tbuckley/cabot-search huggingface dataset:
Histological assessment of the Sydney classification of endoscopic gastritis.
Authors: S I Khakoo, A J Lobo, N A Shepherd, S P Wilkinson
Journal: Gut (1994)

To determine the significance of the endoscopic classification of gastritis proposed by a working party at the World Congress of Gastroenterology in Sydney 1990, 167 patients undergoing upper alimentary endoscopy were prospectively assessed by comprehensive endoscopic and histological methods. Ninety eight patients had endoscopic mucosal changes of gastritis according to the Sydney classification. Twenty six (27%) of these had histologically normal biopsy specimens. This was not statistically significantly different to the 26 (38%) of 69 with normal endoscopies whose biopsy specimens were histologically normal (chi 2 = 1.857, p &gt; 0.1). Forty three (62.5%) patients with normal endoscopies had histological gastritis. No histological counterpart was found for the macroscopic appearances of the gastric mucosa said to show inflammation proposed by the Sydney classification of gastritis. These findings confirm the inappropriateness of an endoscopic diagnosis of gastritis and it is suggested such a term should be reserved for the histological findings.
Role of Environmental Toxins in Endemic (Balkan) Nephropathy
Authors: Arthur P. Grollman, Bojan Jelaković
Journal: Journal of the American Society of Nephrology (2007)

An international symposium, held in Zagreb, Croatia, in October 2006, brought together basic scientists and clinical investigators engaged in research on endemic (Balkan) nephropathy, a chronic renal tubulointerstitial disease of previously unknown cause that often is accompanied by upper urinary tract urothelial cancer. Although this disease is endemic in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, a similar clinical entity occurs throughout Europe, Asia, and North America. Recent advances in the understanding of endemic nephropathy now favor the causative role of aristolochic acid over the ubiquitous mycotoxin known as ochratoxin A. Specifically, aristolactam-DNA adducts have been found in renal tissues and urothelial cancers of affected patients. A "signature" p53 mutation in the upper urothelial cancer associated with this disease provides evidence of long-term exposure to aristolochic acid. In addition, the renal pathophysiology and histopathology observed in endemic nephropathy most closely resemble the entity known as aristolochic acid nephropathy. Public health authorities in countries harboring this disease are encouraged to reduce the potential for dietary exposure to Aristolochia clematitis.
CCL19 and CXCL12 Trigger<b><i>in Vitro</i></b>Chemotaxis of Human Mantle Cell Lymphoma B Cells
Authors: Anna Corcione, Nicoletta Arduino, Elisa Ferretti, Lizzia Raffaghello, Silvio Roncella, Davide Rossi, Franco Fedeli, Luciano Ottonello, Livio Trentin, Franco Dallegri, Gianpietro Semenzato, Vito Pistoia
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Few data are available in the literature on chemokine receptor expression and migratory capability of mantle cell lymphoma (MCL) B cells. Information on these issues may allow us to identify novel mechanisms of chemokine-driven tumor cell migration. Experimental Design: The research was designed to investigate: (a) expression of CCR1 to CCR7 and CXCR1 to CXCR5 chemokine receptors; and (b) chemotaxis to the respective ligands in MCL B cells and in their normal counterparts, i.e., CD5+ B cells. Results: Malignant B cells from MCL patients and normal counterparts displayed similar chemokine receptor profiles. MCL B cells were induced to migrate by CXCL12 and CCL19, whereas normal CD5+ B cells migrated to the former, but not the latter chemokine. Overnight culture of MCL B cells and their normal counterparts with CXCL12 cross-sensitized other chemokine receptors to their ligands in some tumor samples but not in CD5+ B cells. Conclusions: CCR7 and CXCR4 ligands may play a key role in tumor cell migration and spreading in vivo. CXCL12 may additionally contribute by sensitizing MCL B cells to respond to the ligands of other chemokine receptors.
Latent Disease in Far East P.o.W.s
Authors: F. E. d. W. Cayley
Journal: BMJ (1945)

The relationship between parents and clinician is critical to the care and treatment of children with life-limiting conditions (LLCs) and life-threatening illnesses (LTIs). This relationship is built and maintained largely in consultations. In this article we lay out factors that bear on the success of clinical consultations and the maintenance of the essential clinician–parent relationship at progression or deterioration of LLCs or LTIs. We suggest an approach to engaging parents in conversations about care and treatment that recognises and appreciates the dilemmas which clinicians and parents face and in so doing provides a way for everyone to live with the decisions that are made. A close analysis of a consultation at progression and excerpts of encounters among parents, clinician and researcher are used to illustrate our approach to research, analysis and development of recommendations for clinical practice.
The Effect of Gene Overlapping on the Rate of RNA Virus Evolution
Authors: Etienne Simon-Loriere, Edward C. Holmes, Israel Pagán
Journal: Molecular Biology and Evolution (2013)

Gene overlapping is widely employed by RNA viruses to generate genetic novelty while retaining a small genome size. However, gene overlapping also increases the deleterious effect of mutations as they affect more than one gene, thereby reducing the evolutionary rate of RNA viruses and hence their adaptive capacity. Although there is general agreement on the benefits of gene overlapping as a mechanism of genomic compression for rapidly evolving organisms, its effect on the pace of RNA virus evolution remains a source of debate. To address this issue, we collected sequence data from 117 instances of gene overlapping across 19 families, 30 genera, and 55 species of RNA viruses. On these data, we analyzed how genetic distances, selective pressures, and the distribution of RNA secondary structures and conserved protein functional domains vary between overlapping (OV) and nonoverlapping (NOV) regions. We show that gene overlapping generally results in a decrease in the rate of RNA virus evolution through a reduction in the frequency of synonymous mutations. However, this effect is less pronounced in genes with a terminal rather than an internal gene overlap, which might result from a greater proportion of protein functional conserved domains in NOV than in OV regions, in turn reducing the number of nonsynonymous mutations in the former. Overall, our analyses clarify the role of gene overlapping as a modulator of the evolutionary rates exhibited by RNA viruses and shed light on the factors that shape the genetic diversity of this important group of pathogens.
The erbB Family: Targets for Therapeutic Development Against Cancer and Therapeutic Strategies Using Monoclonal Antibodies and Tyrosine Kinase Inhibitors
Authors: Eric K. Rowinsky
Journal: Annual Review of Medicine (2004)

The overexpression and aberrant function of members of the erbB family of receptors, particularly erbB1 (also known as epidermal growth factor receptor), and its ligands in many human cancers have provided a rationale for targeting this signaling network with novel approaches. erbB1 is a selective target for inhibiting cancers because its activation often confers a proliferative advantage. Activation of the erbB1 tyrosine kinase provides signals that drive dysregulated proliferation, invasion, metastasis, angiogenesis, and cell survival, and its inhibition has potential in both the treatment and prevention of these malignancies. Based on the structure and function of erbB1, two therapeutic strategies have been developed. The first uses human monoclonal antibodies (MAbs) generated against the receptor's ligand-binding extracellular domain. These MAbs block binding of receptor-activating ligands, and, in some cases, can induce receptor endocytosis and downregulation. The second uses small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thereby blocking receptor activation and the transduction of postreceptor signals. Early clinical studies suggest that both approaches are well tolerated and can induce clinical activity in many common malignancies.
Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Authors: Roger Stupp, Warren P. Mason, Martin J. van den Bent, Michael Weller, Barbara Fisher, Martin J.B. Taphoorn, Karl Belanger, Alba A. Brandes, Christine Marosi, Ulrich Bogdahn, Jürgen Curschmann, Robert C. Janzer, Samuel K. Ludwin, Thierry Gorlia, Anouk Allgeier, Denis Lacombe, J. Gregory Cairncross, Elizabeth Eisenhauer, René O. Mirimanoff
Journal: New England Journal of Medicine (2005)

Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival.A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
Functional polymorphisms in the promoters of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12 and MMP-13 are not associated with hepatocellular carcinoma risk
Authors: Y. Zhai, W. Qiu, X.-J. Dong, X.-M. Zhang, W.-M. Xie, H.-X. Zhang, X.-Y. Yuan, G.-Q. Zhou, F.-C. He
Journal: Gut (2007)

The matrix metalloproteinases (MMPs) play an important role in several steps of cancer development by regulating cancer-cell growth, differentiation, apoptosis, invasion, metastasis, angiogenesis and immune surveillance.1 Several polymorphisms in the promoters of a number of MMP genes, which are thought to affect the respective MMP production in an allele-specific manner, have been well characterised.2–4 There is increasing evidence indicating that these functional polymorphisms may contribute to interindividual differences in susceptibility to a wide spectrum of cancers.2–7 The role of the MMPs polymorphisms in hepatocellular carcinoma (HCC), however, has never been specifically investigated. As MMPs are plausible HCC candidate genes, we sought to examine whether the MMP polymorphisms have any bearing on the risk of HCC. Among the candidate polymorphisms, we focused on seven in the promoters of six MMP genes. These polymorphisms were MMP-1 -1607 1G/2G (rs1799750), MMP-2 C-1306T (rs243865) and C-735T (rs2285053), MMP-3 -1612 5A/6A (rs3025058), MMP-9 C-1562T (rs3918242), MMP-12 G-82A (rs2276109), and MMP-13 G-77A (rs17860523), respectively.2–7

We genotyped these seven polymorphisms in 434 incident patients with HCC and 480 controls …
ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine
Authors: P. Ceppi, M. Volante, S. Novello, I. Rapa, K.D. Danenberg, P.V. Danenberg, A. Cambieri, G. Selvaggi, S. Saviozzi, R. Calogero, M. Papotti, G.V. Scagliotti
Journal: Annals of Oncology (2006)
Prospective, Randomized Trial of Two Different Modalities of Flushing Central Venous Catheters in Pediatric Patients With Cancer
Authors: Simone Cesaro, Gloria Tridello, Mara Cavaliere, Laura Magagna, Patrizia Gavin, Riccardo Cusinato, Nicola Zadra, Giovanni Franco Zanon, Luigi Zanesco, Modesto Carli
Journal: Journal of Clinical Oncology (2009)

There are limited prospective data on whether the method of flushing affects the complication rate of tunnelled central venous catheters (CVCs).During a 25-month period, 203 pediatric patients who had newly placed Broviac-Hickman CVCs were randomly assigned to standard flushing with heparin solution or to experimental flushing with normal saline via a positive-pressure cap.Two hundred twenty-one complications were recorded among 75,249 CVC-days (2.94 per 1,000 CVC-days). A higher incidence of CVC occlusion (83 v 41 episodes; P = .0002) and bacteremia (24 v 9; P = .01) were found in the experimental arm. The cumulative probability of developing at least one CVC complication was higher in the experimental arm than in the standard arm (65.1% [95% CI, 55% to 75%] v 43.8% [95% CI, 34% to 54%], respectively; P = .01). No difference was found in either the cause or the frequency of premature removal of CVCs between the two study arms. After a median follow-up of 360 days (range, 4 to 1,073), CVC survival was similar: 77% (95% CI, 66% to 84%) for the experimental arm and 69% (95% CI, 53% to 80%) for the standard arm (P = .7). The factors associated with the occurrence of CVC complication were a diagnosis of leukemia/lymphoma, double-lumen CVC, and experimental flushing. The only factor significantly associated with premature removal of a CVC was a diagnosis of leukemia/lymphoma (hazard rate, 2.3; 95% CI, 1.1 to 4.7).An increased complication rate was found with normal saline flushing, but additional investigation is warranted to clarify whether it is related to saline use or to once-a-week flushing.
Respiratory mechanics in ventilated COPD patients: forced oscillation versus occlusion techniques
Authors: R Farre, M Ferrer, M Rotger, A Torres, D Navajas
Journal: European Respiratory Journal (1998)

The respiratory mechanics of artificially ventilated chronic obstructive pulmonary disease (COPD) patients were investigated by means of the forced oscillation (FOT) and the end-inspiratory airway occlusion (AOT) techniques. FOT was applied to measure respiratory resistance (Rrs) and reactance (Xrs) from 0.25-16 Hz. Maximum (Rmax) and minimum (Rmin) resistances, static elastance (Est) and time constant (T) were computed by AOT. FOT and AOT data were interpreted with models featuring airway wall shunt, tissue viscoelasticity and parallel inhomogeneity. Rrs* and Xrs*, predicted from the AOT data, were computed and compared with Rrs and Xrs measured by FOT. Rrs and Xrs (hPa x s x L(-1)) decreased from 31.2+/-10.3 to 5.9+/-4.6 and increased from -20.3+/-7.1 to -8.0+/-4.4 from 0.25-16 Hz, respectively. Central resistance (Rc) and peripheral resistance (Rp) (in hPa x s x L(-1)), and shunt elastance (Esh) and tissue elastance (Et) (in hPa x L(-1)) were 4.4+/-5.4, 28.4+/-153, 723+/-393 and 31.8+/-10.1, respectively. Rmin, Rmax and Est were 18.4+/-5.9, 28.4+/-12.8 and 18.1+/-4.2 respectively, and T=0.76+/-0.25 s. The frequency dependence of predicted Rrs* and Xrs* differed markedly from that of measured Rrs and Xrs. The use of different models to interpret the measured data suggests that both airway and tissue properties determined the frequency dependence of respiratory resistance and respiratory reactance in ventilated chronic obstructive pulmonary disease patients at the investigated frequencies (0.25-16 Hz).
Structural basis for T cell recognition of altered peptide ligands: a single T cell receptor can productively recognize a large continuum of related ligands.
Authors: G J Kersh, P M Allen
Journal: The Journal of Experimental Medicine (1996)

T cells recognize short linear peptides bound to major histocompatibility complex (MHC)-encoded molecules. Subtle molecular changes in peptide antigens produce altered peptide ligands (APLs), which induce different T cell responses from those induced by the antigenic ligand. A molecular basis for how these slight molecular variations lead to such different consequences for the T cell has not been described. To address this issue, we have made amino acid substitutions at the primary T cell receptor (TCR) contact residue of the murine hemoglobin determinant, Hb(64-76)/I-Ek and produced 12 peptides that interact with the TCR of the T cell clone 3.L2. The 3.L2 T cell responds to these peptides, which vary 1 million-fold in their activity, and enables them to be ranked according to their relative ability to signal through the 3.L2 TCR. Such a ranking reveals that the ability of the 3.L2 T cell to respond to these peptides depends on how well the structure of the side chain at the primary TCR contact site mimics that of the Asn residue present in the antigenic ligand. The reactivity of the 3.L2 T cell also depends on an MHC contact residue that is next to the primary TCR contact residue, suggesting that conformation of the Asn side chain is also important. By using nonnatural amino acids at a TCR contact residue, we have demonstrated that APLs can be rationally designed based on structure. These data are consistent with a model in which the affinity of a peptide-MHC complex for the TCR determines how the T cell will respond.
Heterogeneity of Parathyroid Hormone. CLINICAL AND PHYSIOLOGIC IMPLICATIONS
Authors: Robert Silverman, Rosalyn S. Yalow
Journal: Journal of Clinical Investigation (1973)

When immunoreactive human parathyroid hormone (hPTH), extracted by three different solvents (20% acetone in 1% acetic acid, 8 M urea, or normal saline) from parathyroid glandular tissue was subjected to Sephadex G-100 gel filtration and immunoassay using two different antisera (273 and C-329), four distinct fractions were observed. The first (I), a void volume peak, was detected by both antisera with similar immunoreactivity, as was a second (II), which had the elution and sedimentation properties of highly purified bovine parathyroid hormone (bPTH); a third (III) eluted between [(125)I]growth hormone and [(125)I]insulin, sedimented with the velocity of a molecule of approximately 6,000 mol wt, and was detected primarily by antiserum 273; a final fraction (IV), detected primarily by C-329, eluted just prior to [(125)I]insulin. The elution profiles of the acetone-acetic acid and 8 M urea extracts were similar and contained fraction II as their major component. In saline extracts, however, fraction III predominated. Three fractions, having gel filtration and immunologic characteristics similar to fractions II, III, and IV, respectively, of saline glandular extracts, were detected in the plasma of patients with both primary (adenomatous or carcinomatous) and secondary hyperparathyroidism. The predominant component in every plasma was the intermediate fraction that, like III, was detected primarily by antiserum 273, while the least abundant form was consistently the final fraction, detected primarily by antiserum C-329. The first fraction, like II, was detected with about equal potency by both antisera and had an elution volume on Sephadex corresponding to that of intact bPTH. It bore a reciprocal relationship to serum calcium and disappeared from the plasma of a uremic patient during calcium infusion or following parathyroidectomy with a half-time of no more than 20 min. This component therefore probably represents biologically active hormone. The intermediate and final fractions had turnover times in the plasma of a uremic patient more than 100 times greater than the active form, remained elevated even in the presence of post-parathyroidectomy hypoparathyroidism in this patient and were presumed to be biologically inactive. The ratio of biologically inactive fragments to the active form was greater in secondary hyperparathyroidism. The evidence presented favors a glandular origin for the fragments. Comparison of hormonal assays with the two antisera reveals a striking advantage in the preoperative diagnosis of primary hyperparathyroidism with antiserum 273 that is due to the enhanced sensitivity occasioned by its detection of a biologically inactive as well as the biologically active hormonal form.
152 HBV, HCV, HDV AND HEV COINFECTIONS IN A COHORT OF HIV POSITIVE PATIENTS IN CAMEROON
Authors: R. Salpini, L. Ceccarelli, J. Fokam, A. Nanfack, J. Torimiro, L. Sarmati, M. Andreoni, V. Colizzi, C.F. Perno, O. Njoya
Journal: Journal of Hepatology (2012)
Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits.
Authors: A Mügge, J H Elwell, T E Peterson, T G Hofmeyer, D D Heistad, D G Harrison
Journal: Circulation Research (1991)

The endothelium-derived relaxing factor is rapidly inactivated by superoxide radicals, and atherosclerotic vessels generate excess radical species. We tested the hypothesis that an imbalance between intrinsic superoxide dismutase (SOD) activity and the generation of superoxide radicals in atherosclerotic arteries may result in augmented inactivation of endothelium-derived relaxing factor. Vascular SOD was increased in normal and cholesterol-fed (1% cholesterol for 4 months) rabbits approximately twofold by treatment with polyethylene-glycolated SOD (PEG-SOD; 41,000 units/kg/day i.m.) for 1 week. Aortic rings from these animals and nontreated control and atherosclerotic rabbits subsequently were studied in organ chambers. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore A23187 were improved by PEG-SOD in atherosclerotic but not in normal rabbits. PEG-SOD pretreatment did not alter endothelium-independent relaxations to nitroprusside. Thus, treatment with PEG-SOD can partially restore impaired endothelium-dependent relaxation of atherosclerotic arteries. We conclude that generation of oxygen-derived radicals likely contributes to endothelial dysfunction of atherosclerotic arteries.