tbuckley/cabot-search huggingface dataset:
Abstract 1201: Inhibition of ASK1 through phosphorylation of serine 967 by PI3K/Akt-mediated pathways
Authors: Mary C. Puckett, Erinn Goldman, Lisa Cockrell, Fadlo Khuri, Haian Fu
Journal: Cancer Research (2010)

Abstract Cancer is characterized in part by dysregulation of cell survival and cell death signals. In particular, many tumors show upregulated PI3K/Akt activity, leading to sustained cell survival and suppressed cell death. Here we report the identification of the apoptosis signal-regulating kinase 1 (ASK1) as a downstream effector of the PI3K/Akt survival signaling pathway. ASK1 can be suppressed by PI3K/Akt signaling, leading to inhibition of apoptotic signaling. ASK1 normally functions as a mitogen activated protein kinase kinase kinase (MAP3K) that, when activated by stress signals, can evoke a signaling cascade leading to activation of the MAPKs JNK and p38. This activation can result in many cellular responses, but ASK1 is most notably known for its role as a critical regulator of apoptosis. Because of its crucial role in the balance between survival and death, ASK1 activity is tightly controlled. In particular, 14-3-3 can bind ASK1 and inhibit its activity when the kinase is phosphorylated at serine 967. However, the signals that regulate this phosphorylation event are currently unknown. Recent evidence suggests that PI3K/Akt mediated pathways may be involved in phosphorylation of serine 967 and, subsequently, inhibition of ASK1. Specifically, treatment of cells with growth factors including IGF-1 and PDGF increased phosphorylation of serine 967, as did overexpression of a constitutively active Akt mutant. In addition, expression of a kinase dead Akt mutant blocked growth factor induced serine 967 phosphorylation, indicating that Akt plays a role in mediating survival signals leading to inhibition of ASK1. In support of this notion, treatment with the inhibitors of Akt and PI3K also reduced serine 967 phosphorylation. Interestingly, treatment of cells with IGF-1 or overexpression of Akt was also able to protect serine 967 from H2O2 induced dephosphorylation. Taken together, our study reveals a novel effector site in ASK1 for the action of PI3K/Akt, which may offer a potential target for cancer therapeutic development. This work was supported by the NIH Pharmacological Sciences Training Grant T32 GM008602 and NIH/NCI Grant PO1CA116676 and USAMRMC05075002 to FRK and HF. 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 1201.
Coronary stents improve outcome in acute myocardial infarction: immediate and long term results of the GRAMI trial
Authors: A.E. Rodriguez, V.H. Bernardi, O.A. Santaera, C. Mauvecin, F. Ayala, J. Martinez, G. Roubin, I.F. Palacios, J.A. Ambrose
Journal: Journal of the American College of Cardiology (1998)
PLEURITIC EXUDATES IN CHILDREN.
Authors: MELINDA KNAPHEIDE-GERMANN
Journal: JAMA (1906)

I do not find the literature on this subject very extensive. While attending lectures in Paris I observed many interesting cases in the "Hôpitaux Des Enfants Trouvés," which I had the privilege of visiting daily for a month in company with the physician in charge. Since then it has been my fortune to encounter a number of cases in my own practice. Last winter, especially, pleurisy seemed very prevalent, accompanying as well as following the different forms of acute pneumonia. We seldom find pleurisy a primary disease. In my experience effusions of the right side predominate over the left. Pleuritic exudate, either serous or purulent, is common in infancy and childhood; more particularly the latter, especially before the fifth year of life. As the chest wall at this age is more resilient than in the adult, large exudates are better borne, producing fewer pressure symptoms. <h3>ETIOLOGY.</h3> The etiology is at
Arriving with Little Notice — A New Health Chief for HEW
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1975)

An enduring quality of the public process in Washington is its incapacity for focusing on matters that occupy the broad range between cosmic catastrophe and inconsequential trivia.The fall of Saigon or a senator's carping at a bit of research money for an inquiry into marital discord — these are events that affect official Washington as rabbits affect hound dogs. In partial way of explanation, they are discrete happenings, easily seen and dealt with by the press, and easily manageable for purposes of Congressional rhetoric. But with rare exception, the middle range goes by unnoted. A case in point is . . .
Study indicates salt is an acquired taste
Authors: Elizabeth Rasche González
Journal: JAMA (1983)

Which comes first to an infant born in this salt-loving culture? A taste<i>for</i>salt, or a taste<i>of</i>it? Probably the latter, according to David L. Yeung, PhD, who presented a report at the recent Chicago meeting of the Federation of American Societies for Experimental Biology: Children's taste for salt at the age of 4 years appears to be determined by the amount of salt their parents feed them in infancy. This finding is the most recent in a long-term, longitudinal study of nutrition in infants and children. The study, which has been under way since 1977, is sponsored by the H. J. Heinz Company of Canada, Ltd, Toronto—where Yeung, who is also associate professor of nutritional sciences at the University of Toronto Faculty of Medicine, serves as corporate nutrition coordinator. In the salt substudy, Yeung and colleagues first examined the sodium chloride intake of 403 infants, half of
Reversible and Irreversible Depression of Ischemic Myocardium
Authors: Edmund H. Sonnenblick, Richard Gorlin
Journal: New England Journal of Medicine (1972)

Since surgical restoration of blood flow to ischemic myocardium is now possible,1 reliable methods of evaluating performance of cardiac muscle in areas of both acute and chronic deprivation of coronary blood flow are very much needed. Such methods are necessary to assess risk as well as the potential benefit of the surgical procedures being used.It is important to recognize that one is dealing with three conditions: chronic, partial obstruction of coronary arteries, with areas of permanently damaged and fibrotic heart muscle; acute obstruction of coronary arteries with ischemia or evolving myocardial infarction (cell death); and chronic obstructive coronary disease . . .
Thyrotoxic Graves's disease after primary hypothyroidism.
Authors: S Olczak, A J McCulloch, F Clark
Journal: BMJ (1978)

perforation.3Perhaps, significantly (more so had the number of cases been greater), all six were women with an average age of 45.Our patient was also a woman, who was 52.Our patient presented with rectal bleeding at defaecation.No such case has been reported.Possibly the bleeding may have been due to haemorrhoids, but against this no bleeding has occurred since resection of the diverticulum, despite her piles still being present and untreated.The barium enema findings strongly suggested the presence of a polyp and this led to erroneous diagnosis and difficulties at laparotomy.The confusion seems best explained by the partially barium-filled diverticulum overlying the barium-filled colon on the radiographs giving the appearance of "a lobulated lesion, probably a polyp."This phenomenon should be borne in mind by all those searching for elusive polyps.
Hydroxyprogesterone Caproate Enhancement of Diuretic Action in Man.
Authors: R. G. Page
Journal: Annals of Internal Medicine (1963)

s1 April 1963Hydroxyprogesterone Caproate Enhancement of Diuretic Action in Man.R. G. Page, M.D. (Associate)R. G. Page, M.D. (Associate)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-744_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptProgesterone has been shown to have a natruretic effect due to its ability to antagonize aldosterone. We have noted an enhancement of the effectiveness of diuretics following the use of spironolactone, also an aldosterone antagonist, in patients with edema secondary to congestive heart failure. It seemed to us that progesterone might also increase the natruresis that follows the administration of diuretics in this group of patients.Patients with congestive heart failure and edema were admitted to the research floors of The University of Chicago Hospitals and Clinics and maintained on constant diets. Daily weight, urinary volume, urinary sodium, potassium, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: R. G. Page, M.D. (Associate)Affiliations: Chicago, Ill. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 744-744KeywordsAldosteroneDietDiureticsEdemaHeart failureHospitalsPotassiumProgesteroneSodium ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...
Empyema of Frontal Sinus simulating Osteomyelitis
Authors: P. J. McNicholas
Journal: BMJ (1947)

On admission for further investigation the boy felt perfectly well, the diarrhoea having ceased.He was thin and rather pale, and was afebrile; pulse 90.The tonsils were slightly enlarged, as were the glands of the left side of the neck, which were discrete and rubbery.The spleen and liver were not palpable.There were no symptoms or signs referable to the nervous system.No other abnormality was noted, except that on Nov. 7 the white cell count was 52,300 (76.5 % small lymphocytes).The Wassermann reaction, Mantoux test, and Paul-Bunnell reaction were all negative.By Nov. 20 the white cell count had dropped to 11,100 (51% small lymphocytes, 40% neutrophil polymorphs, and 3% eosinophils).He was then discharged to the out-patient department, and on Nov. 26 the white cells numbered 13,300 per c.mm. (lymphocytes 25%).He felt well and there were no abnormal signs.COMMENT This case is typical of infectious lymphocytosis, especially in the mild abdominal symptoms, the paucity of physical signs, the cervical adenitis, the leucocytosis with relative and absolute lymphocytosis due to increase in normal small lymphocytes, lasting three to five weeks, and the negative heterophile agglutination test.If the disease is due to a virus, as is to be supposed in the absence of a demonstrable bacterial agent, the blood changes are very unusual, since viral infections are characterized by leucopenia, the apparent lymphocytosis being only relative.As in the cases reported by Finucane and Philips a mild eosinophilia appeared as the total count fell.
Status Epilepticus Complicating Pregnancy
Authors: J. F. Goodwin, C. W. Lawson
Journal: BMJ (1947)

MEDBICTURNAL some success, used high-fat diets or given 1 oz. (28ml.) of olive oil before meals in the treatment of our hypogly- caemic cases.Ephedrine by its sympatheticomimetic action raises the blood sugar and has also proved useful in pre- venting reactive hypoglycaemia.It has been given in j-gr.(32-mg.)doses half an hour before the three main meals.Fig. 3 shows its effect in a patient with moderately severe hypoglycaemia.Owing to their reduced gastric capacity these patients often feel better having six small meals a day instead of the usual three large ones. SummaryPostprandial hypoglycaemia occurred in 17 out of 45 consecu- tive patients on whom a partial gastrectomy had been performed for peptic ulcer, and constituted the commonest complication of the operation in this series.The symptoms produced were severe enough in five patients to preclude them from earning a livelihood.It is suggested that rapid gastric evacuation is the basis of this hypoglycaemia, and that the " dumping " syndrome has identical clinical manifestations and an identical aetiology, so that the two conditions need not be distinguished.The most effective method of treatment has proved to be a high-fat diet, six small meals a day instead of three large ones, and 1/2 gr. (32mg.) of ephedrine before the three main meals. REFERENCES
Human Pulmonary Circulation Is an Important Site for Both Clearance and Production of Endothelin-1
Authors: Jocelyn Dupuis, Duncan J. Stewart, Peter Cernacek, Gilbert Gosselin
Journal: Circulation (1996)

Background Animal studies suggest a major role of the pulmonary circulation in the clearance of circulating endothelin-1 (ET-1). The contribution of the human pulmonary circulation to plasma ET-1 clearance, however, has never been quantified. The absence of an AV gradient in plasma ET-1 has previously been interpreted as evidence that the lungs do not have a role in modulating circulating ET-1 levels. This study was designed to quantify and discern between pulmonary ET-1 clearance and production in humans. Methods and Results We studied 13 subjects by combining the multiple indicator-dilution technique with the measurement of immunoreactive ET-1 (irET-1). All patients had normal left ventricular ejection fractions (61±7%, mean±SD) and baseline hemodynamics. Mean pulmonary ET-1 extraction was 47±7%. The ET-1 extracted does not return to circulation and can be characterized by a sequestration rate constant: K seq =0.048±0.019 s −1 . There was no significant difference between irET-1 levels from the pulmonary artery and aorta (0.61±0.29 and 0.68±0.33 pg/mL, respectively; P =.22); the normal lung consequently produces an amount of ET-1 that is quantitatively similar to the amount that has been extracted. Conclusions The human lung is an important site for both clearance and production of ET-1. There is a normal physiological balance of ET-1 across the pulmonary circulation, which explains the absence of difference in AV ET-1 levels despite a 47±7% clearance. Reduced pulmonary clearance or increased production of this peptide may contribute to the increase in circulating levels found in various cardiovascular conditions.
Peptide therapies for ocular surface disturbances based on fibronectin–integrin interactions
Authors: Teruo Nishida, Makoto Inui, Motoyoshi Nomizu
Journal: Progress in Retinal and Eye Research (2015)

The condition of the corneal epithelium is a critical determinant of corneal transparency and clear vision. The corneal epithelium serves as a barrier to protect the eye from external insults, with its smooth surface being essential for its optical properties. Disorders of the corneal epithelium include superficial punctate keratopathy, corneal erosion, and persistent epithelial defects (PEDs). The prompt resolution of these disorders is important for minimization of further damage to the cornea. Currently available treatment modalities for corneal epithelial disorders are based on protection of the ocular surface in order to allow natural healing to proceed. PEDs remain among the most difficult corneal conditions to treat, however. On the basis of characterization of the pathobiology of PEDs at the cell and molecular biological levels, we have strived to develop new modes of treatment for these defects. These treatments rely on two key concepts: provision of a substrate, such as the adhesive glycoprotein fibronectin, for the attachment and migration of corneal epithelial cells, and activation of these cells by biological agents such as the combination of substance P and insulin-like growth factor-1 (IGF-1). Central to both approaches is the role of the fibronectin–integrin system in corneal epithelial wound healing. Determination of the minimum amino acid sequences required for the promotion of corneal epithelial wound closure by fibronectin (PHSRN) and by substance P (FGLM-amide) plus IGF-1 (SSSR) has led to the development of peptide eyedrops for the treatment of PEDs that are free of adverse effects of the parent molecules.
Do selective serotonin reuptake inhibitors cause suicide?: Authors' reply to Raven
Authors: Andrea Cipriani, Corrado Barbui, John R Geddes
Journal: BMJ (2005)

Do selective serotonin reuptake inhibitors cause suicide? Risk of suicide should be assessed for whole class of antidepressantsEditor-Gunnell et al's report on suicide risk with selective serotonin reuptake inhibitors (SSRIs) raises several issues. 1 Firstly, clinicians have observed that the first weeks of treatment of severe depression with an antidepressant are accompanied by a higher risk of suicide because of a drug induced motor disinhibition that is not yet accompanied by mood improvement. 2 Secondly, the authors' finding of a trend towards a protective effect of SSRIs against suicidal thoughts (odds ratio 0.77) compared with a trend towards an increased risk of self harm (odds ratio 1.57) is paradoxical.More surprising is the heterogeneity of results among SSRIs.Why would sertraline show a protective effect for suicidal thoughts and simultaneously increase the risk of self harm?The risk difference between citalopram and its active S-enantiomere, escitalopram, is also strange.No strong biological rationale can explain such heterogeneity among drugs with the same mechanism of action.Thirdly, the authors mention that the Medicine and Healthcare products Regulatory Agency found little evidence for a risk difference between SSRIs and the other antidepressants.The two accompanying papers show that the suicidal risk seems similar for serotoninergic and tricyclic antidepressants. 3 4The risk of suicide must be assessed for the whole class of antidepressants.The next stage would be to measure the risk of suicide according to the time since starting an antidepressant.Initially, the risks are higher than the benefits.To confirm old clinical observations by evidence based methods would be interesting and useful.
Possible Naproxen-Induced Relapse of Subacute Cutaneous Lupus Erythematosus
Authors: Aurora Parodi, Giampiero Rivara, Marcella Guarrera
Journal: JAMA (1992)

<h3>To the Editor.</h3> —A 59-year-old woman had been diagnosed as having subacute cutaneous lupus erythematosus (SCLE) 2 years previously and was given chloroquine and prednisone (250 mg/d), which cleared her skin lesions. In such a quiescent state, she began taking calcitonin and 250 to 500 mg per day of naproxen sodium. One month later, in spring, without any recreational or occupational sun exposure, typical SCLE lesions developed on her upper chest and forearms (Figure). The patient was given azathioprine (50 mg/d) and hydroxychloroquine sulfate (500 mg/d) without any benefit. Azathioprine was discontinued 15 days later and naproxen 1 month later. Only then did the SCLE lesions clear. Results of routine laboratory tests were normal or negative, but her creatinine level was high (190 μmol/L; normal, &lt;100 μmol/L), and creatinine clearance was low (0.44 mL/s; normal, 1.24 to 2.08 mL/s). Before naproxen treatment she had anti-SS-A/Ro antibodies at 1:4 titer that
What do I want from health research and researchers when I am a patient?
Authors: I. Chalmers
Journal: BMJ (1995)

I have attempted to adopt the perspective of a patient--albeit one with a rather atypical background--to explore what I want from health research and researchers. This has left me with the impression that health researchers could serve the interests of the public more effectively in a variety of ways, and that they would be helped to do so by greater lay involvement in planning and promoting health research.
Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules.
Authors: S Kozlowski, M Corr, T Takeshita, L F Boyd, C D Pendleton, R N Germain, J A Berzofsky, D H Margulies
Journal: The Journal of Experimental Medicine (1992)

T cell stimulation by the human immunodeficiency virus 1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules in a cell-free system was found to require proteolytic cleavage. This extracellular processing was mediated by peptidases present in fetal calf serum. In vitro processing of p18 resulted in a distinct reverse phase high performance liquid chromatography profile, from which a biologically active product was isolated and sequenced. This peptide processing can be specifically blocked by the angiotensin-1 converting enzyme (ACE) inhibitor captopril, and can occur by exposing p18 to purified ACE. The ability of naturally occurring extracellular proteases to convert inactive peptides to T cell antigens has important implications for understanding cytotoxic T lymphocyte responses in vivo, and for rational peptide vaccine design.
Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer
Authors: Liang Zhang, Xiaoen Wang, Andrea J. Bullock, Marcella Callea, Harleen Shah, Jiaxi Song, Kelli Moreno, Barbara Visentin, Douglas Deutschman, David C. Alsop, Michael B. Atkins, James W. Mier, Sabina Signoretti, Manoj Bhasin, Roger A. Sabbadini, Rupal S. Bhatt
Journal: Clinical Cancer Research (2015)

Abstract Purpose: VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC. Experimental Design: In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK–S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Results: Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Conclusions: Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy. Clin Cancer Res; 21(8); 1925–34. ©2015 AACR.