tbuckley/cabot-search huggingface dataset:
Impaired Expression of the Cell Cycle Regulator <b> <i>BTG2</i> </b> Is Common in Clear Cell Renal Cell Carcinoma
Authors: Kirsten Struckmann, Peter Schraml, Ronald Simon, Katja Elmenhorst, Martina Mirlacher, Juha Kononen, Holger Moch
Journal: Cancer Research (2004)

Abstract The prognosis of patients with renal cell carcinoma (RCC) is poor. A full understanding of the molecular genetics and signaling pathways involved in renal cancer development and in the metastatic process is of central importance for developing innovative and novel treatment options. In this study, BD Atlas Human Cancer 1.2 cDNA microarrays were used to identify genes involved in renal tumorigenesis. By analyzing gene expression patterns of four clear cell RCC (cRCC) cell lines and normal renal tissue, 25 genes were found differentially expressed. To determine the relevance of these genes, RNA in situ hybridization was performed on a tissue microarray generated from 61 snap-frozen primary renal cell carcinomas and 12 normal renal cortex biopsies. B-cell translocation gene 2 (BTG2), a negative cell cycle regulator, which was expressed in normal renal tissue but down-regulated in cRCC cell lines and primary cRCCs, was selected for additional experiments. Quantitative BTG2 mRNA expression analysis in 42 primary cRCCs and 18 normal renal cortex biopsies revealed up to 44-fold reduced expression in the tumor tissues. Decrease of BTG2 expression was not associated with tumor stage, grade, and survival. Cell culture experiments demonstrated that BTG2 expression was weakly inducible by the phorbolester 12-O-tetradecanoylphorbol-13-acetate in one of four cRCC cell lines. In contrast, increasing cell density led to elevated BTG2 mRNA expression in three of four cRCC cell lines. In both experiments, BTG2 mRNA levels did not reach values observed in normal renal tissue. These data suggest that down-regulation of BTG2 is an important step in renal cancer development.
Lessons from Chernobyl
Authors: D. Williams
Journal: BMJ (2001)

We have just passed the 15th anniversary of Chernobyl, the world's worst nuclear disaster. The explosion of the reactor at this nuclear power station in Belarus in 1986 released huge amounts of radioactive isotopes, about 1019 becquerels, and heavy fallout affected large areas of Belarus and northern Ukraine and a small part of Russia, with lesser amounts detected throughout the northern hemisphere. The response of international organisations to the need to study the long term health consequences of the explosion was at first uncoordinated and is still inadequate.

In 1990 the World Health Organization was given $20m (£14m) by Japan to investigate the health effects,1 but expenditure was effectively controlled by one official, much of the money was spent inappropriately, and little of value resulted. Also in 1990 the International Atomic Energy Agency carried out a separate investigation. Though informed of cases of childhood thyroid cancer, it was generally reassuring about possible health consequences.2 The United States and the European Union signed separate treaties with the governments involved, allowing them to investigate the health effects. Initially the European Union and WHO Europe played a major part in drawing attention to the increase in the incidence of childhood thyroid cancer3-5 but then set up separate studies, as did the Sasakawa Memorial Health Foundation of Japan. Unesco, …
PM-15 * C11orf95-RELA FUSION ALONE IS SUFFICIENT TO FORM HUMAN SUPRATENTORIAL EPENDYMOMA-LIKE TUMOR IN MICE
Authors: T. Ozawa, D. Ellison, R. Gilbertson, E. Holland
Journal: Neuro-Oncology (2014)

Ependymomas (EMs) are primary tumors of the central nervous system that preferentially occur in children. Recent deep molecular analyses have revealed that these tumors are divided into molecularly distinct subgroups; particularly supra- and infratentorial EMs have significantly different genetic alterations. Chromothripsis is a massive genomic rearrangement event rarely occurring in various types of tumors, potentially resulting in oncogenic gene fusion. Recently, several types of C11orf95-associated fusion gene caused by gene rearrangements via chromothripsis were identified in a large fraction of supratentorial EMs. These fusion genes have been shown to be oncogenic when transferred to CNS stem cells in allograft model, these fusion genes may be promising therapeutic targets for the tumor type. Pysiologically relevant genetic mouse models are useful for the understanding of oncogenic mechanisms and drivers and for the exploration of theraputic targets in particular tumor types. Therefore, we used the RCAS/tv-a system to determine the ability for the C11orf95-RELA fusion to induce the formation of ependymomas in vivo in mice. When RCAS vector expressing the C11orf95-RELA fusion was introduced into Nestin/tv-a mice, tumors formed in a few months. Additional Cdkn2a loss in the context leads to an increased tumor penetrance. These tumors were observed as a circumscribed tumor adjacent to ventricular surface and formed abundant branching vascular network in the tumor, likely recapitulating histologic features of the human counterpart. This model should be a useful tool for understanding EM biology, therapeutic response, and recurrence.
Echocardiographic determination of left ventricular stress-velocity relations.
Authors: M A Quinones, W H Gaasch, J S Cole, J K Alexander
Journal: Circulation (1975)

The time course of left ventricular (LV) circumferential stress and fiber shortening velocity (Vcf) were determined at 20 msec intervals in 30 patients from simultaneous recordings of LV pressure (micromanometer) and LV dimensions (echography). In 12 patients with normal LV function, endocardial and midwall maximal (max) Vcf, Vcf at peak stress, and endocardial mean Vcf were significantly greater than in eight patients with myocardial disease. Peak stress was less in the normal subjects (mean equal 241 gl/cm2, range 180 to 310 g/cm2) than in those with myocardial diseases (mean equals 371 g/cm2, range 280 to 513 g/cm2). Vcf was reduced in five out of seven patients with chronic LV volume overload, while peak stress ranged from normal in three to increased in four. Max Vcf, mean Vcf, and peak stress were normal in three patients with chronic LV pressure overload; Vcf at peak stress was normal in two. Good correlation was observed between angiographic determinations of mean Vcf and endocardial max Vcf, Vcf at peak stress and mean Vcf. Induced changes in preload in five patients (dextran infusion at constant heart rate) produced a 12.2 per cent increase in peak stress (P small than 0.05), and insignificant changes in max Vcf (3.7 per cent increase, P = NS), in Vcf at peak stress (5 per cent decrease, P smaller than 0.05), in mean Vcf (0.7 per cent increase, P = NS). Increasing afterload with angiotensin in seven patients (peak stress increased by 45 per cent, P smaller than 0.01) reduced max Vcf, Vcf at peak stress and mean Vcf by 33 per cent, 39 per cent respectively. Lowering afterload in one patient (amyl nitrite) produced an increase in Vcf. Improvement in Vcf was observed in all instances during positive inotropic stimulation (isoproterenol in three normals, digoxin in four with myocardial disease). Thre response of endocardial and midwall Vcf to loading and contractility were similar. In man Vcf is an index of myocardial contractility which is affected minimally by changes in preload but responds inversely to changes in afterload. Its sensitivity to acute afterload changes may, at times, limit its clinical applicability.
On the proper generalization for Broca's aphasia comprehension pattern: Why argument movement may not be at the source of the Broca's deficit
Authors: Maria Mercedes Piñango
Journal: Behavioral and Brain Sciences (2000)

The comprehension problem in Broca's patients does not stem from an inability to represent argument traces. There can be good comprehension in the presence of (object) traces and impaired comprehension can result in constructions where there are no (object) argument traces. This leads to an alternative understanding of Broca's comprehension, one that places the locus of the impairment in an inability to construct syntactic representation on time.
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
Authors: Gunnar C. Hansson, Malin E.V. Johansson
Journal: Gut Microbes (2010)

We have recently shown that the colon is protected by an inner mucus layer that efficiently separates the bacteria in the outer mucus from the epithelial cells. The inner mucus is impervious for bacteria and built by a network formed by the MUC2 mucin. Lack or defects in this inner mucus layer allow bacteria to reach the epithelia, something that triggers colon inflammation.
SKIN REACTIONS TO FILTRATES OF HAEMOLYTIC STREPTOCOCCI IN ACUTE AND SUBACUTE NEPHRITIS 1
Authors: Oscar C. Hansen-Pruss, Warfield T. Longcope, D. P. O'Brien
Journal: Journal of Clinical Investigation (1929)

In a previous communication (1) it was noted that haemolytic streptococci isolated from the tonsils, adenoids or accessory nasal sinuses of cases of acute and subacute glomerular nephritis produced, in broth cultures, "toxins" which caused skin reactions similar to those caused by the "Dick Toxin."While studying the property of these filtrates, it was observed that intense skin reactions often occurred in patients suffering from acute and subacute nephritis associated with infections caused by haemolytic streptococci.A systematic study was, therefore, made of the incidence and intensity of the skin reac- tions to these bouillon filtrates of haemolytic streptococci in three groups of cases; first, patients suffering from acute and subacute nephritis; secondly, normal individuals and patients affected with miscellaneous conditions, and thirdly, patients suffering from uncom- plicated acute tonsillitis.There will be no attempt to discuss at this time the nature of these filtrates.It is, however, to be noted that many observers have found that haemolytic streptococci recovered from various forms of infection are capable of elaborating "toxic" substances when grown in broth (2, 3, 4, 5, 6, 7, 8, 9, 10, 11).Although these filtrates are usually more resistant to heat and less potent than the "Dick Toxin," yet they possess other properties in common with the "Dick Toxin," for they are frequently neutralizable by antiscarlatinal serum (3,7,9,10) and are considered by some to differ only quantitatively from the "Dick Toxin," though qualitative differences have also been observed (10, 11, 13, 13a).
Sopley: medical services for refugees.
Authors: A H Houston
Journal: BMJ (1979)

Although 543 Vietnamese refugees are housed in a reception camp at Sopley, the health authorities still await formal notification of their arrival.This paper discusses some of the problems encountered in providing medical services, and we hope that it will be useful to others faced with a similar problem in their own health district. General administrative and medical arrangementsThe Home Office delegated overall administrative responsibility for the camp to the British Council for Aid to Refugees (BCAR), and asked the British Red Cross Society (BRCS) to co-ordinate medical and nursing input.The National Health Service was expected to provide support at the expense of locally agreed priorities, and without any formal management control.Attempts to plan medical services were frustrated by lack of information.The numbers of refugees, dates of arrival, and ports of entry were not confirmed until a few hours before the event, and the
Intra-articular glucocorticoid injections decrease the number of steroid hormone receptor positive cells in synovial tissue of patients with persistent knee arthritis
Authors: Marlies C van der Goes, Rainer H Straub, Marion J G Wenting, Silvia Capellino, Johannes W G Jacobs, Zalima N Jahangier, Luise Rauch, Johannes W J Bijlsma, Floris P J G Lafeber
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To explore changes in the number of steroid hormone receptor positive cells in synovial tissue (ST) after intra-articular glucocorticoid injection, to correlate these changes with changes in clinical variables, and to evaluate whether the number of steroid hormone receptor positive cells predicted the clinical response to glucocorticoid injection. <h3>Methods</h3> Fourteen patients with persistent knee arthritis despite at least two previous injections in an outpatient setting received an intra-articular injection with glucocorticoids, followed by 3 days of admission with bed rest. Clinical efficacy was assessed at 6 and 12 weeks. ST biopsies were performed 2 weeks before and 12 weeks after the injection. The presence of different cell types (T cells, macrophages, fibroblast-like synoviocytes) and numbers of glucocorticoid, androgen and oestrogen α and β receptor positive cells were evaluated by histochemistry. <h3>Results</h3> Patients showed, despite previous failures, good clinical response to glucocorticoid injection, with significant improvement in erythrocyte sedimentation rate, visual analogue scale (VAS) for pain, and joint disability score. The number of steroid hormone receptor positive cells decreased markedly (p&lt;0.05 for all four receptors). The decrease in oestrogen receptor α positive cells correlated significantly with the improvement in VAS for pain and joint disability score. The number of glucocorticoid, androgen and oestrogen α and β receptor positive cells before injection did not predict the effect of treatment. <h3>Conclusions</h3> Intra-articular glucocorticoid injections followed by bed rest for persistent arthritis are clinically effective and significantly decrease the number of steroid hormone receptor positive cells in ST. The relevance of the latter needs further study.
Binding of straight-chain saturated dicarboxylic acids to albumin.
Authors: J H Tonsgard, S A Mendelson, S C Meredith
Journal: Journal of Clinical Investigation (1988)

Dicarboxylic acids are prominent features of several diseases, including Reye's syndrome. Long-chain dicarboxylic acids have profound effects on the function and structure of isolated mitochondria, suggesting that they could contribute to the mitochondrial dysfunction in Reye's syndrome. Binding of fatty acids to albumin and the intracellular fatty acid-binding proteins is important in regulating the transport and metabolism of fatty acids and protects against the toxic effects of unbound fatty acids. We studied the binding of dicarboxylic acids to defatted albumin using equilibrium dialysis to assess to what extent dicarboxylic acids are likely to be bound in the plasma of patients. Dicarboxylic acids bind weakly to albumin in a molar ratio of 3.8, 4.2, 1.6, 0.8, and 0.7 to 1 for octadecanedioic, hexadecanedioic, tetradecanedioic, dodecanedioic, and decanedioic acid, respectively. The dissociation constants for long-chain dicarboxylic acids are 100-1,000-fold larger than those of comparable monocarboxylic acids. Oleate competes with dicarboxylic acid and reduces the moles of dicarboxylic acid bound per mol of albumin to less than 1. Octanoate inhibits dicarboxylic acid binding. Our observations indicate that in Reye's syndrome, substantial concentrations of dicarboxylic acids of patients may be free and potentially toxic to mitochondria and other cellular processes.
Transfusion-Related Acute Lung Injury
Authors: Patricia M. Kopko, Carol S. Marshall, Malcolm R. MacKenzie, Paul V. Holland, Mark A. Popovsky
Journal: JAMA (2002)

Transfusion-related acute lung injury (TRALI) is a syndrome that includes dyspnea, hypotension, bilateral pulmonary edema, and fever. TRALI is the third leading cause of transfusion-related mortality, but it is probably underdiagnosed and underreported.To determine if blood products from a frequent plasma donor, whose blood product was implicated in a fatal case of TRALI, caused symptoms of TRALI in other recipients of her plasma.Retrospective chart review (conducted from November 2000 through April 2001) of 50 patients who received blood components within 2 years (October 1998 through October 2000) from a donor linked to a transfusion-related fatality.Occurrence of mild/moderate (dyspnea with fever, chills, hypotension, and/or hypoxemia) or severe (acute pulmonary edema or need for mechanical ventilation) reaction associated with transfusion.Superimposed illness prevented assessment of TRALI in 14 patients. Of the 36 patient charts that could be reviewed, 7 mild/moderate reactions were reported in 6 patients (16.7%) and 8 severe reactions were reported in 8 patients (22.2%). Of 5 patients who received multiple transfusions from the same donor, 2 experienced 2 reactions: one had 2 mild/moderate reactions and the other had both a mild/moderate and a severe reaction. While 5 of the 7 mild/moderate reactions were reported to the hospital transfusion service, only 2 of the 8 severe reactions were reported. Only 2 reactions (1 mild/moderate and 1 severe) were reported to the regional blood collection facility.TRALI was frequently underdiagnosed and underreported in recipients of blood products from a donor whose blood products may have caused TRALI in several transfusion recipients. Clinical education and awareness of this often-overlooked diagnosis are imperative for appropriate prevention and treatment.
Effect of interstitial lung disease macrophages on T-cell signal transduction.
Authors: J C Weissler, C Mendelson, F Moya, W C Yarbrough
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Some types of interstitial lung disease (ILD) are characterized by an abnormal proliferation and activation of lymphocytes in the alveolus and interstitium. Recent data have suggested that membrane signals on alveolar macrophages (AM) in normal lung play a crucial role in limiting lymphocyte activation by altering early events in receptor-mediated signal transduction in lymphocytes. In the current study fixed AM from normal volunteers and from patients with either sarcoidosis or idiopathic pulmonary fibrosis were compared for the ability to inhibit CD3-mediated increases in intracellular calcium concentration [(Ca2+)i]. All normal AM inhibited CD3-mediated increases in (Ca2+)i, whereas seven of 10 ILD AM were permissive of this early event in T-lymphocyte activation. Patients with ILD and permissive AM displayed significantly greater mean BAL lymphocytes than did those with suppressive AM (42 versus 12%, respectively). The inhibitory effect of normal AM could be partially duplicated by incubation of lymphocytes with surfactant (SF) obtained from normal lungs. Analysis of one SF component, SF protein A, in normal and in ILD AM membranes disclosed reduced SF protein A in ILD AM. These results demonstrate alterations in AM in patients with ILD and a lymphocytic alveolitis that renders AM permissive for early events in T-cell activation.
Complexities of oestradiol pharmacology in pulmonary arterial hypertension
Authors: Ping Yuan, Lan Gao, Zhi-Cheng Jing
Journal: European Respiratory Journal (2013)

PH, and that E 2 induces right ventricle-pulmonary vasculature uncoupling: despite more severe PAH, females had significantly reduced right ventricular hypertrophy, and ovariectomy exacerbated the increase in right ventricular mass, an effect that was reversed by exogenous E 2 [2, 7].Therefore, MCT-PH may not be the best model for studying the complexities of oestrogen pharmacology in human PAH.The concept that E 2 deficiency is involved in MCT-PH may be correct; but this concept may be incorrect in human PAH.Monocrotaline is a toxin that, in male rats, reduces plasma testosterone levels by 50%, and gonadal toxicity could be the reason for reduced E 2 levels.Furthermore, in the YUAN et al.[1] study, animals were not synchronised for oestrous cycle, and this may also have contributed to differences in plasma E 2 levels.It is noteworthy that recent clinical data suggest that female sex and increased, rather than decreased, E 2 levels and P450 Cyp19 (aromatase) activity are associated with greater risk of developing portopulmonary PAH [8].Oestradiol may exert beneficial effects on the right ventricle, yet may exacerbate PAH and pulmonary vascular lesions.The question of whether oestradiol is good, bad, or both in human PAH requires further investigation.We view E 2 as a doubleedged sword in human PAH.
Abstract A24: Low mir-200c expression correlates with an aggressive, invasive, and chemoresistant phenotype of non-small cell lung cancer
Authors: Paolo Ceppi, Giridhar Mudduluru, Regalla Kumarswamy, Ida Rapa, Scagliotti V. Giorgio, Papotti Mauro, Allgayer Heike
Journal: Clinical Cancer Research (2010)

Abstract The development of metastasis is the main reason for cancer-related death in non-small cell lung cancer (NSCLC). Initiation of metastasis involves an increase in cell motility mediated by the loss of cell-cell adhesion caused by E-cadherin repression, in a process commonly known as epithelial-to-mesenchymal transition (EMT). A central role for microRNA-200 family members in regulating EMT has been recently indicated, but data regarding the significance of their expression in lung tumors are still unavailable. The present study investigated the expression of mir-200c in a panel of NSCLC cell lines (n=9) and found a strong inverse correlation with cell invasive potential. Forced re-introduction of mir-200c into highly invasive/aggressive NSCLC cells induced a loss of mesenchymal phenotype, by restoring E-cadherin and reducing N-cadherin expression, and inhibited in vitro cell invasion as well as in vivo metastasis formation, as evaluated by chicken embryo metastasis assay. Moreover, mir-200c overexpression restored the sensitivity towards cisplatin and cetuximab, two chemotherapeutic agents widely used in the treatments of thoracic cancers, of the drug-resistant NCI-H1299 cells. Hyper-methylation of the promoter region was found to be the mechanism behind the loss of mir-200c in invasive cells, as evaluated by 5-aza-dC treatment and methylation specific PCR. In primary tumor specimens obtained from 45 consecutively resected NSCLC patients, mir-200c expression confirmed its role in malignant tumor progression, being significantly inversely associated with a poor grade of differentiation (p=0.01) and a higher propensity to lymph node metastases (p&amp;lt;0.01). In conclusion, these data indicate that loss of miR-200c expression plays an important role in the initiation of an aggressive, invasive, and chemoresistant phenotype. The determination of its expression in tumors can be used for the stratification of the patients to be treated with anti-metastatic therapy. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A24
Bone Imaging of Hyoid Bone Metastasis
Authors: HANS JACOBSSON, HANS F. BERGSTEDT
Journal: Clinical Nuclear Medicine (1989)

A metastasis from breast carcinoma in the hyoid bone gave rise to a characteristic appearance of increased activity at bone imaging. Bone metastases tend to spread to skeletal parts with active red bone marrow. The body of the hyoid contains active marrow in adults, although in small amounts. Therefore, metastases theoretically may appear here as well. In spite of this fact, the authors have neither observed a metastasis at this location before, nor, after having reviewed the literature, seen it previously reported.