tbuckley/cabot-search huggingface dataset:
733. Integration Site Distribution and Clonal Selection Related to the Insertion of Lentiviral SIN-Vectors
Authors: Cynthia C. Bartholomae, Manfred Schmidt, Rafael J. Yanez-Munoz, Steven J. Howe, Sonja Schmidt, Claudia Prinz, Adrian J. Thrasher, Christof von Kalle
Journal: Molecular Therapy (2006)

Previous observations of retroviral vector induced oncogenesis in preclinical models and in a clinical SCID-X1 gene therapy study have prompted large-scale integration site analysis. In vitro and in vivo studies indicate that lentiviral vectors may lower the risk of insertional mutagenesis compared to common retroviral vectors. Several studies could show that integration site distribution is vector dependent (MLV, HIV, SIV, ASLV) and the type of LTR may play a crucial role. Here, we have analyzed the possible influence of distinct internal promoters and transgenes on integration site distribution and clone survival. To analyze the influence of different vector elements on target site selection of lentiviral vector integration we transduced HeLa cells with three different lentiviral SIN-HIV-based vectors (promoter: CMV, SFFV; transgene: GFP, Mertk; SFFV-vectors contained WPRE) and compared the integration site distribution (971 integration events) at various time points (1d, 30d, 60d). Overall integration site distribution of the three vectors showed no difference in integration frequency in RefSeq genes. 66–69% of the integration events were detected in RefSeq genes, 81–88% were in RefSeq genes including the surrounding 10kb of sequence. Chromosomal distribution analysis showed no significant difference between the vectors. Integration site comparison at 30 days and 60 days after transduction revealed over-representation of genes with specific molecular functions, most significantly with transferase activity, ATP binding or protein serine/threonine kinase activity. Interestingly, these categories showed a strong increase in significance over time, indicating that lentiviral SIN-vectors induce clonal selection in vitro. The clustering of more than 10% of the integrations as common integration sites (CIS) also points to a vector related selective advantage of individual clones. Our findings indicate for the first time that lentiviral SIN-vector architecture, potentially independently of internal vector elements, may influence the clonal growth of targeted cells. The character of such effects and any putative relevance of such genotoxicity for the in vivo situation will have to be investigated in detail for the role of individual vector/cell type configurations. Especially if strong internal promoter/enhancer combinations are used, even lentiviral SIN-vectors may not be completely biologically inert with relation to their genomic environment, and in vitro assays may be highly useful in early detection of such interactions. MS and CvK hold US-patent on LAM-PCR.
Abnormally Decreased HbA1c Can Be Assessed With Erythrocyte Creatine in Patients With a Shortened Erythrocyte Age
Authors: Yufei Jiao, Toshika Okumiya, Toshiji Saibara, Keunsik Park, Masahide Sasaki
Journal: Diabetes Care (1998)

OBJECTIVE To investigate whether erythrocyte creatine can serve as a corrective index for HbA1c in patients with a shortened mean age of erythrocytes. RESEARCH DESIGN AND METHODS HbA1c and creatine in density-fractionated erythrocytes from 18 normal subjects were measured. HbA1c and erythrocyte creatine in the whole blood of 43 patients with liver cirrhosis (LC), 14 patients with hemolytic anemia (HA), 38 other patients with high reticulocyte counts (HRC) (&amp;gt;2.2%), and 59 normal subjects were also measured. The patients in this study all had normal blood glucose levels. A correction formula derived from the linear regression equation for the correlation between HbA1c and erythrocyte creatine was used to correct the patients' HbA1c values. RESULTS Among density-fractionated erythrocytes, the young cells exhibited low HbA1c and high creatine values. With progressively increasing density, HbA1c gradually increased and creatine gradually decreased. In the whole blood samples, the HbA1c values were significantly lower (P &amp;lt; 0.001) in LC, HA, and HRC patients than in normal subjects. By contrast, the erythrocyte creatine values were significantly higher (P &amp;lt; 0.001) in LC, HA, and HRC patients than in normal subjects. A linear correlation between HbA1c Cy) and erythrocyte creatine (x) was observed (y = −0.224x + 5.00; n = 154; r = −0.70; P &amp;lt; 0.001). Based on the regression equation, a correction formula was obtained. Low HbA1c values (&amp;lt;4.3%) were found in 24 of the 43 LC patients, 12 of the 14 HA patients, and 20 of the 38 HRC patients. After correction of the HbA1c values, 15 of the 24 LC patients, 9 of the 12 HA patients, and 16 of the 20 HRC patients had HbAlc values within the normal range. CONCLUSIONS HbA1c decreased in inverse proportion to the increase in erythrocyte creatine because of a shortened mean age of erythrocytes. The abnormally decreased HbA1c value could be assessed with erythrocyte creatine.
Human Colon Cancer Stem Cells: A New Paradigm in Gastrointestinal Oncology
Authors: Bruce M. Boman, Emina Huang
Journal: Journal of Clinical Oncology (2008)

For the past half century, oncologists have had systemic drugs available, agents that are able to induce tumor responses in patients with colorectal cancer. However, in cases of advanced colorectal cancer, these regimens are almost never curative. The recently introduced concept that cancer stem cells (SCs) drive tumor growth suggests a reason for these therapeutic failures--current chemotherapeutics target rapidly dividing cells but cancer SCs divide only slowly, and, they are relatively resistant to cytotoxic systemic therapies. It also suggests a solution--development of therapeutics that target cancer SCs. However, there is a paucity of information about the mechanisms by which SC populations are maintained and about the mechanisms by which tumor SCs are involved in colon cancer development. In this article, we discuss these mechanisms and recent developments in the identification and isolation of colon cancer SCs using new SC markers. We then discuss the role of SCs in homeostasis of normal colonic epithelium, and mechanisms by which dysregulation of crypt mechanisms can lead to initiation and progression of colon cancer. Our hypothesis, which has received recent experimental support, is that the mechanism that links abnormalities at the gene level (eg, APC mutations) and abnormalities at the tissue level (eg, proliferative shift, dysplasia, carcinoma) from cancer initiation to metastasis is SC overpopulation. Finally, we discuss the concept that symmetric cancer SC division is an essential mechanism that drives tumor growth, and that development of a new generation of therapeutics that target colon cancer SCs by inhibiting symmetric SC division holds promise for truly curative approaches for patients with advanced colorectal cancers.
Role of verapamil in atrial fibrillation: effect on trigger or on substrate? Data from the VeRAF study
Authors: Giovanni L. Botto, Giuseppina Belotti, Antonio Ciró, Vigilio Ziacchi, Massimo Romanò, Massimo Pala, Antonio Sagone, Antonino Piti, Antonello Vincenti, Giampaolo Gelmini
Journal: Journal of the American College of Cardiology (2002)
Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers.
Authors: A M Richards, G A Wittert, E A Espiner, T G Yandle, H Ikram, C Frampton
Journal: Circulation Research (1992)

The effects of endopeptidase 24.11 inhibition on angiotensin-induced changes in plasma angiotensin II, aldosterone, and atrial natriuretic factor concentrations and blood pressure were assessed in normal volunteers. Two groups, each consisting of eight normal volunteers, received stepwise infusions of angiotensin II (2, 4, and 8 ng/kg per minute) on day 5 of dose administration with 25 mg every 12 hours (group 1) or 100 mg every 12 hours (group 2) of an oral inhibitor of endopeptidase 24.11 (UK 79300, candoxatril) or placebo in balanced randomized, double-blind, placebo-controlled crossover studies. Both doses of candoxatril significantly enhanced achieved plasma angiotensin II concentrations during infusions (group 1, p < 0.001; group 2, p < 0.01; overall treatment effect for combined data, p < 0.001). This effect was most pronounced at the highest dose of angiotensin II (treatment-time interaction, p < 0.0001 for combined data) and tended to be more marked with the higher dose of candoxatril (treatment-group interaction, p = 0.08). The pressor response to angiotensin II was clearly enhanced by the lower dose of candoxatril; peak systolic and diastolic pressures exceeded placebo values by approximately 10 mm Hg (p < 0.001 and p < 0.05 for systolic and diastolic pressures, respectively). This effect of candoxatril was absent in group 2, which (unlike group 1) had exhibited a modest natriuretic response (sustained cumulative negative sodium balance, -70 +/- 21 mmol; p < 0.01) to the higher dose of inhibitor. Baseline plasma aldosterone concentrations and the incremental aldosterone response to angiotensin II infusions were not significantly altered by low-dose (group 1) candoxatril.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of IgE and IgG Antibody Responses to <i>Dermatophagoides farinae</i> in Rats
Authors: S. L. NORDVALL, S. DALE, B. BJÖRKSTÉN
Journal: Allergy (1985)

Rats (Brown Norway/Wistar Fu) that were pretreated or not pretreated with cyclophos‐phamide were immunized with varying amounts of Dermatophagoides farinae allergen extract with alum as adjuvant. Sera were analysed by RAST and by crossed radioimmunoelectro‐phoresis (CRIE). The highest IgE antibody responses were recorded in animals pretreated with cyclophosphamide that had received low immunizing doses of antigen. The IgE antibody pattern in CRIE was, however, not influenced by the dose of antigen or by cyclophosphamide pretreatment. The IgG pattern in CRIE closely resembled the IgE pattern, demonstrating a similar specificity of the antibody responses of the two isotypes. This indicates non‐class specific control of the specificity of antibody responses.
Study Looks at PTSD Among Workers in Twin Towers During 9/11 Attack
Authors: Mike Mitka
Journal: JAMA (2011)

unable to produce myelin; without myelin, the children develop progressive language and motor problems. Those with the most severe form of the disease die in early childhood. If the trial is successful, ffrench-Constant said, “it would be an important proof of principle” with implications for MS. Coetzee cautioned that unlike MS, Pelizaeus-Merzbacher disease doesn’t have an inflammatory component. “In MS, you always have to think about [inflammation],” he said. Even if restorative therapies prove successful in clinical trials, future therapies for MS will likely entail a combination of antiinflammatory, restorative, and neuroprotective agents. “There are no silver bullets,” he said.
Prognostic Benefit of Optimum Left Ventricular Lead Position in Cardiac Resynchronization Therapy
Authors: Anna C. Kydd, Fakhar Z. Khan, William D. Watson, Peter J. Pugh, Munmohan S. Virdee, David P. Dutka
Journal: JACC Heart Failure (2014)

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: –24 ± 15% vs. –12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up.
Mutations in hepatitis B DNA polymerase associated with resistance to lamivudine do not confer resistance to adefovirin vitro
Authors: Xiaofeng Xiong, Carmina Flores, Huiling Yang, John J. Toole, Craig S. Gibbs
Journal: Hepatology (1998)

To determine whether adefovir is active against lamivudine-resistant hepatitis B virus (HBV), the inhibition constants of adefovir diphosphate and lamivudine triphosphate for wild-type and mutant human HBV DNA polymerases, which contain amino acid substitutions associated with lamivudine resistance, were compared. Recombinant wild-type and mutant human HBV DNA polymerases were expressed and substantially purified using a baculovirus expression system and immunoaffinity chromatography. HBV DNA polymerase mutants M552I, M552V, and L528M/M552V showed resistance to lamivudine triphosphate with inhibition constants (Ki) increased by 8.0-fold, 19.6-fold, and 25.2-fold compared with that of wild-type HBV DNA polymerase. However, these mutants remained sensitive to adefovir diphosphate with the inhibition constants increasing by 1.3-fold and 2.2-fold or decreasing by 0.79-fold. The L528M single mutation, identified in patients with increasing HBV DNA levels during therapy with famciclovir, also remained sensitive to adefovir diphosphate with the inhibition constant increased by only 2.3-fold.
Drugs and Valvular Heart Disease
Authors: Bryan L. Roth
Journal: New England Journal of Medicine (2007)

In 1997, Connolly et al. reported that both racemic fenfluramine (Pondimin) and dexfenfluramine (Redux) were associated with valvular heart disease.1 The valvular abnormalities seen in patients treated with these agents were distinctive. On echocardiography, leaflet thickening as well as chordal thickening and retraction were observed. Surgically removed valves were noted to have a glistening white surface, with histologic evidence of a plaque-like process extending along the leaflet surfaces and encasing the chordae tendineae. These findings were similar to those in patients with heart-valve damage induced by serotonin-secreting carcinoid tumors.1 This association of racemic fenfluramine and dexfenfluramine with valvular heart disease . . .
Diagnosis of Primary Aldosteronism in Chronic Kidney Disease by I-131 NP-59 SPECT/CT Imaging
Authors: Yi-Chun Chen, Yu-Chieh Su, Jainn-Shiun Chiu, Chih-En Tseng
Journal: Clinical Nuclear Medicine (2012)

Primary aldosteronism (PA) may be missed in patients with chronic kidney disease (CKD), because CKD may disturb the renin-angiotensin-aldosterone system. Adrenal vein sampling has increased risks in patients with CKD. We report the case of a 58-year-old man with CKD and suspected PA. Left adrenal aldosteronism was diagnosed by NP-59 SPECT/CT. Left adrenalectomy demonstrated adrenocortical nodular hyperplasia. Plasma aldosterone normalized and blood pressure stabilized after surgery. NP-59 SPECT/CT may be a helpful diagnostic tool for detecting and lateralizing PA in CKD patients.
Loss of Thioredoxin-Binding Protein-2/Vitamin D3 Up-Regulated Protein 1 in Human T-Cell Leukemia Virus Type I-Dependent T-Cell Transformation
Authors: Yumiko Nishinaka, Akira Nishiyama, Hiroshi Masutani, Shin-ichi Oka, Kaimul Md. Ahsan, Yukie Nakayama, Yasuyuki Ishii, Hajime Nakamura, Michiyuki Maeda, Junji Yodoi
Journal: Cancer Research (2004)

Abstract Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia (ATL). However, the low incidence of ATL among HTLV-I-infected carriers, together with a long latent period, suggests that multiple host-viral events are involved in the progression of HTLV-I-dependent transformation and subsequent development of ATL. Human thioredoxin (TRX) is a redox active protein highly expressed in HTLV-I-transformed cell lines, whereas the TRX-binding protein-2/vitamin D3 up-regulated protein 1 (TBP-2/VDUP1) was recently identified as a negative regulator of TRX. We report here that expression of TBP-2 is lost in HTLV-I-positive, interleukin-2-independent T-cell lines but maintained in HTLV-I-positive, interleukin-2-dependent T-cell lines, as well as HTLV-I-negative T-cell lines. Ectopic overexpression of TBP-2 in HTLV-I-positive T cells resulted in growth suppression. In the TBP-2-overexpressing cells, a G1 arrest was observed in association with an increase of p16 expression and reduction of retinoblastoma phosphorylation. The results suggest that TBP-2 plays a crucial role in the growth regulation of T cells and that the loss of TBP-2 expression in HTLV-I-infected T cells is one of the key events involved in the multistep progression of ATL leukemogenesis.
Blood-Borne Pathogens in Sports
Authors: Eric E. Mast
Journal: Annals of Internal Medicine (1995)

Letters15 October 1995Blood-Borne Pathogens in SportsEric E. Mast, MD, MPH, Richard A. Goodman, MD, MPH, and D. Peter Drotman, MD, MPHEric E. Mast, MD, MPHCenters for Disease Control and Prevention; Atlanta, GA 30333Search for more papers by this author, Richard A. Goodman, MD, MPHCenters for Disease Control and Prevention; Atlanta, GA 30333Search for more papers by this author, and D. Peter Drotman, MD, MPHCenters for Disease Control and Prevention; Atlanta, GA 30333Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-8-199510150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Drs. Karjalainen and Friman for their letter about our recent report on the risk for and prevention of infection with blood-borne pathogens in sports. They refer to an outbreak of hepatitis B among track-finders in Sweden in the 1960s. Although we were aware of this outbreak, we did not cite it in our review because the published reports had not epidemiologically established the manner in which hepatitis B virus was transmitted. We recommend using standard epidemiologic and laboratory methods to investigate the occurrence of infectious diseases in sports so that we may understand the risks and ... Author, Article, and Disclosure InformationAffiliations: Centers for Disease Control and Prevention; Atlanta, GA 30333 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1995Volume 123, Issue 8Page: 636KeywordsEpidemiologyHepatitis BHepatitis B virusInfectious disease epidemiologyInfectious diseasesPathogensResearch laboratoriesRisk managementSports ePublished: 15 August 2000 Issue Published: 15 October 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Myocardial Triglyceride Content and Improves Myocardial Function
Authors: Sebastiaan Hammer, Marieke Snel, Hildo J. Lamb, Ingrid M. Jazet, Rutger W. van der Meer, Hanno Pijl, Edo A. Meinders, Johannes A. Romijn, Albert de Roos, Johannes W.A. Smit
Journal: Journal of the American College of Cardiology (2008)
Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome
Authors: Tai-Ming Ko, Wen-Hung Chung, Chun-Yu Wei, Han-Yu Shih, Jung-Kuei Chen, Chia-Hsien Lin, Yuan-Tsong Chen, Shuen-Iu Hung
Journal: Journal of Allergy and Clinical Immunology (2011)
More on Desert Storm-Reply
Authors: Jill R. Keeler
Journal: JAMA (1991)

In Reply.  —We limit our response to Dr Sarno to issues raised about pyridostigmine. Clearly, this is of concern as the number of women in military service increases and the threat of chemical warfare in the world persists. Since the safety of pyridostigmine during pregnancy or lactation in humans has not been established, the use of pyridostigmine in women who may become pregnant requires weighing the drug's potential benefits (ie, survival in a nerve agent attack) against its possible hazards to mother and child.  Sarno stated that pyridostigmine is classified as risk factor C because no controlled studies in women have been done, or because studies in women and animals are not available.1In fact, controlled studies in rats and monkeys have been done and showed no direct teratogenic effects or significant ill effects on fertility and reproductive performance (Hoffman-La Roche Inc, proprietary information).2  Importantly, pyridostigmine has been
Glycoxidized low-density lipoprotein enhances monocyte chemoattractant protein-1 mRNA expression in human umbilical vein endothelial cells: Relation to lysophosphatidylcholine contents and inhibition by nitric oxide donor
Authors: Kazuo Sonoki, Mototaka Yoshinari, Masanori Iwase, Kenzo Iino, Kojiro Ichikawa, Shigehiro Ohdo, Shun Higuchi, Mitsuo Iida
Journal: Metabolism (2002)
Don't Forget Tobacco
Authors: Steven A. Schroeder, Kenneth E. Warner
Journal: New England Journal of Medicine (2010)

At a time when all eyes are focused on health care reform, escalating medical costs, and childhood obesity, cigarette smoking remains by far the most common cause of preventable death and disability in the United States. Because important strides have been made in tobacco control, in terms of both interventions (tax hikes and laws creating smoke-free workplaces) and outcomes (smoking prevalence that has more than halved since the early 1960s [see graph]), it is tempting to believe that the battle is largely won and that we should move on to other pressing public health issues. But the prevalence of smoking . . .
Blood Pressure and Culture
Authors: H.B.M. Murphy
Journal: Psychotherapy and Psychosomatics (1982)

It is well known that mean blood pressure levels tend to be low in non-westernized tribal peoples and that these levels tend to rise, particularly in the older age groups, among persons of the same origins who come into more contact with modern Western life-styles. That tendency can be attributed to many factors – increased salt intake, increased obesity, acculturation anxiety, information overload, increased competitiveness, envious resentment, etc. Disentangling these various hypothesized factors is virtually impossible when studying patients or population samples from a single sociocultural group, but cross-cultural comparisons may under favorable circumstances permit some such disentangling. Using data from Micronesia, Polynesia, and East Africa, an attempt will be made to assess which types of psychological stress are most likely to conduce to hypertension, and how certain traditional cultures may have been reducing these stresses.
THE EXTENDED LEGS AS AN ABNORMALITY IN THE FOETAL ATTITUDE
Authors: H. Briggs
Journal: BMJ (1924)

FUETAL.ATTITUDE. M. and Wales.At that time there were twenty-five county boroughs and -counties in -which there were -more deaths from puerperal sepsis than there were cases notified.In eleven other areas the deaths and the notifications -were equal in number.The official report for the year 1921 shows that:In 10 areas there were 16 deaths and 0 notifications.,,28 ,, ,, 114 ,, 63 ,, 28 ,, ,,