tbuckley/cabot-search huggingface dataset:
Progression of allergy and asthma through childhood to adolescence.
Authors: E von Mutius
Journal: Thorax (1996)

<b>Background and aim:</b> Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study. <b>Subjects and methods:</b> A total of 587 <i>Helicobacter pylori</i> infected subjects were randomised to receive a one week course of anti-<i>Helicobacter</i> therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression. <b>Results:</b> Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent <i>H pylori</i> infection, age &gt;45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09–0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent <i>H pylori</i> infection (OR 2.13 (95% CI 1.41–3.24)), age &gt;45 years (OR 1.92 (95% CI 1.18–3.11)), alcohol use (OR 1.67 (95% CI 1.07–2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13–2.67)) were independent risk factors associated with IM progression. <b>Conclusion:</b> Eradication of <i>H pylori</i> is protective against progression of premalignant gastric lesions.
Behavior of left ventricular mechanoreceptors with myelinated and nonmyelinated afferent vagal fibers in cats.
Authors: B N Gupta, M D Thames
Journal: Circulation Research (1983)

The purpose of this study was to determine the behavior of left ventricular mechanoreceptors with myelinated vagal afferents and to compare them with endings with nonmyelinated vagal afferents. Single unit activity was recorded from 13 endings with nonmyelinated vagal afferents (conduction velocity 2.1 +/- 0.3 m/sec) and from 16 endings with myelinated vagal afferents (conduction velocity 7.3 +/- 1.3 m/sec). Resting discharge frequencies of nonmyelinated afferents and of myelinated vagal afferents were 1.7 +/- 0.3 and 2.7 +/- 0.5 imp/sec (P less than 0.1), respectively (at left ventricular end diastolic pressure of 6 mm Hg for both groups). Ten of 16 myelinated vagal afferents had pulse synchronous discharge under basal condition, whereas only 3 of 13 nonmyelinated vagal afferents had such activity. During aortic occlusion, the discharge of myelinated vagal afferents increased 1.7 +/- 0.3 imp/sec per mm Hg, whereas nonmyelinated vagal afferents increased significantly (P less than 0.05) less (0.5 +/- 0.1 imp/sec per mm Hg). Discharge for both groups was linearly related to left ventricular end-diastolic pressure but not to left ventricular systolic pressure. Increases in left ventricular systolic pressure alone did not increase firing for either group. During aortic occlusion, the maximum discharge rates of myelinated vagal afferents (43 +/- 7 imp/sec) were significantly higher than those of nonmyelinated vagal afferents (14 +/- 3 imp/sec) at left ventricular end-diastolic pressure of 30 +/- 2 and 24 +/- 2 mm Hg, respectively. Both groups increased their discharge during volume expansion with myelinated vagal afferents showing greater sensitivity than nonmyelinated vagal afferents. All endings studied were in the inferoposterior wall of the left ventricle. All nonmyelinated vagal afferents were in or near the epicardium. In contrast, myelinated vagal afferents were equally distributed between the endocardium and the epicardium. Myelinated vagal afferents had discrete receptive fields (1-2 mm2) whereas those of nonmyelinated vagal afferents were much larger (1 cm2). In conclusion, the discharge of left ventricular endings with nonmyelinated vagal afferents and myelinated vagal afferents both appear to be determined mainly by changes in left ventricular end-diastolic pressure. They may be located at different depths in the left ventricular wall. Myelinated vagal afferents have greater sensitivity and maximum firing frequencies than nonmyelinated vagal afferents.
An incidental pulmonary part-solid ground-glass nodule in a patient under anticoagulant therapy
Authors: Jo-Yu Chen, Huang-Chun Lien, Jin-Shing Chen, Yeun-Chung Chang
Journal: Thorax (2015)

A 53-year-old man with a history of recurrent PE during 2008–2010, under long-term warfarin (Coumadin) therapy, had an incidental finding of a small subpleural part-solid ground-glass nodule (GGN) in the right upper lobe from a screening CT in December 2013 (figure 1A). The first follow up CT in April 2014 showed no significant interval change. The second follow-up CT in October 2014 showed enlargement of the part-solid GGN with pleural retraction (figure 1B), and malignancy was suspected. Video-assisted thoracoscopic wedge resection of the part-solid GGN was performed in November 2014.



Figure 1 
(A) CT …
The relevance of symptom association analysis in GORD patients undergoing anti-reflux surgery
Authors: Edoardo Savarino, Patrizia Zentilin, Simona Inferrera, Vincenzo Savarino
Journal: Gut (2011)

We read with great interest the article by Broeders et al 1 on the effects of anti-reflux surgery on weakly acidic reflux and belching. The authors evaluated 31 gastro-oesophageal reflux disease (GORD) patients, refractory to proton pump inhibitors, by means of upper gastrointestinal endoscopy, validated symptoms questionnaires, stationary oesophageal manometry and 24-hour impedance–pH monitoring off antisecretory therapy before and 6 months after laparoscopic Nissen fundoplication (LNF). They observed that LNF reduced oesophageal acid exposure time (AET) and proximal migration of reflux events and similarly controlled …
Decrease of vascular endothelial growth factor in macrophages from long-term smokers
Authors: K. Nagai, T. Betsuyaku, Y. Ito, Y. Nasuhara, M. Nishimura
Journal: European Respiratory Journal (2005)

Vascular endothelial growth factor (VEGF), a survival factor for endothelial cells and a promoter of angiogenesis, is reportedly expressed in alveolar macrophages (AMs). To investigate whether long-term smoking with age affects VEGF expression in AMs, bronchoalveolar lavage (BAL) was performed on 18 young and 23 older volunteers with various smoking histories. The expressions of VEGF and its functional receptor, fms-like tyrosine kinase (Flt)-1, were quantified in AMs by real-time RT-PCR and, further, the level of VEGF in BAL fluid was determined by ELISA. VEGF mRNA in AMs demonstrated a 1.8-fold reduction in current smokers compared with nonsmokers in older subjects and, furthermore, a 1.5-fold downregulation in those with emphysema, although there was no difference between current smokers and nonsmokers among the young subjects. The downregulation in total VEGF mRNA was supported by the substantial reduction of VEGF121 and VEGF165 isoforms. However, in contrast, Flt-1 mRNA did not differ within the older groups, whereas it was upregulated in young current smokers compared with age-matched nonsmokers. VEGF in BAL fluid is significantly decreased in current smokers compared with nonsmokers, regardless of their age. In conclusion, these data imply that the biological availability of vascular endothelial growth factor in alveolar macrophages is impaired in older current smokers with long-term smoking histories.
Suppression of the Negative Regulator LRIG1 Contributes to ErbB2 Overexpression in Breast Cancer
Authors: Jamie K. Miller, David L. Shattuck, Ellen Q. Ingalla, Lily Yen, Alexander D. Borowsky, Lawrence J.T. Young, Robert D. Cardiff, Kermit L. Carraway, Colleen Sweeney
Journal: Cancer Research (2008)

Abstract The ErbB2 receptor tyrosine kinase is overexpressed in ∼25% of breast tumors and contributes to poor patient prognosis and therapeutic resistance. Here, we examine the role of the recently discovered ErbB negative regulator LRIG1 in ErbB2+ breast cancer. We observe that LRIG1 protein levels are significantly suppressed in ErbB2-induced mammary tumors in transgenic mice as well as in the majority of ErbB2+ human breast tumors. These observations raise the possibility that LRIG1 loss could contribute to the initiation or growth of ErbB2+ breast tumors. RNA interference–mediated knockdown of endogenous LRIG1 in the ErbB2-overexpressing breast tumor cell lines MDA-MB-453 and BT474 further elevates ErbB2 in these cells and augments cellular proliferation. In contrast, ectopic expression of LRIG1 reverses these trends. Interestingly, we observe that LRIG1 protein levels are suppressed in response to ErbB receptor activation in breast tumor cells but are unaffected by ErbB activation in immortalized nontransformed breast epithelial cells. Our observations indicate that the suppression of LRIG1 protein levels is a common feature of breast tumors. Moreover, our observations point to the existence of a feed-forward regulatory loop in breast tumor cells where aberrant ErbB2 signaling suppresses LRIG1 protein levels, which in turn contributes to ErbB2 overexpression. [Cancer Res 2008;68(20):8286–94]
Long-term treatment of systemic juvenile idiopathic arthritis with tocilizumab: results of an open-label extension study in Japan
Authors: Shumpei Yokota, Tomoyuki Imagawa, Masaaki Mori, Takako Miyamae, Syuji Takei, Naomi Iwata, Hiroaki Umebayashi, Takuji Murata, Mari Miyoshi, Minako Tomiita, Norihiro Nishimoto, Tadamitsu Kishimoto
Journal: Annals of the Rheumatic Diseases (2012)

Systemic-onset juvenile idiopathic arthritis (sJIA) is a chronic childhood disease associated with many complications.1–5 Treatments comprise non-steroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs and biologics,6–9 including tocilizumab, an interleukin-6 receptor monoclonal antibody.10

Results of a randomised, placebo-controlled, phase III trial of tocilizumab in sJIA patients at eight Japanese hospitals, as well as the first 48 weeks of an open-label extension, have been published.3 Protocols and amendments for this extension phase were approved by the Japanese Ministry of Health, Labor and Welfare and the institutional review board at each centre. Of 56 patients initially enrolled, six withdrew during the open-label, lead-in phase (anti-tocilizumab antibodies, three; anaphylactoid reaction, one; gastrointestinal haemorrhage, one; non-efficacy, one). During the double-blind phase, one patient from each treatment arm withdrew because of adverse events (AEs) but re-entered the open-label extension after the resolution of AEs. In total, 50 patients responding to tocilizumab and needing further treatment entered the open-label extension; two patients subsequently withdrew within the first year because of AEs. Herein, the long-term efficacy and safety of treatment through 144 weeks are presented. …
Twisted Signatures of GC-Biased Gene Conversion Embedded in an Evolutionary Stable Karyotype
Authors: Carina F. Mugal, Peter F. Arndt, Hans Ellegren
Journal: Molecular Biology and Evolution (2013)

The genomes of many vertebrates show a characteristic heterogeneous distribution of GC content, the so-called GC isochore structure. The origin of isochores has been explained via the mechanism of GC-biased gene conversion (gBGC). However, although the isochore structure is declining in many mammalian genomes, the heterogeneity in GC content is being reinforced in the avian genome. Despite this discrepancy, which remains unexplained, examinations of individual substitution frequencies in mammals and birds are both consistent with the gBGC model of isochore evolution. On the other hand, a negative correlation between substitution and recombination rate found in the chicken genome is inconsistent with the gBGC model. It should therefore be important to consider along with gBGC other consequences of recombination on the origin and fate of mutations, as well as to account for relationships between recombination rate and other genomic features. We therefore developed an analytical model to describe the substitution patterns found in the chicken genome, and further investigated the relationships between substitution patterns and several genomic features in a rigorous statistical framework. Our analysis indicates that GC content itself, either directly or indirectly via interrelations to other genomic features, has an impact on the substitution pattern. Further, we suggest that this phenomenon is particularly visible in avian genomes due to their unusually low rate of chromosomal evolution. Because of this, interrelations between GC content and other genomic features are being reinforced, and are as such more pronounced in avian genomes as compared with other vertebrate genomes with a less stable karyotype.
Utility of HbA1c Levels for Diabetes Case Finding in Hospitalized Patients With Hyperglycemia
Authors: Laura S. Greci, Mala Kailasam, Samir Malkani, David L. Katz, Ilja Hulinsky, Ramin Ahmadi, Haq Nawaz
Journal: Diabetes Care (2003)

OBJECTIVE—We evaluated the role of a single measurement of HbA1c in a diabetes case finding in hospitalized patients with random hyperglycemia at admission. RESEARCH DESIGN AND METHODS—From 20 March to 31 July 2000, 508 patients admitted through the emergency department of one hospital were tested for random hyperglycemia (plasma glucose [PG] &amp;gt;125 mg/dl). Consenting patients with hyperglycemia (without preexisting diabetes or on corticosteroids) underwent testing for HbA1c levels, two fasting PG levels, and an outpatient oral glucose tolerance test (OGTT) if necessary. RESULTS—Of the patients, 50 (9.8%) met the inclusion criteria. Of these, 70% (n = 35) completed the study, and 60% (n = 21) were diagnosed with diabetes. Patients with diabetes had higher HbA1c levels than subjects without diabetes (6.8 ± 0.4 vs. 5.3 ± 0.1%, P = 0.002). An HbA1c level &amp;gt;6.0% was 100% specific (14/14) and 57% sensitive (12/21) for the diagnosis of diabetes. When a lower cutoff value of HbA1c at 5.2% was used, specificity was 50% (10/21) and sensitivity was 100% (7/14). CONCLUSIONS—In acutely ill patients with random hyperglycemia at hospital admission, an HbA1c &amp;gt;6.0% reliably diagnoses diabetes, and an HbA1c level &amp;lt;5.2% reliably excludes it (paralleling the operating characteristics of the standard fasting glucose measurements); however, the rapidity of the HbA1c level can be useful for diabetes case finding and treatment initiation early in the hospital course.
Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer
Authors: Subhash C. Chauhan, Kelley Vannatta, Mara C. Ebeling, Namita Vinayek, Akira Watanabe, Krishan K. Pandey, Maria C. Bell, Michael D. Koch, Hiroyuki Aburatani, Yuhlong Lio, Meena Jaggi
Journal: Cancer Research (2009)

MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue microarrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH(2) kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P < 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer.
Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy.
Authors: B Fournier, J M Saudubray, B Benichou, S Lyonnet, A Munnich, H Clevers, B T Poll-The
Journal: Journal of Clinical Investigation (1994)

We have cloned the cDNA encoding human peroxisomal acyl-CoA oxidase, the first enzyme in the peroxisomal beta-oxidation of very long chain fatty acids. Its nucleotide sequence was found to be highly homologous (85%) to the rat cDNA counterpart. An 88% homology between rat and human was found in the COOH-terminal end of the cDNA which includes the Ser-Lys-Leu peroxisomal targeting signal common to many peroxisomal proteins. The gene spans approximately 30-40 kb and is poorly polymorphic. Southern blot analyses were performed in two previously reported siblings with an isolated peroxisomal acyl-CoA oxidase deficiency (pseudoneonatal adrenoleukodystrophy). A deletion of at least 17 kb, starting down-stream from exon 2 and extending beyond the 3' end of the gene, was observed in the two patients. These observations provide a molecular basis for the observed acyl-CoA oxidase deficiency in our family. In addition, our study will enable the characterization of the genetic defect in unrelated families with suspected acyl-CoA oxidase disorders.
OC-153 Ultrasound–detected gallbladder polypoid lesions, what is next?
Authors: A Kambal, C Brown, R Kannan, O Jalil, A Feroz, A Rasheed
Journal: Gut (2012)

<h3>Introduction</h3> To determine the nature and assess the current clinical pathways for the ultrasound-detected gallbladder polyps (GBP) and propose a follow-up and a therapeutic strategy based on size and symptomatology. <h3>Methods</h3> A retrospective search of the US database for “polyp” in gallbladder for the period between 1st January 2009 and 31st December 2010 was conducted. A database was then constructed including demographics, clinical presentation, principal symptoms, management and pathology. Histologic findings were analysed in patients who underwent cholecystectomy. The electronic medical records were searched to check the clinical outcome, pathologic data and follow-up arrangements. <h3>Results</h3> Ultrasound detected gallbladder polyps were reported in 347 patients, 214 female and 133 males with an age range between 14 and 93 yrs, (Median 5, IQR=41–58). Polyps were found during the course of investigation for the possibility of gallbladder disease in 125 patients (36%). The rest were incidental finding during investigation of other illnesses. The majority of referrals for the US came from primary care (60%), the rest came from hospital physicians in (24%) and surgeons in (13%) of cases. Forty two percent of the reports made no mention of polyp actual size and 39% reported the polypoid lesion to be <h3>Conclusion</h3> Our preliminary data confirm that the majority of the US detected “polypoid lesions” are incidental findings and are not true epithelial polyps. The majority of patients with symptomatic polyps who underwent cholecystectomy had cholelithiasis on histology. The current management strategy of asymptomatic polyps relies on its size and hence must be included in the US report which was poorly complied with in this series. Small (10 mm should be offered cholecystectomy. A well defined long term follow-up of patients is necessary to allow better understanding of this pathological entity and a nationwide registry or large longitudinal observational study is warranted as these might represent a missed opportunity for early detection of cancer. <h3>Competing interests</h3> None declared.
Clinical course of patients with normal or slightly or moderately abnormal coronary arteriograms: 10-year follow-up of 521 patients.
Authors: W L Proudfit, V G Bruschke, F M Sones
Journal: Circulation (1980)

The clinical course was followed for 10 years in 521 patients whose coronary arteriograms did not show any severe obstruction. Coronary disease had been suspected in all patients before arteriography. Two of 357 patients thought to have normal arteriograms died from coronary disease and two of 101 patients died who had less than 30% estimated narrowing of at least one coronary artery. Ten deaths ascribed to coronary disease occurred in 63 patinets who had 30-50% narrowing of at least one major coronary artery. The difference in death rates between the normal or mildly diseased groups and the group that had moderate narrowing was significant (p &lt; 0.01). Coronary events (death from coronary disease, subsequent myocardial infarction, or arteriographic evidence of progression of coronary obstruction) occurred in 2.1% of those who had normal arteriograms, 13.8% of the group with mild lesions, and 33% of those with moderate degree of coronary arterial narrowing.
Small airways in asthma: their independent contribution to the severity of hyperresponsiveness: Table 1–
Authors: Eef D. Telenga, Maarten van den Berge, Nick H.T. ten Hacken, Roland A. Riemersma, Thys van der Molen, Dirkje S. Postma
Journal: European Respiratory Journal (2013)

To the Editor: 

Bronchial hyperresponsiveness (BHR), i.e. increased narrowing of the airways after exposure to non-allergic stimuli, is a hallmark of asthma. BHR is a risk factor for asthma development and, additionally, a marker of worse disease outcome in asthma [1, 2]. It is generally acknowledged that obstruction of the large airways due to inflammation and remodelling contributes to more severe BHR. This is plausible, given that BHR is expressed as the concentration or dose of a stimulus that induces a 20% fall in forced expiratory volume in 1 s (FEV1). Recent studies suggest that asthmatics with BHR have more severe small airways obstruction [3, 4]. However, little is known about the converse, i.e. the association between small airways obstruction and the severity of BHR. Our aim was to assess: 1) whether asthma patients with small airways obstruction express more severe BHR than those without small airways obstruction; and 2) whether small airways obstruction is associated with more severe BHR independently of FEV1.

We analysed data from patients with mild-to-moderate asthma who were included in a previously published study on inhaled corticosteroids (ICS) in primary care [5]. All subjects underwent spirometry before and after 1 mg terbutaline, measuring FEV1, forced vital capacity (FVC) and mean expiratory flow at 50% of FVC (MEF50). BHR was assessed using a histamine challenge test, measuring the provocative dose causing a 20% fall in FEV1 (PD20) (histamine). All patients were hyperresponsive to histamine (PD …