tbuckley/cabot-search huggingface dataset:
Familial Vesicoureteral Reflux: Testing Replication of Linkage in Seven New Multigenerational Kindreds
Authors: Simone Sanna-Cherchi, Adam Reese, Terry Hensle, Gianluca Caridi, Claudia Izzi, You Yeun Kim, Anita Konka, Luisa Murer, Francesco Scolari, Roberto Ravazzolo, Gian Marco Ghiggeri, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2005)

Vesicoureteral reflux (VUR) (OMIM %193000), a common cause of childhood renal failure, is strongly influenced by hereditary factors. Familial VUR most closely conforms to autosomal-dominant inheritance, but because of variable penetrance and expressivity, large multigenerational pedigrees tractable to linkage analysis have been difficult to ascertain. A single genome-wide study of familial VUR has demonstrated linkage to chromosome 1p13, with 78% locus heterogeneity. Previous studies in humans have also suggested loci on chromosomes 6p21, 10q26, and 19q13, whereas mutations in ROBO2 were recently reported in some patients with VUR. Replication of these studies was attempted in seven previously undescribed families from Italy and the United States. Simulation studies, assuming 50% locus heterogeneity, showed that these kindreds had 85% power to replicate linkage and 53% power to achieve genome-wide significance at candidate intervals. Thirty-five markers on chromosomes 1p13, 3p12, 6p21, 10q26, and 19q13 were genotyped and analysis of linkage under a variety of models was performed. Parametric analysis excluded linkage to all candidate loci under genetic homogeneity; moreover, the data did not support statistically significant linkage under models of locus heterogeneity. Similarly, nonparametric, allele-sharing analysis did not reveal any evidence of linkage at any of the loci tested. Thus, despite sufficient power, linkage of familial VUR to previously reported candidate intervals could not be replicated. These data demonstrate substantial genetic heterogeneity of VUR and suggest that mapping strategies relying on a large number of kindreds or single "loaded" pedigrees will be most effective to achieve replication or detection of linkage.
Antigen-specific multifunctional T-cells in sarcoidosis patients with Löfgren’s syndrome
Authors: Maria Wikén, Mahyar Ostadkarampour, Anders Eklund, Matthew Willett, Edward Chen, David Moller, Johan Grunewald, Jan Wahlström
Journal: European Respiratory Journal (2011)

Sarcoidosis is a granulomatous disease of unknown aetiology, mainly affecting the lungs. Recently, T-cell responses towards a specific mycobacterial protein, catalase–peroxidase (mKatG), were observed in sarcoidosis patients. Bronchoalveolar lavage (BAL) fluid and peripheral blood were obtained from a total of 23 sarcoidosis patients, of whom 13 had Löfgren’s syndrome and lung accumulations of T-cell receptor AV2S3+ T-cells. Using six-colour flow cytometry in combination with intracellular cytokine staining, T-cell subsets were studied with regard to interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin-2 production, after stimulation with mKatG or Mycobacterium tuberculosis purified protein derivate (PPD). Stimulation with mKatG resulted in higher simultaneous IFN-γ and TNF production, but less single IFN-γ production, from total BAL fluid CD4+ T-cells of Löfgren’s syndrome patients, when compared with non-Löfgren’s patients. In contrast, PPD stimulation gave rise to largely similar cytokine responses in both patient subgroups. Furthermore, mKatG stimulated higher IFN-γ production in BAL fluid and blood AV2S3+ T-cells than AV2S3- T-cells, whereas the opposite was seen in BAL fluid with PPD stimulation. Our finding that patients with Löfgren’s syndrome exhibited a more pronounced multifunctional cytokine profile (simultaneous IFN-γ and TNF production) towards the mycobacterial protein mKatG may help to explain the distinct disease presentation in this patient subgroup.
A Host-Based RT-PCR Gene Expression Signature to Identify Acute Respiratory Viral Infection
Authors: Aimee K. Zaas, Thomas Burke, Minhua Chen, Micah McClain, Bradly Nicholson, Timothy Veldman, Ephraim L. Tsalik, Vance Fowler, Emanuel P. Rivers, Ronny Otero, Stephen F. Kingsmore, Deepak Voora, Joseph Lucas, Alfred O. Hero, Lawrence Carin, Christopher W. Woods, Geoffrey S. Ginsburg
Journal: Science Translational Medicine (2013)

To improve the diagnosis of respiratory viral infection, a multiplex RT-PCR assay based on the host response was derived from experimentally infected subjects and validated in patients with febrile illness.
Cooling Heads and Hearts Versus Cooling Our Heels
Authors: Lance B. Becker
Journal: Circulation (2010)

E vidence suggests that full implementation of therapeutic hypothermia after cardiac arrest could save thousands of lives each year.Critical unanswered questions persist, beginning with a lack of evidence in regard to how early cooling should be initiated, which cooling strategy is most effective at cooling the brain, and, ultimately, what method of cooling is most optimal for survival.Two reports in this issue of Circulation, from Castren et al 1 and Bernard et al, 2 begin to provide some of these needed data.Given the immense logistic difficulty of performing randomized field studies, the teams of investigators involved in both studies are to be congratulated for conducting this important research.The presented results begin to explore the important question of how quickly and by what methods cooling should be started in the field.Although they provide some answers, they also provoke new questions.For clinicians using therapeutic hypothermia with cardiac arrest patients, it is important to clearly understand the pros and cons of earlier cooling initiated in the field with the newer techniques explored in these 2 reports.It is also important to understand the differences between the findings in these studies, along with the practical implications and limitations of each technique, before conclusions are drawn about the manner in which these studies may influence practice.
Abstract 3437: Differential transcript expression in nasopharyngeal carcinoma by cDNA microarray analysis
Authors: Timothy T.C. Yip, Dora L.W. Kwong, Roger K.C. Ngan, Cadmon K.P. Lim, Wai Wai Cheng, Victor W.S. Ma, Stephen C.K. Law, Loretta Tse
Journal: Cancer Research (2014)

Abstract By cDNA microarray, expression profiling was carried out in 360 paired tumor &amp; normal biopsies from 60 nasopharyngeal cancer (NPC) patients at 3 time points, namely, at diagnosis of NPC, on treatment with an anti-inflammatory drug, Celecoxib (Celec) and on radiotherapy (RT). We found 1 cluster of 82 transcripts with statistically significant difference in expression between tumor &amp; normal tissues at diagnosis, a second cluster of 214 tumor versus normal transcripts on Celec treatment and finally a third cluster of 202 tumor versus normal transcripts on RT. Differential expression of selected tumor associated transcripts was confirmed by RT-PCR. These include 8 tumor up-regulated transcripts with 3 encoding for immunological/inflammatory molecules, IL8, CXCL9 &amp; CXCL10, 1 matrix metallopeptidase, MMP12, which break down extracellular matrix and thus is associated with cancer metastasis, 1 osteonectin protein which is involved in cell shape changes and thus related to cancer invasion, SPARC, 1 bone morphogenic protein with a role in tissue differentiation, GREM1, 1 GTPase-activating protein for phorbol ester receptor, CHN1 and a sorting nexin family member with a role in intracellular trafficking, SNX10. Genes which were prominently down-regulated in tumor were a variety of polymorphic xenobiotic detoxification enzyme genes or genes with antioxidant function (e.g. GSTA1, GSTA2, GSTA3, CYP4B1, ALDH1A1, ADHFE1, MAOB, NQO1 &amp; OAT) which can detoxify carcinogens or other harmful chemicals or have anti-oxidant effects. Many genes were also down-regulated by RT in tumor tissues and one notable example was TOP2A which encodes topoisomerase 2A involving in chromosome condensation &amp; chromatid separation during DNA replication, CLDN1 which has tight junction adhesion function, ANLN which is required for cytokinesis, and STMN1 which can regulate microtubule filament. These genes had good potential in applying for clinical applications in diagnosis or treatment of NPC in the future. Further exploration of the clinical applications of these genes is underway. Citation Format: Timothy T.C. Yip, Dora L.W. Kwong, Roger K.C. Ngan, Cadmon K.P. Lim, Wai Wai Cheng, Victor W.S. Ma, Stephen C.K. Law, Loretta Tse. Differential transcript expression in nasopharyngeal carcinoma by cDNA microarray analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3437. doi:10.1158/1538-7445.AM2014-3437
Leishmaniasis in rheumatology, haematology and oncology: epidemiological, immunological and clinical aspects and caveats: Figure 1
Authors: Christian Bogdan
Journal: Annals of the Rheumatic Diseases (2012)

Leishmaniasis is an intracellular protozoan infection that can lead to cutaneous, mucocutaneous, visceral or systemic manifestations depending on the parasite species and virulence and on the host immune response. It is endemic in countries of Europe (Mediterranean basin), Asia, Africa, Central and South America, but autochthonous cases begin to emerge outside classical disease areas. CD4+ T helper cells, interferon γ, dendritic cells and macrophages are the key components of antileishmanial defence. Leishmaniasis is an important differential diagnosis in patients with chronic lesions of the skin or mucous membranes or with fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, histocytosis, haemophagocytic syndrome or glomerulonephritis. Organ transplant recipients and patients with autoimmune syndromes are at particular risk of developing visceral leishmaniasis following immunosuppressive therapy (eg, with steroids, methotrexate, ciclosporin or tumour necrosis factor-neutralising biological agents). Diagnosis and adequate treatment of leishmaniasis requires the combined use of culture, microscopic and nucleic acid amplication methods and species identification by sequencing and other molecular techniques. Standard regimens for the treatment of visceral leishmaniasis are intravenous liposomal amphotericin B (3 mg/kg body weight for 10 days) or oral miltefosine (150 mg/day for 28 days).
The Proinflammatory Cytokine Interleukin 1β and Hypoxia Cooperatively Induce the Expression of Adrenomedullin in Ovarian Carcinoma Cells through Hypoxia Inducible Factor 1 Activation
Authors: Stilla Frede, Patricia Freitag, Teresa Otto, Christina Heilmaier, Joachim Fandrey
Journal: Cancer Research (2005)

Abstract Adrenomedullin (ADM) is a potent hypotensive peptide produced by macrophages and endothelial cells during ischemia and sepsis. The molecular mechanisms that control ADM gene expression in tumor cells are still poorly defined. It is known, however, that hypoxia potently increases ADM expression by activation of the transcription factor complex hypoxia inducible factor 1 (HIF-1). Proinflammatory cytokines produced by tumor invading macrophages likewise activate expression of ADM. Herein, we show that apart from hypoxia, the proinflammatory cytokine interleukin 1β (IL-1β) induced the expression of ADM mRNA through activation of HIF-1 under normoxic conditions and enhanced the hypoxia-induced expression in the human ovarian carcinoma cell line OVCAR-3. IL-1β significantly increased accumulation and nuclear translocation of HIF-1α under normoxic conditions and amplified hypoxic HIF-1 activation. IL-1β treatment affected neither HIF-1α mRNA levels nor the hydroxylation status of HIF-1α and, thus, stability of the protein. Instead cycloheximide effectively prevented the increase in HIF-1α protein, indicating a stimulatory effect of IL-1β on HIF-1α translation. Finally, treatment of HIF-1α with short interfering RNA revealed a significant role for HIF-1 in the IL-1β–dependent stimulation of ADM expression.
Repeat treatment with iodine-131-rituximab is safe and effective in patients with relapsed indolent B-cell non-Hodgkin's lymphoma who had previously responded to iodine-131-rituximab
Authors: M.J. Bishton, M.F. Leahy, R.J. Hicks, J.H. Turner, A.D. McQuillan, J.F. Seymour
Journal: Annals of Oncology (2008)
Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells
Authors: Michel Gilliet, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2002)

Although CD8 T cell–mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand–activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand–activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-γ upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-γ, and no IL-4, IL-5, nor transforming growth factor (TGF)-β. The addition of anti–IL-10–neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10–producing anergic CD8 T cells. IL-10–producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-β. IL-10–producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10–producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10–producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell–mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.
Neoplastic and Nonneoplastic Lesions in Aging (C57BL/6N × C3H/HeN)F1 (B6C3F1) Mice2
Authors: J. M. Ward, D. G. Goodman, R. A. Squire, K. C. Chu, M. S. Linhart
Journal: JNCI Journal of the National Cancer Institute (1979)

Neoplastic and nonneoplastic lesions in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenesis tests were tabulated and evaluated. The most common neoplasms in 2,543 male mice were hepatocellular adenomas and carcinomas. In 2,522 female mice, common tumors were lymphomas, leukemias, pulmonary adenomas and carcinomas, hepatocellular adenomas and carcinomas, and pituitary adenomas. The risk of developing most neoplasms increased with the age of the mouse. Hepatocellular carcinomas metastasized in 12% of the animals with these tumors. Other than lymphomas and leukemias, few other tumors metastasized. Nonneoplastic lesions included cystic hyperplasia of the uterus, nephritis, ovarian and uterine cysts, inflammatory lesions of the lung, mineralization in the brain, and focal hyperplasias in several tissues. The focal hyperplasias in lung and pituitary, adrenal, and thyroid glands were suggestive of the early stages of neoplasia. Comparative aspects of lesions in aging mice and their interpretation in carcinogenesis tests are discussed.
Akathisia: A Side Effect To Be Remembered
Authors: DAVID E. RASKIN
Journal: American Journal of Psychiatry (1972)

Because of its subtle symptoms, a diagnosis of akathisia is often overlooked when a patient's symptoms worsen during drug treatment. The symptoms, which include restlessness and anxiety, are much like those of such conditions as tardive dyskinesia, restless legs syndrome, and "molimina crurum nocturna." The author warns that the phenothiazines, thioxanthenes, and butyrophenones exacerbate akathisia and that a careful diagnosis should be made before increasing a patient's medication.
SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing
Authors: Muhammad Tariq, John W Belmont, Seema Lalani, Teresa Smolarek, Stephanie M Ware
Journal: Genome biology (2011)

Abstract Background Heterotaxy-spectrum cardiovascular disorders are challenging for traditional genetic analyses because of clinical and genetic heterogeneity, variable expressivity, and non-penetrance. In this study, high-resolution SNP genotyping and exon-targeted array comparative genomic hybridization platforms were coupled to whole-exome sequencing to identify a novel disease candidate gene. Results SNP genotyping identified absence-of-heterozygosity regions in the heterotaxy proband on chromosomes 1, 4, 7, 13, 15, 18, consistent with parental consanguinity. Subsequently, whole-exome sequencing of the proband identified 26,065 coding variants, including 18 non-synonymous homozygous changes not present in dbSNP132 or 1000 Genomes. Of these 18, only 4 - one each in CXCL2 , SHROOM3 , CTSO , RXFP1 - were mapped to the absence-of-heterozygosity regions, each of which was flanked by more than 50 homozygous SNPs, confirming recessive segregation of mutant alleles. Sanger sequencing confirmed the SHROOM3 homozygous missense mutation and it was predicted as pathogenic by four bioinformatic tools. SHROOM3 has been identified as a central regulator of morphogenetic cell shape changes necessary for organogenesis and can physically bind ROCK2, a rho kinase protein required for left-right patterning. Screening 96 sporadic heterotaxy patients identified four additional patients with rare variants in SHROOM3 . Conclusions Using whole exome sequencing, we identify a recessive missense mutation in SHROOM3 associated with heterotaxy syndrome and identify rare variants in subsequent screening of a heterotaxy cohort, suggesting SHROOM3 as a novel target for the control of left-right patterning. This study reveals the value of SNP genotyping coupled with high-throughput sequencing for identification of high yield candidates for rare disorders with genetic and phenotypic heterogeneity.
A Drug Resistance Screen Using a Selective MET Inhibitor Reveals a Spectrum of Mutations That Partially Overlap with Activating Mutations Found in Cancer Patients
Authors: Ralph Tiedt, Elisa Degenkolbe, Pascal Furet, Brent A. Appleton, Sabrina Wagner, Joseph Schoepfer, Emily Buck, David A. Ruddy, John E. Monahan, Michael D. Jones, Jutta Blank, Dorothea Haasen, Peter Drueckes, Markus Wartmann, Clive McCarthy, William R. Sellers, Francesco Hofmann
Journal: Cancer Research (2011)

The emergence of drug resistance is a primary concern in any cancer treatment, including with targeted kinase inhibitors as exemplified by the appearance of Bcr-Abl point mutations in chronic myeloid leukemia (CML) patients treated with imatinib. In vitro approaches to identify resistance mutations in Bcr-Abl have yielded mutation spectra that faithfully recapitulated clinical observations. To predict resistance mutations in the receptor tyrosine kinase MET that could emerge during inhibitor treatment in patients, we conducted a resistance screen in BaF3 TPR-MET cells using the novel selective MET inhibitor NVP-BVU972. The observed spectrum of mutations in resistant cells was dominated by substitutions of tyrosine 1230 but also included other missense mutations and partially overlapped with activating MET mutations that were previously described in cancer patients. Cocrystallization of the MET kinase domain in complex with NVP-BVU972 revealed a key role for Y1230 in binding of NVP-BVU972, as previously reported for multiple other selective MET inhibitors. A second resistance screen in the same format with the MET inhibitor AMG 458 yielded a distinct spectrum of mutations rich in F1200 alterations, which is consistent with a different predicted binding mode. Our findings suggest that amino acid substitutions in the MET kinase domain of cancer patients need to be carefully monitored before and during treatment with MET inhibitors, as resistance may preexist or emerge. Compounds binding in the same manner as NVP-BVU972 might be particularly susceptible to the development of resistance through mutations in Y1230, a condition that may be addressed by MET inhibitors with alternative binding modes.
Identification of polymorphisms on the <i>MDR1</i> gene among Turkish population and their effects on multidrug resistance in acute leukemia patients
Authors: Pelin Kaya, Ufuk Gündüz, Fikret Arpaci, Ali Uĝur Ural, Sefik Guran
Journal: American Journal of Hematology (2005)

Abstract Multidrug‐resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over‐expression of which is responsible for the multidrug‐resistance phenotype in many cancer types, is P‐glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single‐nucleotide polymorphisms (SNPs) C3435T, G2677T, and T‐129C in the MDR1 gene were shown to be correlated with lower P‐glycoprotein expression in normal tissues. It was suggested that this might have an advantage in cancer chemotherapy by resulting in a low drug‐resistance phenotype. The frequencies of these SNPs were studied in 45 acute leukemia patients (25 of which were primary refractory and 20 of which were drug‐sensitive) and 17 healthy individuals, forming a Turkish population of 62 individuals. In the first part of the study, these polymorphisms were compared with other populations. Marked differences were apparent between African and Turkish populations for the C3435T polymorphism. On the other hand, similarities were found between other Caucasian/Asian and Turkish populations ( P &lt; 0.001). However, for the G2677T polymorphism, the Turkish population is different than Japanese and German populations ( P &lt; 0.001). For the T‐129C polymorphism, all individuals in the studied population were homozygous for the T/T genotype. In the second part of this study, drug‐resistant and drug‐sensitive acute leukemia patients were compared for these SNPs. These polymorphisms did not seem to have a significant effect on P‐glycoprotein‐mediated drug resistance in the patients studied. Am. J. Hematol. 80:26–34, 2005. © 2005 Wiley‐Liss, Inc.
Stoichiometry of Gata4, Mef2c, and Tbx5 Influences the Efficiency and Quality of Induced Cardiac Myocyte Reprogramming
Authors: Li Wang, Ziqing Liu, Chaoying Yin, Huda Asfour, Olivia Chen, Yanzhen Li, Nenad Bursac, Jiandong Liu, Li Qian
Journal: Circulation Research (2014)

Generation of induced cardiac myocytes (iCMs) directly from fibroblasts offers great opportunities for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate of fibroblasts to fully reprogrammed iCMs, which could in part be attributed to unbalanced expression of reprogramming factors Gata4 (G), Mef2c (M), and Tbx5 (T) using the current gene delivery approach.
A follow-up study of superficial radiotherapy for benign dermatoses: recommendations for the use of X-rays in dermatology
Authors: N. R. ROWELL
Journal: British Journal of Dermatology (1973)

Journal Article A follow‐up study of superficial radiotherapy for benign dermatoses: recommendations for the use of X‐rays in dermatology Get access N. R. ROWELL N. R. ROWELL University Department of Dermatology, General Infirmary, Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 88, Issue 6, 1 June 1973, Pages 583–590, https://doi.org/10.1111/j.1365-2133.1973.tb08023.x Published: 01 June 1973 Article history Accepted: 26 November 1972 Published: 01 June 1973