tbuckley/cabot-search huggingface dataset:
Comparison of allergic rhinitis and vasomotor rhinitis patients on the basis of a computer questionnaire
Authors: S. Lindberg, L. Malm
Journal: Allergy (1993)

From 1 July 1990 to 31 December 1991, all patients referred to the Allergy Section of the ENT Department, University Hospital, Lund, Sweden, ( n =678) answered a 134‐item questionnaire presented on the screen of a personal computer by pressing Y (for yes) or N (for no) on the keyboard. The objective of this study was to compare the questionnaire responses from patients with allergic rhinitis (AR) with those of patients with perennial nonallergic rhinitis or vasomotor rhinitis (VMR). Nasal blockage was the predominant symptom in the VMR group, whereas the AR patients mainly suffered from eye irritation, sneezing, and, to some extent, rhinorrhea. Concomitant asthma was more prevalent in the AR group than in the VMR group, whose histories were characterized by symptoms associated with airway infections. About 60% of both groups reported problems with such nonspecific airway irritants as cigarette smoke and perfumes. With respect to the diagnostic reliability of the history, in the AR group the order of accuracy (according to the skin prick test results) of reported hypersensitivity to allergens was as follows: cat &gt; timothy &gt; birch &gt; dust mite &gt; mugwort. A history of hypersensitivity to molds as a cause of symptoms was of no diagnostic value. The findings suggest that there are several differences in the medical histories of AR and VMR patients that merit further investigation.
Mutational status of naevus-associated melanomas
Authors: D. Shitara, G. Tell-Martí, C. Badenas, M.M.S.S. Enokihara, L. Alós, A.B. Larque, N. Michalany, J.A. Puig-Butille, C. Carrera, J. Malvehy, S. Puig, E. Bagatin
Journal: British Journal of Dermatology (2015)

The origin of melanoma has always been a debated subject, as well as the role of adjacent melanocytic naevi. Epidemiological and histopathological studies point to melanomas arising either de novo or from a naevus.To evaluate the presence of mutations in genes from well-known melanomagenesis pathways in a large series of naevus-associated melanomas.Sixty-one melanomas found in association with a pre-existing naevus were microdissected, after careful selection of cell subpopulations, and submitted to Sanger sequencing of the BRAF, NRAS, c-KIT, PPP6C, STK19 and RAC1 genes. Each gene was evaluated twice in all samples by sequencing or by sequencing and another confirmation method, allele-specific fluorescent polymerase chain reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis. Only mutations confirmed via two different molecular methods or twice by sequencing were considered positive.The majority of cases presented concordance of mutational status between melanoma and the associated naevus for all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS mutations, including one case in which both the melanoma and the adjacent naevus harboured V600E and Q61K double mutations. In two cases, both melanoma and associated naevus located on acral sites were BRAF mutated, including an acral lentiginous melanoma.To our knowledge this is the largest naevus-associated melanoma series evaluated molecularly. The majority of melanomas and adjacent naevi in our sample share the same mutational profile, corroborating the theory that the adjacent naevus and melanoma are clonally related and that the melanoma originated within a naevus.
Chemotactic peptide activation of human neutrophils and HL-60 cells. Pertussis toxin reveals correlation between inositol trisphosphate generation, calcium ion transients, and cellular activation.
Authors: K H Krause, W Schlegel, C B Wollheim, T Andersson, F A Waldvogel, P D Lew
Journal: Journal of Clinical Investigation (1985)

The mechanism of neutrophil activation by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) has been studied by pretreatment of human neutrophils with pertussis toxin. Upon stimulation with FMLP, the cytosolic-free calcium concentration, [Ca2+]i, is increased both by stimulation of calcium influx and mobilization of cellular calcium. We have measured [Ca2+]i as well as the generation of the phospholipid breakdown product inositol trisphosphate (IP3), which is thought to mediate Ca2+ mobilization. As the phosphoinositide pool in human neutrophils is difficult to prelabel with [3H]myoinositol, experiments were also carried out in the cultured human promyelocytic leukemia cell line HL-60 after differentiation with dimethylsulfoxide. Pertussis toxin pretreatment of both cell types inhibited FMLP stimulated membrane depolarization, exocytosis, and superoxide production in a dose-dependent manner. This toxin effect was selective for the receptor agonist, since stimulation of these parameters by two substances bypassing the transduction mechanism, the calcium ionophore ionomycin and the phorbolester phorbol myristate acetate, were unaffected. Rises in [Ca2+]i, as well as generation of IP3 in response to FMLP, were inhibited in parallel; for the inhibition of functional responses, slightly lower toxin concentrations were required. The attentuation of the [Ca2+]i rise was more marked in the absence of extracellular calcium, i.e., when the rise is due only to calcium mobilization. The results provide evidence that phospholipase C stimulation by FMLP resulting in IP3 generation is involved in the signal transduction mechanism. Coupling of FMLP receptor occupancy to phospholipase C activation is sensitive to pertussis toxin, suggesting the involvement of a GTP binding protein (N protein), which has been shown to be a pertussis toxin substrate. The parallel changes in [Ca2+]i and IP3 further support the hypothesis that IP3 is the calcium-mobilizing mediator in FMLP-activated cells.
The Retinoblastoma Gene Undergoes Rearrangements in <i>BRCA1</i>-Deficient Basal-like Breast Cancer
Authors: Göran Jönsson, Johan Staaf, Johan Vallon-Christersson, Markus Ringnér, Sofia K. Gruvberger-Saal, Lao H. Saal, Karolina Holm, Cecilia Hegardt, Adalgeir Arason, Rainer Fagerholm, Camilla Persson, Dorthe Grabau, Ellinor Johnsson, Kristina Lövgren, Linda Magnusson, Päivi Heikkilä, Bjarni A. Agnarsson, Oskar T. Johannsson, Per Malmström, Mårten Fernö, Håkan Olsson, Niklas Loman, Heli Nevanlinna, Rosa B. Barkardottir, Åke Borg
Journal: Cancer Research (2012)

Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we used gene expression profiling to molecularly subtype 577 breast tumors, including 73 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated, and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter methylation but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1-deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1 hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer but rarely in BRCA2 hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings show the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1 status.
Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy
Authors: J L Cook, C R Purdam
Journal: British Journal of Sports Medicine (2008)

Overuse tendinopathy is problematic to manage clinically. People of different ages with tendons under diverse loads present with varying degrees of pain, irritability, and capacity to function. Recovery is similarly variable; some tendons recover with simple interventions, some remain resistant to all treatments. The pathology of tendinopathy has been described as degenerative or failed healing. Neither of these descriptions fully explains the heterogeneity of presentation. This review proposes, and provides evidence for, a continuum of pathology. This model of pathology allows rational placement of treatments along the continuum. A new model of tendinopathy and thoughtful treatment implementation may improve outcomes for those with tendinopathy. This model is presented for evaluation by clinicians and researchers.
Analysis and Evolution of Two Functional Y-Linked Loci in a Plant Sex Chromosome System
Authors: Ivan Atanassov, Catherine Delichère, Dmitry A. Filatov, Deborah Charlesworth, Ioan Negrutiu, Françoise Monéger
Journal: Molecular Biology and Evolution (2001)

White campion (Silene latifolia) is one of the few examples of plants with separate sexes and with X and Y sex chromosomes. The presence or absence of the Y chromosome determines which type of reproductive organs—male or female—will develop. Recently, we characterized the first active gene located on a plant Y chromosome, SlY1, and its X-linked homolog, SlX1. These genes encode WD-repeat proteins likely to be involved in cell proliferation. Here, we report the characterization of a novel Y-linked gene, SlY4, which also has a homolog on the X chromosome, SlX4. Both SlY4 and SlX4 potentially encode fructose-2,6-bisphosphatases. A comparative molecular analysis of the two sex-linked loci (SlY1/SlX1 and SlY4/SlX4) suggests selective constraint on both X- and Y-linked genes and thus that both X- and Y-linked copies are functional. Divergence between SlY4 and SlX4 is much greater than that between the SlY1 and SlX1 genes. These results suggest that, as for human XY-linked genes, the sex-linked plant loci ceased recombining at different times and reveal distinct events in the evolutionary history of the sex chromosomes.
Anti-TNF- therapy for orofacial granulomatosis: proceed with caution
Authors: D R Gaya
Journal: Gut (2006)

A 36 year old female patient was reviewed at the gastrointestinal clinic. She had, since the age of 15 years, been affected by troublesome orofacial granulomatosis (OFG) manifest as lower lip swelling together with a midline fissure. In the past she had received numerous therapies, including intralesional and systemic corticosteroid (short term benefit only), cinnamon and a benzoate free diet (lack of compliance), azathioprine (intolerance), and topical tacrolimus (ineffective).

In 2001, due to increasing distress about her appearance compounded by her forthcoming wedding, we decided to treat her with an infliximab infusion at 5 mg/kg. Within seven days there was a noticeable improvement, followed by complete healing of her labial fissure six weeks later, just prior to her wedding. Two weeks after this she found out she was pregnant. She subsequently gave birth to a healthy baby boy …
Effects of nucleotide sequence alignment on phylogeny estimation: a case study of 18S rDNAs of apicomplexa
Authors: D. A. Morrison, J. T. Ellis
Journal: Molecular Biology and Evolution (1997)

The reconstruction of phylogenetic history is predicated on being able to accurately establish hypotheses of character homology, which involves sequence alignment for studies based on molecular sequence data. In an empirical study investigating nucleotide sequence alignment, we inferred phylogenetic trees for 43 species of the Apicomplexa and 3 of Dinozoa based on complete small-subunit rDNA sequences, using six different multiple-alignment procedures: manual alignment based on the secondary structure of the 18S rRNA molecule, and automated similarity-based alignment algorithms using the PileUp, ClustalW, TreeAlign, MALIGN, and SAM computer programs. Trees were constructed using neighboring-joining, weighted-parsimony, and maximum-likelihood methods. All of the multiple sequence alignment procedures yielded the same basic structure for the estimate of the phylogenetic relationship among the taxa, which presumably represents the underlying phylogenetic signal. However, the placement of many of the taxa was sensitive to the alignment procedure used; and the different alignments produced trees that were on average more dissimilar from each other than did the different tree-building methods used. The multiple alignments from the different procedures varied greatly in length, but aligned sequence length was not a good predictor of the similarity of the resulting phylogenetic trees. We also systematically varied the gap weights (the relative cost of inserting a new gap into a sequence or extending an already-existing gap) for the ClustalW program, and this produced alignments that were at least as different from each other as those produced by the different alignment algorithms. Furthermore, there was no combination of gap weights that produced the same tree as that from the structure alignment, in spite of the fact that many of the alignments were similar in length to the structure alignment. We also investigated the phylogenetic information content of the helical and nonhelical regions of the rDNA, and conclude that the helical regions are the most informative. We therefore conclude that many of the literature disagreements concerning the phylogeny of the Apicomplexa are probably based on differences in sequence alignment strategies rather than differences in data or tree-building methods.
Next-Generation Sequencing Reveals High Concordance of Recurrent Somatic Alterations Between Primary Tumor and Metastases From Patients With Non–Small-Cell Lung Cancer
Authors: Stéphane Vignot, Garrett M. Frampton, Jean-Charles Soria, Roman Yelensky, Frédéric Commo, Christian Brambilla, Gary Palmer, Denis Moro-Sibilot, Jeffrey S. Ross, Maureen T. Cronin, Fabrice André, Philip J. Stephens, Vladimir Lazar, Vincent A. Miller, Elisabeth Brambilla
Journal: Journal of Clinical Oncology (2013)

Purpose Characterization of the genomic changes that drive an individual patient's disease is critical in management of many cancers. In patients with non–small-cell lung cancer (NSCLC), obtaining tumor samples of sufficient size for genomic profiling on recurrence is often challenging. We undertook this study to compare genomic alterations identified in archived primary tumors from patients with NSCLC with those identified in metachronous or synchronous metastases. Patients and Methods Primary and matched metastatic tumor pairs from 15 patients were analyzed by using a targeted next-generation sequencing assay in a Clinical Laboratory Improvement Amendments laboratory. Genomic libraries were captured for 3,230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to high coverage. Results Among 30 tumors, 311 genomic alterations were identified of which 63 were known recurrent (32 in primary tumor, 31 in metastasis) and 248 were nonrecurrent (likely passenger). TP53 mutations were the most frequently observed recurrent alterations (12 patients). Tumors harbored two or more (maximum four) recurrent alterations in 10 patients. Comparative analysis of recurrent alterations between primary tumor and matched metastasis revealed a concordance rate of 94% compared with 63% for likely passenger alterations. Conclusion This high concordance suggests that for the purposes of genomic profiling, use of archived primary tumor can identify the key recurrent somatic alterations present in matched NSCLC metastases and may provide much of the relevant genomic information required to guide treatment on recurrence.
Etiology, Management, and Outcome of the Budd-Chiari Syndrome
Authors: Sarwa Darwish Murad
Journal: Annals of Internal Medicine (2009)

Background: The Budd–Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Primary Funding Source: Fifth Framework Programme of the European Commission.
Sustained-Release Bupropion for Pharmacologic Relapse Prevention after Smoking Cessation
Authors: J. Taylor Hays, Richard D. Hurt, Nancy A. Rigotti, Raymond Niaura, David Gonzales, Michael J. Durcan, David P.L. Sachs, Troy D. Wolter, A. Sonia Buist, J. Andrew Johnston, Jonathan D. White
Journal: Annals of Internal Medicine (2001)

Background: Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse. Objective: To evaluate the efficacy of bupropion to prevent smoking relapse. Design: Randomized, placebo-controlled trial. Participants: 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day. Intervention: The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking. Measurement: Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less. Results: The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016). Conclusions: In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.
CXCR4/CXCL12 Axis in Non Small Cell Lung Cancer (NSCLC) Pathologic Roles and Therapeutic Potential
Authors: Ori Wald, Oz M. Shapira, Uzi Izhar
Journal: Theranostics (2013)

Lung cancer is the second most common malignancy and the leading cause of cancer-related death in the western world. Moreover, despite advances in surgery, chemotherapy and radiotherapy, the death rate from lung cancer remains high and the reported overall five-year survival rate is only 15%. Thus, novel treatments for this devastating disease are urgently needed. Chemokines, a family of 48 chemotactic cytokines interacts with their 7 transmembrane G-protein-coupled receptors, to guide immune cell trafficking in the body under both physiologic and pathologic conditions. Tumor cells, which express a relatively restricted repertoire of chemokine and chemokine receptors, utilize and manipulate the chemokine system in a manner that benefits both local tumor growth and distant dissemination. Among the 19 chemokine receptors, CXCR4 is the receptor most widely expressed by malignant tumors and whose role in tumor biology is most thoroughly studied. The chemokine CXCL12, which is the sole ligand of CXCR4, is highly expressed in primary lung cancer as well as in the bone marrow, liver, adrenal glands and brain, which are all sites for lung cancer metastasis. This review focuses on the pathologic role of the CXCR4/CXCL12 axis in NSCLC and on the potential therapeutic implication of targeting this axis for the treatment of NSCLC.
Excerpts from a Family Medical Dictionary
Authors: John Quin
Journal: BMJ (2004)

How to write about the death of your mother? That is the burden Rebecca Brown admirably shoulders in this short and valuable memoir. Each pithy chapter is titled after a medical term, an ever serious litany that charts the downward spiral of a life.

Brown's mother was an active soul who rarely complained, a keen driver based in New Mexico who travelled across the vast spaces of American desert to …