and PCV-13 had incremental cost effectiveness ratios ranging from €31 250 to €52 947 per QALY. <b>Conclusions</b> The current Dutch infant vaccination programme of four doses of PCV-7 is not cost effective because of increases in invasive disease caused by non-vaccine serotypes, which reduces the overall direct effects of vaccination and offsets potential positive herd protection benefits in unvaccinated individuals. The 10 valent and 13 valent pneumococcal vaccines could have better net health benefits than PCV-7 through less replacement disease and increased herd protection. Both these effects could substantially reduce the incremental cost effectiveness ratio to possibly acceptable levels, if total programme costs can be lowered by reduced schedules, reductions in vaccine prices, or both.
At the crossroads of SUMO and NF-kappaB.
Authors: Martin P Kracklauer, Christian Schmidt
Journal: Molecular Cancer (2003)

Recognition of pathogens by immune receptors leads to activation of macrophages, dendritic cells, and lymphocytes. Signals are communicated to enhance expression of target molecules such as cytokines and adhesion molecules, depending on activation of various inducible transcription factors, among which the family NF-κB transcription factors plays an evolutionarily conserved and critical role. Classical activation of NF-κB involves phosphorylation, polyubiquitination and subsequent degradation of the inhibitor molecules of NF-κB, referred to as IκB. Modification of IκBα, one of the mammalian IκB isoforms, with the small ubiquitin-like modifier (SUMO) results its protection from degradation. SUMO-IκBα localizes in the nucleus. The nuclear SUMO-IκBα pool may be dynamic. SUMO-IκBα functions as synergy control factor. Immunoprecipitation from cellular fractions, 35S methionine pulse-chase, and FRET assays should reveal the localization of SUMO-IκBα and the dynamics of the pool. Expression of SUMOylation defective IκBα in an IκBα -/- background should yield insights into the function of SUMO-IκBα. IκBα contains the required SUMOylation motif but IκBβ does not. The suggested study would provide evidence whether or not IκBα and IκBβ can substitute each other. In addition, the suggested assays would reveal a possible redundancy in controlling transcriptional activity of NF-κB.
The BATTLE Trial: A Bold Step toward Improving the Efficiency of Biomarker-Based Drug Development
Authors: Eric H. Rubin, Keaven M. Anderson, Christine K. Gause
Journal: Cancer Discovery (2011)

Abstract Successful completion of the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, reported in this issue of Cancer Discovery, is an important advance in the effort to improve clinical trial approaches to the simultaneous development of new therapeutics with matching diagnostic tests so that patients most likely to benefit from these therapies can be identified. Cancer Discovery; 1(1); 17–20. ©2011 AACR. Commentary on Kim et al., p. 44
Chemokine responsiveness of CD4+ CD25+ regulatory and CD4+ CD25− T cells from atopic and nonatopic donors
Authors: D. Ahern, C. M. Lloyd, D. S. Robinson
Journal: Allergy (2009)

Allergic inflammation is associated with Th2-type T cells, which can be suppressed by CD4+ CD25+ regulatory T cells (Tregs). Both express chemokine receptors (CCR) 4 and CCR8, but the dynamics of expression and effect of atopic status are unknown.
Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells
Authors: Marina Pisano, Gabriella Pagnan, Monica Loi, Maria Elena Mura, Maria Giovanna Tilocca, Giuseppe Palmieri, Davide Fabbri, Maria Antonietta Dettori, Giovanna Delogu, Mirco Ponzoni, Carla Rozzo
Journal: Molecular Cancer (2007)

Abstract Background Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic activity on melanoma cells. We tested eugenol together with six natural and synthetic eugenol-related compounds for their capability to inhibit cell growth on primary melanoma cell lines established from patients' tissue samples. Results Eugenol and isoeugenol monomers and their respective O -methylated forms did not show to inhibit melanoma cells proliferation. Conversely, the dimeric forms (biphenyls) showed some antiproliferative activity which was mild for dehydrodieugenol, higher for its O,O'- methylated form ( O,O' -dimethyl-dehydrodieugenol), and markedly pronounced for the racemic mixture of the brominated biphenyl ( 6,6' -dibromo-dehydrodieugenol) (S7), being its enantiomeric form ( S ) the most effective compared to the other compounds. Such activity resulted to be selective against tumour cells, without affecting cultured normal human skin fibroblasts. Dose and time dependence curves have been obtained for the enantiomeric form S7-( S ). Then IC 50 and minimal effective doses and times have been established for the melanoma cell lines tested. TUNEL and phosphatidylserine exposure assays demonstrated the occurrence of apoptotic events associated with the antiproliferative activity of S7-( S ). Cytotoxic activity and apoptosis induced by treating melanoma cells with eugenol-related biphenyls was partially dependent by caspase activation. Conclusion Our findings demonstrate that the eugenol related biphenyl ( S )- 6,6' -dibromo-dehydrodieugenol elicits specific antiproliferative activity on neuroectodermal tumour cells partially triggering apoptosis and its activity should be further investigated on in vivo melanoma models in order to evaluate the real anticancer effectiveness on such tumour.