tbuckley/cabot-search huggingface dataset:
Common and epithelioid variants of hepatic angiomyolipoma exhibit clonal growth and share a distinctive immunophenotype
Authors: P Flemming, U Lehmann, T Becker, J Klempnauer, H Kreipe
Journal: Hepatology (2000)

Angiomyolipoma represents a rare liver tumor of uncertain histogenesis that is commonly considered a hamartoma. A series of 12 hepatic angiomyolipomas, including 3 samples of the epithelioid subtype, was analyzed for clonality using the human androgen receptor gene locus (HUMARA). Four of 6 informative cases revealed monoclonality. The polyclonal pattern in the 2 remaining cases was most probably caused by excessive infiltration of inflammatory cells. Monoclonality with an identical X-chromosomal inactivation pattern in all nodules was found in a multifocal recurrent tumor indicating a metastatic process. Despite the morphologic heterogeneity, all tumors displayed an identical immunohistochemical labeling pattern. It is concluded that different subtypes of hepatic angiomyolipoma exhibit a monoclonal and hence probably neoplastic growth and share an identical immunophenotype suitable for their identification even in small biopsy specimens. The epithelioid subtype may give rise to intrahepatic metastasis.
Effects of CD2-associated protein deficiency on amyloid-β in neuroblastoma cells and in an APP transgenic mouse model
Authors: Fan Liao, Hong Jiang, Subhashini Srivatsan, Qingli Xiao, Katheryn B Lefton, Kaoru Yamada, Thomas E Mahan, Jin-Moo Lee, Andrey S Shaw, David M Holtzman
Journal: Molecular Neurodegeneration (2015)

CD2-associated protein (CD2AP) is an SH3-containing scaffold adaptor protein which regulates the actin cytoskeleton. Recently, CD2AP was identified as a genetic risk factor for Alzheimer's disease (AD) by several genome-wide association studies. One of the hallmarks of AD is the accumulation of aggregated forms of Amyloid-β (Aβ) in the brain. In humans, CD2AP AD susceptibility locus (rs9349407) is associated with an increased plaque burden. Aβ production is highly regulated by endocytosis and is influenced by lysosomal function. Lysosomal trafficking is influenced by CD2AP. In this study, we decreased CD2AP levels in N2a neuroblastoma cultures and PS1APP mice and analyzed Aβ levels and plaque burden. Our data show that suppressing CD2AP expression using shRNA in N2a-APP695 cells results in decreased cell membrane amyloid precursor protein, decreased Aβ release and a lower Aβ42/Aβ40 ratio. CD2AP protein is expressed in the brain as detected by western blot, and the expression level is dependent on gene dosage. In 1-month old PS1APP mice, complete loss of CD2AP in brain resulted in a decreased Aβ42/Aβ40 ratio in brain tissue lysates while there was no effect on Aβ deposition or accumulation in PS1APP mice expressing one copy of CD2AP. CD2-Associated Protein affects Aβ levels and Aβ42/Aβ40 ratio in vitro. The effect of CD2-Associated Protein on Aβ metabolism is subtle in vivo.
Inhibition of feline collateral vessel development following experimental thrombolic occlusion.
Authors: R G Schaub, K M Meyers, R D Sande, G Hamilton
Journal: Circulation Research (1976)

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.
TWO POPULATIONS OF T LYMPHOCYTES IMMUNE TO THE LYMPHOCYTIC CHORIOMENINGITIS VIRUS
Authors: Mogens Volkert, Ole Marker, Klaus Bro-Jørgensen
Journal: The Journal of Experimental Medicine (1974)

In this report seven different parameters were employed to investigate the spleen and lymph node cells from mice at the early and the late state of immunity to the lymphocytic choriomeningitis (LCM) virus. Distinct differences were observed. Morphological studies revealed a different size distribution of the cells in the preparations from the early and the late state of immunity. The cell mixtures of early immune cells contained many more large and blast-like lymphoid cells than the other. Where the cell function was concerned, the cytotoxic activity against LCM virus-infected target cells was almost entirely a function of the early immune cells, and our data strongly indicate that enhancement does not play any role for the disappearance by time of this cell activity. The antiviral effect after transfer to acutely infected animals was also predominantly a function of the early immune cells and the same was the case concerning the ability to protect against a lethal acute infection. However, the early immune cells were almost inactive after transfer to chronically infected virus carriers, whereas transplants of late immune cells to such mice had a very strong antiviral effect. The resistance to X irradiation also varied. Even high X-ray doses could not destroy the function of early immune cells, whereas the function of the late immune cells was readily impaired by X-ray treatment. The early and the late immune cells have one thing in common-both are susceptible to treatment with anti-theta serum. Because of the differences observed between the early and the late immune cells, it is concluded that they belong to different cell populations. However, because of the common susceptibility to anti-theta serum, probably both populations are T-cell lymphocytes. The implications of the results and the role of the different cells in the combat of the viral infection are discussed.
VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF
Authors: Astrid F. Nottebaum, Giuseppe Cagna, Mark Winderlich, Alexander C. Gamp, Ruth Linnepe, Christian Polaschegg, Kristina Filippova, Ruth Lyck, Britta Engelhardt, Olena Kamenyeva, Maria Gabriele Bixel, Stefan Butz, Dietmar Vestweber
Journal: The Journal of Experimental Medicine (2008)

We have shown recently that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial-specific membrane protein, associates with vascular endothelial (VE)–cadherin and enhances VE-cadherin function in transfected cells (Nawroth, R., G. Poell, A. Ranft, U. Samulowitz, G. Fachinger, M. Golding, D.T. Shima, U. Deutsch, and D. Vestweber. 2002. EMBO J. 21:4885–4895). We show that VE-PTP is indeed required for endothelial cell contact integrity, because down-regulation of its expression enhanced endothelial cell permeability, augmented leukocyte transmigration, and inhibited VE-cadherin–mediated adhesion. Binding of neutrophils as well as lymphocytes to endothelial cells triggered rapid (5 min) dissociation of VE-PTP from VE-cadherin. This dissociation was only seen with tumor necrosis factor α–activated, but not resting, endothelial cells. Besides leukocytes, vascular endothelial growth factor also rapidly dissociated VE-PTP from VE-cadherin, indicative of a more general role of VE-PTP in the regulation of endothelial cell contacts. Dissociation of VE-PTP and VE-cadherin in endothelial cells was accompanied by tyrosine phoshorylation of VE-cadherin, β-catenin, and plakoglobin. Surprisingly, only plakoglobin but not β-catenin was necessary for VE-PTP to support VE-cadherin adhesion in endothelial cells. In addition, inhibiting the expression of VE-PTP preferentially increased tyrosine phosphorylation of plakoglobin but not β-catenin. In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not β-catenin.
Separate visual representations in the planning and control of action
Authors: Scott Glover
Journal: Behavioral and Brain Sciences (2004)

Evidence for a dichotomy between the planning of an action and its on-line control in humans is reviewed. This evidence suggests that planning and control each serve a specialized purpose utilizing distinct visual representations. Evidence from behavioral studies suggests that planning is influenced by a large array of visual and cognitive information, whereas control is influenced solely by the spatial characteristics of the target, including such things as its size, shape, orientation, and so forth. Evidence from brain imaging and neuropsychology suggests that planning and control are subserved by separate visual centers in the posterior parietal lobes, each constituting part of a larger network for planning and control. Planning appears to rely on phylogenetically newer regions in the inferior parietal lobe, along with the frontal lobes and basal ganglia, whereas control appears to rely on older regions in the superior parietal lobe, along with the cerebellum.
Is a consultation needed?
Authors: Frank Sullivan, Jeremy C Wyatt
Journal: BMJ (2005)

People with health concerns no longer have to become patients by consulting a health professional. Electronic health (eHealth) tools provide access to many resources that may satisfy their requirements. This article describes ways that patients can investigate health issues before, or instead of, a consultation.

Ms Amulya Patel is a 48 year old accountant whose mother has recently been diagnosed with breast cancer. Ms Patel wonders about her own level of risk, and uses the internet to search for patient resources 

As a professional, Ms Patel (see box opposite) can access health resources on the internet at work and at home. She may subscribe to a mobile internet service provider through her telephone or palmtop computer. Internet access is not restricted to affluent people in western societies. In the United Kingdom, the 2003 national statistics omnibus survey showed that 48% of households have home internet access, and the figures from the United States are even higher (60% of households have access). Internet cafes can be found worldwide, and library services often provide time online for free. The public can pay for “push technologies” from publishers that supply health alerts, but most people search for the information they need.



Google search results for “breast cancer and family” 



Internet search engines are software tools that index and catalogue websites. People with little or no prior knowledge of a subject, but with some experience of searching the internet, often use search engines to begin an inquiry.

If Ms Patel types “breast cancer and family” into a search …
Minister to look again at NHS bill's threat to GMC
Authors: J. Warden
Journal: BMJ (1999)

British doctors' concerns about government interference with the current system of professionalself regulation by the General Medical Council were voiced during the second reading of the HealthBill in the House of Lords last week. The discussion led to a junior health minister promising to reconsider the issue.

The bill empowers the government to modify the regulatory system by order in council rather than the current requirement for primary legislation. A former GMC president, Lord Walton, called thenew …
Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk
Authors: Jane Green, Benjamin J Cairns, Delphine Casabonne, F Lucy Wright, Gillian Reeves, Valerie Beral
Journal: The Lancet Oncology (2011)

Epidemiological studies have shown that taller people are at increased risk of cancer, but it is unclear if height-associated risks vary by cancer site, or by other factors such as smoking and socioeconomic status. Our aim was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors.Information on height and other factors relevant for cancer was obtained in 1996-2001 for middle-aged women without previous cancer who were followed up for cancer incidence. We used Cox regression models to calculate adjusted relative risks (RRs) per 10 cm increase in measured height for total incident cancer and for 17 specific cancer sites, taking attained age as the underlying time variable. We also did a meta-analysis of published results from prospective studies of total cancer risk in relation to height.1 297 124 women included in our analysis were followed up for a total of 11·7 million person-years (median 9·4 years per woman, IQR 8·4-10·2), during which time 97 376 incident cancers occurred. The RR for total cancer was of 1·16 (95% CI 1·14-1·17; p<0·0001) for every 10 cm increase in height. Risk increased for 15 of the 17 cancer sites we assessed, and was statistically significant for ten sites: colon (RR per 10 cm increase in height 1·25, 95% CI 1·19-1·30), rectum (1·14, 1·07-1·22), malignant melanoma (1·32, 1·24-1·40), breast (1·17, 1·15-1·19), endometrium (1·19, 1·13-1·24), ovary (1·17, 1·11-1·23), kidney (1·29, 1·19-1·41), CNS (1·20, 1·12-1·29), non-Hodgkin lymphoma (1·21, 1·14-1·29), and leukaemia (1·26, 1·15-1·38). The increase in total cancer RR per 10 cm increase in height did not vary significantly by socioeconomic status or by ten other personal characteristics we assessed, but was significantly lower in current than in never smokers (p<0·0001). In current smokers, smoking-related cancers were not as strongly related to height as were other cancers (RR per 10 cm increase in height 1·05, 95% CI 1·01-1·09, and 1·17, 1·13-1·22, respectively; p=0·0004). In a meta-analysis of our study and ten other prospective studies, height-associated RRs for total cancer showed little variation across Europe, North America, Australasia, and Asia.Cancer incidence increases with increasing adult height for most cancer sites. The relation between height and total cancer RR is similar in different populations.Cancer Research UK and the UK Medical Research Council.
Coalesced Multicentric Analysis of 2,351 Patients With Myelodysplastic Syndromes Indicates an Underestimation of Poor-Risk Cytogenetics of Myelodysplastic Syndromes in the International Prognostic Scoring System
Authors: Julie Schanz, Christian Steidl, Christa Fonatsch, Michael Pfeilstöcker, Thomas Nösslinger, Heinz Tuechler, Peter Valent, Barbara Hildebrandt, Aristoteles Giagounidis, Carlo Aul, Michael Lübbert, Reinhard Stauder, Otto Krieger, Guillermo Garcia-Manero, Hagop Kantarjian, Ulrich Germing, Detlef Haase, Elihu Estey
Journal: Journal of Clinical Oncology (2011)

The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort.In total, 2,351 patients with MDS who have records in the German-Austrian and the MD Anderson Cancer Center databases were included and analyzed in univariate and multivariate models regarding overall survival and risk of transformation to acute myeloid leukemia (AML). The data were analyzed separately for patients treated with supportive care without specific therapy, with AML-like chemotherapy, or with other therapy regimens (low-dose chemotherapy, demethylating agents, immune modulating agents, valproic acid, and cyclosporine).The prognostic impact of poor-risk cytogenetic findings (as defined by the IPSS classification) on overall survival was as unfavorable as an increased (> 20%) blast count. The hazard ratio (compared with an abnormal karyotype or a bone marrow blast count < 5%) was 3.3 for poor-risk cytogenetics, 4.8 for complex abnormalities harboring chromosomes 5 and/or 7, and 3.1 for a blast count of 21% to 30% (P < .01 for all categories). The predictive power of the IPSS cytogenetic subgroups was unaffected by type of therapy given.The independent prognostic impact of poor-risk cytogenetics on overall survival is equivalent to the impact of high blast counts. This finding should be considered in the upcoming revision of the IPSS.
Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival
Authors: K.D. Miller, T. Weathers, L.G. Haney, R. Timmerman, M. Dickler, J. Shen, G.W. Sledge Jr
Journal: Annals of Oncology (2003)

Background: As screening central nervous system (CNS) imaging is not routinely performed, the incidence and clinical relevance of occult CNS metastases in advanced breast cancer is unknown.Patients and methods: All patients screened for participation in one of four clinical trials were included; each of the trials excluded patients with known CNS involvement and required screening CNS imaging. A cohort of breast cancer patients with symptomatic CNS metastases was identified from the IU Cancer Center Tumor Registry for comparison.Results: From November 1998 to August 2001, 155 screening imaging studies were performed. Twenty-three patients (14.8%) had occult CNS metastases. HER-2 overexpression (P = 0.02) and number of metastatic sites (P = 0.03) were predictive of CNS involvement by multivariate analysis. Median survival from time of metastasis (1.78 versus 2.76 years; P <0.0001) and from screening (4.67 versus 10.4 months;P = 0.0013) was shorter in patients with than without occult CNS metastasis. Survival among patients with occult CNS metastasis was similar to patients with symptomatic CNS disease.Conclusions: Patients with CNS involvement, whether occult or symptomatic, have an impaired survival. Occult CNS metastasis is relatively common, but impact on survival of treating occult CNS disease in patients with progressive systemic metastases is questionable.
Repeatability of physical signs in airways obstruction
Authors: S. Godfrey, R. H. T. Edwards, E. J. M. Campbell, P. Armitage, E. A. Oppenheimer
Journal: Thorax (1969)

We have examined the observer variation in the detection of physical signs in airways obstruction. In the first study, 10 relatively experienced physicians examined 11 patients for the presence of six familiar signs and seven less well-known signs. Six experienced observers then underwent a training period after which they examined another group of 21 patients. The repeatability of all the signs fell about midway between that expected by chance and the maximum possible. There was no difference between the familiar and unfamiliar signs. The training period resulted in a slight but not significant improvement in reliability.
Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy
Authors: Rohit Anthony Sinha, Seo-Hee You, Jin Zhou, Mobin M. Siddique, Boon-Huat Bay, Xuguang Zhu, Martin L. Privalsky, Sheue-Yann Cheng, Robert D. Stevens, Scott A. Summers, Christopher B. Newgard, Mitchell A. Lazar, Paul M. Yen
Journal: Journal of Clinical Investigation (2012)

For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid β-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo. Furthermore, blockade of autophagy by autophagy-related 5 (ATG5) siRNA markedly decreased TH-mediated fatty acid β-oxidation in cell culture and in vivo. Consistent with this model, autophagy was altered in livers of mice expressing a mutant TR that causes resistance to the actions of TH as well as in mice with mutant nuclear receptor corepressor (NCoR). These results demonstrate that THs can regulate lipid homeostasis via autophagy and help to explain how THs increase oxidative metabolism.
Fasting Indicators of Insulin Sensitivity: Effects of Ethnicity and Pubertal Status
Authors: Tanja C. Adam, Rebecca E. Hasson, Christianne J. Lane, Jaimie N. Davis, Marc J. Weigensberg, Donna Spruijt-Metz, Michael I. Goran
Journal: Diabetes Care (2011)

OBJECTIVE To examine the relationship of fasting indicators of insulin sensitivity with a more invasive measure of insulin sensitivity (frequently sampled intravenous glucose tolerance test [FSIVGTT]) and the effect of Tanner stage and ethnicity on that relationship. RESEARCH DESIGN AND METHODS Data were analyzed from 149 overweight girls (97 Hispanic and 52 African American) who were either in the early stages of maturation defined by Tanner stages 1 or 2 (52 Hispanic and 18 African American) or in the later stages of maturation defined by Tanner stages 4 and 5 (45 Hispanic and 34 African American). Fasting indicators of insulin sensitivity (IS) included fasting insulin and glucose and the homeostasis model assessment of insulin resistance (HOMA-IR). IS was derived from an FSIVGTT with minimal modeling. RESULTS In Tanner stages 1 and 2, all fasting indicators were significantly associated with IS: (fasting insulin: r = −0.67, P &amp;lt; 0.01; HOMA: r = −0.66, P &amp;lt; 0.01) with no significant influence of ethnicity on these relationships. In Tanner stages 4 and 5, however, all fasting indicators were associated with IS in African American girls (fasting insulin: r = −0.55, P &amp;lt; 0.01; HOMA: r = −0.47, P &amp;lt; 0.01), but none of the indicators were significantly associated with IS in Hispanic girls. CONCLUSIONS Fasting indicators were reflective of IS for girls in Tanner stages 1 and 2, regardless of ethnicity and may provide a clinical measure of future risk for type 2 diabetes. In the latter stages of maturation, however, more invasive measures are warranted to adequately determine IS in clinical practice.
Effects of aging on surfactant forms in rats
Authors: T. Ueda, G. Cheng, Y. Kuroki, H. Sano, K. Sugiyama, S. Motojima, T. Fukuda
Journal: European Respiratory Journal (2000)

Surfactant present in the alveolar space exists in two major forms: functional large aggregate forms (LA) and nonfunctional small aggregate forms (SA), but there is no information about the changes of surfactant forms and the rate of conversion of LA to SA in the aged lungs. The purpose of the present study was to investigate the developmental aspects of surfactant forms in newborn, young, middle-aged and aged rats, LA and SA were recovered from alveolar lavages of rats. The rate of conversion from LA to SA was then analysed using a surface-area cycling technique. Age-related changes of saturated phosphatidylcholine (Sat-PC) and surfactant protein A (SP-A) pool sizes were also evaluated in alveolar lavages. The alveolar lavages recovered from aged rats contained a significantly higher proportion of LA than did those obtained from young or newborn rats. There was also an age-related decrease in the rate of conversion from LA to SA in vitro. The Sat-PC pool sizes in the alveolar lavages decreased with age, but the SP-A contents were similar between young and aged rats. These results suggested that decreased form conversion may contribute to maintaining functional surfactant pool sizes in the lungs of aged rats.