tbuckley/cabot-search huggingface dataset:
Identification of carcinoembryonic antigen-producing cells circulating in the blood of patients with colorectal carcinoma by reverse transcriptase polymerase chain reaction.
Authors: S Jonas, S Windeatt, A O-Boateng, C Fordy, T G Allen-Mersh
Journal: Gut (1996)

Application of the reverse transcriptase polymerase chain reaction (RT-PCR) to identification of circulating tumour cells in colorectal cancer.To assess whether circulating malignant cells in patients with colorectal liver metastasis could be identified by RT-PCR recognition of mRNA coding for the tumour marker carcinoembryonic antigen (CEA).A total of 31 with colorectal liver metastases and 22 no-cancer controls.Specific cDNA primers for CEA transcripts were used to apply RT-PCR to tissue biopsy specimens, colon carcinoma cell lines, and peripheral blood samples from patients with colorectal liver metastases. A strongly CEA-expressive HT115 colorectal carcinoma cell line was used to spike blood samples from no-cancer control subjects.The limit for detection of CEA cDNA by Southern blotting using HT115 cells was 50 cells per 14 ml of spiked blood. There was a significant difference (p = 0.007) in RT-PCR positive expression between patients with liver metastasis (26/31) compared with controls (5/22). There was no significant relation between the prevalence of CEA cDNA amplification and serum CEA level or metastasis volume in patients with liver metastasis.This is the first study to suggest that identification of circulating colorectal cancer cells using RT-PCR for detection of CEA cDNA is feasible.
Effect of primary-care spirometry on the diagnosis and management of COPD
Authors: P. P. Walker, P. Mitchell, F. Diamantea, C. J. Warburton, L. Davies
Journal: European Respiratory Journal (2006)

Primary-care spirometry has been promoted as a method of facilitating accurate diagnosis of chronic obstructive pulmonary disease (COPD). The present study examined whether improving rates of diagnosis lead to improvements in pharmacological and nonpharmacological management. From 1999 to 2003, the current authors provided an open-access spirometry and reversibility service to a local primary-care area, to which 1,508 subjects were referred. A total of 797 (53%) had pre-bronchodilator airflow obstruction (AFO). Of the subjects who underwent reversibility testing, 19.3% were no longer obstructed post-bronchodilator. The results and records of a subgroup of 235 subjects with post-bronchodilator AFO were examined. Of the 235 subjects, 130 received a new diagnosis, most commonly COPD. The patients with COPD were significantly undertreated before spirometry and testing led to a significant increase in the use of anticholinergics (37 <i>versus</i> 18%), long-acting β-agonists (25 <i>versus</i> 8%) and inhaled steroids (71 <i>versus</i> 52%). More than three quarters of smokers received smoking cessation advice but very few were referred for pulmonary rehabilitation. In conclusion, primary-care spirometry not only increases rates of chronic obstructive pulmonary disease diagnosis, but it also leads to improvements in chronic obstructive pulmonary disease treatment. The use of bronchodilator reversibility testing in this setting may be important to avoid misdiagnosis.
ACE Inhibitors for Patients with Vascular Disease without Left Ventricular Dysfunction — May They Rest in PEACE?
Authors: Bertram Pitt
Journal: New England Journal of Medicine (2004)

Angiotensin-converting–enzyme (ACE) inhibitors are effective in reducing mortality and morbidity from cardiovascular events among patients who have chronic heart failure due to left ventricular systolic dysfunction and in those who have acute myocardial infarction with or without left ventricular systolic dysfunction. ACE inhibitors are also effective in reducing mortality and morbidity from cardiovascular events in high-risk patients with diabetes mellitus as well as those with renal dysfunction. In addition, ACE inhibitors are effective antihypertensive agents, although current data suggest that they are not more effective in reducing mortality and morbidity from cardiovascular events than other classes of antihypertensive agents with . . .
Patellar dislocation and lesions of the patella tendon
Authors: John King
Journal: British Journal of Sports Medicine (2000)

Surgeon at the Royal London Hospital.He has been active for many years in BASEM management and in postgraduate sports medicine education.His special interest is knee surgery and he has published several papers on the subject of jumper's knee and other lesions of the patellar tendon.This review is in two sections covering patellar dislocation and patellar tendinopathy.Anterior knee pain and patellar fractures were not part of the author's brief for the article, while lesions of articular cartilage are to be included in the next paper in the series.There is current interest in the medial patellofemoral ligament and the potential for its reconstruction as a major restraint in preventing lateral displacement. 1This will become a topical consideration alongside the techniques described in the review.The role of the impinging lower pole of the patella in patellar tendinosis is another topical subject under consideration and mentioned in the review.Such concepts appeal to the orthopaedic surgeon because they give mechanical clues to the cause and, by implication, the surgical treatment in these conditions.In practice, the treatments should always be conservative if possible; however, functional deficiency, implying functional rehabilitation as treatment, is much more difficult to quantify.Until our evidence base for treatment is more than just empirical, there is an important message in the article urging treatment of the patient rather than the imaging appearance.
Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis
Authors: Dylan T. Jones, Kanagasabai Ganeshaguru, Robert J. Anderson, Trevor R. Jackson, K. Richard Bruckdorfer, Sylvia Y. Low, Lars Palmqvist, H. Grant Prentice, A. Victor Hoffbrand, Atul B. Mehta, R. Gitendra Wickremasinghe
Journal: Blood (2003)
Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit
Authors: Assunta Senatore, Simona Colleoni, Claudia Verderio, Elena Restelli, Raffaella Morini, Steven B. Condliffe, Ilaria Bertani, Susanna Mantovani, Mara Canovi, Edoardo Micotti, Gianluigi Forloni, Annette C. Dolphin, Michela Matteoli, Marco Gobbi, Roberto Chiesa
Journal: Neuron (2012)

SummaryHow mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies.Highlights•Mutant PrP dysrupts glutamatergic transmission in cerebellar granule neurons (CGNs)•Mutant PrP impairs depolarization-evoked calcium dynamics in CGNs•Mutant PrP binds to the α2δ-1 subunit of voltage-gated calcium channels (VGCCs)•Mutant PrP misfolding and intracellular retention impairs membrane delivery of VGCCs
Associations Between Bipolar Disorder and Other Psychiatric Disorders During Adolescence and Early Adulthood: A Community-Based Longitudinal Investigation
Authors: J G Johnson, P Cohen, J S Brook
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The study investigated cross-sectional and longitudinal associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood. METHOD: Psychiatric interviews were administered to a representative community sample of 717 youths and their mothers in 1983 (mean age of youths=14 years) and again in 1985–1986, and 1991–1993. RESULTS: A wide range of psychiatric disorders co-occurred with bipolar disorder during adolescence and early adulthood. Adolescent anxiety disorders were uniquely associated with increased risk for early adulthood bipolar disorder after adolescent bipolar disorder was accounted for. Manic symptoms during adolescence were associated with increased risk for anxiety and depressive disorders during early adulthood after adolescent anxiety and depressive disorders were accounted for. CONCLUSIONS: Adolescents with anxiety disorders may be at increased risk for bipolar disorder or clinically significant manic symptoms during early adulthood. Adolescents with manic symptoms may be at increased risk for anxiety and depressive disorders during early adulthood.
Altered Metabolism of LDL in the Arterial Wall Precedes Atherosclerosis Regression
Authors: Emil D. Bartels, Christina Christoffersen, Marie W. Lindholm, Lars B. Nielsen
Journal: Circulation Research (2015)

Rationale: Plasma cholesterol lowering is beneficial in patients with atherosclerosis. However, it is unknown how it affects entry and degradation of low-density lipoprotein (LDL) particles in the lesioned arterial wall. Objective: We studied the effect of lipid-lowering therapy on LDL permeability and degradation of LDL particles in atherosclerotic aortas of mice by measuring the accumulation of iodinated LDL particles in the arterial wall. Methods and Results: Cholesterol-fed, LDL receptor–deficient mice were treated with either an anti-Apob antisense oligonucleotide or a mismatch control antisense oligonucleotide once a week for 1 or 4 weeks before injection with preparations of iodinated LDL particles. The anti - Apob antisense oligonucleotide reduced plasma cholesterol by ≈90%. The aortic LDL permeability and degradation rates of newly entered LDL particles were reduced by ≈50% and ≈85% already after 1 week of treatment despite an unchanged pool size of aortic iodinated LDL particles. In contrast, the size, foam cell content, and aortic pool size of iodinated LDL particles of aortic atherosclerotic plaques were not reduced until after 4 weeks of treatment with the anti-Apob antisense oligonucleotide. Conclusions: Improved endothelial barrier function toward the entry of plasma LDL particles and diminished aortic degradation of the newly entered LDL particles precede plaque regression.
Fetal Deaths Related to Maternal Injury
Authors: H B Weiss, T J Songer, A Fabio
Journal: JAMA (2001)

ContextMaternal and fetal trauma is an important cause of adverse fetal outcomes. However, systematic exclusion from US injury surveillance programs of even the most severe outcome, fetal/neonatal death, has led to a lack of understanding about frequency, causes, and prevention.ObjectiveTo determine the rate of traumatic fetal deaths reported in state fetal death registries and the types of trauma and physiologic diagnoses associated with these deaths.Design and SettingRetrospective descriptive study of fetal death certificates from 1995 through 1997 obtained from 16 states, which accounted for 55% of US live births and approximately 15 000 fetal death registrations per year.Main Outcome MeasureRate of fetal injury deaths, based on fetal death certificates coded with an underlying cause of death due to maternal injury at 20 weeks' gestation or later, by cause.ResultsDuring the 3-year study period, 240 traumatic fetal injury deaths were identified (3.7 fetal deaths per 100 000 live births). Motor vehicle crashes were the leading trauma mechanism (82% of cases; 2.3 fetal deaths per 100 000 live births), followed by firearm injuries (6% of cases) and falls (3% of cases). In 3 states, reported crash-related fetal deaths exceeded that of crash-related infant deaths. Placental injury was mentioned in 100 cases (42%) and maternal death was noted in 27 cases (11%). A peak rate of 9.3 fetal deaths per 100 000 live births was observed among 15- to 19-year-old women.ConclusionsMotor vehicle crashes are the leading cause of fetal deaths related to maternal trauma. Improved tracking of traumatic fetal injury deaths is important to stimulate and guide research and efforts to reduce the risks to women and fetuses from injury during pregnancy.
Phylogeny of the Bovidae (Artiodactyla, Mammalia), based on mitochondrial ribosomal DNA sequences.
Authors: J Gatesy, D Yelon, R DeSalle, E S Vrba
Journal: Molecular Biology and Evolution (1992)

Portions of the 12S and 16S mitochondrial ribosomal genes for 16 species representing nine tribes in the mammal family Bovidae were compared with six previously published orthologous sequences. Phylogenetic analysis of variable nucleotide positions under different constraints and weighting schemes revealed no robust groupings among tribes. Consensus trees support previous hypotheses of monophyly for four clades, including the traditional subfamily Bovinae. However, the basal diversification of bovid tribes, which was largely unresolved by morphological, immunodiffusion, allozyme, and protein sequence data, remains unresolved with the addition of DNA sequence data. The intractability of this systematic problem is consistent with a rapid radiation of the major bovid groups. Several analyses of our data show that monophyly of the Bovidae, which was weakly supported by previous morphological and molecular work, is questionable.
Effects of enalaprilat on venoconstriction to norepinephrine: role of prostaglandins
Authors: T Dzeka
Journal: Cardiovascular Research (2003)

Objective: Most patients with cardiovascular disease continue to receive both aspirin and an angiotensin-converting enzyme (ACE) inhibitor. This is despite the fact that ACE inhibition also inhibits the enzyme kininase II and leads to accumulation of bradykinin which increases prostaglandins. We hypothesized that in normal veins, vasodilator prostaglandins contribute significantly to ACE inhibitor dilation of norepinephrine-induced venoconstriction, and this would be blocked by cyclooxygenase inhibition. Methods: The study was performed using the in vivo dorsal hand vein technique for measuring vascular responses directly. Venoconstriction to norepinephrine infusions (0.5–1024 ng/min) was assessed in eight normal subjects (46±5 years, mean±S.E.M.) during coinfusion of saline in one hand (control) and enalaprilat (1000 μg/min) in the contralateral hand. On a second morning (7±1 days apart, mean±S.E.M., random order), the same procedure was repeated with indomethacin (3 μg/min) coinfusion in both hands. Results: Enalaprilat shifted the norepinephrine dose–response curve to the right (P = 0.024) and increased the norepinephrine log ED50 (dose required to cause 50% venoconstriction) from 1.70±0.08 to 2.31±0.11 log ng/min (P = 0.001). Indomethacin shifted the norepinephrine dose–response curve to the left (P = 0.018) and decreased the norepinephrine log ED50 from 1.70±0.08 to 1.09±0.18 log ng/min (P = 0.002). In the presence of indomethacin, enalaprilat caused only a small but significant increase in the norepinephrine log ED50, from 1.09±0.18 to 1.29±0.18 log ng/min (P = 0.041). Conclusions: The results suggest that vasodilator prostaglandins contribute significantly to the attenuation of sympathetic venoconstriction by enalaprilat. This may have clinical relevance in patients receiving aspirin and ACE inhibitors in the setting of increased sympathetic activity.
The Hypereosinophilic Syndrome Revisited
Authors: Florence Roufosse, Elie Cogan, Michel Goldman
Journal: Annual Review of Medicine (2003)

Clinical and biological features of patients with the idiopathic hypereosinophilic syndrome (HES) are heterogeneous. Recent evidence suggests at least two distinct underlying hematological disorders involving myeloid and lymphoid cells, respectively. We therefore suggest that the term idiopathic should be abandoned in the classification of HES. This review defines the “myeloproliferative” and “lymphocytic” variants of the HES and addresses the management of each variant, focusing on diagnosis and treatment of the newly identified lymphocytic variant.
Effect of Mechanical Ventilation on Inflammatory Mediators in Patients With Acute Respiratory Distress Syndrome
Authors: V. Marco Ranieri, Peter M. Suter, Cosimo Tortorella, Renato De Tullio, Jean Michel Dayer, Antonio Brienza, Francesco Bruno, Arthur S. Slutsky
Journal: JAMA (1999)

DISTRESSsyndrome (ARDS) is a clinical syndrome characterized by severe hypoxemia, stiff lungs, and decreased respiratory system compliance.Early ARDS is characterized by acute and diffuse endothelial and epithelial injury termed diffuse alveolar damage, 1 which leads to increased vascular permeability with protein-rich exudative edema.Although originally thought to be relatively homogeneous, a number of recent studies have highlighted the marked heterogeneity of the pathological process with consolidation in the dependent regions of the lung and relatively normal aeration of the nondependent regions. 2,3espite apparent improvement in management and outcome of ARDS, the mortality rate of ARDS remains high, ranging from 35% to 65%. 4,5echanical ventilation delays mortality in many patients with acute respiratory failure and is used to maintain adequate systemic oxygenation and to rest the respiratory muscles.However, over the last 2 decades, it has become evident that mechanical ventilation
Injection sclerotherapy for oesophageal varices: a prospective randomised trial of different treatment schedules.
Authors: D Westaby, W M Melia, B R Macdougall, J E Hegarty, R Williams
Journal: Gut (1984)

A prospective randomised study to compare the efficacy and complications of injection sclerotherapy carried out at intervals of one week and three weeks up to the time obliteration of varices was achieved, was undertaken in 55 patients (48 cirrhosis, six portal vein thrombosis, one nodular regenerative hyperplasia). The number of courses of injection required for obliteration of the varices was not different in the two groups and despite a shorter time scale for obliteration in the weekly treated patients the frequency with which further episodes of bleeding occurred before that was not significantly less. Mucosal ulceration during the period required for obliteration was observed at endoscopy more frequently in the weekly treated patients but was not associated with a greater frequency of postinjection pain, dysphagia or of long term stricture formation.
Effect of Secreted Bacteroides Proteases on Human Intestinal Brush Border Hydrolases
Authors: Stan P. Riepe, Jeffrey Goldstein, David H. Alpers
Journal: Journal of Clinical Investigation (1980)

Selected bacteroides species secreted various amounts of protease and glycosidase into their growth medium. Bacteroides vulgatus, distasonis, and ovatus secreted the most (31-60% of total). The secreted protease was similar in action to the protease within the organism, in that it had a broad pH optimum of 6-9, a Km app. for casein of 0.1 μM, and was inhibited by benzamidine, phenylmethylsulfonyl fluoride, diisopropylfluorophosphate (DIFP), and by an elastase inhibitor, Ac(Ala)3AlaCH2Cl.
N-Myc Downstream-Regulated Gene 4 ( NDRG4 ): A Candidate Tumor Suppressor Gene and Potential Biomarker for Colorectal Cancer
Authors: Veerle Melotte, Marjolein H. F. M. Lentjes, Sandra M. van den Bosch, Debby M. E. I. Hellebrekers, Joep P. J. de Hoon, Kim A. D. Wouters, Kathleen L. J. Daenen, Iris E. J. M. Partouns-Hendriks, Filip Stessels, Joost Louwagie, Kim M. Smits, Matty P. Weijenberg, Silvia Sanduleanu, Carolina A. J. Khalid-de Bakker, Frank A. Oort, Gerrit A. Meijer, Daisy M. A. E. Jonkers, James G. Herman, Adriaan P. de Bruïne, Manon van Engeland
Journal: JNCI Journal of the National Cancer Institute (2009)

Identification of hypermethylated tumor suppressor genes in body fluids is an appealing strategy for the noninvasive detection of colorectal cancer. Here we examined the role of N-Myc downstream-regulated gene 4 (NDRG4) as a novel tumor suppressor and biomarker in colorectal cancer.NDRG4 promoter methylation was analyzed in human colorectal cancer cell lines, colorectal tissue, and noncancerous colon mucosa by using methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing. NDRG4 mRNA and protein expression were studied using real-time-PCR and immunohistochemistry, respectively. Tumor suppressor functions of NDRG4 were examined by colony formation, cell proliferation, and migration and invasion assays in colorectal cancer cell lines that were stably transfected with an NDRG4 expression construct. Quantitative methylation-specific PCR was used to examine the utility of NDRG4 promoter methylation as a biomarker in fecal DNA from 75 colorectal cancer patients and 75 control subjects. All P values are two-sided.The prevalence of NDRG4 promoter methylation in two independent series of colorectal cancers was 86% (71/83) and 70% (128/184) compared with 4% (2/48) in noncancerous colon mucosa (P < .001). NDRG4 mRNA and protein expression were decreased in colorectal cancer tissue compared with noncancerous colon mucosa. NDRG4 overexpression in colorectal cancer cell lines suppressed colony formation (P = .014), cell proliferation (P < .001), and invasion (P < .001). NDRG4 promoter methylation analysis in fecal DNA from a training set of colorectal cancer patients and control subjects yielded a sensitivity of 61% (95% confidence interval [CI] = 43% to 79%) and a specificity of 93% (95% CI = 90% to 97%). An independent test set of colorectal cancer patients and control subjects yielded a sensitivity of 53% (95% CI = 39% to 67%) and a specificity of 100% (95% CI = 86% to 100%).NDRG4 is a candidate tumor suppressor gene in colorectal cancer whose expression is frequently inactivated by promoter methylation. NDRG4 promoter methylation is a potential biomarker for the noninvasive detection of colorectal cancer in stool samples.
Prevalence of Behcet's disease in an Arab community in Israel
Authors: L Jaber
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To evaluate the prevalence of Behçet9s disease (BD) in an Israeli Arab town (Taibe). Methods: Questionnaires about the occurrence and prevalence of aphthous ulcers were distributed randomly to the parents of children attending a paediatric centre in Taibe. The parents were asked whether they or any of their children aged between 10 and 20 years had recurrent aphthous stomatitis. Any who had had more than four aphthous episodes (each episode lasting more than seven days) during the previous year were invited for an extensive interview and examination by a rheumatologist or a paediatrician. Results: A total of 4876 subjects were included in this survey, of whom six (one male, five female) were diagnosed as having BD. Of these six, two were siblings (a brother and a sister). Five had skin lesions, four had visual involvement, and all had genital ulcers and joint symptoms; one in two patients had a positive pathergy test. Five of the six carried HLA-B5 antigens. The results showed a prevalence of 12/10 000 in Taibe. Conclusion: The prevalence of BD found in our survey is high and concurs with that found in other Mediterranean and Asian countries.