tbuckley/cabot-search huggingface dataset:
Spatial programming and the representation of salience
Authors: Jay A. Edelman, Jacqueline Gottlieb, Michael E. Goldberg
Journal: Behavioral and Brain Sciences (1999)

The posterior parietal cortex and frontal eye field contain maps of visual salience on which the decision to choose a saccade may be based. However, an averaging express saccade is not represented by a victorious unimodal representation in the superior colliculus. Normalization as described by Findlay &amp; Walker is not necessary for the generation of saccades.
The Choice of a Medical Career: Essays on the Fields of Medicine
Authors: Herbert Rattner
Journal: JAMA (1961)

This is an excellent book which consists of a collection of original essays written by physicians prominent in their respective branches of medicine, including such special fields, as rehabilitation, medical administration, and public health. The authors state simply that  is intended to convey to the student or the physician on the threshold of a medical career as complete a picture as possible of the profession to which he is dedicating himself and the opportunities that it presents. On a practical level it is intended to serve as a guide for the channeling of his life within that profession.  It is an especially timely book, for, as they state, a profession that was once an art, and to some extent a science, has become an aggregate of various sciences, yet striving to remain to every possible degree an art—and not always succeeding, apparently, in the face of economic and political
Oblimersen Sodium (Genasense bcl-2 Antisense Oligonucleotide)
Authors: Roy S. Herbst, Stanley R. Frankel
Journal: Clinical Cancer Research (2004)

Abstract Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies. Oblimersen sodium is an antisense oligonucleotide compound designed to specifically bind to human bcl-2 mRNA, resulting in catalytic degradation of bcl-2 mRNA and subsequent decrease in bcl-2 protein translation. Both small cell and non-small cell lung cancer show baseline and inducible expression of bcl-2, which may contribute to resistance to therapy. Preclinical studies have shown that combining bcl-2 antisense with chemotherapy improves antitumor response, increases apoptosis of tumor cells, and increases survival. Preliminary data from a large international randomized trial in melanoma show a trend toward increased survival and significantly improved response rates and response duration when oblimersen is added to dacarbazine. Phase I studies in small cell lung cancer patients demonstrate that oblimersen can be combined with paclitaxel or carboplatin and etoposide. The combination of docetaxel and oblimersen has been shown to be feasible in Phase I studies and is currently undergoing evaluation in comparison with docetaxel alone as first-line salvage therapy in patients refractory or relapsed after one prior chemotherapy regimen. Enhancement of the efficacy of anticancer treatments with oblimersen bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy.
Assessment of painful episode frequency in sickle-cell disease
Authors: Maxwell P. Westerman, Keeya Bailey, Sally Freels, Robert Schlegel, Patrick Williamson
Journal: American Journal of Hematology (1997)

Frequency of painful episodes in sickle-cell disease is considered to be related to clinical severity and possibly to other aspects of the disease. Measurements of frequency often include only hospital-related or more severe, longer-lasting episodes. Since painful episodes, however, may regularly occur in nonhospital settings or be shorter-lasting with possible different pathologic effects, we measured all painful episodes in 10 adults with sickle-cell disease for 1.0-3.8 years, using a daily questionnaire. The results were related to other indices of disease severity and to possible precipitating factors, such as cold weather and menses. Sixty-one percent (on average) of the total number of episodes (243) were nonhospital-related, and 33% (on average) were shorter-lasting. Episode frequencies, whether determined as total, hospital-related, nonhospital-related, or shorter-lasting, were not related to each other or to other indicators of disease severity. The highest incidence of episode frequency occurred in the winter. The association of episodes with menses was moderately close in individual patients. The findings suggest that nonhospital-related painful episodes and shorter-lasting episodes may contribute significantly to episode frequency. Measurement of frequency of all painful episodes would require consideration when evaluating episode frequency and its relationship to disease severity, to possible precipitating factors of episodes, and to treatment of the disease, and for study of the natural course of the disease.
Alopecia areata in children: treatment with diphencyprone
Authors: M-LA. SCHUTTELAAR, J.J. HAMSTRA, E.P.B. PLINCK, J.D.R. PEEREBOOM-WYNIA, V.D. VUZEVSKI, P.G.H. MULDER, A.P. ORANJE
Journal: British Journal of Dermatology (1996)

We assessed the efficacy of diphencyprone (DPCP) treatment in a total of 26 children with alopecia areata (AA). Sixteen children had alopecia areata totalis (AAT) and 10 had alopecia areata localis (AAL). DPCP is an absolute contact sensitizer. Twenty-five children could be sensitized with a 2% DPCP solution, whereas one child could not be sensitized. Patients were treated, once a week for at least 3 months, for up to 1 year. Twenty-one of the 25 (84%) children showed hair regrowth to a greater or lesser extent after DPCP treatment. Eight of the 25 (32%) children showed cosmetically acceptable hair regrowth. Cosmetically acceptable regrowth at the end of the study was seen in four of the 15 (27%) children with AAT and in four of the 10 (40%) children with AAL. These results are comparable with those reported in an earlier study in children with AA. Our opinion is that DPCP is a beneficial therapeutic agent in children with severe AAT and AAL showing no spontaneous remission.
Transforming growth factor beta1 gene polymorphism in rheumatoid arthritis
Authors: Y Sugiura
Journal: Annals of the Rheumatic Diseases (2002)

<b>Objective:</b> Rheumatoid arthritis (RA) is a chronic inflammatory disease and synovial cells, antigen presenting cells, lymphocytes, and their cytokines might be associated with the disease. Transforming growth factor β1 (TGFβ1) has been reported to have important roles in unresolved inflammation, immune suppression, fibrosing processes, and angiogenesis. TGFβ1 is highly expressed in joints in RA and is considered to be a regulator of anti-inflammation in RA. Polymorphisms of TGFβ1 have been reported to be associated with the production of TGFβ1 protein, and to increase the risk of acquiring several diseases. It was speculated that these polymorphisms might also be involved in RA, and therefore the TGFβ1 codon 10 T869C polymorphism in a series of patients and controls was investigated. <b>Method:</b> A total of 155 patients with RA and 110 healthy subjects were studied. DNA was extracted from peripheral leucocytes and TGFβ1 codon 10 T869C polymorphism was determined by polymerase chain reaction restriction fragment polymorphism. <b>Results:</b> A significantly higher proportion of patients with RA with the T allele (CT type or TT type) was found compared with the CC type (p=0.039). <b>Conclusion:</b> The T allele, previously reported to be linked with production of TGFβ1, may be associated with an increased risk of RA.
Endotoxin Triggers Nuclear Factor-κB–dependent Up-regulation of Multiple Proinflammatory Genes in the Diaphragm
Authors: Alexandre Demoule, Maziar Divangahi, Linda Yahiaoui, Gawiyou Danialou, Dusanka Gvozdic, Katherine Labbe, Weisheng Bao, Basil J. Petrof
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Sepsis-induced diaphragmatic force loss and failure are associated with an increased exposure of the muscle to proinflammatory mediators.Our objectives were to test the hypothesis that force-inhibiting mediators may arise in large part from the diaphragm itself and to evaluate the roles of mechanical stress, free radicals, and the nuclear factor (NF)-kappaB transcription factor pathway in endotoxin (LPS)-induced proinflammatory responses of the diaphragm.Murine diaphragm and limb muscle cells were exposed to LPS in vitro and in vivo. Proinflammatory gene expression was measured using RNase protection assays (tumor necrosis factor [TNF]-alpha, TNF-alpha receptor p55, interleukin [IL]-1alpha, IL-1beta, IL-6, macrophage inflammatory peptide-2, intercellular adhesion molecule-1, Fas ligand, and inducible nitric oxide synthase) and ELISAs (TNF-alpha, IL-6, and macrophage inflammatory peptide-2). Cyclical muscle cell stretch and free-radical scavengers (N-acetylcysteine and catalase) were used to alter mechanical and oxidative stress levels, respectively. Pharmacologic (pyrrolidinedithiocarbamate) and dominant-negative transfection strategies were used to inhibit the NF-kappaB pathway.In primary diaphragm muscle cell cultures, modulation of mechanical stress levels or free-radical exposure did not alter responses to LPS stimulation. However, pharmacologic blockade of the NF-kappaB pathway and dominant-negative molecular inhibition of IKB kinase-beta strongly suppressed LPS-induced proinflammatory gene expression. In vivo, acute endotoxemia induced significantly greater mRNA and protein levels for proinflammatory mediators in the diaphragm as compared with limb muscle. Basal expression levels of proinflammatory genes were significantly higher in the diaphragm.Constitutive and LPS-induced proinflammatory gene expression are exaggerated in the diaphragm compared with limb muscles and are critically dependent on the NF-kappaB pathway. We suggest the diaphragm may be relatively predisposed to proinflammatory responses.
Primary hepatic cryptococcosis
Authors: G P Davidson
Journal: BMJ (1983)

ProTx-II, an inhibitory cysteine knot toxin from the tarantula <i>Thrixopelma pruriens</i>, inhibits voltage-gated sodium channels. Using the cut-open oocyte preparation for electrophysiological recording, we show here that ProTx-II impedes movement of the gating charges of the sodium channel voltage sensors and reduces maximum activation of sodium conductance. At a concentration of 1 μM, the toxin inhibits 65.3 ± 4.1% of the sodium conductance and 24.6 ± 6.8% of the gating current of brain Na<sub>v</sub>1.2a channels, with a specific effect on rapidly moving gating charge. Strong positive prepulses can reverse the inhibitory effect of ProTx-II, indicating voltage-dependent dissociation of the toxin. Voltage-dependent reversal of the ProTx-II effect is more rapid for cardiac Na<sub>v</sub>1.5 channels, suggesting subtype-specific action of this toxin. Voltage-dependent binding and block of gating current are hallmarks of gating modifier toxins, which act by binding to the extracellular end of the S4 voltage sensors of ion channels. The mutation L833C in the S3-S4 linker in domain II reduces affinity for ProTx-II, and mutation of the outermost two gating-charge-carrying arginine residues in the IIS4 voltage sensor to glutamine abolishes voltage-dependent reversal of toxin action and toxin block of gating current. Our results support a voltage-sensor-trapping model for ProTx-II action in which the bound toxin impedes the normal outward gating movement of the IIS4 transmembrane segment, traps the domain II voltage sensor module in its resting state, and thereby inhibits channel activation.
On the Antigenic Identity of Human Serum Beta and Alpha-2 Lipoproteins, and Their Identification in the Aortic Intima
Authors: RICHARD E. TRACY, EDMUND B. MERCHANT, VINCENT C. KAO.
Journal: Circulation Research (1961)

By the use of immunoelectrophoresis, it was demonstrated that ultracentrifugally isolated, very-low-density (alpha-2) lipoproteins migrate faster toward the anode in electro-phoresis and diffuse more slowly in agar than do low-density (beta) lipoproteins. However, these two lipoprotein fractions were found to be antigenically indistinguishable with this technique. Extracts of the intima of aortas were shown to contain material with all the physical properties consistent with those of the low-density (beta) lipoproteins. Further-more, this was the only serum protein which was consistently found in high concentration in washed aortas. Beta lipoprotein was frequently found in plaque-free intimae. The impression was obtained that this lipoprotein was present in greater concentration in early atheromatous plaques than in plaque-free intimae, and that it was much more concentrated in the intimae of severely sclerotic aortas than in those of moderately or uninvolved aortas. However, it has not been demonstrated in the gruel from far-advanced plaques.
Serum Lipoprotein(a) in Patients With Diabetes Mellitus
Authors: Francis R Heller, Jacques Jamart, Patrick Honore, Geneviève Derue, Vicky Novik, Laurence Galanti, Alex Parfonry, Jean-Claude Hondekijn, Martin Buysschaert
Journal: Diabetes Care (1993)

OBJECTIVE To investigate subjects with different types of diabetes mellitus regarding their serum levels of lipoprotein(a). High serum Lp(a) concentration is associated with a high risk of coronary heart disease. Diabetic patients are prone to developing coronary heart disease. RESEARCH DESIGN AND METHODS The subjects were 66 type I diabetic patients, 100 type II diabetic patients treated with diet alone or diet combined with oral hypoglycemic agents, and 46 insulin-requiring type II diabetic patients. Subjects were compared with 142 nondiabetic outpatients. RESULTS Subjects with insulin-requiring type II diabetes mellitus were found to have an increase both in serum Lp(a) concentration and in prevalence of serum Lp(a) concentration &amp;gt;30 mg/dl compared with the other groups of diabetic patients and nondiabetic control subjects. A nonsignificant increase in the prevalence of coronary heart disease was also found in insulin-requiring type II diabetic patients. The levels of serum concentrations of Lp(a) were not significantly related to the degree of glycemic control, duration of diabetes, presence of macrovascular disease, or intake of female hormone therapy. High levels of Lp(a) in this group of diabetic patients could not be explained by the presence of albuminuria. CONCLUSIONS Insulin-requiring type II diabetic patients have high levels of Lp(a). Chronic hyperinsulinemia might be an eventual causal factor.
Interactions between endothelin-1 and the renin–angiotensin–aldosterone system
Authors: Gian Paolo Rossi, Alfredo Sacchetto, Maurizio Cesari, Achille C Pessina
Journal: Cardiovascular Research (1999)

The renin–angiotensin–aldosterone (RAA) system and the endothelin (ET) system entail the most potent vasopressor mechanisms identified to date. Although they were studied in depth in relation to arterial hypertension and cardiovascular diseases, limited information on their interrelationships in causing hypertension and related target organ damage exists. The identification of consensus sequences for jun in the regulatory region of the preproendothelin-1 (ppET-1) gene raised the possibility of its transcriptional regulation by angiotensin II (Ang II). This was confirmed by the finding that stimulation with Ang II of cultured vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) induced expression of the ppET-1 gene and synthesis of ET-1. Endogenously produced ET-1 was found to contribute to the hypertrophic response of cardiomyocytes to Ang II and thereby to cardiac hypertrophy. Furthermore, ET-1 exerts multifaceted effects on the RAA system, such as dose-dependent inhibition of renin synthesis, and stimulation of aldosterone secretion. The finding of abundant specific ET-1 receptors in the adrenocortical zona glomerulosa (ZG) suggested a direct secretagogue effect of ET-1. In rats, ETB receptors mediate such an effect, whilst in humans, both ETA and ETB receptor subtypes intervene in regulating the transcription of the aldosterone synthase gene. In addition, ET-1 stimulates DNA synthesis and proliferation of ZG cells via ETA receptors and, therefore, might play a role in cell turnover of the normal adrenal cortex and in the onset of adrenal tumours. Studies on the in vivo interactions between ETs and the RAA system have given conflicting results, insofar as some suggested a participation of ET-1 in the pressor and cellular effects of exogenously administered Ang II, whereas others did not in the transgenic TGR(Ren 2m)27 rats and in the two-kidney, one clip.
On the Physical Death of Jesus Christ
Authors: James V. Warren
Journal: JAMA (1986)

<h3>To the Editor.—</h3> I am writing with regard to the SPECIAL COMMUNICATION entitled "On the Physical Death of Jesus Christ."<sup>1</sup>The matter of death by crucifixion is elegantly described in the article. I believe, however, that one factor is missing in the analysis. An additional, perhaps even major, factor in the death would be the occurrence of vasodepressor syncope with a fatal outcome. This was originally suggested to me many years ago by my mentor, Dr Soma Weiss,<sup>2</sup>the Hersey Professor of The Theory and Practice of Physics at Harvard. He was a student of various forms of syncope, and since then I have continued these studies. Vasodepressor (or vasovagal) syncope with sudden loss of consciousness has been carefully studied pathophysiologically. It occurs in a situation that the individual finds untenable and desires to escape, such as an increased muscle blood flow. Some of the mechanisms for flight
TISSUE MORPHOLOGY IN IN-STENT RE-RESTENOSIS LESIONS AFTER PACLITAXEL-ELUTING BALLOON DILATATION AND PLAIN OLD BALLOON ANGIOPLASTY FOR IN-STENT RESTENOSIS LESIONS: IMPACT OF PREVIOUS STENT
Authors: Takeshi Tada, Kazushige Kadota, Seiji Habara, Hiroyuki Tanaka, Yasushi Fuku, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2014)
Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas
Authors: Cristina Blázquez, Luis González-Feria, Luis Álvarez, Amador Haro, M. Llanos Casanova, Manuel Guzmán
Journal: Cancer Research (2004)

Abstract Cannabinoids inhibit tumor angiogenesis in mice, but the mechanism of their antiangiogenic action is still unknown. Because the vascular endothelial growth factor (VEGF) pathway plays a critical role in tumor angiogenesis, here we studied whether cannabinoids affect it. As a first approach, cDNA array analysis showed that cannabinoid administration to mice bearing s.c. gliomas lowered the expression of various VEGF pathway-related genes. The use of other methods (ELISA, Western blotting, and confocal microscopy) provided additional evidence that cannabinoids depressed the VEGF pathway by decreasing the production of VEGF and the activation of VEGF receptor (VEGFR)-2, the most prominent VEGF receptor, in cultured glioma cells and in mouse gliomas. Cannabinoid-induced inhibition of VEGF production and VEGFR-2 activation was abrogated both in vitro and in vivo by pharmacological blockade of ceramide biosynthesis. These changes in the VEGF pathway were paralleled by changes in tumor size. Moreover, intratumoral administration of the cannabinoid Δ9-tetrahydrocannabinol to two patients with glioblastoma multiforme (grade IV astrocytoma) decreased VEGF levels and VEGFR-2 activation in the tumors. Because blockade of the VEGF pathway constitutes one of the most promising antitumoral approaches currently available, the present findings provide a novel pharmacological target for cannabinoid-based therapies.
Abstract 3397: Rational targeting of protein translation for cancer treatments
Authors: Elizabeth Chang, Duc Nguyen, Qingyuan Yang, France Carrier
Journal: Cancer Research (2014)

Abstract Deregulation of protein translation is associated with a growing number of human diseases including tumorigenesis. New anti cancer therapies targeting the protein translation regulator mammalian Target Of Rapamycin (mTOR) highlight the importance of this signaling pathway. However, feedback mechanisms that can compensate for this general protein translation pathway limit the clinical efficiency of this approach. New drugs that could rationally target protein translation in cancer cells are therefore needed. We have identified the heterogenous ribonucleoprotein A18 (hnRNP A18) as a new regulator of protein translation in cancer cells. hnRNP A18 is up regulated in several human tumors including prostate, breast, colon and as shown here in melanoma tumors. hnRNP A18 regulates protein translation of its targeted transcripts by binding to a specific RNA signature motif in their 3’UTRs. Our data indicate that the hypoxia mimetic agent CoCl2 increases hnRNP A18 protein levels in melanoma cells but not in normal melanocytes. In addition, down regulation of hnRNP A18 sensitizes melanoma cells to CoCl2 and Temozolimide. The functional significance of this effect was evaluated in a mouse xenograft model where hnRNP A18 down regulation reduced melanoma tumor growth by more than 70%. RNA immunoprecipitation assay indicate that hnRNP A18 binds to a number of transcripts associated with tumor growth including the Hypoxia Inducible Factor 1α (HIF-1α). Levels of hnRNP A18 also directly affect HIF-1α protein levels in response to CoCl2. Taken together these data indicate that hnRNP A18 is a new regulator of protein translation that could be targeted to develop new mechanism based therapy for the rational inhibition of protein translation in cancer cells. Citation Format: Elizabeth Chang, Duc Nguyen, Qingyuan Yang, France Carrier. Rational targeting of protein translation for cancer treatments. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3397. doi:10.1158/1538-7445.AM2014-3397
132 IMPROVEMENT OF HEPATIC INJURY AND STEATOSIS BY THE BILE ACID-PHOSPHOLIPID CONJUGATE UR- SODEOXYCHOLYL LYSOPHOSPHATIDYLETHANOLAMIDE IN A HIGH-FAT INDUCED DIETARY MODEL OF NONALCOHOLIC FATTY LIVER DISEASE
Authors: A. Pathil, A. Warth, W. Chamulitrat, W. Stremmel
Journal: Journal of Hepatology (2009)