tbuckley/cabot-search huggingface dataset:
Abstract 1559: Targeting the PH domain of Tiam-1 to inhibit breast cancer metastasis
Authors: Sylvestor A. Moses, Zuohe Song, Lei Du-Cuny, Garth Powis, Eugene Mash, Shuxing Zhang, Emmanuelle J. Meuillet
Journal: Cancer Research (2010)

Abstract TIAM-1 (T-lymphoma invasion and metastasis-inducing protein-1) is a highly conserved guanine nucleotide exchange factor and contains an N-terminal pleckstrin homology domain (PHn) and a Dbl homology (DH)/C-terminal PH domain (PHc). While no crystal structure exists for the PHn of TIAM-1, the crystal structure of DH-PHc of TIAM-1 in complex with Rac-1 has been reported. TIAM-1 has been found to be over-expressed in breast, colon and prostate cancers. An increase in TIAM-1 expression has been shown to be associated with increased metastatic potential of breast cancer cell lines. TIAM-1 is thus an ideal PH domain drug target directly related to cancer progression, metastasis and patient survival. In this study, we have identified novel small molecule inhibitors targeting the phosphoinositide (PtdIns) lipid binding PHc domain of TIAM-1 in order to selectively inhibit cell migration and survival. Utilizing an In Silico screen of our internal and Maybridge library and the crystal structure of TIAM-1, we have found 29 compounds that bind to PHc TIAM-1. In vitro assays have revealed that compound PH-210 and #10 significantly reduced the amount of active Rac1 and binds to PHc-TIAM-1 with high affinity (KD in the micromolar range) using surface plasmon resonance (SPR) spectrometry. Both compounds displace PtdIns-3,4,5-P3 in a SPR competitive binding assay. Ongoing in vivo studies using MDA-231 breast cancer cell lines will determine the anti-tumor activity of these compounds. Overall, these novel compounds could exhibit the ability to significantly reduce breast cancer metastasis by binding to PHc-TIAM-1 and could have the potential to be used with other chemotherapeutic compounds as part of an effective breast cancer treatment regimen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1559.
Resistance to EGFR-TKI Can Be Mediated through Multiple Signaling Pathways Converging upon Cap-Dependent Translation in EGFR-Wild Type NSCLC
Authors: Manish R. Patel, Joe Jay-Dixon, Ahad A. Sadiq, Blake A. Jacobson, Robert A. Kratzke
Journal: Journal of Thoracic Oncology (2013)
MENTAL AND ELECTROENCEPHALOGRAPHIC CHANGES FOLLOWING INTRAVENOUS BARBITURATES IN ORGANIC DISEASE OF THE BRAIN
Authors: PHILIP S. BERGMAN, HANS H. STROO, RHODA FEINSTEIN
Journal: American Journal of Psychiatry (1954)

1. Simultaneous comparisons were made between the mental state and the EEG changes induced by intravenous barbiturates in subjects with and without organic brain disease. 2. Normal subjects did not become disoriented following intravenous sodium amytal and the EEG effects were the same as those noted by others. 3. Although disorientation often followed the drug in subjects with structural lesions and normal records, the EEG changes were not different from those occurring in controls. In abnormal records, there was a reduction or disappearance of slow activity after the drug concomitant with the development of an organic mental syndrome. 4. Focal abnormalties were occasionally elicited, or, if previously present, accentuated by the drug. 5. Under the conditions of the experiment, the mental state did not parallel the state of the EEG. Possible reasons for this discrepancy are discussed.
Rapid Platelet-Function Assay
Authors: Jeffrey W. Smith, Steven R. Steinhubl, A. Michael Lincoff, Jacqueline C. Coleman, Theodore T. Lee, Robert S. Hillman, Barry S. Coller
Journal: Circulation (1999)

Background —The platelet glycoprotein (GP) IIb/IIIa receptor is important in mediating platelet thrombus formation, and the GP IIb/IIIa antagonist abciximab (c7E3 Fab; ReoPro) is effective in preventing thrombotic ischemic cardiovascular complications of unstable angina and percutaneous coronary interventions. Small-molecule antagonists of GP IIb/IIIa based on the Arg-Gly-Asp (RGD) sequence show similar benefit, and some of these agents are orally active. However, there may be significant interindividual variation in response to such antagonists, especially with chronic oral therapy. It will be essential to balance the beneficial antithrombotic effect of these drugs with their potential for causing bleeding. In response to this need, we have developed a rapid platelet-function assay (RPFA), a point-of-care system that provides a quantitative measure of the competence of the GP IIb/IIIa receptor as reflected in the ability of platelets to agglutinate fibrinogen-coated beads. Methods and Results —Polystyrene beads were coated with fibrinogen and placed in a cartridge along with a lyophilized peptide that activates the thrombin receptor. Anticoagulated whole blood was added to the cartridge, and then a microprocessor-controlled operation mixed the reagents and detected agglutination between platelets and coated beads. Quantitative digital results were displayed within 3 minutes. Because there is no dilution of the blood, the assay can be used to measure platelet activity in samples that have been treated with GP IIb/IIIa antagonists with high dissociation rates. RPFA results of whole-blood samples treated with different GP IIb/IIIa antagonists correlated well with both conventional turbidimetric platelet aggregation ( r 2 =0.95) and the percentage of free GP IIb/IIIa molecules in the sample ( r 2 =0.96). The mean difference in measurements between RPFA and aggregometry was –4% (±4% SD), and the mean difference in measurements between RPFA and free GP IIb/IIIa receptors was –2% (±6% SD). Conclusions —The RPFA provides rapid information on platelet function that mirrors turbidimetric platelet aggregation and reflects GP IIb/IIIa receptor blockade.
STUDIES ON UROBILIN PHYSIOLOGY AND PATHOLOGY
Authors: Robert Elman, Philip D. McMaster
Journal: The Journal of Experimental Medicine (1925)

Methods are presented for the development of clear fluorescent solutions from urobilin-containing urine, feces, and bile obtained from the dog. Conversion of the urobilinogen to urobilin is accomplished during the procedures. Measurement of the urobilin content is effected by comparing its fluorescence at great dilution with a standard containing acriflavine, calibrated in turn against pure urobilin. Means have been found to avoid the influence of the factors responsible in part for the inaccuracy of urobilin determinations. The method will quantitate exceedingly small amounts of urobilin and estimations on the same material agree within 10 per cent. Though designed for experimental procedures on the dog, the methods would seem adapted for clinical uses as well.
Randomised open controlled trial of colloidal bismuth subcitrate tablets and cimetidine in the treatment of duodenal ulcer.
Authors: G Vantrappen, P Rutgeerts, L Broeckaert, J Janssens
Journal: Gut (1980)

In a study of 28 outpatients with endoscopically proven duodenal ulcers, 14 patients (with a total of 15 ulcers) were treated with bismuth tablets (colloidal bismuth subcitrate, De-Nol, Gist-Brocades NV) and 14 patients (14 ulcers) were treated with cimetidine (Smith, Kline, and French). Clinical and endoscopic assessments were made after four and six weeks' therapy. After four weeks, 10 of the bismuth treated ulcers (67%) and eight of the cimetidine treated ulcers (57%) were completely healed. After six weeks of therapy, complete healing was seen in 86% of both the bismuth treated and the cimetidine treated ulcers. Twenty of the 24 completely healed ulcer patients (10 of each group) cooperated in a three month follow-up study. Pain recurred in three patients of the bismuth group and four of the cimetidine group and they were examined endoscopically. A recurrent ulcer was found in one of the bismuth treated patients and in three of the cimetidine treated patients. These observations indicate that colloidal bismuth subcitrate was at least as effective as cimetidine in the healing of duodenal ulcer.
Natural History of Chronic Pyelonephritic Scarring
Authors: C. J. Hodson, S. Wilson
Journal: BMJ (1965)

The large irregular scar seen in the natural specimen is nearly always associated with destruction of the related renal pyramid. It differs from the scar due to infarction in that with the latter the associated pyramid remains, albeit reduced in size (Smith, 1962). It is thus easily recognized in excretion pyelography when this procedure is conducted so that the renal outlines are defined (either by careful preliminary preparation of the abdomen or by means of tomography). The scar reveals itself as a localized narrowing of the renal substance, often only a few millimetres thick, which is associated with distortion, blunting, or complete absence of the adjacent pyramid, depending on its size and age. There may or may not be a flattening or depres sion in the renal outline at the site (Hodson, 1959). In fact, in many cases the renal outline is remarkably smooth. This appearance can be exactly mimicked by chronic ulcerating tuberculosis, by back-pressure atrophy behind a calculus jammed in a calix, and by what has become known as the  phenacetin  kidney, except that in the last instance necrotizing papillitis results in the frequent sloughing and separation of the pyramid, which has not yet been seen in our series of pyelonephritic scars. When generalized throughout the kidney such scarring is often confused with generalized back-pressure atrophy due to prolonged obstruction of urine-flow at the renal pelvis or in the ureter. This also presents as a flattening or recession of the actual pyramids associated with narrowing of the renal sub stance, but without scarring. Also, these effects are present uniformly and to an equal degree throughout and produce a radiological appearance which is quite different from the very irregular result of renal scarring. The two can be clearly differentiated, except sometimes in the very small contracted kidney. In fact, experience over 10 years, often checked by surgical and necropsy evidence, has shown that radiology pro vides a very reliable means of diagnosing this scarred form of chronic pyelonephritis during life, and thus a means of studying the life-history of this condition in a manner not possible by other methods of observation. It must be emphasized that often a scar can be so extensive that it must represent the gross destruction of a tissue mass amounting at times to most of an upper or lower renal pole.
Coarctation of the Aorta and Pregnancy
Authors: L. Rosenthal
Journal: BMJ (1955)

Wakefield General HospitalCoarctation of the aorta is an uncommon finding in adults and shows its higher incidence in males in a proportion of 3 males to 1 female (Abbott, 1928).The association of this anomaly with pregnancy must therefore be of some rarity.Benham (1949) was able to find records of only 53 cases in the literature and added three personal reports.To these can be added the following cases:
Biologic Therapies for Chronic Plaque Psoriasis and Cardiovascular Events
Authors: Thrasivoulos Tzellos, Athanassios Kyrgidis, Konstantinos Toulis
Journal: JAMA (2011)

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“New Twist” in <i>Diabetes Care</i> for HbA1c Reporting: “It Takes Two to Tango”!
Authors: William T. Cefalu, M. Sue Kirkman
Journal: Diabetes Care (2012)

Most likely everyone, at some point in an everyday conversation, has heard the phrase, “ it takes two to tango . ” The saying originated in a song, “Takes Two to Tango,” which was written and composed in 1952 by Al Hoffman and Dick Manning (1). Apparently this particular phrase was incorporated in the lyrics of a song about romance, but this expression has been applied to a much broader range of situations. For example, it might be used to describe an activity between two individuals or organizations that cannot be completed unless both are in complete agreement and cooperate. The phrase, perhaps accompanied by throwing up one’s hands, may also describe why certain activities are not brought to fruition: because one or the other party refuses to cooperate or does not hold up their end of the bargain, or because both parties are to blame. Given these variations on the theme, we suggest that, given the focus on HbA1c in this issue of Diabetes Care , the phrase “it takes two to tango” is an appropriate description of our new policy at the journal to require dual reporting of units for HbA1c.

Readers may be curious why so much focus is placed on HbA1c in the current issue. First, there is an original research article on a metric assessing discordance between HbA1c and blood glucose, termed the glycation gap (2). We also feature a review on the history and standardization of HbA1c by Dr. David Sacks (3), a very thoughtful commentary on the original research and HbA1c review by Cohen and Lindsell (4), and our new initiative (Profiles in Progress) about …
Nonaffective Psychosis After Prenatal Exposure to Rubella
Authors: Alan S. Brown, Patricia Cohen, Steven Greenwald, Ezra Susser
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors’ goal was to investigate the suggestion of previous investigations that prenatal viral exposures might increase the later risk of psychotic disorders. METHOD: They conducted a follow-up study in young adulthood of a birth cohort that was previously documented, by clinical examination and serological testing, to have in utero rubella exposure during the 1964 rubella epidemic. Data were also obtained from an unexposed birth cohort and from the Epidemiological Catchment Area survey. Young adult subjects were administered a standard psychiatric diagnostic interview. The authors compared the proportions of subjects with nonaffective psychosis in the exposed and unexposed cohorts. RESULTS: The rubella-exposed subjects, most of whom were exposed in the first trimester, demonstrated a substantially greater risk for nonaffective psychosis than the subjects who were not exposed to rubella (relative risk=5.2). CONCLUSIONS: There is an association between clinically and serologically diagnosed prenatal viral infection and nonaffective psychosis in adulthood.
Reversal of Unawareness of Hypoglycemia
Authors: Stephanie Amiel
Journal: New England Journal of Medicine (1993)

Brain function depends on an adequate supply of glucose from the blood, and the principal danger of an inadequate supply is the loss of cognitive function. Hypoglycemia sufficient to cause cognitive dysfunction does not normally occur, because small decreases in blood glucose concentrations elicit efficient protective neurohumoral responses, which include activation of the sympathetic nervous system, diminution of endogenous insulin secretion, and release of hyperglycemic hormones such as glucagon, catecholamines, and cortisol. These responses not only act to raise the blood glucose concentration but are also associated with symptoms such as sweating, hunger, and shakiness. Symptoms of neuroglycopenia such as . . .
Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.
Authors: K Hartung, M P Baur, R Coldewey, M Fricke, J R Kalden, H J Lakomek, H H Peter, D Schendel, P M Schneider, S A Seuchter
Journal: Journal of Clinical Investigation (1992)

In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE.
1073. Down-Regulation of Epithelial Glycoprotein-2 and VEGF-D by Engineered Zinc Finger Protein Transcription Factors
Authors: Willemijn M. Gommans, Robbert H. Cool, Pamela M.J. McLaughlin, Olli H. Laitinen, Seppo Yla-Herttuala, Bert J. van der Zaal, Hidde J. Haisma, Marianne G. Rots
Journal: Molecular Therapy (2005)

Engineered zinc finger protein (ZFP) transcription factors are emerging as powerful tools to regulate endogenous gene expression as they are capable of selectively down- or upregulate all (splice) variants of a gene (family), in contrast to siRNA. Zinc finger proteins consist of modular building blocks recognizing 3|[ndash]|4 base pairs each. Stitching these fingers together results in the recognition of an extended and therefore unique DNA sequence. The small size of these transcription factors allows easy manipulation for efficient delivery and multiple transcription factors can be delivered utilizing one vector. As the target DNA sequence does not have to be palindromic, it is feasible to specifically target virtually any DNA sequence in the human genome.
Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
Authors: Peter S Sever, Björn Dahlöf, Neil R Poulter, Hans Wedel, Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Östergren
Journal: The Lancet (2003)
Effect of zolpidem on sleep and ventilatory patterns at simulated altitude of 4,000 meters.
Authors: M Beaumont, F Goldenberg, D Lejeune, H Marotte, A Harf, F Lofaso
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The purpose of this study was to assess the effect of zolpidem 1 0 mg, a new imidazopyridine hypnotic drug, on sleep and respiratory patterns at a simulated altitude of 4,000 meters. Eight male subjects spent three nights in a decompression chamber. The first study night was spent at the ambient pressure corresponding to sea level. The two other nights were spent at a simulated altitude of 4,000 meters with either zolpidem or a placebo in random order according to a double-blind, crossover design. All subjects showed periodic breathing (PB) during sleep at simulated high altitude. Furthermore, altitude was associated with decreases in total sleep time (TST), slow-wave sleep (SWS), and REM sleep, and with significant increases in Stage 1 duration and in the arousal index. Most arousals were synchronous with the hyperpneic phase of PB. The main finding of our study is that zolpidem improved sleep characteristics at high altitude, inducing a decrease in sleep onset latency (placebo, 22 +/- 12 min versus zolpidem, 10 +/- 6 min), an increase in SWS duration (placebo, 46 +/- 28 min versus zolpidem, 69 +/- 28 min), and a reduction in the arousal index during SWS (placebo, 7.4 +/- 4.1 per h versus zolpidem: 2.4 +/- 1.0 per h). Furthermore, none of the respiratory parameters were significantly affected by zolpidem in any sleep stage. In conclusion, zolpidem improved sleep quality at high altitude without adversely affecting respiration.
Chip pile workers and mould exposure A preliminary clinical and hygienic survey
Authors: P. Jäppinen, T. Haahtela, J. Liira
Journal: Allergy (1987)

Chip pile workers are exposed to high concentrations of airborne mould spores. Few sporadic cases of allergic alveolitis have been reported in Finland. Eight non‐smoking workers, six on chip piles and two on bark piles, were examined to study the immunological and clinical response to continuous mould spore exposure. The spore exposure ranged between 10 4 and 10 5 spores/m 3 . Three of the six chip pile workers had precipitating serum antibodies against Aspergillus fumigatus. The three antibody‐positive workers had a tendency to decreased total pulmonary diffusion capacity and vital capacity. Significant respiratory symptoms were not noted. Long‐term spore exposure may include an occupational health risk to chip pile workers.
Health issues in ethnic minorities: awareness and action
Authors: M Memon, F Abbas, M Khaonolakar, J Dixon, I Singh
Journal: Journal of the Royal Society of Medicine (2002)

A key issue in health provision is the approach to health inequalities. In the UK, black and ethnic minority populations are disadvantaged in this respect. We obtained annual/public health reports from 13 health authorities (HAs) and 22 primary care trusts/groups (PCT/Gs) serving conurbations with large black and ethnic minority populations, and examined them for mention of special health issues for these groups and the action being taken. 22 of the 35 reports referred to such issues but only 17 referred to special initiatives; the most frequently mentioned were diabetes and coronary heart disease. We recommend that HAs and PCT/Gs serving large black and ethnic minority populations state specifically in their annual reports their awareness of health-equality issues and the action being taken to address them.