tbuckley/cabot-search huggingface dataset:
The role of inhaled corticosteroids in the management of acute asthma
Authors: B. H. Rowe, D. Vethanayagam
Journal: European Respiratory Journal (2007)

Acute exacerbations are common occurrences for asthmatics. Contact with airway irritants ( e.g. viral upper respiratory tract infections, aero-allergens) and nonadherence to controller medications, along with the natural history of the disease can result in deterioration in lung function, increased symptoms and an increased need for reliever medication. It is estimated that nearly 2 million emergency department (ED) asthma visits occur annually in the USA alone 1. Since the frequency of exacerbations is related to asthma severity on the one hand, and increasing degrees of airway eosinophilia are associated with increased disease severity on the other 2, understanding the pathophysiology of exacerbations is critically important to disease control.

The medical consequences of these events can range from minor life interruptions to severe illness. These severe exacerbations often result in ED presentation or unscheduled visits to health professionals for urgent care, and may require hospital admission. While rare, death from exacerbations does occur. The economic consequences of asthma have been well documented 3, 4 and the acute attack has been estimated to represent ∼25% of overall asthma costs 5. The control of chronic asthma with the use of inhaled corticosteroids (ICS), with or without the use of additional agents ( e.g. long-acting β-agonists or leukotriene receptor antagonists), anticholinergics and in some cases newer biological agents, have proven effective in reducing the frequency and severity of these exacerbations. In addition, nonpharmacological approaches (regular follow-up, action plans, immunisation, asthma education) have also proven to be effective but adherence to these can be low 6, 7.

Despite these advances, a gap between what is known and what is practiced hampers efforts to improve the quality of life of patients with asthma. This gap may be the result of poor access to care and resources, failure of physicians to treat the disease …
Lymphocyte and lymphocyte subset numbers in blood and bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis.
Authors: J M Grange, J L Stanford, J S Beck
Journal: Thorax (1992)

<b>2673</b> <h3><b>Introduction:</b></h3> Calcific uremic arteriolopathy, also known as calcific vasculopathy or calciphylaxis, is characterized by necrosis of the skin and fatty tissues. The cause is largely related to calcium deposition in soft tissues causing small blood vessel occlusion and skin necrosis. The disease is associated with renal failure and has high 1-year mortality rate of more than 50% (1). Diagnosis is based on clinical suspicion, imaging with radiographs, CT and bone scans, and tissue biopsy. This educational exhibit highlights the role of imaging modalities in early diagnosis and localization of this mortal disease. <h3><b>Methods:</b></h3> We retrospectively evaluated referred cases to our department for bone scan with high clinical suspicion for calciphylaxis. Multi-imaging data was collected and their role in evaluation of the disease was assessed. Finally the histopathology results were used to confirm the calcific vasculopathy. <h3><b>Results:</b></h3> Presented in the exhibit are picturesque illustration of calcific vasculopathy lesions (clinical presentation), evaluated on Bone scan, radiographs and CT scan. The cases include peripheral (truncal and appendicular) as well as visceral calciphylaxis and their pathology confirmation. <h3><b>Conclusions:</b></h3> Calcific uremic arteriolopathy aka calcific vasculopathy is an uncommon and serious disease. Recent data shows about 1% of patients on dialysis being affected. Patients usually present with imbalance in calcium metabolism, with calcium deposition in the wall of the arterioles causing occlusion and necrosis of the overlying skin, leading to painful ulcers (2). Skin biopsy is the standard for diagnosis, however, can cause non-healing and worsening of the ulcers. Imaging modalities play an important role in localization and diagnosis formation. Radiographs demonstrate vascular calcification within the skin, however cannot differentiate from the renal patients without calciphylaxis. Bone scintigraphy demonstrate increased tracer uptake in calciphylaxis affected regions with enhanced uptake in indurated plaques. CT scan works similar to radiographs with higher resolution and may help in evaluation of visceral lesions. Treatment is directed towards normalizing the calcium and phosphate blood levels and meticulous wound management. Calcific vasculopathy is a challenging disease and early diagnosis is imperative for regulating calcium and improving overall quality of life for this subset of patients. References: Mazhar AR, Johnson RJ, Gillen D, et al. Risk factors and mortality associated with calciphylaxis in end-stage renal disease. Kidney Int. 2001;60(1):324–32. Mochel MC, Arakaki RY, Wang G, Kroshinsky D, Hoang MP. Cutaneous calciphylaxis: a retrospective histopathologic evaluation. Am J Dermatopathol. 2013;35(5):582–6.
T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation
Authors: Tadashi Ariga, Noriko Oda, Koji Yamaguchi, Nobuaki Kawamura, Hideaki Kikuta, Shoichiro Taniuchi, Yohnosuke Kobayashi, Kihei Terada, Hisami Ikeda, Michael S. Hershfield, Kunihiko Kobayashi, Yukio Sakiyama
Journal: Blood (2001)
Monoclonal antibodies to guinea pig Ia antigens. II. Effect on alloantigen-, antigen-, and mitogen-induced T lymphocyte proliferation in vitro.
Authors: R Burger, E M Shevach
Journal: The Journal of Experimental Medicine (1980)

Four xenographic monoclonal antibodies to guinea pig Ia antigens were tested for their inhibitory effects on antigen-, alloantigen-, and mitogen-induced T cell proliferation. All four monoclonal antibodies reacted with strain 2 Ia antigens, and all four were capable of inhibiting the strain 13 against strain 2 mixed leukocyte reaction (MLR) by 50-70%; the two monoclonals that reacted with strain 13 Ia antigens were also capable of inhibiting the strain 2 against strain 13 MLR. In contrast, an analysis of the effects of a single monoclonal antibody on the responses to several antigens demonstrated a selective monoclonal pattern of inhibition in that the responses to some, but not all, antigens were inhibited. These results suggest that monoclonal antibodies react with different parts of Ia molecules that may have different functional roles and that certain parts of an Ia molecule participate in the presentation of certain antigens, whereas other regions of the same molecule present different antigens.
Genome-wide functional analysis of human 5' untranslated region introns
Authors: Can Cenik, Adnan Derti, Joseph C Mellor, Gabriel F Berriz, Frederick P Roth
Journal: Genome biology (2010)

Approximately 35% of human genes contain introns within the 5' untranslated region (UTR). Introns in 5'UTRs differ from those in coding regions and 3'UTRs with respect to nucleotide composition, length distribution and density. Despite their presumed impact on gene regulation, the evolution and possible functions of 5'UTR introns remain largely unexplored.We performed a genome-scale computational analysis of 5'UTR introns in humans. We discovered that the most highly expressed genes tended to have short 5'UTR introns rather than having long 5'UTR introns or lacking 5'UTR introns entirely. Although we found no correlation in 5'UTR intron presence or length with variance in expression across tissues, which might have indicated a broad role in expression-regulation, we observed an uneven distribution of 5'UTR introns amongst genes in specific functional categories. In particular, genes with regulatory roles were surprisingly enriched in having 5'UTR introns. Finally, we analyzed the evolution of 5'UTR introns in non-receptor protein tyrosine kinases (NRTK), and identified a conserved DNA motif enriched within the 5'UTR introns of human NRTKs.Our results suggest that human 5'UTR introns enhance the expression of some genes in a length-dependent manner. While many 5'UTR introns are likely to be evolving neutrally, their relationship with gene expression and overrepresentation among regulatory genes, taken together, suggest that complex evolutionary forces are acting on this distinct class of introns.
Conception during 'Diane' therapy—a successful outcome
Authors: B.N. Statham, W.J. Cunliffe, J.K. Clayton
Journal: British Journal of Dermatology (1985)

Journal Article Conception during ‘Diane’ therapy—a successful outcome Get access B.N. Statham, B.N. Statham Department of Dermatology, The General Infirmary, Leeds LSI 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.J. Cunliffe, W.J. Cunliffe Department of Dermatology, The General Infirmary, Leeds LSI 3EX, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.K. Clayton J.K. Clayton Department of Obstetrics, St Luke's Hospital, Bradford, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue 3, 1 September 1985, Page 374, https://doi.org/10.1111/j.1365-2133.1985.tb02097.x Published: 01 September 1985
The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
Authors: V Brichard, A Van Pel, T Wölfel, C Wölfel, E De Plaen, B Lethé, P Coulie, T Boon
Journal: The Journal of Experimental Medicine (1993)

Lymphocytes of melanoma patients can be restimulated in vitro with autologous tumor cells to generate antitumor cytolytic T lymphocytes (CTL). Previous reports have indicated that, when such CTL are obtained from HLA-A2 melanoma patients, they often display broad reactivity on A2 melanoma cell lines. Such antitumor CTL clones, which appeared to recognize the same antigen, were isolated from two patients. We report here the cloning of a cDNA that directs the expression of the antigen recognized by these CTL. This cDNA corresponds to the transcript of the tyrosinase gene. The gene was found to be active in all tested melanoma samples and in most melanoma cell lines. Among normal cells, only melanocytes appear to express the gene. The tyrosinase antigen presented by HLA-A2 may therefore constitute a useful target for specific immunotherapy of melanoma. But possible adverse effects of antityrosinase immunization, such as the destruction of normal melanocytes and its consequences, will have to be examined before clinical pilot studies can be undertaken.
DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation
Authors: Samuel F. Bakhoum, Lilian Kabeche, John P. Murnane, Bassem I. Zaki, Duane A. Compton
Journal: Cancer Discovery (2014)

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN.The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities.
Hemoglobin Levels and Erythropoietin Doses in Hemodialysis and Peritoneal Dialysis Patients in the United States
Authors: Jon J. Snyder, Robert N. Foley, David T. Gilbertson, Edward F. Vonesh, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Erythropoietic agents, a cornerstone of management, are a major component of the cost of renal replacement therapy. The objectives of this study were to compare (on a month-by-month basis) U.S. hemodialysis and peritoneal dialysis patients in terms of the proportion of patients receiving erythropoietin, erythropoietin doses, and hemoglobin levels after initiation of erythropoietin. Patients studied (hemodialysis, n = 121,970; peritoneal dialysis, n = 7129) began dialysis between 1995 and 2000, had Medicare as their primary payer, were 65 yr old or older at dialysis inception, had no erythropoietin claims before dialysis inception, and did not have a switch in dialysis modality in the first 6 mo of dialysis therapy. Total monthly erythropoietin doses and average monthly hemoglobin levels were calculated from Medicare claims. The proportion of patients who received erythropoietin plateaued at 3 mo in both groups: 25% in peritoneal dialysis patients and 80% in hemodialysis patients. However, monthly erythropoietin doses plateaued at 30,000 units in peritoneal dialysis patients and 60,000 units in hemodialysis patients, a disparity not explicable by differences in baseline characteristics. Among subjects who received erythropoietin, mean hemoglobin levels were similar at steady state in both populations and met the National Kidney Foundation Dialysis Outcomes Quality Initiative hemoglobin target level of 11 to 12 g/dl. Hemoglobin levels in U.S. hemodialysis and peritoneal populations are similar. However, erythropoietin doses are dramatically higher in hemodialysis patients. E-mail: [email protected]
Psychometric Evaluation of the Adherence in Diabetes Questionnaire
Authors: Lene J. Kristensen, Mikael Thastum, Anne H. Mose, Niels H. Birkebaek
Journal: Diabetes Care (2012)

OBJECTIVE To assess the psychometric properties of a short, new, self-administered questionnaire (17–19 items) for evaluating the adherence behavior of children and adolescents with type 1 diabetes and their caregivers. This instrument has separate versions depending on the means of insulin administration, i.e., continuous subcutaneous insulin infusion (Adherence in Diabetes Questionnaire [ADQ]-I), or conventional insulin injection (ADQ-C). RESEARCH DESIGN AND METHODS A total of 1,028 caregivers and 766 children and adolescents 2–17 years of age were recruited through the Danish Registry of Childhood Diabetes and completed the national web survey, including the ADQ and psychosocial measures of self-efficacy, parental support, family conflict, and aspects of diabetes-related quality of life. Blood samples were obtained for central HbA1c analysis. The psychometric properties of the ADQ were evaluated, and the association with glycemic control was assessed. RESULTS There was good internal consistency for both the youth and caregiver reports and strong agreement between the caregiver and youth reports. Higher ADQ scores, indicating better adherence, were associated with better self-efficacy, more parental support, less diabetes-related conflict, and less experience with treatment barriers. Factor analysis supported maintaining the one-factor structure of the ADQ. Higher ADQ scores were associated with lower HbA1c levels. CONCLUSIONS The ADQ showed good psychometric properties. Although the test-retest reliability and sensitivity to change of the instrument still need to be established, the ADQ appears to be a valuable tool for assessing adherence in families with children and adolescents with type 1 diabetes in both clinical and research settings.
Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization
Authors: Virginie Driffort, Ludovic Gillet, Emeline Bon, Séverine Marionneau-Lambot, Thibauld Oullier, Virginie Joulin, Christine Collin, Jean-Christophe Pagès, Marie-Lise Jourdan, Stéphan Chevalier, Philippe Bougnoux, Jean-Yves Le Guennec, Pierre Besson, Sébastien Roger
Journal: Molecular Cancer (2014)

NaV1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expression level is associated with metastatic occurrence and patients' death. In breast cancer cells, NaV1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness. In this study, we showed that the extinction of NaV1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 μM) inhibited NaV1.5 currents in breast cancer cells and reduced NaV1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by NaV1.5-expressing human breast cancer cells. Taken together, our results demonstrate the importance of NaV1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with NaV activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.
Sequence of a cDNA for mouse thymidylate synthase reveals striking similarity with the prokaryotic enzyme.
Authors: S M Perryman, C Rossana, T L Deng, E F Vanin, L F Johnson
Journal: Molecular Biology and Evolution (1986)

We report the nucleotide sequence of a cloned cDNA, pMTS-3, that contains a 1-kb insert corresponding to mouse thymidylate synthase (E.C. 2.1.1.45). The open reading frame of 921 nucleotides from the first AUG to the termination codon specifies a protein with a molecular mass of 34,962 daltons. The predicted amino acid sequence is 90% identical with that of the human enzyme. The mouse sequence also has an extremely high degree of similarity (as much as 55% identity) with prokaryotic thymidylate synthase sequences, indicating that thymidylate synthase is among the most highly conserved proteins studied to date. The similarity is especially pronounced (as much as 80% identity) in the 44-amino-acid region encompassing the binding site for deoxyuridylic acid. The cDNA sequence also suggests that mouse thymidylate synthase mRNA lacks a 3' untranslated region, since the termination codon, UAA, is followed immediately by a poly(A) segment.
DISTRIBUTION OF A CROSS-REACTIVE IDIOTYPIC SPECIFICITY IN INBRED STRAINS OF MICE
Authors: Laura L. Pawlak, Alfred Nisonoff
Journal: The Journal of Experimental Medicine (1973)

The expression of an idiotype characteristic of anti-p-azophenylarsonate antibodies of all A/J mice was explored in F1 progeny, in other inbred strains, and in congenic mice. Of the strains tested only those closely related to A/J produced antibodies with the cross-reactive idiotype (CRI). None of the mice synthesized intermediate levels of CRI. No relationship between H-2 type and idiotype was noted. Congenic mice with a strain A background but a different H-2 type produced CRI in amounts quantitatively equivalent to those of strain A mice. Conversely, the presence of the H-2 genotype of strain A on an unrelated background was not associated with the formation of CRI. Nearly all F1 progeny of strain A mice formed CRI, indicating that failure of the other (non-A) parental strain to produce CRI is not attributable to the presence of a gene controlling the synthesis of a suppressor of CRI. NZB mice, which have the same heavy chain allotype as strain A, but are unrelated in origin, failed to produce CRI, although allotype has been shown to be linked to idiotype in congenic strains.
Career prospects in dermatology
Authors: A.G. SMITH
Journal: British Journal of Dermatology (1988)

Journal Article Career prospects in dermatology Get access A.G. SMITH A.G. SMITH Department of Dermatology Central Out‐Patients Department Hartshill Road, Stoke on Trent ST4 7PA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 4, 1 April 1988, Page 589, https://doi.org/10.1111/j.1365-2133.1988.tb02481.x Published: 01 April 1988
Pathogenesis of hepatic steatosis in the parenterally fed rat.
Authors: R I Hall, J P Grant, L H Ross, R A Coleman, M G Bozovic, S H Quarfordt
Journal: Journal of Clinical Investigation (1984)

Hepatic steatosis frequently complicates total parenteral nutrition (TPN). Some of the mechanisms responsible were examined in rats receiving calories as dextrose (CHO-TPN) or dextrose plus lipid emulsion (Lipid-TPN). Hepatic triglyceride content increased approximately threefold after CHO-TPN and twofold after Lipid-TPN (P less than 0.02). Hepatic triglyceride fatty acid composition reflected endogenous synthesis. Hepatic acetyl-Coenzyme A carboxylase specific activity increased fourfold after CHO-TPN and twofold after Lipid-TPN, and it correlated positively with hepatic lipid content (r = 0.82). The activities of the microsomal enzymes of complex lipid synthesis were unchanged in the TPN groups. Both TPN regimens suppressed hepatic triglyceride secretion, measured by the rise in plasma triglyceride and the incorporation of [14C]palmitic acid into plasma triglyceride after intravenous Triton. Hepatic triglyceride secretion correlated negatively with total hepatic lipid content (r = -0.89). CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both. Both adipose and cardiac lipase were higher for Lipid-TPN animals than for CHO-TPN or control animals. Hepatic 14C-triglyceride content was increased in both TPN groups as compared with controls after the injection of 1-[14C]-palmitic acid. This increment was proportional to the decreased hepatic secretion. Triglyceride fatty acid oxidation was significantly suppressed by CHO-TPN, less so by Lipid-TPN. Free fatty acid oxidation was suppressed only by CHO-TPN. The results suggest that the steatosis induced by TPN in rats was due to enhanced hepatic synthesis of fatty acid and reduced triglyceride secretion. Reduced hepatic triglyceride uptake, enhanced fatty acid oxidation, and enhanced peripheral tissue plasma triglyceride lipolysis when CHO-TPN is supplemented with lipid may modulate the accumulation of hepatic triglyceride and, along with reduced synthesis of fatty acid, lead to a lower hepatic triglyceride content.
Transcriptional Regulation of Endothelial Cell and Vascular Development
Authors: Changwon Park, Tae Min Kim, Asrar B. Malik
Journal: Circulation Research (2013)

The establishment and maintenance of the vascular system is critical for embryonic development and postnatal life. Defects in endothelial cell development and vessel formation and function lead to embryonic lethality and are important in the pathogenesis of vascular diseases. Here, we review the underlying molecular mechanisms of endothelial cell differentiation, plasticity, and the development of the vasculature. This review focuses on the interplay among transcription factors and signaling molecules that specify the differentiation of vascular endothelial cells. We also discuss recent progress on reprogramming of somatic cells toward distinct endothelial cell lineages and its promise in regenerative vascular medicine.