tbuckley/cabot-search huggingface dataset:
The atrial natriuretic peptide and cGMP: Novel activators of the heat shock response in rat livers
Authors: Alexandra K. Kiemer, Alexander L. Gerbes, Manfred Bilzer, Angelika M. Vollmar
Journal: Hepatology (2002)

Preischemic treatment with atrial natriuretic peptide (ANP) attenuates ischemia-reperfusion injury of the rat liver via cyclic guanosine monophosphate (cGMP). The attenuated activation of nuclear factor κB (NF-κB) seems to contribute to this effect. The aim of this study was to determine whether heat shock proteins are involved in these molecular pathways. Livers of male Sprague-Dawley rats were continuously perfused with Krebs-Henseleit (KH) buffer with or without ANP or 8-Br-cGMP. In different experiments livers were perfused with or without ANP for 20 minutes, kept in cold storage solution for 24 hours, and reperfused. Activation of heat shock transcription factor (HSF) (by electrophoretic mobility shift assay), heat shock protein 70 (HSP70), and glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA (by reverse transcription polymerase chain reaction [RT-PCR]), as well as HSP70 (by Western blot) were investigated in freeze-clamped liver samples. During continuous perfusion ANP as well as 8-Br-cGMP activated HSF, HSP70 protein concentrations paralleled HSF-activation. ANP pretreated livers exhibited elevated HSF after 24 hours of ischemia and elevated HSP70 mRNA levels during reperfusion. ANP prevented the marked decrease of HSP70 protein during reperfusion. Coimmunoprecipitation studies showed increased binding of HSP70 to inhibitory factor κB (IκB) in ANP-treated livers. In conclusion, we showed the cGMP-mediated activation of HSF by ANP, which resulted in elevated HSP70 mRNA and protein concentrations and correlated with enhanced binding of HSP70 to IκB. This could be an important mechanism of ANP-mediated prevention of hepatic preservation damage.
Development of Asthma, Allergic Rhinitis and Atopic Dermatitis by the Age of Five Years: A Prospective Study of 543 Newborns
Authors: R. LUOMA, A. KOIVIKKO, M. VIANDER
Journal: Allergy (1983)

543 children were followed up from birth to 5 years of age. Children with a positive history of parents' atopy had a 51% occurrence of respiratory or dermal symptoms of atopy vs. a 19% occurrence among children with no family history of atopy. There was an association between asthma and allergic rhinitis while atopic dermatitis occurred equally in children with or without respiratory symptoms. The clinical course of atopic symptoms could not be correlated to the family history of atopy. The significance of date of birth, nasal eosinophilia and serum IgE levels seemed to be relatively low in atopic dermatitis while these parameters had a correlation to the development of respiratory atopies.
Evolution of Circular Permutations in Multidomain Proteins
Authors: J. Weiner
Journal: Molecular Biology and Evolution (2006)

Modular rearrangements play an important role in protein evolution. Functional modules, often tantamount to structural domains or smaller fragments, are in many cases well conserved but reoccur in a different order and across many protein families. The underlying genetic mechanisms are gene duplication, fusion, and loss of sequence fragments. As a consequence, the sequential order of domains can be inverted, leading to what is known as circularly permutated proteins. Using a recently developed algorithm, we have identified a large number of such rearrangements and analyzed their evolutionary history. We searched for examples which have arisen by one of the three postulated mechanisms: independent fusion/fission, "duplication/deletion," and plasmid-mediated "cut and paste." We conclude that all three mechanisms can be observed, with the independent fusion/fission being the most frequent. This can be partly attributed to highly mobile domains. Duplication/deletion has been found in modular proteins such as peptide synthases.
Natural history of hepatopulmonary syndrome: Impact of liver transplantation
Authors: Karen L. Swanson, Russell H. Wiesner, Michael J. Krowka
Journal: Hepatology (2005)

Few data exist concerning survival after the diagnosis of hepatopulmonary syndrome (HPS). Although orthotopic liver transplantation (OLT) frequently results in complete resolution of HPS, the relationship between transplantation and survival has not been described. The study rationale was to describe long-term survival in patients with HPS. Data were derived from patients diagnosed with HPS at Mayo Clinic (n = 61) between 1985 and 2002, including those undergoing OLT (n = 24) and those who did not (n = 37). A case-control, Kaplan-Meier survival analysis between HPS patients and 77 patients without HPS matched for liver disease cause, model for end-stage liver disease (MELD), severity of liver disease by the Child classification, and age was described for OLT and non-OLT groups. Patients with HPS had a mean partial pressure of arterial oxygen (PaO(2)) decline of 5.2 + 2.3 mm Hg per year awaiting OLT. For HPS patients, despite similar baseline PaO(2), brain uptake of technetium macroaggregated albumin ((99m)TcMAA), or measures of hepatic dysfunction, 5-year survival associated with OLT was 76% versus 23% who did not undergo transplantation (P < .0001). Comparing those who did not undergo transplantation, HPS patients had worse 5-year survival than matched controls (P = .0003). However, reasons to deny OLT (comorbidity) in the setting of HPS may well have contributed to observed survival differences. Baseline PaO(2) </=50 mm Hg was associated with worse survival irrespective of the decision to perform OLT. In conclusion, hypoxemia of HPS is frequently progressive. As OLT outcome relates to pretransplantation PaO(2), additional MELD points should advance the priority for OLT in HPS.
The Ultimate Expedition
Authors: Mark Scott
Journal: JAMA (1984)

Tim was the kind of boy that everyone took to. He was just 13 and had acute myelogenous leukemia. We all knew his prognosis was dreadful, but we pursued chemotherapy with a vengeance. Tim had the usual side effects of hair loss, nausea and vomiting, mouth ulcers, and weakness, but he weathered them pretty well. As the weeks and a few months passed by, Tim's hospitalizations for treatment or supportive care from the dangerous side effects of his toxic drugs became increasingly frequent. His parents, divorced and anxious, took turns visiting and staying with him at the hospital. Even when it became clear that Tim was in for his last hospitalization he resisted well-intentioned efforts of staff and his parents to discuss the imminence of his death. His corner room became a fortress protected from the outside world. Instead Tim developed a metaphor of his own—he wanted to go camping.
Systemic Endothelin Receptor Blockade Decreases Peripheral Vascular Resistance and Blood Pressure in Humans
Authors: William G. Haynes, Charles J. Ferro, Kevin P. J. O’Kane, David Somerville, Charmaine C. Lomax, David J. Webb
Journal: Circulation (1996)

Background Although local inhibition of the generation or actions of endothelin-1 has been shown to cause forearm vasodilatation, the systemic effects of endothelin receptor blockade in healthy humans are unknown. We therefore investigated the cardiovascular effects of a potent peptide endothelin ET A/B receptor antagonist, TAK-044, in healthy men. Methods and Results Two randomized, placebo-controlled, crossover studies were performed. In nine subjects, TAK-044 (10 to 1000 mg IV over a 15-minute period) caused sustained dose-dependent peripheral vasodilatation and hypotension. Four hours after infusion of the highest dose (1000 mg), there were decreases in mean arterial pressure of 18 mm Hg and total peripheral resistance of 665 AU and increases in heart rate of 8 bpm and cardiac index of 0.9 L·min −1 ·m −2 compared with placebo. TAK-044 caused a rapid, dose-dependent increase in plasma immunoreactive endothelin (from 3.3 to 35.7 pg/mL within 30 minutes after 1000 mg). In a second study in eight subjects, intravenous administration of TAK-044 at doses of 30, 250, and 750 mg also caused peripheral vasodilatation, and all three doses abolished local forearm vasoconstriction to brachial artery infusion of endothelin-1. Brachial artery infusion of TAK-044 caused local forearm vasodilatation. Conclusions The endothelin ET A/B receptor antagonist TAK-044 decreases peripheral vascular resistance and, to a lesser extent, blood pressure; increases circulating endothelin concentrations; and blocks forearm vasoconstriction to exogenous endothelin-1. These results suggest that endogenous generation of endothelin-1 plays a fundamental physiological role in maintenance of peripheral vascular tone and blood pressure. The vasodilator properties of endothelin receptor antagonists may prove valuable therapeutically.
Fusobacterium nucleatum
Authors: Emma Allen-Vercoe, Jaclyn Strauss, Kris Chadee
Journal: Gut Microbes (2011)

The Gram-negative, non-sporulating, obligately anaerobic species, Fusobacterium nucleatum, is rapidly gaining notoriety as a pathogen with a surprising number of associated diseases. Recently, we have found that F. nucleatum is a more common resident of the GI tract than originally thought, and thus, through several studies, we have attempted to determine its gut-relevant potential for virulence. We have found that F. nucleatum possesses a number of pathogenic traits with relevance to gut diseases such as inflammatory bowel disease (IBD), however, we have also documented strain-associated differences in virulence. An intriguing picture emerges that paints F. nucleatum as both conferring beneficial as well as detrimental effects on host cells; and we suggest that the ultimate effects of F. nucleatum infection in the gut are a consequence of the microbes with which this species aggregates.
Clinical guidelines in 1994
Authors: G. Feder
Journal: BMJ (1994)

episode the International Committee of Journal Editors (the Vancouver group) drew up criteria for authorship, based on the concept that "each author should have par- ticipated sufficiently in the work to take public responsibil- ity for the content."6Editors, readers, funding agencies, and society generally expect someone to take responsibility for work that comes into the public domain: they want someone to defend it, to debate it, to admit mistakes if necessary.As Shapiro et al say, the signing of scientific papers by their authors "con- fers credit and denotes responsibility."4The Vancouver guidelines try to define the activities that allow an author to take credit and satisfy readers' demands for responsibility.They suggest that authorship should be based only on sub- stantial contributions to "(a) conception and design or analysis and interpretation of data; (b) drafting the article or revising it critically for important intellectual content, and (c) final approval of the version to be published."7The guidelines explicitly reject fund raising, collecting data, and supervising the research group as justifications for authorship, though these and other contributions should be acknowledged.The guidelines do, however, make it clear that between them the authors must take responsibility for all aspects of
Synthesis of an M Component by Circulating B Lymphocytes in Severe Combined Immunodeficiency
Authors: Raif S. Geha, Eveline Schneeberger, John Gatien, Fred S. Rosen, Ezio Merler
Journal: New England Journal of Medicine (1974)

SEVERE combined immunodeficiency is a hereditary disease characterized by considerable impairment of both cellular and humoral immunity and is assumed to result from a defect in lymphoid stem-cell maturation into thymus-derived (T) and bone-marrow-derived (B) lymphocytes.1 High numbers of circulating immunoglobulin-bearing (B) cells have been reported in a number of cases of the disorder2 , 3 although the functional potential of such cells is not known. We have observed a case with a very high percentage of circulating IgM-bearing cells that lacked a surface receptor for complement component C3. These cells behaved as B cells, transforming with pokeweed mitogen and secreting an . . .
CROHN'S DISEASE: HAS THE PHENOTYPE CHANGED?
Authors: E Bredin, P O'Leary, F Shanahan
Journal: Gut (2013)

<h3>Introduction</h3> The long-held image of “the typical patient with Crohn9s disease” is of undernourishment – the opposite of the elevated BMI state associated with higher incidence of adverse cardiovascular risk factors in population studies. Cardiovascular risk is increased in patients with a number of chronic inflammatory disorders. The importance of this in Crohn9s disease is not generally addressed. <h3>Aims/Background</h3> The BMI and cardiovascular risk profile of a cohort of patients with Crohn9s disease attending a specialist clinic in a tertiary referral hospital is evaluated. <h3>Method</h3> The BMI was measured in 75 out-patients with Crohn9s disease over a 2 month period. Blood pressure, fasting lipoprotein profile and fasting glucose were also measured. Studied patients completed a questionnaire about their disease and its activity, their past medical history and smoking status. <h3>Results</h3> 49% of the patients had a BMI &gt;25–33% overweight, 16% obese. Of the patients with an increased BMI, 10% were taking corticosteroids at the time of measurement. 15% of patients were either hypertensive or on antihypertensive medications, 23% were current smokers and 27% had a total cholesterol of &gt;5mmol/l. <h3>Conclusion</h3> In this small study we have found that the prevalence of elevated BMI in patients with Crohn9s Disease is common in contrast to the past. Additional cardiovascular risk factors are also noted, even in this relatively young and small patient cohort. Going forward cardiovascular risk factors should be assessed and managed as part of a total care package in this patient group. Further studies are needed to evaluate the mechanism of this increase in BMI.
FDA Workshop Explores Growth Factor Uses
Authors: Charles Marwick
Journal: JAMA (1989)

THE Food and Drug Administration's (FDA) Division of Cytokine Biology recently held a workshop to explore the clinical uses of hematopoietic growth factors (HGF), the hormonelike proteins that control the development and differentiation of blood cells (See From the FDA , page 1296).  Nine potential human HGFs have been identified, their genes cloned, and their chromosomal locations pinpointed. They have been produced in quantity by recombinant DNA methods.  In the past 2 years, several HGFs have been evaluated in clinical trials. Some of the investigators conducting these trials presented the emerging applications for the agents.  Cancer Therapy.—  Jordan Gutterman, MD, of the M. D. Anderson Cancer Center, Houston, Tex, chaired a session on the use of two HGFs, granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF), as adjuvants in cancer chemotherapy. Gutterman said that early results of several studies indicate that the agents have reduced periods of severe neutropenia
Adverse Bioenergetic Consequences of Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger–Mediated Ca <sup>2+</sup> Influx in Cardiac Myocytes
Authors: Michael Kohlhaas, Christoph Maack
Journal: Circulation (2010)

In heart failure, the Na+-Ca²+ exchanger (NCX) is upregulated and mediates Ca²+ influx (instead of efflux) during the cardiac action potential. Although this partly compensates for impaired sarcoplasmic reticulum Ca²+ release and supports inotropy, the energetic consequences have never been considered. Because NCX-mediated Ca²+ influx is rather slow and mitochondrial Ca²+ uptake (which stimulates NADH production by the Krebs cycle) is thought to be facilitated by high Ca²+ gradients in a "mitochondrial Ca²+ microdomain," we speculated that NCX-mediated Ca²+ influx negatively affects the bioenergetic feedback response. Methods and Results- With the use of a patch-clamp-based approach in guinea-pig myocytes, cytosolic and mitochondrial Ca²+ ([Ca²+](c) and [Ca²+](m), respectively) was determined within the same cell after varying Ca²+ influx via L-type Ca²+ channels (I(Ca,L)) or the NCX. The efficiency of mitochondrial Ca²+ uptake, indexed by the slope of plotting [Ca²+](m) against [Ca²+](c) during each Ca²+ transient, was maximal during I(Ca,L)-triggered sarcoplasmic reticulum Ca²+ release. Depletion of sarcoplasmic reticulum Ca²+ load and increased contribution of the NCX to cytosolic Ca²+ influx independently reduced the efficiency of mitochondrial Ca²+ uptake. The upstroke velocity of cytosolic Ca²+ transients closely correlated with the efficiency of mitochondrial Ca²+ uptake. Despite comparable [Ca²+](c), sarcoplasmic reticulum Ca²+ release, but not NCX-mediated Ca²+ influx, led to stimulation of Ca²+-sensitive dehydrogenases of the Krebs cycle. Conclusions- Increased contribution of the NCX to cytosolic Ca²+ transients, which occurs in cardiac myocytes from failing hearts, impairs mitochondrial Ca²+ uptake and the bioenergetic feedback response. This mechanism could contribute to energy starvation of failing hearts.
MACULAR ERYTHEMA IN A PATIENT WITH A TRAUMATIC HAEMATOMA IN THE ABDOMEN
Authors: C. RASCH
Journal: British Journal of Dermatology (1924)

Journal Article MACULAR ERYTHEMA IN A PATIENT WITH A TRAUMATIC HÆMATOMA IN THE ABDOMEN Get access C. RASCH C. RASCH Director of the Dermatological Clinic at the Rigshospital, Copenhagen Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 36, Issue 4, 1 April 1924, Pages 157–159, https://doi.org/10.1111/j.1365-2133.1924.tb09175.x Published: 01 April 1924
Abstract 4515: A novel obatoclax derivative is a promising agent to overcome bortezomib's resistance in acute leukemia cells
Authors: Chun-Yu Liu, Chung-Wai Shiau, Hsin-Yu Kuo, Ann-Lii Cheng, Cheng-Hwai Tzeng, Kuen-Feng Chen
Journal: Cancer Research (2011)

Abstract Background: Our previous work showed that bortezomib, a reverse-inhibitor of the 26S proteasome, exerts differential cytotoxic effects to acute leukemia cells through down-regulation of phosphor-Akt (AACR 2010 abstract 1575). Interestingly, some acute leukemia cells (MOLT-3 and K562) are resistant to bortezomib. One of the resistant mechanisms of bortezomib involves the abnormality in intrinsic apoptotic pathway members, the bcl-2 family. Of particular, it has been shown that bortezomib induces upregulation of Mcl-1 and that Mcl-1 accumulation may delay bortezomib-induced apoptosis. Obatoclax, a small molecule inhibitor of pro-survival BCL-2 members, including MCL-1, synergizes with bortezomib in mantle cell lymphoma (Blood 2007) and may overcome bortezomib resistance. Here, we designed a novel Mcl-1 inhibitor deriving from obatoclax, SC-2001, to overcome the resistance. Methods: MOLT-3 and K562 cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Gene silencing was done by small interference RNA (siRNA). Results: MOLT-3 and K562 were resistant to bortezomib up to 100nM. Upregulation of Mcl-1 expression after bortezomib treatment were evident in these cells. Interestingly, the addition of either obatoclax or SC-2001, restored the sensitivity of K562 and MOLT-3 cells to bortezomib. SC-2001, comparing to obatoclax, exerted better efficacy in sensitivity restoration of bortezomib in association with Mcl-1 downregulation in MOLT-3 cells. Moreover, down-regulation of Mcl-1 by siRNA overcame the apoptotic resistance to bortezomib in K562 cells. These data indicate that novel Mcl-1 inhibitors could restore bortezomib sensitivity in resistant acute leukemia cells. Conclusions: a novel Mcl-1 inhibitor SC-2001, is a promising agent to overcome bortezomib's resistance in acute leukemia, further elucidating the drug mechanism regulating Mcl-1 inhibition is needed. Supported by VGHTPE 99DHA0100332 and 100DHA0100591 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4515. doi:10.1158/1538-7445.AM2011-4515
History of the Community Psychiatry Movement
Authors: JACK R. EWALT, PATRICIA L. EWALT
Journal: American Journal of Psychiatry (1969)

The authors trace the history of community psychiatry along six lines of development—social psychiatry, changes in hospital programs, development of clinics, evolution of the mental health professions, growth of federally supported programs, and the citizens' mental health movement. Future progress, they believe, must involve "informed activism" to change our national goals and priorities, better use of what we now know, and the development of new knowledge.
Plasma somatomedin-C levels in psoriasis
Authors: B.J. NICKOLOFF, PRATIMA MISRA, VERA B. MORHENN, R.L. HINTZ, R.G. ROSENFELD
Journal: British Journal of Dermatology (1987)

Journal Article Plasma somatomedin‐C levels in psoriasis Get access B.J. NICKOLOFF, B.J. NICKOLOFF Departments of Dermatology, Stanford University School of Medicine, Stanford, California, U.S.A. Dr Brian J.Nickoloff, Department of Dermatology, R‐166, Stanford University, Stanford, California 94305, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar PRATIMA MISRA, PRATIMA MISRA Departments of Dermatology, Stanford University School of Medicine, Stanford, California, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar VERA B. MORHENN, VERA B. MORHENN Departments of Dermatology, Stanford University School of Medicine, Stanford, California, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar R.L. HINTZ, R.L. HINTZ Departments of Pediatrics, Stanford University School of Medicine, Stanford, California, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar R.G. ROSENFELD R.G. ROSENFELD Departments of Pediatrics, Stanford University School of Medicine, Stanford, California, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 1, 1 January 1987, Pages 15–20, https://doi.org/10.1111/j.1365-2133.1987.tb05786.x Published: 01 January 1987
ADVERSE LEFT VENTRICULAR REMODELING DUE TO AORTIC INSUFFICIENCY POST TRANSCATHETER AORTIC VALVE REPLACEMENT AND DOWNSTREAM IMPACT ON ALL-CAUSE MORTALITY
Authors: Sumeet Pawar, Matthew Schoenfeld, Muhammad A. Haidar, Polydoros Kampaktsis, Amiran Baduashvili, Kalliope Pastella, Ryan Kaple, Geoffrey Bergman, Robert Minutello, Arash Salemi, Karl Krieger, Evelyn Horn, Shing-Chiu Wong, Harsimran Singh, Ingrid Hriljac, Richard Devereux, Fay Lin
Journal: Journal of the American College of Cardiology (2014)
The PI3K pathway drives the maturation of mast cells via microphthalmia transcription factor
Authors: Peilin Ma, Raghuveer Singh Mali, Veerendra Munugalavadla, Subha Krishnan, Baskar Ramdas, Emily Sims, Holly Martin, Joydeep Ghosh, Shuo Li, Rebecca J. Chan, Gerald Krystal, Andrew W. Craig, Clifford Takemoto, Reuben Kapur
Journal: Blood (2011)