tbuckley/cabot-search huggingface dataset:
Structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in acute promyelocytic leukemia
Authors: Maoxiang Qian, Wen Jin, Xuehua Zhu, Xiaohong Jia, Xianwen Yang, Yanzhi Du, Kankan Wang, Ji Zhang
Journal: Journal of Hematology & Oncology (2013)

Transcription factor PU.1, a member of the ETS family, is a master regulator of myeloid differentiation whose functional disruption is often associated with acute myeloid leukemia (AML). Although much has been learned about PU.1 over the past decades, relatively little is known about cis-elements that interact with this factor under physiological or pathological conditions, especially in the whole-genome scale. We aimed to define the cistrome of PU.1 in acute promyelocytic leukemia (APL) cells and characterize the cis-elements bound by PU.1.Chromatin immunoprecipitation with specific antibody coupled with deep sequencing (ChIP-seq) was used to investigate the in vivo PU.1 binding sites at the whole-genome scale in APL-derived NB4 cells. The ChIP-quantitative (q)-PCR and luciferase reporter assays were used to validate the binding events and trans-activity, respectively. Various computational analyses, including motif mining, evolutionary conservation analysis and functional enrichment analysis, were performed to characterize the cis-elements that interacted with PU.1.A total of 26,907 significantly enriched binding regions of PU.1 were identified under the false discovery rate 0.1% in NB4 cells. PU.1 bound to various types of genomic regions and acted as a promoter-enhancer dual binding transcription factor. Based on the sequence length and composition, two types of representative motifs were identified in PU.1 binding sites: a long and a short motif. The long motif, characterized by high sequence specificity and binding affinity, predominantly resided in the promoter-distal regions. In contrast, the short one, with strong evolutionary constraint, represented the primary PU.1 cis-elements in the promoter-proximal regions. Interestingly, the short one showed more preference to be correlated with the binding of other factors, especially PML/RARα. Moreover, genes targeted by both PU.1 and PML/RARα were significantly involved in categories associated with oncogenesis, hematopoiesis and the pathogenesis of acute myeloid leukemia.Our results demonstrate that structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in APL, suggesting that the sequence diversity of cis-elements might be a critical mechanism by which cells interpret the genome, and contribute to distinct physiological and/or pathological function.
Urinary Connective Tissue Growth Factor Excretion in Patients With Type 1 Diabetes and Nephropathy
Authors: Richard E. Gilbert, Aysel Akdeniz, Stephen Weitz, William R. Usinger, Christopher Molineaux, Susan E. Jones, Robyn G. Langham, George Jerums
Journal: Diabetes Care (2003)

OBJECTIVE—Excretion of growth factors in the urine has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. In this cross-sectional study, we sought to examine the urinary excretion of the profibrotic cytokine connective tissue growth factor (CTGF) in type 1 diabetic patients with incipient and overt diabetic nephropathy. RESEARCH DESIGN AND METHODS—We recruited 31 subjects with type 1 diabetes from a hospital diabetes outpatient clinic. Of these, 10 subjects were normoalbuminuric, 8 were microalbuminuric and not receiving ACE inhibitor treatment, and 13 were macroalbuminuric, 8 of whom were receiving ACE inhibitor treatment. Urinary CTGF NH2-terminal fragment (CTGF-N) was determined by enzyme-linked immunosorbent assay and expressed relative to urinary creatinine. RESULTS—Urinary CTGF-N was closely correlated with the degree of albuminuria (r = 0.76, P &amp;lt; 0.001). In comparison with normoalbuminuric subjects, urinary CTGF-N was increased 10- and 100-fold in micro- and untreated macroalbuminuric subjects, respectively (CTGF-N–to–creatinine ratio: normoalbuminuria 0.23 ×/÷ 1.3 ng/mg, microalbuminuria 2.1 ×/÷ 1.7 ng/mg, untreated macroalbuminuria 203 ×/÷ 3.8 ng/mg, and geometric mean ×/÷ tolerance factor; P &amp;lt; 0.05 for normoalbuminuria versus microalbuminuria, P &amp;lt; 0.001 for microalbuminuria versus macroalbuminuria). Urinary CTGF-N was lower (&amp;lt;30-fold) in macroalbuminuric subjects treated with ACE inhibitors (6.5 ×/÷ 1.7 ng/mg; P &amp;lt; 0.01 vs. untreated macroalbuminuria) compared with their untreated counterparts. CONCLUSIONS—In this cross-sectional study, the magnitude of urinary CTGF-N excretion was related to the severity of diabetic nephropathy. In the context of its known profibrotic actions, these findings suggest that CTGF may contribute to the chronic tubulointerstitial fibrosis that accompanies proteinuric renal disease. Prospective and interventional studies will be needed to determine whether urinary CTGF-N may provide a reliable surrogate marker of renal injury and a meaningful indicator of response to therapy.
Discrete Subaortic Stenosis
Authors: D. T. KELLY, E. WULFSBERC, RICHARD D. ROWE
Journal: Circulation (1972)

Twenty-five patients with discrete subaortic stenosis were reviewed. Twenty were operated on for severe obstruction. Review of available data suggests there is a wide spectrum of the disease which may be divided into two main types designated I and II. Type I is a thin discrete membrane immediately under the aortic valve obstructing the outflow but not associated with narrowing of it. Type II is situated about 1 cm below the valve and consists of a fibrous ring, thicker than type I, and associated with muscular hypertrophy which narrows the outflow tract, encroaches on the anterior leaflet of the mitral valve, and may extend 1-2 cm downward. Both have a characteristic angiographic appearance. Results of surgery are good for type I but not satisfactory for type II. Aortic incompetence is likely to increase or develop following operation in both types.
Treatment of bleeding oesophageal varices by infusion of vasopressin into the superior mesenteric artery
Authors: I. M. Murray-Lyon, R. N. H. Pugh, H. B. Nunnerley, J. W. Laws, J. L. Dawson, R. Williams
Journal: Gut (1973)

Seventeen patients bleeding from oesophageal varices were treated by continuous infusion of vasopressin through a catheter inserted percutaneously and positioned in the superior mesenteric artery and in two other patients catheterization proved technically impossible. Bleeding was completely controlled on only four out of 18 occasions in the 17 patients treated. In seven patients, bleeding was controlled for two or more days but then recurred although the infusion was continued with an increased dose of vasopressin. There was a high incidence of complications, including bleeding from the site of catheter insertion in the groin and septicaemias. Sengstaken balloon tamponade and oesophageal transection had to be used to control bleeding in some patients but only six out of 17 survived to leave hospital.
Bone building with bortezomib
Authors: G David Roodman
Journal: Journal of Clinical Investigation (2008)

In this issue of the JCI, Mukherjee et al. report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of mesenchymal stem/progenitor cells (MSCs) — rather than mature osteoprogenitor cells — into osteoblasts, resulting in new bone formation (see the related article beginning on page 491). These results were observed when MSCs were implanted subcutaneously in mice or were used to treat a mouse model of postmenopausal bone loss. Others have reported that immunomodulatory drugs (e.g., thalidomide and lenalidomide), which are active against myeloma, also block the activity of bone-resorbing osteoclasts. These results reflect the utility of targeting endogenous MSCs for the purpose of tissue repair and suggest that combining different classes of agents that are antineoplastic and also inhibit bone destruction and increase bone formation should be very beneficial for myeloma patients suffering from severe bone disease.
Medical eponyms: taxonomies, natural history, and the evidence
Authors: J. K. Aronson
Journal: BMJ (2014)

<h3>ABSTRACT</h3> <h3>Background</h3> Correct clinical diagnosis at the first episode of psychosis may be difficult due to many non-specific symptoms. We aimed to determine the factors associated with a correct diagnosis among patients with a first episode of psychosis in Uganda. <h3>Methods</h3> A cross sectional study design was performed at the Butabika National Referral Mental Hospital in Uganda. We included treatment naïve participants aged 18 to 60 years with a diagnosis of a psychotic disorder. Patients with organic disorders like HIV/AIDS, syphilis and substance use disorders were excluded. The MINI international neuropsychiatric inventory was administered to confirm the clinical diagnosis. Concordance was based on the percentage agreement and kappa statistic between the admission chart diagnosis and the MINI diagnosis. <h3>Results</h3> 178 participants with a first episode of psychosis were included into the final analysis. The agreement between the MINI diagnosis and clinician diagnosis was 0.385, (P &lt; 0.001) with a concordance of 49.5%. After controlling for nationality and the household’s source of income, duration of untreated psychosis, [p-value 0.028(95%CI: 0.07-0.89)], living with a primary family member, [p-value 0.038(95%CI:0.95-2.86)] and cadre of the clinician who made the initial diagnosis[Medical officer, [p-value 0.011(95%CI: 0.18-0.80)] were associated with a correct diagnosis. <h3>Conclusion</h3> We found low agreement between clinician diagnoses and MINI diagnoses at the first episode of psychosis. Improved training of staff while considering the duration of untreated psychosis and the living arrangements of the patient are required to improve diagnostic accuracy in this population.
Symptomatic manubriosternal joint involvement in rheumatoid arthritis.
Authors: A Doube, A K Clarke
Journal: Annals of the Rheumatic Diseases (1989)

The manubriosternal joint is commonly involved in rheumatoid arthritis but rarely gives rise to symptoms. A patient is reported with seropositive, erosive rheumatoid arthritis, who developed symptoms resembling pleuritic pain, arising from synovitis of the manubriosternal joint. Treatment with intra-articular steroid injection resolved these symptoms rapidly.
Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Older Adults: Geriatric Principles in the Transplant Clinic
Authors: Tanya M. Wildes, Derek L. Stirewalt, Bruno Medeiros, Arti Hurria
Journal: Journal of the National Comprehensive Cancer Network (2014)

Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies. Given the high transplant-related morbidity, these treatment strategies were initially restricted to younger patients, but are increasingly being used in older adults. The incidence of most hematologic malignancies increases with age; with the aging of the population, the number of potential older candidates for HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly increased risk of specific toxicities (such as cardiac toxicities and mucositis) and have modestly lower effectiveness (in the case of lymphoma). However, auto-HCT remains a feasible, safe, and effective therapy for selected older adults with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT) is a potential therapeutic option for selected older adults, although fewer data exist on allo-HCT in older patients. Based on currently available data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an auto-HCT or allo-HCT may identify additional problems or geriatric syndromes, which may not be detected during the standard pretransplant evaluation. Further research is needed to establish the utility of CGA in predicting toxicity and to evaluate the quality of survival in older adults undergoing HCT.
Regulation of exogenous and endogenous glucose metabolism by insulin and acetoacetate in the isolated working rat heart. A three tracer study of glycolysis, glycogen metabolism, and glucose oxidation.
Authors: R R Russell, G W Cline, P H Guthrie, G W Goodwin, G I Shulman, H Taegtmeyer
Journal: Journal of Clinical Investigation (1997)

Myocardial glucose use is regulated by competing substrates and hormonal influences. However, the interactions of these effectors on the metabolism of exogenous glucose and glucose derived from endogenous glycogen are not completely understood. In order to determine changes in exogenous glucose uptake, glucose oxidation, and glycogen enrichment, hearts were perfused with glucose (5 mM) either alone, or glucose plus insulin (40 microU/ml), glucose plus acetoacetate (5 mM), or glucose plus insulin and acetoacetate, using a three tracer (3H, 14C, and 13C) technique. Insulin-stimulated glucose uptake and lactate production in the absence of acetoacetate, while acetoacetate inhibited the uptake of glucose and the oxidation of both exogenous glucose and endogenous carbohydrate. Depending on the metabolic conditions, the contribution of glycogen to carbohydrate metabolism varied from 20-60%. The addition of acetoacetate or insulin increased the incorporation of exogenous glucose into glycogen twofold, and the combination of the two had additive effects on the incorporation of glucose into glycogen. In contrast, the glycogen content was similar for the three groups. The increased incorporation of glucose in glycogen without a significant change in the glycogen content in hearts perfused with glucose, acetoacetate, and insulin suggests increased glycogen turnover. We conclude that insulin and acetoacetate regulate the incorporation of glucose into glycogen as well as the relative contributions of exogenous glucose and endogenous carbohydrate to myocardial energy metabolism by different mechanisms.
Crucial role of the melanocortin receptor MC1R in experimental colitis
Authors: C Maaser
Journal: Gut (2006)

<b>Background and aims:</b> α-Melanocyte stimulating hormone (αMSH) is known to exert anti-inflammatory effects, for example in murine DSS (dextran sodium sulphate induced) colitis. The anti-inflammatory functions of αMSH are mediated by the melanocortin1-receptor (MC1R) in an autoregulatory loop. The aim of this study was therefore to determine whether a breakdown of the αMSH–MC1R pathway leads to worsening of disease. <b>Methods:</b> Experimental colitis was induced in mice with a frameshift mutation in the MC1R gene (MC1Re/e), C57BL/6 wild type mice, and MC1Re/e-C57BL/6 bone marrow chimeras. The course of inflammation was monitored by weight loss, histological changes in the colon, and myeloperoxidase activity. In addition, MC1R expression was analysed in intestinal epithelial cells. <b>Results:</b> While the colon of untreated MC1Re/e appeared normal, the course of DSS-colitis in MC1Re/e mice was dramatically aggravated, with a significantly higher weight loss and marked histological changes compared to C57BL/6WT. The inflammation eventually led to death in all MC1Re/e, while all C57BL/6WT survived. Similar observations were detected in a transmissible murine colitis model induced by <i>Citrobacter rodentium</i>. Infected MC1Re/e showed delayed clearance of infection. To determine whether missing haematopoietic cell expressed MC1R was responsible, DSS colitis was induced in MC1Re/e-C57BL/6 bone marrow chimeras. MC1Re/e mice receiving MC1R+ bone marrow showed a similar course of inflammation to non-transplanted MC1Re/e. Likewise, transplantation of MC1R bone marrow into C57BL/6WT mice did not lead to any worsening of disease. <b>Conclusions:</b> This is the first study to show a functional role of MC1R in intestinal inflammation. The data suggest a pivotal role of non-haematopoietic cell expressed MC1R in the host’s response to pathogenic stimuli.
Diagnosing pulmonary hypertension: is there a revival of the electrocardiogram?
Authors: R. Speich
Journal: European Respiratory Journal (2011)

Even in the most recent and largest series of patients with pulmonary arterial hypertension (PAH), the time interval between the onset of symptoms and eventual diagnosis was a mean of 27 months 1. This represents an absolutely unacceptable delay, which is tragically even longer than the mean of 2 yrs in the first series of the US National Institutes of Health (NIH) registry about 20 yrs ago 2. Nowadays, three-quarters of patients are in World Health Organization (WHO) functional classes III or IV, have a 6-min walk distance of ∼330 m and a pulmonary vascular resistance of almost 1,000 dyn·s·cm−5 at the time of diagnosis 1. The mean pulmonary artery pressure ( P pa) of patients included in large randomised studies remains at values >50 mmHg, with 60 mmHg in the epoprostenol trial in 1996 3 and 52 mmHg in the Endothelin Antagonist Trial in Mildly Symptomatic Pulmonary Arterial Hypertension Patients (EARLY) study in 2008 4. Remarkably, the latter intended to include only patients in WHO class II, which implies that even patients with a clinically early form of the disease in fact suffer from an advanced stage of PAH, comparable to those in WHO functional class III–IV. Hence, despite advances in therapeutic options, there is no faint hope of improvement in diagnosing PAH during the past decades. Not unexpectedly, the overall 3-yr survival is still only ∼60% 5, 6, a modest 20% better than our ancestors’ empirical observations.

Our poor diagnostic performance with respect to the two forms of pre-capillary pulmonary hypertension (PH), i.e. PAH and chronic thromboembolic PH, is even more surprising if one considers the obviousness of the clinical presentation. Although PH symptoms are nonspecific, there are hardly any differential diagnoses for the classical triad of 1) dyspnoea or fatigue on …
Neuromuscular training may reduce injuries of the anterior cruciate ligament in female athletes
Authors: Dafne P Nascimento, C Christine Lin
Journal: British Journal of Sports Medicine (2011)

1. Yoo JH, 2. Lim BO, 3. Ha M, 4. et al . Knee Surg Sports Traumatol Arthrosc 2010;18:824–30. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Injuries to the anterior cruciate ligament (ACL) are common. Hewett et al 1 suggested that neuromuscular training reduces ACL injuries in female athletes, based on a systematic review where six studies were included. However, most of the studies were not randomised controlled trials and hence the review only provides preliminary evidence on the effectiveness of neuromuscular training. To evaluate the effectiveness of neuromuscular training in preventing ACL injuries in female athletes and to identify factors (age, type of sports, training time, programme component) that were associated with an effective programme. Four reviewers who were experienced in ACL injuries conducted a literature search in two databases (Medline and Cochrane Database for Systematic Reviews) … [1]: {openurl}?query=rft.jtitle%253DKnee%2Bsurgery%252C%2Bsports%2Btraumatology%252C%2Barthroscopy%2B%253A%2B%2Bofficial%2Bjournal%2Bof%2Bthe%2BESSKA%26rft.stitle%253DKnee%2BSurg%2BSports%2BTraumatol%2BArthrosc%26rft.aulast%253DYoo%26rft.auinit1%253DJ.%2BH.%26rft.volume%253D18%26rft.issue%253D6%26rft.spage%253D824%26rft.epage%253D830%26rft.atitle%253DA%2Bmeta-analysis%2Bof%2Bthe%2Beffect%2Bof%2Bneuromuscular%2Btraining%2Bon%2Bthe%2Bprevention%2Bof%2Bthe%2Banterior%2Bcruciate%2Bligament%2Binjury%2Bin%2Bfemale%2Bathletes.%26rft_id%253Dinfo%253Adoi%252F10.1007%252Fs00167-009-0901-2%26rft_id%253Dinfo%253Apmid%252F19760399%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1007/s00167-009-0901-2&link_type=DOI [3]: /lookup/external-ref?access_num=19760399&link_type=MED&atom=%2Fbjsports%2F45%2F8%2F680.atom [4]: /lookup/external-ref?access_num=000277789600022&link_type=ISI
Differential expression of sets of highly homologous variable region gene products in selected and preimmune repertoires of inbred mouse strains.
Authors: D Primi, A M Drapier, P A Cazenave
Journal: The Journal of Experimental Medicine (1986)

Using mAb that selectively recognize the various allelic forms of the VHT15 and Vk21D-E genes' products, we analyzed the influence of VH and Vk polymorphism on the probability of expression of these gene segments. Our data show that the frequency to which the VHT15 gene product becomes available in the preimmune repertoire is strongly influenced by the polymorphism of the relevant structural gene, suggesting therefore that VH genes cannot be randomly used in the various strains. Contrary to this, the frequency of Vk21D-E+ clones is similar in all mouse strains tested, and in all cases is higher than the frequency of VHT15 clones. This observation strongly suggests that Vk genes can be randomly expressed, and/or that their number is lower than that of their VH counterpart. Finally, analysis of the specificity associated to the expression of the VHT15 segment revealed that VH polymorphism strongly influences not only the probability of expression of each V gene, but also the specificity of the antibodies on which these VH genes are used.
Analysing the protective potential of padded soccer goalkeeper shorts
Authors: K U Schmitt, M Nusser, S Derler, P Boesiger
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the potential of currently available padded soccer goalkeeper shorts to prevent hip injuries sustained in side jumps was investigated. Design Within the scope of this study, a survey among professional and amateur goalkeepers, trainers and the medical staff was performed. In addition, commercially available shorts were impact-tested using an artificial hip model. The results were compared with requirements established for hip protectors for elderly. Results The results of the survey found that contusions and abrasions were observed most often for all players. Fractures and arthritis were only reported by amateur players, whereas bursitis was more frequently observed by professional players. Amateurs have a significantly higher risk of injury than professional players, and the higher injury risk during training is significantly higher compared with the injury risk during a match. No difference of the injury risk was found between goalkeepers wearing padded shorts and those who did not. Impact tests indicated a wide range of performance of the currently available products. The padded shorts generally reduce impact forces, but mostly perform poorly. Only shorts that were made of visco-elastic foam fulfilled the basic requirements requested for hip protectors for elderly. Conclusions The quality of most of the currently available goalkeeper shorts needs to be improved to effectively prevent hip injury sustained in side jumps.