tbuckley/cabot-search huggingface dataset:
Enhancement of Erythroid Target Cells for Friend Murine Leukemia Virus by Intravenous Pyran Treatment&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G B Schuller, P S Morahan
Journal: JNCI Journal of the National Cancer Institute (1979)

Male BALB/c mice that received prophylactic iv treatment with pyran had significantly enhanced splenomegaly, an increased number of splenic foci induced by the spleen focus forming virus (SFFV) in the Friend murine leukemia virus (F-MuLV) complex, and a slightly decreased mean survival time as compared with untreated controls infected with F-MuLV. A corresponding increase in the lymphatic leukemia virus component of the F-MuLV complex was not observed, which suggests that the enhancement of the disease was due primarily to a selective increase in the SFFV component of the F-MuLV complex. That the enhancement was related to an increased number of target cells for SFFV was substantiated by data concerning erythropoiesis in iv pyran-treated animals. Increases in splenic hematocrits and in uptake of 59Fe in the spleens of animals treated iv with pyran provided quantitative evidence for the histologic finding of increased erythroid precursors in the spleens.
Nonimmunogenic Sarcomas Induced by 3-Methylcholanthrene Treatment of Murine Fibroblasts in Diffusion Chambers2
Authors: Giusi Carbone, Giorgio Parmiani
Journal: JNCI Journal of the National Cancer Institute (1975)

A 30-mug dose of 3-methylcholanthrene (MCA) was applied for 1 week to normal BALB/c fibroblasts in cell-impermeable diffusion chambers (DC) in the peritoneal cavities of BALB/c micemtwo groups of DC cultures, in which the carcinogen was given during weeks 1 and 5 of cultivation, respectively, were compared for the frequency of malignant transformation and for the immunogenicity of the resulting neoplasms. The cells from each DC were transplanted sc into immunodepressed semisyngeneic mice for assay of their tumorigenicity. Although tumor yield was similar in the 2 groups (25 and 22%, respectively), there was clear difference in immunogenicity; 10 of 16 sarcomas from fibroblasts treated during week 1 of culture were nonimmunogenic, whereas 8 of 9 tumors from the older cultures were immunogenic (P less than 0.02). A kinetic study of normal fibroblasts in DC revealed that cells proliferated rapidly, with a peak at day 4 after seeding, then grew progressively more slowly and ceased to replicate between 14 and 28 days of culture. Thus there was a notable difference at the moment of MCA application in the growth phase of the target cell population of the first as compared with the fifth week of culture, possible related to the different expression of tumor-associated transplantation antigens in the resulting neoplasms.
Outcomes of early interferon-gamma release assay (IGRA) testing in recent contacts of smear positive pulmonary tuberculosis (TB)
Authors: Raman Verma, Hemu Patel, Helen Thuraisingam, Gerrit Woltmann, Pranabashis Haldar
Journal: European Respiratory Journal (2013)

Introduction  Interpretation of single point IGRA testing with QuantiFERON-TB Gold In Tube (QFT) to identify recently acquired latent M.tuberculosis infection (LTBI) in contacts of active TB may be confounded by previous exposure (false positive) or testing too soon after exposure, prior to development of adaptive immunity (false negative).  Aim  To determine the relationship between exposure duration & quantitative QFT in household contacts of smear positive pulmonary TB with heterogeneous risk of remote LTBI. We hypothesise a closer association of QFT with exposure time in contacts at low risk of remote LTBI.  To estimate the exposure duration needed prior to testing for QFT to reliably identify LTBI.  Method  136 QFT tested contacts of 14 smear positive pulmonary TB cases were studied. Quantitative QFT & index symptom duration (days) were recorded. Risk of remote LTBI was scored by age & country of birth and contacts were categorised into low, moderate and high risk subgroups.  Result  There was a weak correlation between QFT value in contacts and their exposure duration (R 2 = 0.06; p=0.01). Subgroup analysis identified this correlation to be significant in contacts at low risk of remote LTBI [UK born,  2 =0.31; p 120 days after onset of index symptoms. In contrast, 3 of 33 at moderate risk and 15 of 32 at high risk of remote LTBI were QFT positive with earlier (  Conclusion  Adaptive immunity to recently acquired LTBI is detectable with QFT testing if delayed 120 days after onset of index symptoms in close contacts at low risk of previous LTBI.
Non-invasive mechanical ventilation for cystic fibrosis patients--a potential bridge to transplantation
Authors: ME Hodson, BP Madden, MH Steven, VT Tsang, MH Yacoub
Journal: European Respiratory Journal (1991)

The case histories of six cystic fibrosis patients awaiting heart-lung transplantation are reviewed. They all deteriorated with severe hypoxia and hypercapnia before donor organs became available. Nasal intermittent positive pressure ventilation was used in preference to conventional ventilation with excellent results in four patients. There were no episodes of hypotension or toxaemia and the patients were in a stable condition at the time of surgery and made an excellent post-operative recovery. The patients who were transplanted and the patient who died, for whom suitable donor organs did not become available, probably had a more comfortable time than they would have done if treated with conventional ventilation. This method of ventilation appears to be a useful bridge to transplantation when a patient suddenly deteriorates. It gives them a chance of survival for a few more days or even weeks during which time an urgent search for donor organs can be made. This is also a very cost effective method of ventilation and does not encroach on conventional Intensive Care Unit (ICU) facilities.
Reactivity of Human Sera With Adenovirus Type-12 Hamster Tumor Antigens in the Complement-Fixation Test&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G. L. van Hoosier, J. J. Trentin
Journal: JNCI Journal of the National Cancer Institute (1968)

Sera from 269 patients, most of whom had some type of neoplastic disease, and sera from 103 normal individuals were tested for complement-fixing (CF) antibodies against adenovirus type-12 (A-12) hamster tumor antigens. Twenty-seven percent of the patients and thirty-seven percent of the controls were positive at dilutions ranging from 1:4–1:32, although most of the reactions were at the lower dilutions, i.e.,1:4 and 1:8. Neutralization tests performed on sera from 140 patients indicate a positive correlation between CF antibodies against A-12 tumor antigen and A-12-neutralizing antibodies. No major differences between the tumor-antigen-positive and -negative patients were observed in regard to tumor type, blood group, Rh factor, sex, or color.
Use of Beta-Blocking Agents with Group Therapy in a Smoking Withdrawal Clinic
Authors: Robert J Dow, Walter M Fee
Journal: Journal of the Royal Society of Medicine (1984)

A controlled trial was carried out into the relative efficacy of two beta-blocking agents (oxprenolol and metoprolol) as adjuncts to group therapy in a smoking withdrawal clinic. There was no evidence to indicate that these were of specific value in assisting smoking withdrawal.
Long Term Use of Transcutaneous Electrical Nerve Stimulation at Newcastle Pain Relief Clinic
Authors: M I Johnson, C H Ashton, J W Thompson
Journal: Journal of the Royal Society of Medicine (1992)

This retrospective study of long-term use of transcutaneous electrical nerve stimulation (TENS) at Newcastle Pain Relief Clinic indicates that TENS has been a successful analgesic treatment for 58.6% of 1582 patients attending the clinic over a period of 10 years. A wide range of pain conditions were found to respond to TENS and many patients continued to use the treatment for several years. Most patients not responding to TENS (during a home trial) returned stimulators at the first follow-up appointment. Thus TENS should be considered as a simple, safe and reusable first line treatment for many pain conditions.
Beta-adrenoceptor-stimulated renin release is blunted in old rats.
Authors: C Baylis, K Engels, W H Beierwaltes
Journal: Journal of the American Society of Nephrology (1998)

Plasma renin activity (PRA) was similar in young versus old male Sprague Dawley rats under unstressed conditions (1.3 +/- 0.2 versus 1.8 +/- 0.3 ng angiotensin I/ml per min). Airjet stress increases PRA in young but not old rats (13.9 +/- 3.8 versus 2.9 +/- 0.8 ng angiotensin I/ml per min), respectively. This response is ablated in young rats by beta-adrenoceptor blockade, suggesting that the increased PRA is mediated by beta-adrenoceptors, and this response was blunted in old rats.
Geographic, age, and racial variation in the treatment of local/regional carcinoma of the prostate.
Authors: L Harlan, O Brawley, F Pommerenke, P Wali, B Kramer
Journal: Journal of Clinical Oncology (1995)

Prostate cancer is one of the most common cancers in men. Incidence rates increase with age and are substantially higher in black men than white men. This study examines the variations in the use of radical prostatectomy and radiation by geographic area, age, and race.Data from the National Cancer Institute's Surveillance, Epidemiology, and End-Results Program (SEER) were used to examine treatment differences. Current treatments generally consist of prostatectomy, radiation, or careful observation for clinically localized or regional disease.The age-adjusted proportion of men, age 50 and older, who received radical prostatectomy increased sharply between 1984 and 1991, from 11.0% to 32.3% among men with local/regional disease. The choice of treatment varied widely by geographic regions. In 1991, the proportion that received prostatectomy was highest in Utah (47.8%) and lowest in Connecticut (22.5%) among men with localized and regional disease. The increase in radical prostatectomy was not limited to younger men. Although the rates increased for blacks, black men had lower age-adjusted rates of prostatectomy than whites in all years of the study.The SEER data show a clear trend toward more aggressive treatment, especially prostatectomy. However, the proportion of black men who received prostatectomy was substantially lower than that of white men and this disparity does not appear to be changing.
Thrombopoietin induces rapid resolution of thrombocytopenia after orthotopic liver transplantation through increased platelet production
Authors: Markus Peck-Radosavljevic, Martina Wichlas, Johannes Zacherl, Gabriele Stiegler, Petra Stohlawetz, Michael Fuchsjäger, Anna Kreil, Sylvia Metz-Schimmerl, Simon Panzer, Rudolf Steininger, Ferdinand Mühlbacher, Peter Ferenci, Johann Pidlich, Alfred Gangl
Journal: Blood (2000)
North Carolina Macular Dystrophy Is Caused by Dysregulation of the Retinal Transcription Factor PRDM13
Authors: Kent W. Small, Adam P. DeLuca, S. Scott Whitmore, Thomas Rosenberg, Rosemary Silva-Garcia, Nitin Udar, Bernard Puech, Charles A. Garcia, Thomas A. Rice, Gerald A. Fishman, Elise Héon, James C. Folk, Luan M. Streb, Christine M. Haas, Luke A. Wiley, Todd E. Scheetz, John H. Fingert, Robert F. Mullins, Budd A. Tucker, Edwin M. Stone
Journal: Ophthalmology (2015)

To identify specific mutations causing North Carolina macular dystrophy (NCMD).Whole-genome sequencing coupled with reverse transcription polymerase chain reaction (RT-PCR) analysis of gene expression in human retinal cells.A total of 141 members of 12 families with NCMD and 261 unrelated control individuals.Genome sequencing was performed on 8 affected individuals from 3 families affected with chromosome 6-linked NCMD (MCDR1) and 2 individuals affected with chromosome 5-linked NCMD (MCDR3). Variants observed in the MCDR1 locus with frequencies <1% in published databases were confirmed using Sanger sequencing. Confirmed variants absent from all published databases were sought in 8 additional MCDR1 families and 261 controls. The RT-PCR analysis of selected genes was performed in stem cell-derived human retinal cells.Co-segregation of rare genetic variants with disease phenotype.Five sequenced individuals with MCDR1-linked NCMD shared a haplotype of 14 rare variants spanning 1 Mb of the disease-causing allele. One of these variants (V1) was absent from all published databases and all 261 controls, but was found in 5 additional NCMD kindreds. This variant lies in a DNase 1 hypersensitivity site (DHS) upstream of both the PRDM13 and CCNC genes. Sanger sequencing of 1 kb centered on V1 was performed in the remaining 4 NCMD probands, and 2 additional novel single nucleotide variants (V2 in 3 families and V3 in 1 family) were identified in the DHS within 134 bp of the location of V1. A complete duplication of the PRDM13 gene was also discovered in a single family (V4). The RT-PCR analysis of PRDM13 expression in developing retinal cells revealed marked developmental regulation. Next-generation sequencing of 2 individuals with MCDR3-linked NCMD revealed a 900-kb duplication that included the entire IRX1 gene (V5). The 5 mutations V1 to V5 segregated perfectly in the 102 affected and 39 unaffected members of the 12 NCMD families.We identified 5 rare mutations, each capable of arresting human macular development. Four of these strongly implicate the involvement of PRDM13 in macular development, whereas the pathophysiologic mechanism of the fifth remains unknown but may involve the developmental dysregulation of IRX1.
Mutations in KRT5 and KRT14 cause epidermolysis bullosa simplex in 75% of the patients
Authors: M.C. Bolling, H.H. Lemmink, G.H.L. Jansen, M.F. Jonkman
Journal: British Journal of Dermatology (2010)

Epidermolysis bullosa simplex (EBS) is a mechanobullous genodermatosis that may be caused by mutations in the genes KRT5 and KRT14 encoding the basal epidermal keratins 5 (K5) and 14 (K14). Three main clinical subtypes of EBS exist, differing in onset, distribution and severity of skin blistering. Previous reports of KRT5 and KRT14 mutations suggest a correlation between the location of the mutation and the severity of the associated EBS phenotype.The prevalence of KRT5/KRT14 mutations and the genotype-phenotype correlation in the largest tissue-confirmed EBS population is investigated.KRT5 and KRT14 genomic DNA and cDNA sequences of 76 clinically well-defined unrelated EBS probands were amplified and then subjected to direct sequencing and product length analysis. Immunofluorescence microscopy on patients' skin biopsies with antibodies against K5 and K14 was performed to study protein expression.In 57 of 76 (75%) probands 41 different KRT5 and KRT14 mutations were identified, of which 12 were novel. Mutations affecting the highly conserved helix boundary motifs of the rod domains of K5 and K14, and the K14 helix initiation motif in particular, were associated with the severest, EBS Dowling-Meara, phenotype. In 21 EBS probands (37%) the mutation was de novo. In 19 probands (25%) KRT5 or KRT14 mutations were excluded.The phenotype-genotype correlation observed in this large EBS population underscores the importance of helix boundary motifs for keratin assembly. Only three-quarters of biopsy-confirmed EBS probands have KRT5 or KRT14 mutations, indicating genetic heterogeneity in EBS. Alternative gene candidates are discussed.
Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III
Authors: Jenny Björkqvist, Steven de Maat, Urs Lewandrowski, Antonio Di Gennaro, Chris Oschatz, Kai Schönig, Markus M. Nöthen, Christian Drouet, Hal Braley, Marc W. Nolte, Albert Sickmann, Con Panousis, Coen Maas, Thomas Renné
Journal: Journal of Clinical Investigation (2015)

Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes.
Effect of Ibandronate on Bone Loss and Renal Function after Kidney Transplantation
Authors: WOLFGANG GROTZ, CHRISTIAN NAGEL, DARIA POESCHEL, MARKUS CYBULLA, KARL-GEORG PETERSEN, MARKUS UHL, CHRISTOPH STREY, GU[Combining Diaeresis]NTER KIRSTE, MANFRED OLSCHEWSKI, ACHIM REICHELT, LARS CHRISTIAN RUMP
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Severe osteoporosis frequently is observed after organ transplantation. In kidney transplantation, it adds to pre-existing renal bone disease and strategies to prevent osteoporosis are not established. Eighty kidney recipients were included in a randomized controlled prospective intervention trial. Treated patients ( n = 40) received an injection of ibandronate, a bisphosphonate, immediately before and at 3, 6, and 9 mo after transplantation. The primary outcome measured was the change in bone mineral density. Secondary measures included graft outcome, spinal deformities, fracture rate, body height, and hormonal and metabolic data. Loss of spongy and cortical bone after transplantation was prevented by ibandronate. Changes of bone mineral density (ibandronate versus controls) were as follows: lumbar spine, -0.9 ± 6.1% versus -6.5 ± 5.4% ( P &lt; 0.0001); femoral neck, +0.5 ± 5.2% versus -7.7 ± 6.5% ( P &lt; 0.0001); and midfemoral shaft, +2.7 ± 12.2% versus -4.0 ± 10.9% ( P = 0.024). Fewer spinal deformities developed with ibandronate (7 patients with 7 deformities versus 12 patients with 23 deformities; P = 0.047). Loss of body height was 0.5 ± 1.0 cm versus 1.1 ± 1.0 cm in control subjects ( P = 0.040). Two bone fractures occurred in each group. There were fewer acute rejection episodes with ibandronate (11 versus 22; P = 0.009). Graft function after 1 yr was comparable. Bone loss, spinal deformation, and loss of body height during the first year after kidney transplantation are prevented by injection of ibandronate at intervals of 3 mo. The smaller number of rejection episodes of the ibandronate-treated group should be confirmed and its mechanism should be explored in additional studies.
Histone Deacetylase HDAC8 Promotes Insulin Resistance and β-Catenin Activation in NAFLD-Associated Hepatocellular Carcinoma
Authors: Yuan Tian, Vincent W.S. Wong, Grace L.H. Wong, Weiqin Yang, Hanyong Sun, Jiayun Shen, Joanna H.M. Tong, Minnie Y.Y. Go, Yue S. Cheung, Paul B.S. Lai, Mingyan Zhou, Gang Xu, Tim H.M. Huang, Jun Yu, Ka F. To, Alfred S.L. Cheng, Henry L.Y. Chan
Journal: Cancer Research (2015)

The growing epidemic of obesity, which causes nonalcoholic fatty liver disease (NAFLD) and the more severe phenotype nonalcoholic steatohepatitis (NASH), has paralleled the increasing incidence of hepatocellular carcinoma (HCC). Accumulating evidence demonstrates that overnutrition and metabolic pathways can trigger modifications of DNA and histones via deregulation of chromatin modifiers, resulting in aberrant transcriptional activity. However, the epigenetic regulation of HCC development in NAFLD remains obscure. Here, we uncover key epigenetic regulators using both dietary and genetic obesity-promoted HCC models through quantitative expression profiling and characterize the oncogenic activities of histone deacetylase HDAC8 in NAFLD-associated hepatocarcinogenesis. HDAC8 is directly upregulated by the lipogenic transcription factor SREBP-1 where they are coexpressed in dietary obesity models of NASH and HCC. Lentiviral-mediated HDAC8 attenuation in vivo reversed insulin resistance and reduced NAFLD-associated tumorigenicity. HDAC8 modulation by genetic and pharmacologic approaches inhibited p53/p21-mediated apoptosis and G2-M phase cell-cycle arrest and stimulated β-catenin-dependent cell proliferation. Mechanistically, HDAC8 physically interacted with the chromatin modifier EZH2 to concordantly repress Wnt antagonists via histone H4 deacetylation and H3 lysine 27 trimethylation. In human NAFLD-associated HCC, levels of SREBP-1, HDAC8, EZH2, H4 deacetylation, H3K27me3, and active β-catenin were all correlated positively in tumors compared with nontumor tissues. Overall, our findings show how HDAC8 drives NAFLD-associated hepatocarcinogenesis, offering a novel epigenetic target to prevent or treat HCC in obese patients.
Tumor-Specific Immunogenicity of Transplantable Chemically Induced Tumors, as Demonstrated by Uptake of Tritiated Thymidine by Lymphoid Cells From Isogenic and F1 Hybrid Mice2
Authors: Mildred E. Phillips
Journal: JNCI Journal of the National Cancer Institute (1974)

A marked difference in immunogenicity was demonstrated between two chemically induced tumors as measured by the reactivity of regional lymphoid cells obtained from isologous or F1 hybrid tumor-bearing hosts after subcutaneous tumor grafts. This was assessed by the uptake of 3H-thymidine by lymphoid cells cultured in the presence of tumor cells. After a single graft with 3-methylcholanthrene-induced tumor cells, proliferative response was marked. This effect could be demonstrated only with Sarcoma I after prolonged antigenic stimulation.
Relationship between lung cancer and chronic obstructive pulmonary disease
Authors: Mirian Torres González, Elena Badaran, Julio Sánchez de Cos Escuín, Juan Antonio Riesco Miranda
Journal: European Respiratory Journal (2014)

Introduction: exposure to snuff smoke is a common risk factor for developing lung cancer (LC) and chronic obstructive pulmonary disease (COPD). According to some studies, COPD has been identified as an independent risk factor for the development of LC. However, there is discordance between the severity of COPD and the development of LC.  Aims: to evaluate the prevalence of airway obstruction (AO) in patients diagnosed with LC and to study the relationship between LC and the severity of COPD.  Methods: it was included patients with suspected LC who were admitted to our Deparment during thirteen months. Epidemiological and smoking variables were analyzed. Performing spirometry (SP) and diagnostic tests for the study of LC were evaluated.  Results: 117 patients with suspected LC were included, 88 % males with a mean age of 70.9(SD 10.71). 43.6 % were smokers and 47.9 % former smokers. The median time from smoking cessation to the development of LC was 10 years (1-40). SP was performed in 68.4 % (80/117), having a prevalence of COPD of 61.3 % (49/80) and 65.3% were COPD recent diagnosis (32/49). 55.1 % of COPD patients had moderate AO. The median time between diagnosis of COPD and the development of LC was 48 months (3-180). Emphysema was described on the CT scan in 33%. The most frequent histological strain was squamous cell carcinoma. The diagnosis of LC in advanced stages was performed in most cases (53.1 %, stage IV).  Conclusions: COPD is a highly prevalent disease among patients with suspected LC, having mild to moderate severity AO at diagnosis. This fact suggests the need for close monitoring of these patients according to an earlier diagnosis of LC.