tbuckley/cabot-search huggingface dataset:
<i>ERCC1</i> Codon 118 Polymorphism Is a Predictive Factor for the Tumor Response to Oxaliplatin/5-Fluorouracil Combination Chemotherapy in Patients with Advanced Colorectal Cancer
Authors: Jérôme Viguier, Valérie Boige, Catherine Miquel, Marc Pocard, Bruno Giraudeau, Jean-Christophe Sabourin, Michel Ducreux, Alain Sarasin, Françoise Praz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of our study was to assess whether the polymorphism of the nucleotide excision repair enzyme, excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), had an effect on the tumor response in patients treated with standard chemotherapy regimens for a metastatic colorectal cancer. We have studied the synonymous polymorphism that causes a single nucleotide change C to T at codon 118 converting a codon of common usage (AAC) to a less used codon (AAT), both coding asparagine. This change results in a decreased ERCC1 gene expression, which impairs repair activity. Experimental Design: Ninety-one patients with a median age of 55.1 years treated for a metastatic colorectal cancer were included in our retrospective study. The ERCC1 polymorphism was analyzed in the normal tissue of all patients. Results: Twenty (22%) were homozygous for AAC codon (C/C genotype), 30 were (33%) homozygous for AAT codon (T/T genotype), and 41 (45%) were heterozygous (C/T genotype). The objective response rate to oxaliplatin in combination with 5-fluorouracil (5-FU) was significantly higher in the T/T genotype group compared with the C/T and the C/C genotype groups (61.9%, 42.3%, and 21.4%, respectively; P = 0.018). By contrast, no significant difference was observed when patients were treated with either 5-FU alone (45%, 29.2%, and 33.3%, respectively; P = 0.407) or in combination with irinotecan (46.1%, 25.0%, and 27.3%, respectively; P = 0.305). Conclusions: Our observations allowed us to define the first useful predictive criterion for oxaliplatin/5-FU response in patients with metastatic colorectal cancer.
Improved Vascular Gene Transfer With a Helper-Dependent Adenoviral Vector
Authors: Shan Wen, Shannon Graf, Philip G. Massey, David A. Dichek
Journal: Circulation (2004)

Background— Adenoviral vectors are the most widely used agents for vascular gene transfer. However, the utility of adenoviral vectors for vascular gene transfer is limited by brevity of expression and by the induction of a significant host inflammatory response. Third-generation or “helper-dependent” adenoviral vectors have achieved prolonged recombinant gene expression in liver and muscle with minimal associated inflammation; however, they have never been tested for vascular gene transfer. Methods and Results— We constructed a helper-dependent adenoviral vector expressing rabbit urokinase plasminogen activator (HD-AduPA). HD-AduPA was compared, in a rabbit model of carotid gene transfer, with a first-generation adenovirus, also expressing rabbit uPA (FG-AduPA). uPA expression and vector DNA were measured in arteries harvested from 3 to 56 days after gene transfer. Vector-specific mRNA, vascular inflammation, and neointimal formation were assessed 14 days after gene transfer. uPA expression was lost, and vector DNA declined rapidly in arteries infused with FG-AduPA. In contrast, uPA expression and vector DNA persisted in HD-AduPA arteries for ≥56 days, with stable expression from 14 to 56 days. Increased uPA expression in HD-AduPA arteries was accompanied by high levels of vector-specific uPA mRNA. Moreover, HD-AduPA arteries had significantly less inflammation and neointimal formation than FG-AduPA arteries. Conclusions— Helper-dependent adenoviral vectors can stably express a therapeutic gene in the vascular wall for ≥8 weeks, with minimal associated inflammation. Helper-dependent adenoviral vectors will be useful agents for vascular gene transfer and gene therapy.
Cimetidine and Cryptic `Dyspepsia Meckeli'
Authors: Harry P. Selker
Journal: JAMA (1983)

To the Editor.—  Although cimetidine is widely used in the treatment of peptic disease, little attention has been given to its use in the treatment of Meckel's diverticuli. 1,2 Recently, we cared for a patient for whom cimetidine was a very helpful diagnostic probe as well as temporary treatment of a cryptic Meckel's diverticulum.  Our patient, a 23-year-old man, experienced sharp, nonradiating infraumbilical pain occurring 15 to 30 minutes after eating and lasting about 45 minutes. He had occult blood in his stool and a microcytic hypochromic anemia of 28%. An upper gastrointestinal (GI) tract series, barium enema examination, and colonoscopy were all unrevealing.  When referred for hospital admission, the results of his physical examination were normal except for a cardiac flow murmur and occult blood in his stool. An abdominal roentgenogram was unremarkable, and sonography yielded a poor study because of excess bowel gas.  The clinical impression was that
Association of cytotoxin production and neutrophil activation by strains of Helicobacter pylori isolated from patients with peptic ulceration and chronic gastritis.
Authors: Q B Zhang, I M Nakashabendi, M S Mokhashi, J B Dawodu, C G Gemmell, R I Russell
Journal: Gut (1996)

Helicobacter pylori is associated with neutrophil infiltration within the gastroduodenal mucosa. Neutrophil activation provides a major source of oxygen free radicals, which have been implicated in the pathogenesis of peptic ulceration.To investigate if cytotoxin producing strains of H pylori are associated with the generation of oxidative burst in polymorphonuclear neutrophils (PMNs).76 patients undergoing endoscopy of whom 45 had peptic ulcer and 31 chronic gastritis only were studied.Strains of H pylori were cultured in Brucella broth. After 48 hours, bacteria were harvested by centrifugation and a bacterial suspension prepared as a stimulus for PMN oxidative burst using chemiluminescence. PMNs were prepared from health blood donors. To test the ability of strains to produce cytotoxin, culture supernatants of each were concentrated by polyethylene glycol and tested on cultured Vero cells for intracellular vacuolation.30 of 45 (66.7%) peptic ulcer patients induced cell vacuolation versus nine of 31 (29%) strains from patients with chronic gastritis only (p < 0.01). Cytotoxin positive strains of H pylori regardless of the presence or absence of peptic ulcer displayed an increased induction of respiratory burst in PMNs compared with toxin negative strains from patients with chronic gastritis only (p < 0.05). Among the toxin negative strains, those from patients with peptic ulcer did not show a significant increase of the oxidative burst than those from patients without peptic ulcer (NS).Toxinogenicity of strains of H pylori seems to be correlated with neutrophil respiratory burst and peptic ulceration. The ability of some strains of H pylori to produce cytotoxin and to induce the oxidative burst in neutrophils may be important in the pathogenesis of peptic ulcer disease.
Of Platelets, Their Antagonists, and Transient Cerebral Ischemia
Authors: Donald J. Dalessio
Journal: JAMA (1978)

Call me platelet. Consider the lowly platelet if you will— burdened with an undistinguished name, certainly the least interesting of the formed elements of the blood when viewed adjacent to the ebullient eosinophil, the bristling basophil, and the harlequin polymorphonuclear leukocyte. Yet rather than being merely adequate, to cite the laboratory technician's usual cant, it turns out that the platelet is something of a metabolic furnace. It possesses all of the enzymes of the glycolytic pathway, the pentose shunt, and the citric-acid cycle, besides being capable of protein and lipid synthesis.1,2Platelet functions are equally impressive, including the evolution of clotpromoting activity and the liberation of vasoactive amines that contribute to inflammation.  In a statistical sense, the relationship of transient ischemic attack (TIA) to cerebral infarction is not entirely clear, but to the clinician, it is safe to say that the TIA is a harbinger of a major cerebral
Comments on Dr. Pettey's Article Criticizing the Lambert Treatment for Drug Addictions
Authors: C. C. Wholey
Journal: JAMA (1910)

To the Editor:—  It would appear from a casual reading of Dr. Pettey's article (The Journal, May 14, 1910, p. 1593) that his method of procedure in treating drug addictions is radically opposed to that set forth by Dr. Alexander Lambert (The Journal, Sept. 25, 1909, p. 985). As a matter of fact, the underlying principle and purpose in both treatments are the same. Dr. Pettey's article, on careful analysis, reads not unlike a document designed explain the various steps followed in the Lambert method.  Dr. Pettey lays stress on the fact that he administers the purgatives so that they may act at a time when the paralyzing effect on peristalsis, of the narcotic to which the patient is addicted, is at a minimum. That is, he takes advantage of the habitue's customary absence from his drug during his sleeping hours; when, naturally, peristalsis is being reestablished. Precisely this idea is
A complete theory of psychosis and autism as diametric disorders of social brain must consider full range of clinical syndromes
Authors: Katharine N. Thakkar, Natasha Matthews, Sohee Park
Journal: Behavioral and Brain Sciences (2008)

Abstract We argue that autism and psychosis spectrum disorders cannot be conceptualized as polar extremes of mentalizing ability. We raise two main objections: (1) the autistic-psychotic continuum, as conceptualized by the authors, excludes defining features of schizophrenia spectrum: negative symptoms, which correlate more strongly with mentalizing impairments; and (2) little evidence exists for a relationship between mentalizing ability and positive symptoms.
A New and Validated Clinical Prognostic Model (EPI) for Enteropathy-Associated T-cell Lymphoma
Authors: Laura R. de Baaij, Johannes Berkhof, Jolanda M.W. van de Water, Michal K. Sieniawski, Marijn Radersma, Wieke H.M. Verbeek, Otto J. Visser, Joost J. Oudejans, Chris J.L.M. Meijer, Chris J.J. Mulder, Anne L. Lennard, Saskia A.G.M. Cillessen
Journal: Clinical Cancer Research (2015)

Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma with a poor, though variable prognosis. The International Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma (PIT) have limited predictive value for outcome of EATL. The purpose of this study was to develop and validate a prognostic model for EATL, which can identify high-risk patients who need more aggressive therapy.This retrospective multicenter study was based on 92 patients and included 45 patients diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL prognostic index (EPI) was constructed using the RPART (recursive partitioning and regression trees) procedure. Validation was performed applying the bootstrap method.Three risk groups were distinguished (P < 0.0001): a high-risk group, characterized by the presence of B-symptoms [median overall survival (OS) of 2 months]; an intermediate-risk group, comprising patients without B-symptoms and an IPI score ≥ 2 (7 months); and a low-risk group, representing patients without B-symptoms and an IPI score of 0 to 1 (34 months). Internal validation showed stability of statistical significance and prognostic discrimination. In contrast with the IPI and PIT, the EPI better classified patients in risk groups according to their clinical outcome.Our new, validated, prognostic model EPI accurately predicts survival outcome in EATL and may be used for patient selection for new therapeutic strategies and evaluation of clinical trials.
Molecular structure and transcriptional regulation of the gene for the platelet-derived growth factor alpha receptor in cultured vascular smooth muscle cells.
Authors: Y Kitami, H Inui, S Uno, T Inagami
Journal: Journal of Clinical Investigation (1995)

PDGF has been shown to contribute to hypertrophy in vascular smooth muscle cells (VSMC). PDGF-AA differentially promotes protein synthesis in VSMC from spontaneously hypertensive rats (SHR) but not in those from Wistar-Kyoto rats (WKY). This observation has led us to postulate a role for PDGF alpha receptor (PDGFR-alpha) in the hypertensive hypertrophy of blood vessels. Western and Northern blot analyses demonstrated a high and specific expression of the PDGFR-alpha protein and mRNA in SHR cells but not in WKY cells. To clarify the mechanism of the differential expression of the PDGFR-alpha gene, we isolated the promoter region of the gene. Studies on the promoter functions indicated that this promoter is active in SHR cells but not in WKY cells. The regulatory domain responsible for this difference was narrowed to the sequence between -246 and -139, which enhanced the promoter activity of SHR fivefold over the basal activity. DNase I footprinting and gel-shift assay indicated that this sequence specifically interact with nuclear proteins from VSMC through the binding site for CCAAT/enhancer-binding proteins, and members of the C/enhancer-binding protein family play a significant role in the strain-specific transcription of the PDGFR-alpha gene.
Acute biopsy‐proven lymphocytic myocarditis mimicking Takotsubo cardiomyopathy
Authors: Alida L.P. Caforio, Francesco Tona, Annalisa Vinci, Fiorella Calabrese, Angelo Ramondo, Luisa Cacciavillani, Francesco Corbetti, Loira Leoni, Gaetano Thiene, Sabino Iliceto, Annalisa Angelini
Journal: European Journal of Heart Failure (2009)
INTESTINAL OBSTRUCTION FROM TRAUMATIC RUPTURE OF BLOOD VESSEL
Authors: R. Stewart
Journal: BMJ (1909)

T7HE following case came under my care recently, and X thought it worth recording, owing to the apparently elight injury that caused it., was called on October 18th, 1909, to see a girl aged 13, and found her fully dressed reclining on a coueh by the fire in the tsitting-room of a cottage house.She looked pale and very thin, but sat up shortly after I entered.The pulse was 96, temperature normal.She was suffering from nausea.The
No increase in Australia's illicit tobacco trade is seen after plain packs are introduced
Authors: J. Wise
Journal: BMJ (2015)

No increase has been seen in illicit or contraband tobacco use in Sydney since Australia introduced plain packaging legislation, researchers say.

The study, presented this week at the annual scientific meeting of the Thoracic Society for Australia and New Zealand, was based on two surveys of discarded cigarette packs that were carried out 12 months apart in Sydney.1

Australia brought in plain packaging of tobacco products alongside larger, graphic health …
Inhibition of the expression of hepatitis A and B viruses (HAV and HBV) proteins by interferon in a human hepatocarcinoma cell line (PLC/PRF/5)
Authors: Pascale Berthillon, Jean-Marc Crance, Françoise Leveque, Alain Jouan, Marie-Anne Petit, Robert Deloince, Christian Trepo
Journal: Journal of Hepatology (1996)
Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease
Authors: Kim Midwood, Sandra Sacre, Anna M Piccinini, Julia Inglis, Annette Trebaul, Emma Chan, Stefan Drexler, Nidhi Sofat, Masahide Kashiwagi, Gertraud Orend, Fionula Brennan, Brian Foxwell
Journal: Nature Medicine (2009)
Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia
Authors: N. Tarrier, L. Yusupoff, C. Kinney, E. McCarthy, A. Gledhill, G. Haddock, J. Morris
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To investigate whether intensive cognitive behaviour therapy results in significant improvement in positive psychotic symptoms in patients with chronic schizophrenia. <b>Design:</b> Patients with chronic schizophrenia were randomly allocated, stratified according to severity of symptoms and sex, to intensive cognitive behaviour therapy and routine care, supportive counselling and routine care, and routine care alone. <b>Setting:</b> Adjunct treatments were carried out in outpatient clinics or in the patient9s home. <b>Subjects:</b> 87 patients with persistent positive symptoms who complied with medication; 72 completed treatment. <b>Outcome measures:</b> Assessments of positive psychotic symptoms before treatment and 3 months after treatment. Number of patients who showed a 50% or more improvement in symptoms. Exacerbation of symptoms and rates of readmission to hospital. <b>Results:</b> Significant improvements were found in the severity (F=5.42, df =2,86; P=0.006) and number (F=4.99, df=2,86; P=0.009) of positive symptoms in those treated with cognitive behaviour therapy. The supportive counselling group showed a non-significant improvement. Significantly more patients treated with cognitive behaviour therapy showed an improvement of 50% or more in their symptoms (χ<sup>2</sup>=5.18, df=1; P=0.02). Logistic regression indicated that receipt of cognitive behaviour therapy results in almost eight times greater odds (odds ratio 7.88) of showing this improvement. The group receiving routine care alone also experienced more exacerbations and days spent in hospital. <b>Conclusions:</b> Cognitive behaviour therapy is a potentially useful adjunct treatment in the management of patients with chronic schizophrenia.
Hazel Mary Egan (nee Phillips)
Authors: E. Egan
Journal: BMJ (2010)

After less than two years as a senior house officer, Hazel Mary Phillips left for Nigeria to become the first doctor at the 100-bed Mbaise Hospital in Eastern Region. Such was the anticipation for the arrival of the first formal medical care in the region that she was greeted by a queue of an estimated 2000 patients who had travelled enormous distances seeking her attention.

Each morning, triage was performed by Hazel and one of the nursing nuns walking the length of the queue. Following rapid assessment, the most urgent were directed into the hospital, where Hazel and her team provided whatever medical, surgical, anaesthetic, and obstetric treatment …
North Korean children ravaged by poor nutrition
Authors: S. Gottlieb
Journal: BMJ (1999)

A generation of malnourished North Korean children is at risk of sustaining lifelong physical impairment as disease and years of starvation take their toll, according to international relief workers in North Korea.

The scale of the impending disaster was revealed in a study conducted by international aid agencies, which details the devastation wrought by more than five years of severe food shortages in North Korea and a near total breakdown in the public health system.

Almost two thirds of North …
Vitamin D for your patients with chronic hepatitis C?
Authors: Adeeb H. Rahman, Andrea D. Branch
Journal: Journal of Hepatology (2012)

Vitamin D is increasingly becoming recognized as an important physiological regulator with pleiotropic functions outside of its classical role in skeletal homeostasis. A growing body of clinical evidence highlights the prevalence and risks of vitamin D deficiency in patients suffering from chronic hepatitis C infection, and vitamin D supplementation has been proposed as an adjunct to current standards of care. This review considers the experimental evidence for the anti-inflammatory, antifibrotic and antiviral effects of vitamin D, and discusses the therapeutic potential of vitamin D supplementation to protect against liver disease progression and improve responses to treatment.
Recurrent Exon Shuffling Between Distant P-Element Families
Authors: Danielle Nouaud, Hadi Quesneville, Dominique Anxolabéhère
Journal: Molecular Biology and Evolution (2003)

Two independent stationary P-related neogenes had been previously described in the Drosophila obscura species group and in the Drosophila montium species subgroup. In Drosophila melanogaster, P-transposable elements can encode an 87 kDa transposase and a 66 kDa repressor, but the P-neogenes have only conserved the capacity to encode a 66 kDa repressor-like protein specified by the first three exons. We have previously analyzed the genomic modifications associated with the transition of a P-element into the montiumP-neogene, the coding capacity of which has been conserved for around 20 Myr ( Nouaud, D., and D. Anxolabéhère. 1997. Mol. Biol. Evol. 14:1132–1144). Here we show that the P-neogene of some species of the montium subgroup presents a new structure involving the capture of an additional exon from a very distant P-element subfamily. This additional exon is inserted either upstream or downstream of the first exon of the P-neogene. As a result of alternative splicing, these modified neogenes can produce, in addition to the repressor-like protein, a new protein which differs only by the NH2-terminal region. We hypothesize that this protein diversity within an organism results in a functional diversification due to the selective advantage associated with the domestication of the P-neogene in these species. Moreover, the autonomous P-element which provides the additional exons is still present in the genome. Its nucleotide sequence is more than 45% distant from the previously defined P-type element (M-type, O-type, T-type) and defines a new P-type element subfamily referred to as the K-type.
Physicians Aim to KO Boxers' Injuries; Focus on Eyes as Title Bout Nears
Authors: Marsha F. Goldsmith
Journal: JAMA (1987)

"FIGHTERS FIGHT because it's what we do best, when we're allowed to do it... I assume the risk factor." That's Sugar Ray Leonard, writing in a recent<i>USA Weekend</i>article titled "Why the ring is worth the risk." Leonard, who seeks to gain the World Boxing Council middleweight championship on April 6 from the unbeaten-in-11-years Marvelous Marvin Hagler, says he will enter the ring sure of success and without concern for his future eyesight, despite having suffered severe retinal damage as a result of previous bouts. Several ophthalmologists are somewhat less optimistic. It's not that those interviewed by MEDICAL NEWS &amp; PERSPECTIVES have any special knowledge about the successful repair of Leonard's detached retina in the left eye and a retinal tear in the right—his own ophthalmic surgeon, Ronald Michaels, MD, of Wilmer Eye Institute at Johns Hopkins University School of Medicine, Baltimore, was not permitted by Leonard's attorney to
Isolated perfused rabbit lung: a critical appraisal.
Authors: R W Niemeier
Journal: Environmental Health Perspectives (1976)

The isolated perfused lung (IPL), when compared to available in vitro and in vivo pulmonary systems, is a preparation that fulfills a majority of the ideal criteria for studying metabolism, binding and/or physiological response to xenobiotics. The IPL is an exceptionally useful method when there is a need for concurrent administration of multiple agents in different physical forms. Various details such as physiological and biochemical parameters and the construction of a small animal tracheal valve system are discussed.
Enhanced expression of ephrins and thrombospondins in the dermis of patients with early diffuse systemic sclerosis
Authors: J Avouac, M Clemessy, J M Gasc, B Ruiz, M C Vacher-Lavenu, J Wipff, A Kahan, C Boileau, P Corvol, Y Allanore
Journal: Annals of the Rheumatic Diseases (2010)

Ephrins have emerged as essential regulators of angiogenesis and thrombospondins are inhibitors of angiogenesis and strong promoters of fibrosis that are both involved in systemic sclerosis (SSc). Our aim was to analyse the expression of ephrins and thrombospondins concomitant to VEGF pathway assessment in skin specimens and dermal cultured fibroblasts from patients with SSc.

Skin biopsies were obtained from 8 patients with early diffuse cutaneous subset. In all patients, biopsies were taken from both clinically involved and non-involved skin. Controls …