tbuckley/cabot-search huggingface dataset:
Regulation of the Adenomatous Polyposis Coli Gene by the miR-135 Family in Colorectal Cancer
Authors: Remco Nagel, Carlos le Sage, Begoña Diosdado, Maike van der Waal, Joachim A.F. Oude Vrielink, Anne Bolijn, Gerrit A. Meijer, Reuven Agami
Journal: Cancer Research (2008)

Abstract Inactivation of the adenomatous polyposis coli (APC) gene is a major initiating event in colorectal tumorigenesis. Most of the mutations in APC generate premature stop codons leading to truncated proteins that have lost β-catenin binding sites. APC-free β-catenin stimulates the Wnt signaling pathway, leading to active transcription of target genes. In the current study, we describe a novel mechanism for APC regulation. We show that miR-135a&amp;b target the 3′ untranslated region of APC, suppress its expression, and induce downstream Wnt pathway activity. Interestingly, we find a considerable up-regulation of miR-135a&amp;b in colorectal adenomas and carcinomas, which significantly correlated with low APC mRNA levels. This genetic interaction is also preserved in full-blown cancer cell lines expressing miR-135a&amp;b, regardless of the mutational status of APC. Thus, our results uncover a miRNA-mediated mechanism for the control of APC expression and Wnt pathway activity, and suggest its contribution to colorectal cancer pathogenesis. [Cancer Res 2008;68(14):5795–802]
Preleukemic expression of TL antigens in x-irradiated C57BL/6 mice.
Authors: E Stockert, L J Old
Journal: The Journal of Experimental Medicine (1977)

Anomalous appearance of TL (thymus-leukemia) antigens is a characteristic feature of radiation-induced leukemias of C57bl/6 mice. We now report that thymocytes of irradiated C57BL/6 mice express TL antigens long before the development of overt leukemia. Thus, TL is a marker for preleukemic changes occurring during radiation leukemogenesis. Low levels of murine leukemia virus (MuLV)-related antigens are also detected on preleukemic thymocytes. Comparative tests on individual mice show no direct correlation between TL and MuLV antigen expression.
Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial
Authors: John Strang, Nicola Metrebian, Nicholas Lintzeris, Laura Potts, Tom Carnwath, Soraya Mayet, Hugh Williams, Deborah Zador, Richard Evers, Teodora Groshkova, Vikki Charles, Anthea Martin, Luciana Forzisi
Journal: The Lancet (2010)
Bromide 82 in the Diagnosis of Tuberculous Meningitis
Authors: E. Paul Getaz
Journal: JAMA (1979)

To the Editor.—  In their recent review of 52 patients with tuberculous meningitis (TBM) Kennedy and Fallon (241:264, 1979) noted that delay in diagnosis was an adverse prognostic factor, and they reviewed the difficulties in making the early diagnosis of TBM. They did not mention the radioactive bromide partition test, and I would like to draw attention to this simple procedure.  Following Walter's 1 monograph in 1929 on the blood-brain barrier, the use of the bromide test in disease of the brain and spinal cord became widespread. Nicol and Fawns 2 reported that in 26 cases of lymphocytic meningitis, all of those who had TBM had a decreased blood-CSF ratio. There were no false-negatives. Crook and colleagues 3 reported the use of bromide 82 and found this to be a simple and reliable method using small samples. In separate studies, Mandal et al 4 and I (unpublished data) have subsequently
Multivoxel 1H MR spectroscopy is superior to contrast-enhanced MRI for response assessment after anti-angiogenic treatment of orthotopic human glioma xenografts and provides handles for metabolic targeting
Authors: Bob Hamans, Anna Catharina Navis, Alan Wright, Pieter Wesseling, Arend Heerschap, William Leenders
Journal: Neuro-Oncology (2013)

BackgroundAnti-angiogenic treatment of glioblastoma characteristically results in therapy resistance and tumor progression via diffuse infiltration. Monitoring tumor progression in these patients is thwarted because therapy results in tumor invisibility in contrast-enhanced (CE) MRI. To address this problem, we examined whether tumor progression could be monitored by metabolic mapping using 1H MR spectroscopic imaging (MRSI).
Which One Is Better: AIDS Related or HIV Associated?
Authors: Hüseyin Abali, Gülcan Abali, Sercan Aksoy
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: We have read the article by Francois Boue et al on AIDS-related lymphoma. The authors stated that rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is a simple and effective schedule for HIV-associated lymphoma. The authors used the terms HIV-associated and AIDS-related interchangeably throughout their article. Although everybody who read it surely understood that they are more or less the same entity, it is crucial to use the most correct terminology for scientific communication, in our point of view. Which one defines malignancies developing in individuals infected with HIV better? We have some comments. Caused by HIV, AIDS is the profound immunodeficiency state characterized by opportunistic infections and Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer—the AIDS-defining cancers. By definition, when they are diagnosed in a patient infected with CD4 count less than 200 cells/uL that patient has AIDS. Therefore, the term AIDS-related seems better suited for AIDS-defining cancers. However, non–AIDS-defining cancers do occur in individuals infected with HIV. Several population-based studies indicated that relative risks for such malignancies with the exception of anal cancer is minimally increased during the pre-AIDS period, meaning that HIV positivity does not substantially increase risk of malignancy before inducing AIDS. Therefore, the term AIDS related seems more correct for non–AIDS-defining cancers, as well. Furthermore, highly active antiretroviral therapy prevents immunodeficiency and decreased incidences of malignancies, but can not eradicate HIV. This observation means that AIDS is necessary for the development of most cancers. In conclusion, we kindly suggest that AIDS related be preferred over HIV associated when referring to all malignancies in individuals with HIV infection.
Genetic Dissection of SLE
Authors: Xiaoyan Shi, Chun Xie, Desi Kreska, James A. Richardson, Chandra Mohan
Journal: The Journal of Experimental Medicine (2002)

Genetic dissection of lupus pathogenesis in the NZM2410 strain has recently revealed that Sle1 is a potent locus that triggers the formation of IgG anti-histone/DNA antibodies, when expressed on the B6 background as a congenic interval. B6.lpr mice, in contrast, exhibit distinctly different cellular and serological phenotypes. Both strains, however, do not usually exhibit pathogenic autoantibodies, or succumb to lupus nephritis. In this study, we show that the epistatic interaction of Sle1 (in particular, Sle1/Sle1) with FASlpr leads to massive lymphosplenomegaly (with elevated numbers of activated CD4 T cells, CD4−CD8− double negative (DN) T cells, and B1a cells), high levels of IgG and IgM antinuclear (including anti-ssDNA, anti-dsDNA, and anti-histone/DNA), and antiglomerular autoantibodies, histological, and clinical evidence of glomerulonephritis, and &amp;gt;80% mortality by 5–6 mo of age. Whereas FASlpr functions as a recessive gene, Sle1 exhibits a gene dosage effect. These studies indicate that Sle1 and FASlpr must be impacting alternate pathways leading to lymphoproliferative autoimmunity.
Acute Kidney Injury Is an Early Predictor of Mortality for Patients With Alcoholic Hepatitis
Authors: José Altamirano, Claudia Fagundes, Marlene Dominguez, Elisabet García, Javier Michelena, Andrés Cárdenas, Monica Guevara, Gustavo Pereira, Karina Torres–Vigil, Vicente Arroyo, Juan Caballería, Pere Ginès, Ramón Bataller
Journal: Clinical Gastroenterology and Hepatology (2011)
<i>TREM2</i> Variants in Alzheimer's Disease
Authors: Rita Guerreiro, Aleksandra Wojtas, Jose Bras, Minerva Carrasquillo, Ekaterina Rogaeva, Elisa Majounie, Carlos Cruchaga, Celeste Sassi, John S.K. Kauwe, Steven Younkin, Lilinaz Hazrati, John Collinge, Jennifer Pocock, Tammaryn Lashley, Julie Williams, Jean-Charles Lambert, Philippe Amouyel, Alison Goate, Rosa Rademakers, Kevin Morgan, John Powell, Peter St. George-Hyslop, Andrew Singleton, John Hardy
Journal: New England Journal of Medicine (2012)

Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.
Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo
Authors: Kazuhiro Kakimi, Luca G. Guidotti, Yasuhiko Koezuka, Francis V. Chisari
Journal: The Journal of Experimental Medicine (2000)

We have previously reported that hepatitis B virus (HBV)–specific CD8+ cytotoxic T lymphocytes and CD4+ helper T lymphocytes can inhibit HBV replication in the liver of HBV transgenic mice by secreting interferon (IFN)-γ when they recognize viral antigen. To determine whether an activated innate immune system can also inhibit HBV replication, in this study we activated natural killer T (NKT) cells in the liver of HBV transgenic mice by a single injection of α-galactosylceramide (α-GalCer), a glycolipid antigen presented to Vα14+NK1.1+ T cells by the nonclassical major histocompatibility complex class I–like molecule CD1d. Within 24 h of α-GalCer injection, IFN-γ and IFN-α/β were detected in the liver of HBV transgenic mice and HBV replication was abolished. Both of these events were temporally associated with the rapid disappearance of NKT cells from the liver, presumably reflecting activation-induced cell death, and by the recruitment of activated NK cells into the organ. In addition, prior antibody-mediated depletion of CD4+ and CD8+ T cells from the mice did not diminish the ability of α-GalCer to trigger the disappearance of HBV from the liver, indicating that conventional T cells were not downstream mediators of this effect. Finally, the antiviral effect of α-GalCer was inhibited in mice that are genetically deficient for either IFN-γ or the IFN-α/β receptor, indicating that most of the antiviral activity of α-GalCer is mediated by these cytokines. Based on these results, we conclude that α-GalCer inhibits HBV replication by directly activating NKT cells and by secondarily activating NK cells to secrete antiviral cytokines in the liver. In view of these findings, we suggest that, if activated, the innate immune response, like the adaptive immune response, has the potential to control viral replication during natural HBV infection. In addition, the data suggest that therapeutic activation of NKT cells may represent a new strategy for the treatment of chronic HBV infection.
Abstract 691: Methylation of APC and GSTP1 in non-neoplastic tissue adjacent to prostate tumour and mortality from prostate cancer.
Authors: Chiara Celestina Grasso, Lorenzo Richiardi, Valentina Fiano, Daniela Zugna, Anna Gillio Tos, Luisa Delsedime, Franco Merletti
Journal: Cancer Research (2013)

Abstract Prostate cancer is the most common tumour in men in many populations, with a crude incidence of 120-130 per 105 in Europe and the United States. The incidence of prostate cancer has increased dramatically since the introduction of prostate-specific antigen (PSA) testing at the end of the 1980s; opportunistic PSA-based screening for prostate cancer is widespread, although its ability to decrease mortality is still being debated. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumours (NTAT) in association with prostate cancer mortality, as a marker to discriminate between indolent and aggressive prostate tumours. From two cohorts of consecutive prostate cancer patients diagnosed at one pathology ward in Turin, Italy, we selected 157 patients with available NTAT and followed them up for more than 14 years. We obtained DNA from NTAT in paraffin-embedded prostatic tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters. Prevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostatic tumour tissue for the same two genes as well as with high Gleason. The hazard ratio (HR) of prostate cancer mortality was 2.16 (1.13-4.13) for APC methylation, and 2.83 (1.42-5.65) for GSTP1 methylation in NTAT. It changed to 1.75 (0.95-3.22) and 1.61 (0.80-3.22) after adjusting for Gleason score and methylation in prostatic tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 3.84 (1.83-8.03), which decreased to 2.12 (1.03-4.37) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.03, 95% CI: 1.20-7.67) and in the biopsy sub-cohort (HR: 5.91, 95% CI: 1.00-35.0). This results show that changes in gene methylation are an early event in prostate carcinogenesis and may play a role in cancer progression. Gene methylation in NTAT is a possible prognostic marker. Citation Format: Chiara Celestina Grasso, Lorenzo Richiardi, Valentina Fiano, Daniela Zugna, Anna Gillio Tos, Luisa Delsedime, Franco Merletti. Methylation of APC and GSTP1 in non-neoplastic tissue adjacent to prostate tumour and mortality from prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 691. doi:10.1158/1538-7445.AM2013-691
Preserving Fertility After Cancer
Authors: B. Simon, S. J. Lee, A. H. Partridge, C. D. Runowicz
Journal: CA A Cancer Journal for Clinicians (2005)

In this review, the reproductive impact of treatments for several common cancers and options to maintain fertility in women and men undergoing treatment for these cancers will be discussed. The options available to any particular cancer survivor will depend on her or his age at the time of diagnosis and treatment, cancer type and primary site, stage, and type of treatment.
Pressures under normal feet in standing and walking as measured by foil pedobarography.
Authors: D W Grieve, T Rashdi
Journal: Annals of the Rheumatic Diseases (1984)

An economical method of recording peak pressures under the feet while standing or walking is described for clinical application. Normal values at 10 defined locations are presented. Correlation matrices indicate functional links between regions of support which influence patterns of deviation from the norms.
2012 ACCF/AHA/HRS Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities
Authors: Cynthia M. Tracy, Andrew E. Epstein, Dawood Darbar, John P. DiMarco, Sandra B. Dunbar, N.A. Mark Estes, T. Bruce Ferguson, Stephen C. Hammill, Pamela E. Karasik, Mark S. Link, Joseph E. Marine, Mark H. Schoenfeld, Amit J. Shanker, Michael J. Silka, Lynne Warner Stevenson, William G. Stevenson, Paul D. Varosy
Journal: Circulation (2012)
Hypercoagulability Induced by Hyperlipemia in Rat, Rabbit and Man
Authors: S. Renoud, S. Lecompte
Journal: Circulation Research (1970)

Feeding a butter-rich diet to rats induced a "hypercoagulable state," since multiple large thrombi were observed in response to injection of S. typhosa endotoxin but the same stimulus was ineffective in rats fed a corn oil-rich diet or laboratory chow. In vitro hypercoagulability was noted in blood from the butter-fed rats, the recalcification plasma clotting time (PCT) being reduced by 34 to 45% in comparison with the controls. When a phospholipid suspension replaced the platelets in the plasma clotting test, the reduction was only 5 to 15%, but it was 31 and 43% when the platelets of these rats were washed and resuspended in a given standard plasma. Since lipid extract of these platelets could largely reproduce their activity, the factor involved must have been factor 3. A similar result was obtained in rabbits fed a butter or corn oil diet, or laboratory chow, indicating that, in this species also, the hypercoagulability in response to hyperlipemia was largely due to factor 3. In addition, in rats and rabbits fed butter, the platelets were more susceptible to thrombin-induced aggregation. In 27 human subjects of either sex and various ages, the state of coagulability as determined by the PCT was also mostly related to the platelet factor 3 activity, which was negatively correlated with serum cholesterol.
Elevated Levels of Interleukin-6 in Young Adults With Type 1 Diabetes Without Clinical Evidence of Microvascular and Macrovascular Complications
Authors: Giovanni Targher, Luciano Zenari, Lorenzo Bertolini, Michele Muggeo, Giacomo Zoppini
Journal: Diabetes Care (2001)

The past decade has been characterized by growing interest in the idea that atherosclerosis is an inflammatory disease, and by the finding that serum levels of markers of inflammation can be used to predict the risk of cardiovascular events (1). Elevated concentrations of acute-phase reactants, such as C-reactive protein, soluble intercellular adhesion molecule-1, and fibrinogen, are found in patients with acute coronary syndromes and are predictors of future risk in apparently healthy individuals (123). The inflammatory cytokine interleukin-6 (IL-6) is a powerful inducer of the hepatic acute-phase response, and it has been proposed to be a central mediator in the pathogenesis of coronary heart disease through a combination of autocrine, paracrine, and endocrine mechanisms (4). In fact, in a recent study, serum levels of IL-6 were predictive of the risk of myocardial infarction in apparently healthy individuals, and although the levels of IL-6 were strongly correlated with the levels of C-reactive protein, the association between IL-6 and the risk of myocardial infarction remained significant, even after …
Controlled trial evaluation of an asthma education programme for adults.
Authors: R Yoon, D K McKenzie, A Bauman, D A Miles
Journal: Thorax (1993)

To improve asthma control and reduce readmission rates through increased knowledge and the development of self management skills, a brief (three hour) adult education programme was developed.The course was designed to improve inhaler skills and to teach how to adjust drug doses according to peak flow (PEF) measurements and a treatment plan. It was evaluated in a randomised controlled trial in 76 patients admitted to hospital for asthma by using questionnaires, spirometry, and home monitoring of PEF at entry and at five and 10 months after intervention. The questionnaire provided measures of knowledge about asthma, self management behaviour appropriate to asthma control, asthma symptom frequency and severity, and psychosocial disturbance attributable to asthma.During the 10 months observation period the readmission rate for the educated group was one seventh that of the control group and attendance at accident and emergency departments also decreased. No consistent differential improvements were observed in spirometric results, average PEF, or mean daily variability of PEF. Both groups showed improvements in measures of asthma knowledge, behaviour, symptoms, and psychosocial disturbances. However, the intervention group showed a significantly greater improvement in some measures of asthma knowledge and self management skills.Despite minimal effect on measures of airway function, substantial changes in illness behaviour and use of health care facilities can be achieved by a brief asthma education programme.
Sequence context affects the rate of short insertions and deletions in flies and primates
Authors: Amos Tanay, Eric D Siggia
Journal: Genome biology (2008)

Abstract Background Insertions and deletions (indels) are an important evolutionary force, making the evolutionary process more efficient and flexible by copying and removing genomic fragments of various lengths instead of rediscovering them by point mutations. As a mutational process, indels are known to be more active in specific sequences (like micro-satellites) but not much is known about the more general and mechanistic effect of sequence context on the insertion and deletion susceptibility of genomic loci. Results Here we analyze a large collection of high confidence short insertions and deletions in primates and flies, revealing extensive correlations between sequence context and indel rates and building principled models for predicting these rates from sequence. According to our results, the rate of insertion or deletion of specific lengths can vary by more than 100-fold, depending on the surrounding sequence. These mutational biases can strongly influence the composition of the genome and the rate at which particular sequences appear. We exemplify this by showing how degenerate loci in human exons are selected to reduce their frame shifting indel propensity. Conclusion Insertions and deletions are strongly affected by sequence context. Consequentially, genomes must adapt to significant variation in the mutational input at indel-prone and indel-immune loci.
Cetuximab Therapy and Symptomatic Hypomagnesemia
Authors: Deborah Schrag, Ki Young Chung, Carlos Flombaum, Leonard Saltz
Journal: JNCI Journal of the National Cancer Institute (2005)

We report that patients treated with cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), occasionally develop a magnesium wasting syndrome with inappropriate urinary excretion. We first observed this phenomenon in a 34-year-old male patient with metastatic colorectal cancer who developed profound fatigue and symptomatic hypocalcemia and hypomagnesemia while on cetuximab plus irinotecan therapy. Other medications with the potential to cause magnesium wasting had not been administered. Intravenous magnesium supplementation was required for the duration of cetuximab therapy, but electrolyte abnormalities resolved after discontinuation of treatment. This case prompted review of serum chemistry reports for a consecutive case series of 154 colorectal cancer patients treated with cetuximab. Thirty-four patients (22%) had at least one serum magnesium measurement during cetuximab treatment, and six had grade 3 (< 0.9 mg/dL) and two had grade 4 (< 0.7 mg/dL) hypomagnesemia. Because EGFR is strongly expressed in the kidney, particularly in the ascending limb of the loop of Henle where 70% of filtered magnesium is reabsorbed, EGFR blockade may interfere with magnesium transport. Because symptoms may be rapidly ameliorated with supplementation, we suggest that, when fatigue or hypocalcemia is encountered during cetuximab therapy, serum magnesium level be measured and repleted as necessary.
Holding the Line against Diagnostic Inflation in Psychiatry
Authors: Laura Batstra, Allen Frances
Journal: Psychotherapy and Psychosomatics (2011)

pet diagnoses and from consumer advocacy groups who worry a great deal about false negatives but tend toward indifference about false positives.The only pushback against all of these pressures causing diagnostic inflation comes from those practice guidelines that suggest a cautious, stepped care approach to treatment [5,6] .However, these efforts have not been sufficient to hold the diagnostic line in psychiatry and in primary care practice.Rates of diagnosis and use of psychotropic medication continue to escalate [2,7] .Our purpose here is to suggest an explicitly stepped approach to diagnosis that will increase the acceptance and practicality of stepped care for mental disorders.The goal is to reduce the high rate of false positives without risking undertreatment for those who need it. From Inpatient to Outpatient Psychiatric DiagnosisThe first manual of mental disorders was developed to collect statistics for the 1860 census in the USA.It described just six conditions, all of which were rare and severe enough to warrant long-term, inpatient hospitalization.Until World War I, it was neurologists working in outpatient settings who diagnosed and treated what are now considered psychiatric disorders, often using the popular neurological labels 'neurasthenia' and 'hys-