tbuckley/cabot-search huggingface dataset:
Phase I Study of NGR-hTNF, a Selective Vascular Targeting Agent, in Combination with Cisplatin in Refractory Solid Tumors
Authors: Vanesa Gregorc, Filippo G. De Braud, Tommaso M. De Pas, Roberto Scalamogna, Giovanni Citterio, Alessandra Milani, Sabrina Boselli, Chiara Catania, Giovanni Donadoni, Gilda Rossoni, Domenico Ghio, Gianluca Spitaleri, Cristina Ammannati, Scialini Colombi, Federico Caligaris-Cappio, Antonio Lambiase, Claudio Bordignon
Journal: Clinical Cancer Research (2011)

NGR-hTNF exploits the tumor-homing peptide asparagine-glycine-arginine (NGR) for selectively targeting TNF-α to an aminopeptidase N overexpressed on cancer endothelial cells. Preclinical synergism with cisplatin was displayed even at low doses. This study primarily aimed to explore the safety of low-dose NGR-hTNF combined with cisplatin in resistant/refractory malignancies. Secondary aims included pharmacokinetics (PKs), pharmacodynamics, and activity.NGR-hTNF was escalated using a doubling-dose scheme (0.2-0.4-0.8-1.6 μg/m(2)) in combination with fixed-dose of cisplatin (80 mg/m(2)), both given intravenously once every three weeks. PKs and circulating TNF-receptors (sTNF-Rs) were assessed over the first three cycles.Globally, 22 patients (12 pretreated with platinum) received a range of one to ten cycles. Consistently with the low-dose range tested, maximum-tolerated dose was not reached. No dose-limiting toxicities (DLTs) were observed at 0.2 (n = 4) and 0.4 μg/m(2) (n = 3). One DLT (grade 3 infusion-related reaction) was observed at 0.8 μg/m(2). This dose cohort was expanded to six patients without further DLTs. No DLTs were noted also at 1.6 μg/m(2) (n = 3). NGR-hTNF exposure increased dose-proportionally without apparent PK interactions with cisplatin. No shedding of sTNF-Rs was detected up to 0.8 μg/m(2). At the dose level of 0.8 μg/m(2), expanded to 12 patients for activity assessment, a platinum-pretreated lung cancer patient achieved a partial response lasting more than six months and five patients maintained stable disease for a median time of 5.9 months.The combination of NGR-hTNF 0.8 μg/m(2) with cisplatin 80 mg/m(2) showed favorable toxicity profile and promising antitumor activity.
Expression of neuronal nitric oxide synthase in dermal infiltrated eosinophils in eosinophilic pustular folliculitis
Authors: None MARUO, None KAYASHIMA, None ONO
Journal: British Journal of Dermatology (1999)

Nitric oxide (NO) is produced by a wide variety of human cells and affects physiological and pathophysiological processes. In this study, we demonstrated for the first time that neuronal NO synthase (NOS) is expressed in eosinophils infiltrating into the dermis and follicular epidermis in eosinophilic pustular folliculitis (EPF). EPF is a cutaneous inflammatory follicular disorder first described in Japan. The clinical and histological features of EPF are characterized by erythematous papules, infiltration of numerous eosinophils, and a spongiotic appearance of the follicular epidermis, but the pathophysiology of EPF remains unclear. Our results suggest that NO produced from eosinophils plays an important part in the pathogenesis of EPF. Furthermore, we speculate that NOS inhibitors may be useful in the management of EPF.
266 Evidence of hedgehog signaling pathway activation in hepatocellular carcinoma
Authors: E.R. Lemmer, Y. Chen, S. Yea, E. Wurmbach, M. Schwartz, A. Villanueva, G. Narla, V. Mazzaferro, J. Bruix, S. Waxman, S.L. Friedman, J.M. Llovet Sinai
Journal: Journal of Hepatology (2006)
Recurrent mutations, including NPM1c, activate a BRD4-dependent core transcriptional program in acute myeloid leukemia
Authors: M A Dawson, E J Gudgin, S J Horton, G Giotopoulos, E Meduri, S Robson, E Cannizzaro, H Osaki, M Wiese, S Putwain, C Y Fong, C Grove, J Craig, A Dittmann, D Lugo, P Jeffrey, G Drewes, K Lee, L Bullinger, R K Prinjha, T Kouzarides, G S Vassiliou, B J P Huntly
Journal: Leukemia (2013)

Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML.
Vitamin-A Reversal of Abnormal Dark Adaptation in Cirrhosis
Authors: ROBERT M. RUSSELL
Journal: Annals of Internal Medicine (1978)

Of 26 patients hospitalized with mild to moderate alcohol-associated cirrhosis, 14 had dark-adaptation abnormalities consistent with marginal vitamin-A status. The response of dark adaptation and the plasma retinol transport proteins, retinol-binding protein and prealbumin, was studied in 12 of these patients after daily oral vitamin-A supplements of 3300 microgram. Vitamin-A supplementation was associated with significant (p less than 0.05-0.005) improvement in dark adaptation and increased plasma concentrations of retinyl esters, retinol, and retinol-binding protein. Thus in patients with cirrhosis and marginal vitamin-A status, supplemental vitamin-A therapy appears to stimulate retinol-binding protein release from the liver. This enhancement of plasma retinol transport and delivery of retinol to peripheral tissues such as the retina is one of several factors that may serve to optimize vitamin-A nutritional status in patients with cirrhosis.
Treatment failure in hepatitis C: Mechanisms of non-response
Authors: Andrew W. Tai, Raymond T. Chung
Journal: Journal of Hepatology (2008)

Hepatitis C virus (HCV) has evolved remarkable mechanisms that favor viral persistence by interfering with host innate and adaptive immune responses. These same mechanisms are likely to contribute to resistance to exogenously administered interferon used for HCV treatment. We review the host innate and adaptive immune responses in the context of HCV infection as well as the strategies by which these responses are subverted by the virus. In addition, the contribution of host factors, such as race and insulin resistance, to interferon non-responsiveness is discussed. Our progress in understanding the molecular underpinnings of interferon treatment failure in HCV infection has resulted in several promising and novel treatment strategies for HCV treatment non-responders.
Management of Choledochal Cysts in Adults
Authors: J A Pain, C J Cahill, M E Bailey
Journal: Journal of the Royal Society of Medicine (1986)

The management of 7 adults with choledochal cysts is described. Three patients presented with abdominal pain, 3 with jaundice and one with cholangitis. Three patients underwent total or partial cyst excision and the remaining patients underwent cyst drainage into a Roux-en-Y jejunal loop. There was no operative mortality and all patients have remained well for up to 6 years following surgery. It is argued that total cyst excision is the treatment of choice, but where this is not possible a Roux-en-Y choledochocystojejunostomy is the recommended alternative.
Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat.
Authors: N Barzilai, S Banerjee, M Hawkins, W Chen, L Rossetti
Journal: Journal of Clinical Investigation (1998)

Hyperinsulinemia and increased visceral/abdominal fat (VF) are common features of human aging. To examine the relationships among VF, peripheral, and hepatic insulin sensitivity, we studied 4- and 18-mo-old male Sprague-Dawley rats (n = 42) fed ad libitum (4 AL and 18 AL) or moderately calorie restricted (18 CR) up to 18 mo of age. Total fat mass (FM) and VF were decreased in 18 CR to approximately one-third of that of 18 AL (P < 0.001), while lean body mass (LBM) was unchanged. Most important, 18 CR had more FM (65+/-6 vs. 45+/-6 g) but less VF (7.8+/-0.6 vs. 12.3+/-3.3 g) compared with 4 AL (P < 0.01 for both). Thus, the effects of variable VF on HIS could be assessed, independent of FM and age. Marked hepatic insulin resistance ensued with aging (18 AL) and CR restored hepatic insulin sensitivity to the levels of young rats, while peripheral insulin sensitivity remained unchanged (by insulin clamp of 18 mU/kg/min). In fact, the rates of insulin infusion required to maintain basal hepatic glucose production in the presence of pancreatic clamp were 0.75+/-0.10, 1.41+/-0.13, and 0.51+/-0.12 mU/kg . min, in 4 AL, 18 AL, and 18 CR, respectively (P < 0.01 between all groups), and in 18 CR rats infused with insulin at similar rates as in the 18 AL (1.4 mU/kg/min) hepatic glucose production was decreased by 32% (P < 0. 005). Furthermore, when 18 CR rats were fed AL for 14 d, VF rapidly and selectively increased and severe hepatic insulin resistance was induced. We propose that in this animal model the age-associated decrease in hepatic (rather than peripheral) insulin action is the major determinant of fasting hyperinsulinemia and that increased visceral adiposity plays the major role in inducing hepatic insulin resistance. Thus, interventions designed to prevent the accumulation of VF are likely to represent an effective mean to improve carbohydrate metabolism in aging.
Stridor in children
Authors: L. J. L. Halpin, C. L. Anderson, N. Corriette
Journal: BMJ (2010)

A 6 month old presents to the general practitioner’s surgery with his mother. She is concerned because he has a runny nose and makes a “funny” loud noise when breathing in, which you diagnose as stridor. Stridor is caused by partial upper airway obstruction and is typically heard in inspiration, although it can also be heard on expiration if the obstruction is below the larynx. It sounds different from wheeze , which is a high-pitched whistling expiratory sound, and from stertor , a snoring sound. ### How long has the stridor been present? ### Associated features
Managing Medical References
Authors: John Faughnan
Journal: Annals of Internal Medicine (1990)

Letters and Corrections15 September 1990Managing Medical ReferencesJohn Faughnan, MDJohn Faughnan, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-113-6-484_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors: I read with interest the discussion by Murphy and colleagues (1) of a residency-based information system. They review the use of bibliographic software and Paperchase to create and maintain a collection of reference articles. Although this approach is not unreasonably expensive, less costly alternatives exist.For most physicians "Grateful Med" (supported by the National Library of Medicine) is more cost-effective and efficient than PAPERCHASE. It is available from the National Technical Information Service for both Macintosh and IBM-standard (PC) platforms. A typical search costs less than $4 and the program itself is sold below cost at $30...References1. MurphyJamesWilliamsHillman JNPR. A residency-based information system. Ann Intern Med. 1990;112:961-3. LinkGoogle Scholar2. Sellu D. A comprehensive bibliography database using a microcomputer. Br Med J. 1986;292:1643-5. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Michigan State University College of Human Medicine Escanaba, MI 49829 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1990Volume 113, Issue 6Page: 484-484KeywordsInformation technologyLibraries Issue Published: 15 September 1990 PDF DownloadLoading ...
Letter: Treatment of myeloma kidney.
Authors: T Hamblin
Journal: BMJ (1976)

<h3>Objective</h3> To identify patients with type 2 myocardial infarction (MI) and patients with non-ischaemic myocardial injury (NIMI) and to compare their prognosis with those of patients with type 1 MI. <h3>Methods</h3> A retrospective observational study was performed in 1010 patients admitted to the emergency department of a university hospital with at least one troponin I test between 2012 and 2013. Participants were identified using laboratory records and divided into three groups: type 1 MI (rupture of atheromatous plaque), type 2 MI (imbalance between myocardial oxygen supply and/or demand) and NIMI (patients who did not meet diagnostic criteria for type 1 or type 2 MI). Clinical characteristics and 2-year outcomes were analysed. <h3>Results</h3> Patients with type 2 MI and NIMI were older, with higher proportion of women and more comorbidities than patients with type 1 MI. Absolute mortality and the adjusted risk for all-cause mortality in both groups were significantly higher than that of patients with type 1 MI (39.7%, HR: 1.41 95% CI 1.02 to 1.94, p=0.038 and 40.0%, HR: 1.54 95% CI 1.16 to 2.04, p=0.002, respectively). Patients with type 2 MI and NIMI tended to present more readmissions due to heart failure (16.5%, HR: 1.55 95% CI 0.87 to 2.76, p=0.133 and 12.3%, HR: 1.15 95% CI 0.70 to 1.90, p=0.580) and less readmission rates due to acute coronary syndrome (ACS) than patients with type 1 MI (2.1%, HR: 0.11 95% CI 0.04 to 0.31, p&lt;0.001 and 4.3%, HR: 0.22 95% CI 0.12 to 0.41, p&lt;0.001), <h3>Conclusions</h3> Patients diagnosed with type 2 MI and NIMI have higher rates of mortality and lower readmission rates for ACS compared with patients with type 1 MI.
With what right do we detain?
Authors: J. R. Cohen
Journal: BMJ (2010)

McCartney highlights concern about the poor provision of mental health care for asylum seekers.1 I found that rates of suicide and self harm are higher in this vulnerable group than in the UK prison population.2

In prison “first night” physical and psychological health assessments entail many detailed questions designed to identify those at risk of self harm or suicide. In immigration removal centres, however, only a …
Prolongation of life or prolonging the act of dying?
Authors: W. P. Williamson
Journal: JAMA (1967)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis B
Authors: Vicente Carreño, Stefan Zeuzem, Uwe Hopf, Patrick Marcellin, W.Graham E. Cooksley, Johan Fevery, Moisés Diago, Rajender Reddy, Marion Peters, Karen Rittweger, Ashok Rakhit, Margarita Pardo
Journal: Journal of Hepatology (2000)
Nuclear transport factor 2 represents a novel cross‐reactive fungal allergen
Authors: M. Weichel, P. Schmid‐Grendelmeier, S. Flückiger, M. Breitenbach, K. Blaser, R. Crameri
Journal: Allergy (2003)

Background: Ubiquitously occuring moulds are important allergenic sources known to elicit IgE‐mediated allergic diseases and to share cross‐reactive allergens. Limited information is available about the molecular structures involved in cross‐reactivity. We aimed to clone and characterize cross‐reactive mould allergens. Methods: Phage surface‐displayed Alternaria alternata and Cladosporium herbarum cDNA libraries were screened using sera from Aspergillus fumigatus ‐sensitized patients. Inserts encoding putative allergens were sequenced, and recombinant proteins used to demonstrate cross‐reactivity by inhibition experiments and skin test. Three‐dimensional homology models of cloned putative nuclear transport factor 2 (NTF2) were constructed based on known NTF2 structure to corroborate the functional and structural properties of the novel allergens. Results: After six rounds of affinity selection, the libraries were enriched for clones displaying allergens. Sequencing of inserts showed that some clones derived from Alternaria alternata and Cladosporium herbarum contain open reading frames predicting proteins of 124 and 125 amino acids corresponding to NTF2. The recombinant proteins were able to bind and cross‐inhibit IgE binding and to elicit type I skin reactions in mould‐sensitized individuals, demonstrating the allergenicity of the proteins. Conclusions: NTF2 represents a novel cross‐reactive fungal allergen as demonstrated by sequence homology, three‐dimensional modelling, inhibition experiments and skin test reactivity.
Regulation of the UGT1A1 bilirubin-conjugating pathway: Role of a new splicing event at the UGT1A locus
Authors: Eric Lévesque, Hugo Girard, Kim Journault, Johanie Lépine, Chantal Guillemette
Journal: Hepatology (2006)

UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in a wide range of biological and pharmacological processes because of its critical role in the conjugation of a diverse array of endogenous and exogenous compounds. We now describe a new UGT1A1 isoform, referred to as isoform 2 (UGT1A1_i2), encoded by a 1495-bp complementary DNA isolated from human liver and generated by an alternative splicing event involving an additional exon found at the 3' end of the UGT1A locus. The N-terminal portion of the 45-kd UGT1A1_i2 protein is identical to UGT1A1 (55 kd, UGT1A1_i1); however, UGT1A1_i2 contains a unique 10-residue sequence instead of the 99-amino acid C-terminal domain of UGT1A1_i1. RT-PCR and Western blot analyses with a specific antibody against UGT1A1 indicate that isoform 2 is differentially expressed in liver, kidney, colon, and small intestine at levels that reach or exceed, for some tissues, those of isoform 1. Western blots of different cell fractions and immunofluorescence experiments indicate that UGT1A1_i1 and UGT1A1_i2 colocalize in microsomes. Functional enzymatic data indicate that UGT1A1_i2, which lacks transferase activity when stably expressed alone in HEK293 cells, acts as a negative modulator of UGT1A1_i1, decreasing its activity by up to 78%. Coimmunoprecipitation of UGT1A1_i1 and UGT1A1_i2 suggests that this repression may occur via direct protein-protein interactions.Our results indicate that this newly discovered alternative splicing mechanism at the UGT1A locus amplifies the structural diversity of human UGT proteins and describes the identification of an additional posttranscriptional regulatory mechanism of the glucuronidation pathway.
The Exodus of a Medical School
Authors: Richard S. Panush
Journal: Annals of Internal Medicine (1995)

Letters15 December 1995The Exodus of a Medical SchoolRichard S. Panush, MD and Robert M. Briggs, MDRichard S. Panush, MDSt. Barnabas Medical Center Livingston, NJ 07039Search for more papers by this author and Robert M. Briggs, MDSt. Barnabas Medical Center Livingston, NJ 07039Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-12-199512150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The events related in Dr. Ernst's recent article [1] on the Medical Faculty of Vienna during and after the Nazi Anschluss offered a chilling reminder about what can happen when physicians pervert humanity. We commend Annals for this presentation.After reading Dr. Ernst's reflections, we were surprised to find a copy of Pernkopf's anatomy atlas [2] in our medical center library. Others [3, 4] corroborate most of Dr. Ernst's recollections of Pernkopf—a man who was an “outspoken Nazi,” who was named Dean of the Medical Faculty of Vienna in 1938, who presided over the “cleansing” of the ...References1. Ernst E. A leading medical school seriously damaged: Vienna 1938. Ann Intern Med. 1995;122:789-92. LinkGoogle Scholar2. Ferner H, ed. Eduard Pernkopf Atlas of Topographical and Applied Human Anatomy. 2nd revised edition. Philadelphia: WB Saunders; 1980. Google Scholar3. Weissmann G. Springtime for Pernkopf. Hosp Pract. 1985;20:142-68. CrossrefGoogle Scholar4. Williams DJ. The history of Eduard Pernkopf's Topographische Anatomie des Menchen. J Biocommunication. 1988;15:2-12. MedlineGoogle Scholar5. Angell M. The Nazi hypothermia experiments and unethical research today. N Engl J Med. 1990;322:1462-4. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: St. Barnabas Medical Center Livingston, NJ 07039 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNazi Medicine—Part 2: The Downfall of a Profession and Pernkopf's Anatomy AtlasHow the Pernkopf controversy facilitated a historical and ethical analysis of the anatomical sciences in Austria and Germany: A recommendation for the continued use of the Pernkopf atlasThe tainted legacy of Hans Reiter 15 December 1995Volume 123, Issue 12Page: 963KeywordsChildrenLibraries Issue Published: 15 December 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...