tbuckley/cabot-search huggingface dataset:
Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro
Authors: Gabriele D. Maurer, Isabel Tritschler, Barbara Adams, Ghazaleh Tabatabai, Wolfgang Wick, Roger Stupp, Michael Weller
Journal: Neuro-Oncology (2009)

Cilengitide is a cyclic peptide antagonist of integrins alphavbeta3 and alphavbeta5 that is currently being evaluated as a novel therapeutic agent for recurrent and newly diagnosed glioblastoma. Its mode of action is thought to be mainly antiangiogenic but may include direct effects on tumor cells, notably on attachment, migration, invasion, and viability. In this study we found that, at clinically relevant concentrations, cilengitide (1-100 microM) induces detachment in some but not all glioma cell lines, while the effect on cell viability is modest. Detachment induced by cilengitide could not be predicted by the level of expression of the cilengitide target molecules, alphavbeta3 and alphavbeta5, at the cell surface. Glioma cell death induced by cilengitide was associated with the generation of caspase activity, but caspase activity was not required for cell death since ectopic expression of cytokine response modifier (crm)-A or coexposure to the broad-spectrum caspase inhibitor zVAD-fmk was not protective. Moreover, forced expression of the antiapoptotic protein marker Bcl-X(L) or altering the p53 status did not modulate cilengitide-induced cell death. No consistent effects of cilengitide on glioma cell migration or invasiveness were observed in vitro. Preliminary clinical results indicate a preferential benefit from cilengitide added to temozolomide-based radiochemotherapy in patients with O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation. Accordingly, we also examined whether the MGMT status determines glioma cell responses to cilengitide alone or in combination with temozolomide. Neither ectopic expression of MGMT in MGMT-negative cells nor silencing the MGMT gene in MGMT-positive cells altered glioma cell responses to cilengitide alone or to cilengitide in combination with temozolomide. These data suggest that the beneficial clinical effects derived from cilengitide in vivo may arise from altered perfusion, which promotes temozolomide delivery to glioma cells.
Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts.
Authors: Y Zhou, C H Damsky, K Chiu, J M Roberts, S J Fisher
Journal: Journal of Clinical Investigation (1993)

In normal human pregnancy, invasion of the uterus and its arterial system by cytotrophoblasts extends through the entire decidua and the adjacent third of the myometrium. Our previous work showed that during the first trimester of pregnancy, invasion is accompanied by a marked change in the expression of cell adhesion molecules by invasive cytotrophoblasts. In the pregnancy disorder preeclampsia, cytotrophoblast invasion is limited to the superficial decidua, and few arterioles are breached. The purpose of this study was to determine whether cytotrophoblast expression of adhesion molecules in this disorder is also abnormal. Placental bed biopsy specimens from normal pregnancies and those complicated by preeclampsia were stained with anti-integrin antibodies. The results showed that adhesion molecule switching by invasive cytotrophoblasts is abnormal in preeclampsia, which suggests that this subpopulation of trophoblast cells fails to differentiate properly. A likely result is that the delicate balance of adhesive interactions that normally permit cytotrophoblast invasion is tipped in favor of those which restrain this process, with the net effect of shallow uterine invasion.
Predictive value of bronchoalveolar lavage cell analysis in sarcoidosis.
Authors: L Bjermer, L Rosenhall, T Angstrom, R Hallgren
Journal: Thorax (1988)

Patients with histopathologically proved sarcoidosis were studied serially by means of bronchoalveolar lavage, initially at the time of diagnosis and then six and 12 months later. Two years later they were evaluated by chest radiography and lung function tests and classified in terms of recovery or progression over the previous two years. The recovery of lymphocytes and granulocytes in lavage fluid was of limited prognostic value for persistent lung disease. In contrast, patients with increased numbers of mast cells recovered by lavage were more likely to deteriorate. Significantly increased mast cell counts (greater than or equal to 0.5% of total cells recovered) were seen in at least one lavage investigation in 15 of the 16 patients with more active and progressive disease, but in only eight of 23 patients with inactive disease (p less than 0.001). A persistent increase of mast cells on serial measurement occurred in nine of the 16 patients with active disease and in four of the 23 patients in whom the disease was inactive (p less than 0.02). The finding in the two subsequent lavages of lymphocytosis (lymphocytes greater than 30% of recovered cells) or neutrophilia (neutrophils greater than 15%) combined with mastocytosis (mast cells greater than or equal to 0.5%) occurred in nine of the 16 patients with active disease but in no patients with inactive disease.
Impaired cardiovascular autonomic response to passive tilting in cirrhosis with ascites
Authors: G Laffi
Journal: Hepatology (1996)

The autonomic regulation of cardiovascular function was evaluated in 15 cirrhotic patients with ascites and in 13 healthy subjects by the autoregressive power spectral analysis (PSA) of the intervals between adjacent R waves of the electrocardiogram (RR) interval and arterial pressure variability. Total power, low frequency (LF; index of the sympathetic activity of the heart and circulation), and high frequency (HF; index of vagal tone to the heart) components of the RR interval, systolic, and diastolic arterial pressure were evaluated in the supine position and during passive tilting, together with plasma norepinephrine levels. In the supine position, no significant differences in the PSA data were observed between the control subjects and cirrhotic patients, who had higher plasma norepinephrine levels. In healthy subjects, tilting was associated with an increase in the LF of the RR interval and arterial pressure and a decrease in the HF of the RR interval. In contrast, patients with cirrhosis showed a decrease of both LF and HF. Consequently, the LF/HF ratio significantly increased in healthy subjects, whereas it was unchanged in cirrhotic patients. The LF component of the diastolic pressure also decreased during tilting in cirrhotic patients. Plasma norepinephrine increased after tilting in both groups. These results indicate that the autonomic response to passive tilting is impaired in cirrhotic patients with ascites at both the cardiac and vascular levels, as a result of an altered sympatho-vagal balance, with reduced sympathetic predominance. These alterations occurred despite an appropriate response to the tilting of plasma norepinephrine, pointing to a receptorial or postreceptorial site of the autonomic impairment.
Selective Estrogen Receptor Modulators and Pharmacogenomic Variation in ZNF423 Regulation of BRCA1 Expression: Individualized Breast Cancer Prevention
Authors: James N. Ingle, Mohan Liu, D. Lawrence Wickerham, Daniel J. Schaid, Liewei Wang, Taisei Mushiroda, Michiaki Kubo, Joseph P. Costantino, Victor G. Vogel, Soonmyung Paik, Matthew P. Goetz, Matthew M. Ames, Gregory D. Jenkins, Anthony Batzler, Erin E. Carlson, David A. Flockhart, Norman Wolmark, Yusuke Nakamura, Richard M. Weinshilboum
Journal: Cancer Discovery (2013)

The selective estrogen receptor modulators (SERM) tamoxifen and raloxifene can reduce the occurrence of breast cancer in high-risk women by 50%, but this U.S. Food and Drug Administration-approved prevention therapy is not often used. We attempted to identify genetic factors that contribute to variation in SERM breast cancer prevention, using DNA from the NSABP P-1 and P-2 breast cancer prevention trials. An initial discovery genome-wide association study identified common single-nucleotide polymorphisms (SNP) in or near the ZNF423 and CTSO genes that were associated with breast cancer risk during SERM therapy. We then showed that both ZNF423 and CTSO participated in the estrogen-dependent induction of BRCA1 expression, in both cases with SNP-dependent variation in induction. ZNF423 appeared to be an estrogen-inducible BRCA1 transcription factor. The OR for differences in breast cancer risk during SERM therapy for subjects homozygous for both protective or both risk alleles for ZNF423 and CTSO was 5.71.
Current differences in referral patterns for pulmonary endarterectomy in the UK
Authors: M. Toshner, J. Suntharalingam, K. Goldsmith, A. Niggebrugge, J. Pepke-Zaba, N. W. Morrell, S. Tsui, J. Flowers, D. Jenkins
Journal: European Respiratory Journal (2008)

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK. All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity. Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2 x SD from the national mean rate. The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.
THE SIGNIFICANCE OF M AND T ANTIGENS IN THE CROSS REACTIONS BETWEEN CERTAIN TYPES OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1940)

In any one strain the occurrence of the previously recognized type-specific protein, M, is usually completely correlated with the presence of the recently recognized type-specific antigen, T. Strain C203 is exceptional in having the T substance of type 1 as well as the two type-specific antigens, M and T, characteristic of type 3. It does not have the M antigen of type 1. While other strains with similar antigenic peculiarities have not been encountered, it is probable that they occur, and the existence of such anomalies must be suspected when unusual serological reactions occur.
Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology
Authors: Thomas H. Brandon, Maciej L. Goniewicz, Nasser H. Hanna, Dorothy K. Hatsukami, Roy S. Herbst, Jennifer A. Hobin, Jamie S. Ostroff, Peter G. Shields, Benjamin A. Toll, Courtney A. Tyne, Kasisomayajula Viswanath, Graham W. Warren
Journal: Clinical Cancer Research (2015)

Combustible tobacco use remains the number one preventable cause of disease, disability, and death in the United States. Electronic nicotine delivery systems (ENDS), which include e-cigarettes, are devices capable of delivering nicotine in an aerosolized form. ENDS use by both adults and youth has increased rapidly, and some have advocated these products could serve as harm-reduction devices and smoking cessation aids. ENDS may be beneficial if they reduce smoking rates or prevent or reduce the known adverse health effects of smoking. However, ENDS may also be harmful, particularly to youth, if they increase the likelihood that nonsmokers or formers smokers will use combustible tobacco products or if they discourage smokers from quitting. The American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) recognize the potential ENDS have to alter patterns of tobacco use and affect the public's health; however, definitive data are lacking. AACR and ASCO recommend additional research on these devices, including assessing the health impacts of ENDS, understanding patterns of ENDS use, and determining what role ENDS have in cessation. Key policy recommendations include supporting federal, state, and local regulation of ENDS; requiring manufacturers to register with the FDA and report all product ingredients, requiring childproof caps on ENDS liquids, and including warning labels on products and their advertisements; prohibiting youth-oriented marketing and sales; prohibiting child-friendly ENDS flavors; and prohibiting ENDS use in places where cigarette smoking is prohibited.
Altered performance of rat cardiac muscle follows changes in mechanical stress during relaxation.
Authors: A W Wiegner, O H Bing
Journal: Circulation Research (1977)

We compared two sets of loading conditions for their effect on the mechanical performance of isolated rat trabecular muscle: (1) loading which approximated that of the intact ventricle; (2) nonphysiological afterloaded isotonic contractions. Improved performance, manifested by increased shortening and rate of shortening at constant load, was seen when lengthening occurred at light loads, as in the intact heart. In contrast, lengthening occurring at the same load against with shortening had taken place was followed by diminished performance. Viscous elements in series with the muscle could not account for this phenomenon. The results suggest the presence of an autoregulatory response of myocardium to mechanical stress during relaxation.
Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role
Authors: Luca Giliberto, Dawang Zhou, Richard Weldon, Elena Tamagno, Pasquale De Luca, Massimo Tabaton, Luciano D'Adamio
Journal: Molecular Neurodegeneration (2008)

Regulated intramembrane proteolysis of the beta-amyloid precursor protein by the gamma-secretase yields two peptides. One, amyloid-beta, is the major component of the amyloid plaques found in Alzheimer's disease patients. The other, APP IntraCellular Domain, has been involved in regulation of apoptosis, calcium flux and gene transcription. To date, a few potential target genes transcriptionally controlled by AID, alone or complexed with Fe65/Tip60, have been described. Although the reports are controversial: these include KAI1, Neprilysin, p53, EGFR, LRP and APP itself. Furthermore, p53 has been implicated in AID mediated susceptibility to apoptosis. To extend these findings, and assess their in vivo relevance, we have analyzed the expression of the putative target genes and of the total brain basal transriptoma in transgenic mice expressing AID in the forebrain. Also, we have studied the susceptibility of primary neurons from such mice to stress and pro-apoptotic agents.We found that AID-target genes and the mouse brain basal transcriptoma are not influenced by transgenic expression of AID alone, in the absence of Fe65 over-expression. Also, experiments conducted on primary neurons from AID transgenic mice, suggest a role for AID in sensitizing these cells to toxic stimuli. Overall, these findings hint that a role for AID, in regulating gene transcription, could be induced by yet undefined, and possibly stressful, stimuli in vivo.Overall, these data suggest that the release of the APP intracellular domain may modulate the sensitivity of neuronal cells to toxic stimuli, and that a transcriptional role of AID could be inscribed in signaling pathways thatare not activated in basal conditions.
Long-Term Follow-Up of Incomplete Stent Apposition in Patients Who Received Sirolimus-Eluting Stent for De Novo Coronary Lesions
Authors: Muzaffer Degertekin, Patrick W. Serruys, Kengo Tanabe, Chi Hang Lee, J. Edouardo Sousa, Antonio Colombo, Marie-Claude Morice, Jurgen M.R. Ligthart, Pim J. de Feyter
Journal: Circulation (2003)

Incomplete stent apposition (ISA) has been previously documented after sirolimus-eluting stent (SES) implantation. The aim of this study was to investigate the long-term intravascular ultrasound (IVUS) findings of ISA in patients who received SES.A total of 13 patients who received SES and showed ISA at follow-up IVUS (follow-up I) were investigated. IVUS was performed on all of these patients 12 months later (follow-up II). Quantitative ISA area measurement was also performed at follow-up I and II. No vascular remodeling was observed in the vessel segment with ISA; external elastic membrane area was 19.4+/-6.6 versus 19.5+/-6.4 mm2 at follow-up I and II, respectively. There was also no significant change in external elastic membrane area between vessel segment with ISA and without ISA (+1.5% versus -3.0%, respectively; P=0.27) at late follow-up. The ISA area, either including (2.5+/-1.7 versus 3.8+/-6.3 mm2; P=NS) or excluding (2.5+/-1.8 versus 2.4+/-1.7 mm2; P=NS) a single patient with aneurysm formation, was not significantly different between follow-up I and II. One patient manifested a coronary aneurysm in the stented segment at late follow-up that was probably present at the initial follow-up but masked by thrombus. It was successfully treated with a covered stent. All patients were asymptomatic, and no patient experienced late thrombotic occlusion.Vessel dimensions and area of ISA did not change over time, except for 1 coronary aneurysm that became apparent. ISA after implantation of a SES was not associated with adverse events at late follow-up.
Association of the Auscultatory Gap with Vascular Disease in Hypertensive Patients
Authors: M. Chiara Cavallini
Journal: Annals of Internal Medicine (1996)

Objective: To assess the relation of the auscultatory gap during blood pressure measurement to cardiovascular structure and function. Design: Cross-sectional study. Setting: A hypertension center in a university hospital. Patients: 168 persons with hypertension who were otherwise healthy and were not receiving medication. Measurements: Wideband external pulse recordings and ultrasonographic examination of the left ventricle and extracranial carotid arteries. Vascular stiffness was evaluated using simultaneous carotid pressure waveforms obtained by applanation tonometry of the contralateral carotid artery. Results: Classic auscultatory gaps were present in 21% of patients and were associated with older age (mean age ±SD, 64 ± 11 years for patients with gaps and 55 ± 13 years for patients without gaps; P < 0.001), female sex (67% of patients with gaps and 44% of patients without gaps were female; P < 0.05), and increased arterial stiffness (arterial stiffness index, 8.5 ± 4.6 in patients with gaps and 5.8 ± 3.2 in patients without gaps; P < 0.005). The prevalence of atherosclerotic plaques was increased more than twofold among patients with gaps compared with patients without gaps (50% compared with 22%; P < 0.002). Patients with and without auscultatory gaps had similar blood pressures, left ventricular structure and function, serum cholesterol levels, and smoking history. Logistic regression analysis indicated that only female sex (P < 0.02), arterial stiffness (P < 0.002), and atherosclerotic plaque (P < 0.02) were independently associated with the presence of an auscultatory gap. Conclusions: This study provides strong evidence that auscultatory gaps are related to carotid atherosclerosis and to increased arterial stiffness in hypertensive patients, independent of age. Although these observations need to be confirmed prospectively, they suggest that auscultatory gaps may have prognostic relevance.
MRI Assessment of Gray and White Matter Distribution in Brodmann’s Areas of the Cortex in Patients With Schizophrenia With Good and Poor Outcomes
Authors: Serge A. Mitelman, Lina Shihabuddin, Adam M. Brickman, Erin A. Hazlett, Monte S. Buchsbaum
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. METHOD: T1-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. RESULTS: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.