tbuckley/cabot-search huggingface dataset:
Inotropic effect, binding properties, and calcium flux effects of the calcium channel agonist CGP 28392 in intact cultured embryonic chick ventricular cells.
Authors: S Laurent, D Kim, T W Smith, J D Marsh
Journal: Circulation Research (1985)

CGP 28392 is a recently described dihydropyridine derivative with positive inotropic properties. To study the mechanism of action of this putative calcium channel agonist, we have related the effects of CGP 28392 on contraction (measured with an optical video system) and radioactive calcium uptake to ligand-binding studies in cultured, spontaneously beating chick embryo ventricular cells. CGP 28392 produced a concentration-dependent increase in amplitude and velocity of contraction (EC50 = 2 X 10(-7) M; maximum contractile effect = 85% of the calcium 3.6 mM response). Nifedipine produced a shift to the right of the concentration-effect curve for CGP 28392 without decreasing the maximum contractile response, suggesting competitive antagonism (pA2 = 8.3). Computer analysis of displacement of [3H]nitrendipine binding to intact heart cells by unlabeled CGP 28392 indicated a KD = 2.2 +/- 0.95 X 10(-7) M, in good agreement with the EC50 for the inotropic effect. CGP 28392 increased the rate of radioactive calcium influx (+39% at 10 seconds) without altering beating rate, while nifedipine decreased radioactive calcium influx and antagonized the CGP 28392-induced increase in calcium influx. Our results indicate that, in intact cultured myocytes, CGP 28392 acts as a calcium channel agonist and competes for the dihydropyridine-binding site of the slow calcium channel. In contrast to calcium channel blockers, CGP 28392 increases calcium influx and enhances the contractile state.
ALZHEIMER'S DISEASE—THE SO-CALLED JUVENILE TYPE
Authors: George A. Jervis, Samuel E. Soltz
Journal: American Journal of Psychiatry (1936)

1. Alzheimer's disease is to be considered up to the present as a definite clinico-pathological entity. Its pathology is not pathognomonic, the clinical data being therefore essential for the classification of cases into Alzheimer's disease. 2. The subdivision into a juvenile form of Alzheimer's disease does not seem as yet justified in its material presentation. Of 10 cases, reported in the literature, occurring at an age prior to the presenile stage, seven presented either insufficient pathological and clinical elements or typical pathology but non-characteristic clinical symptoms. Their inclusion in the group of Alzheimer's disease, cannot therefore be made without unduly stretching the original conception of the malady. 3. In addition to the case described in this presentation, three others have been reported in the literature of typical Alzheimer's disease from both the pathological and the clinical aspects, in which the age limit varied at the most between 37 and 41 years. The narrow variation of the age limit and the small number of these cases justifies, we feel, our conservative attitude toward the creation of a nosological variety termed "juvenile form of Alzheimer's disease." 4. The doubt cast on the generally accepted conception of Alzheimer's disease as a presenile psychosis, doubt based upon the occurrence precisely of the disease in its so-called "juvenile form" is therefore somewhat premature. Additional evidence is needed for such a conclusion. 5. A report of a case, in which all clinical and pathological data exclusive of the age, correspond to Alzheimer's disease, illustrates the expressed ideas.
Cancer Among Epileptic Patients Exposed to Anticonvulsant Drugs
Authors: J. H. Olsen, J. D. Boice, J. P. A. Jensen, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1989)

Cancer incidence among 8,004 patients hospitalized for epilepsy between 1933 and 1962 in the Filadelfia treatment community in Denmark was compared to that of the general population. Patients received powerful and prolonged treatment with phenobarbital, phenytoin, and other anticonvulsants. This new survey extends the follow-up from 1976 through 1984. Among 7,864 patients with epilepsy not known to have received radioactive Thorotrast, record linkage with national cancer incidence files identified 789 cancers, compared to 664 expected [relative risk (RR) = 1.19; 95% confidence interval = 1.11–1.27]. Significant risks were found for cancers of the brain and central nervous system (RR = 5.7; n = 118) and the lung (RR = 1.4; n = 106). The excess numbers of brain cancer were concentrated within 10 years of hospitalization (RR = 20.7; n = 80) and decreased significantly over time, which suggests that brain tumors account for the seizure disorder and are not due to phenobarbital exposure as suggested by some epidemiologic studies. No overall risk was apparent when brain cancers were excluded (RR = 1.03). Because bladder cancer was significantly decreased (RR = 0.6; n = 18), the excess risk of lung cancer may not have been related to the "anecdotal" heavy smoking reported among confined groups of epileptic patients in the early years of the study period. The incidence of malignant melanoma was also significantly low (RR = 0.5; n = 7), which suggested limited exposure to sunlight among confined patients. The risk of non-Hodgkin's lymphoma was increased, but not significantly (RR = 1.4; n = 16), which is interesting in view of previous reports suggesting an association with phenytoin. Overall, these data provide little evidence that phenobarbital and phenytoin are carcinogenic to humans, but the excess risks of lung cancer and non-Hodgkin's lymphoma among epileptic patients in our study deserve further evaluation.
Intake of Dairy Products, Calcium, and Vitamin D and Risk of Breast Cancer
Authors: Myung-Hee Shin, Michelle D Holmes, Susan E Hankinson, Kana Wu, Graham A Colditz, Walter C Willett
Journal: JNCI Journal of the National Cancer Institute (2002)

Laboratory data suggest that calcium and vitamin D, found at high levels in dairy products, might reduce breast carcinogenesis. However, epidemiologic studies regarding dairy products and breast cancer have yielded inconsistent results. We examined data from a large, long-term cohort study to evaluate whether high intake of dairy products, calcium, or vitamin D is associated with reduced risk of breast cancer.We followed 88 691 women in the Nurses' Health Study cohort from the date of return of their food-frequency questionnaire in 1980 until May 31, 1996. Dietary information was collected in 1980 and updated in 1984, 1986, 1990, and 1994. We identified 3482 women (premenopausal = 827, postmenopausal = 2345, and uncertain menopausal status = 310) with incident invasive breast cancer. We used pooled logistic regression to estimate multivariable relative risks (RRs) using 2-year time increments. The RRs and 95% confidence intervals (CIs) were calculated for each category of intake compared with the lowest intake group. All statistical tests were two-sided.Intakes of dairy products, calcium, or vitamin D were not statistically significantly associated with breast cancer risk in postmenopausal women. In premenopausal women, however, consumption of dairy products, especially of low-fat dairy foods and skim/low-fat milk, was inversely associated with risk of breast cancer. The multivariable RRs comparing highest (>1 serving/day) and lowest (<or=3 servings/month) intake categories were 0.68 (95% CI = 0.55 to 0.86) for low-fat dairy foods and 0.72 (95% CI = 0.56 to 0.91) for skim/low-fat milk. Dairy calcium (>800 mg/day versus <or=200 mg/day; RR = 0.69, 95% CI = 0.48 to 0.98), total vitamin D (>500 IU/day versus <or=150 IU/day; RR = 0.72, 95% CI = 0.55 to 0.94), and lactose (quintile 5 versus quintile 1; RR = 0.68, 95% CI = 0.54 to 0.86] also had inverse associations with premenopausal breast cancer risk. By taking into account supplemental calcium and vitamin D intake, we found that association with calcium was due mainly to dairy sources whereas the association with vitamin D may be independent of dairy intake.We found no association between intake of dairy products and breast cancer in postmenopausal women. Among premenopausal women, high intake of low-fat dairy foods, especially skim/low-fat milk, was associated with reduced risk of breast cancer. Similar inverse associations were seen with components (calcium and vitamin D) of dairy foods, but their independent associations with breast cancer are difficult to distinguish.
The neuropeptide neuromedin U promotes inflammation by direct activation of mast cells
Authors: Maiko Moriyama, Takahiro Sato, Hiromasa Inoue, Satoru Fukuyama, Hitoshi Teranishi, Kenji Kangawa, Tatsuhiko Kano, Akihiko Yoshimura, Masayasu Kojima
Journal: The Journal of Experimental Medicine (2005)

Neuromedin U (NMU) is a neuropeptide that is expressed in the gastrointestinal tract and central nervous system. NMU interacts with two G protein–coupled receptors, NMU-R1 and NMU-R2. Whereas NMU-R2 localizes predominantly to nerve cells, NMU-R1 is expressed in peripheral tissues including lymphocytes and monocytes, suggesting a role of NMU in immunoregulation. However, the functions of NMU in peripheral tissues have not been clarified. In this study, using NMU-deficient mice, we first demonstrated that NMU plays an important role in mast cell-mediated inflammation. Complete Freund's adjuvant-induced mast cell degranulation as well as edema and neutrophil infiltration, which occurred weakly in mast cell–deficient WBB6F1-W/Wv mice, did not occur in NMU-deficient mice. Moreover, intraplantar injection of NMU into paws induced early inflammatory responses such as mast cell degranulation, vasodilation, and plasma extravasation in WT mice but not in WBB6F1-W/Wv mice. NMU-R1 was highly expressed in primary mast cells, and NMU induced Ca2+ mobilization and degranulation in peritoneal mast cells. These data indicate that NMU promotes mast cell–mediated inflammation; therefore, NMU receptor antagonists could be a novel target for pharmacological inhibition of mast cell–mediated inflammatory diseases.
Changes in Airway Dimensions on Computed Tomography Scans of Children with Cystic Fibrosis
Authors: Pim A. de Jong, Yasutaka Nakano, Wim C. Hop, Frederick R. Long, Harvey O. Coxson, Peter D. Paré, Harm A. Tiddens
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

In cystic fibrosis (CF), chronic bacterial infection and inflammation lead to progressive airway wall thickening and lumen dilatation.To quantify airway wall thickening and lumen dilatation in children with CF over a 2-year interval.Children with CF (n = 23) who had two computed tomography (CT) scans (CT(cf1) and CT(cf2)) combined with pulmonary function tests (PFTs), with a 2-year interval between measurements, were compared with control subjects (n = 21) who had one CT (CT(controls)). On cross-sectional cut airway-artery pairs, airway wall area (WA), airway lumen area (LA) and perimeter, and arterial area (AA) were quantified. LA/AA (= marker of bronchiectasis), airway wall thickness (AWT), and WA/AA (= markers of wall thickness) were calculated. CT scans were scored using four different scoring systems. PFTs were expressed as percent predicted.Airway WA-to-AA ratio was 1.45 (p < 0.001) and airway LA-to-AA ratio was 1.92 times higher (p < 0.001) in children with CF compared with age-matched control subjects. LA/AA and WA/AA remained unchanged from CT(cf1) to CT(cf2) and did not increase with age. AWT as a function of airway size increased from CT(cf1) to CT(cf2) by 2% (0.03 mm; p = 0.02). The change in AWT was inversely related to the change in forced expiratory flow between 25 and 75% of expiratory VC (p = 0.002).In CF, quantitative measurements of airways on CT scans show an increased ratio between airway LA and AA and progressive airway wall thickening. Scoring systems show progression of bronchiectasis but unchanged AWT. PFTs remained stable.
Orphan Nuclear Receptor Nur77 Promotes Acute Kidney Injury and Renal Epithelial Apoptosis
Authors: Savithri Balasubramanian, Marcel Jansen, M. Todd Valerius, Benjamin D. Humphreys, Terry B. Strom
Journal: Journal of the American Society of Nephrology (2012)

Nur77 and its family members Nurr1 and Nor-1 are inducible orphan nuclear receptors that orchestrate cellular responses to diverse extracellular signals. In epithelia, Nur77 can act as a potent proapoptotic molecule in response to cellular stress, suggesting a possible role for this nuclear receptor in the tissue response to injury. Here, we found that Nur77 promotes epithelial cell apoptosis after AKI. Injury of proximal tubular epithelial cells rapidly and strongly induced Nur77, Nor-1, and Nurr1 both in vitro and in vivo. After renal ischemia-reperfusion, Nurr77-deficient mice exhibited less apoptosis of tubular epithelial cells and better renal function than wild-type mice. Nur77-mediated renal injury involved a conformational change of Bcl2 and an increase in the protein levels of proapoptotic Bcl-xS. Ligand-activated retinoic acid receptors repressed Nur77 induction and function. Pretreatment of wild-type mice with retinoic acid before renal ischemia-reperfusion blunted the induction of Nur77, conferred protection of renal function, attenuated renal histologic injury, and reduced the expression of epithelial-derived proinflammatory cytokines. Retinoic acid also inhibited hypoxia-mediated induction of proinflammatory cytokines in cultured renal epithelial cells. Results obtained from proximal tubule cultures derived from Nur77-deficient mice suggested that the inhibition of Nur77 expression mediated the renoprotective effects of retinoic acid. In summary, Nur77 promotes epithelial apoptosis after ischemia-reperfusion injury, and retinoic acid-mediated inhibition of Nur77 expression is a promising therapeutic strategy for the prevention of AKI.
CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial
Authors: Viviane Hess, Bengt Glimelius, Philipp Grawe, Daniel Dietrich, György Bodoky, Thomas Ruhstaller, Emilio Bajetta, Piercarlo Saletti, Arie Figer, Werner Scheithauer, Richard Herrmann
Journal: The Lancet Oncology (2008)
Towards a neural basis of auditory sentence processing
Authors: Angela D. Friederici
Journal: Trends in Cognitive Sciences (2002)

Functional dissociations within the neural basis of auditory sentence processing are difficult to specify because phonological, syntactic and semantic information are all involved when sentences are perceived. In this review I argue that sentence processing is supported by a temporo-frontal network. Within this network, temporal regions subserve aspects of identification and frontal regions the building of syntactic and semantic relations. Temporal analyses of brain activation within this network support syntax-first models because they reveal that building of syntactic structure precedes semantic processes and that these interact only during a later stage.
A Genetically Engineered Anti-CD45 Single-Chain Antibody-Streptavidin Fusion Protein for Pretargeted Radioimmunotherapy of Hematologic Malignancies
Authors: Yukang Lin, John M. Pagel, Donald Axworthy, Anastasia Pantelias, Nathan Hedin, Oliver W. Press
Journal: Cancer Research (2006)

Acute myelogenous leukemia (AML) currently kills the majority of afflicted patients despite combination chemotherapy and hematopoietic cell transplantation (HCT). Our group has documented the promise of radiolabeled anti-CD45 monoclonal antibodies (Ab) administered in the setting of allogeneic HCT for AML, but toxicity remains high, and cure rates are only 25% to 30% for relapsed AML. We now show the superiority of pretargeted radioimmunotherapy (PRIT) compared with conventional radioimmunotherapy using a recombinant tetravalent single-chain Ab-streptavidin (SA) fusion protein (scFv(4)SA) directed against human CD45, administered sequentially with a dendrimeric N-acetylgalactosamine-containing clearing agent and radiolabeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic (DOTA)-biotin. The scFv(4)SA construct was genetically engineered by fusing Fv fragments of the human CD45-specific BC8 Ab to a full-length genomic SA gene and was expressed as a soluble tetramer in the periplasmic space of Escherichia coli. The fusion protein was purified to >95% homogeneity at an overall yield of approximately 50% using iminobiotin affinity chromatography. The immunoreactivity and avidity of the fusion protein were comparable with those of the intact BC8 Ab, and the scFv(4)SA construct bound an average of 3.9 biotin molecules out of four theoretically possible. Mouse lymphoma xenograft experiments showed minimal toxicity, excellent tumor-specific targeting of the fusion protein and radiolabeled DOTA-biotin in vivo, marked inhibition of tumor growth, and cured 100% of mice bearing CD45-expressing tumors. These promising results have prompted large-scale cGMP production of the BC8 fusion protein for clinical trials to be conducted in patients with hematologic malignancies.
Nephrotoxicity of Cisplatin Combination Chemotherapy for Thoracic Malignancy Patients with Comorbidities
Authors: K. Sato, S. Watanabe, Y. Saida, M. Okajima, S. Miura, J. Tanaka, H. Kagamu, H. Yoshizawa, I. Narita
Journal: Annals of Oncology (2013)
Defective Recognition of One’s Own Actions in Patients With Schizophrenia
Authors: N Franck, C Farrer, N Georgieff, M Marie-Cardine, J Daléry, T d'Amato, M Jeannerod
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The possibility that delusions of influence could be related to abnormal recognition of one's own actions was investigated in persons with schizophrenia. METHOD: Schizophrenic patients with (N=6) and without (N=18) delusions of influence were compared with normal subjects (N=29) on an action recognition task. The image of a virtual right hand holding a joystick was presented to the subjects through a mirror so that the image was superimposed on their real hand holding a real joystick. Subjects executed discrete movements in different directions. Angular biases and temporal delays were randomly introduced in some trials, such that the movement of the virtual hand departed from the movement executed by the subjects. After each trial, subjects were asked whether the movement they saw was their own. RESULTS: Compared with normal subjects, both patient groups made significantly more recognition errors in trials with temporal delays. In trials with angular biases, the error rate of patients with delusions of influence significantly differed from that of comparison subjects and from that of patients without delusions of influence. CONCLUSIONS: The findings support the hypothesis that delusions of influence are associated with a quantifiable difficulty in correct self-attribution of actions. This difficulty may be related to a specific impairment of a neural action attribution system.
Use of Transfer Impedance Measurements for Clinical Assessment of Lung Mechanics
Authors: KENNETH R. LUTCHEN, ANTHONY SULLIVAN, FREDERIC T. ARBOGAST, BARTOLOME R. CELLI, ANDREW C. JACKSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Respiratory transfer impedance (Ztr) measured using the forced oscillation technique requires virtually no patient cooperation and provides a noninvasive approach for acquiring data reflective of lung mechanics. Also, model analysis of Ztr provides reliable estimates of separate airway and tissue properties (1), but only if data out to 64 Hz are acquired. The current study evaluated the clinical utility of Ztr from 1–80 Hz for assessing the degree and type of impaired lung function. Spirometry and Ztr measurements were made on 37 individuals: 11 healthy subjects and 26 patients with lung disease including chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and sarcoidosis. Over the entire patient group, 12 were also smokers. We first established normal ranges for several Ztr features and model estimated mechanical properties. The COPD and smokers groups showed significant differences in portions of their Ztr spectra from that of the healthy group. Key Ztr spectral features included Ro, the frequency at which the real part of impedance is zero; and Re4, the real part of impedance at 4 Hz. The key model parameter was airway resistance, Raw. We found Raw, Re4, and Ro to be significantly elevated during disease (p < 0.0005) and to significantly decrease with bronchodilator therapy (p < 0.025). Moreover, we found moderate to strong correlations between Ro, Raw, and Re4 versus FVC and Ro versus FEV1. After bronchodilator, changes in Ro, Re4, and Raw were correlated with changes in several spirometric indices. The Ro feature has not been previously evaluated since it is typically above 32 Hz (well above 32 Hz in diseased individuals) and not encompassed in previous clinical studies.
Genome-wide genetic ancestry measurements to predict lung function in European populations
Authors: Jean-Christophe Bérubé, Maxime Lamontagne, Christian Couture, David Nickle, Wim Timens, Dirkje S. Postma, Don D. Sin, Peter D. Paré, Michel Laviolette, Yohan Bossé
Journal: European Respiratory Journal (2013)

To the Editor: 

A number of models have been proposed to predict spirometric lung function using age, sex, height and self-reported ethnicity [1, 2]. These models are particularly important to derive per cent predicted lung function and establish the severity of lung diseases such as chronic obstructive pulmonary disease (COPD) [3]. Compared to self-reported race and/or ethnicity, genetic data can provide more accurate and objective measurements of ancestry and has the potential to alleviate some of the problems related to the lack of consensus on the definition of race and ethnicity worldwide [4]. A recent report suggested that genetically determined ancestry improves predicted lung-function measurements in African Americans [5]. Here, we test whether genetic ancestry derived from genome-wide genotyping data is useful to predict lung function in a diverse European population.

The population used in this study is part of a lung expression quantitative trait loci (eQTL) mapping study [6, 7]. Briefly, research participants were recruited from three academic sites: Laval University (Quebec, QC, Canada), University of British Columbia (Vancouver, BC, Canada), and Groningen University (Groningen, the Netherlands), henceforth referred to as Laval, UBC, and Groningen, respectively. All subjects were genotyped for ∼1.2 million single nucleotide polymorphisms (SNPs) using the Illumina Human1M-Duo BeadChip (Illumina, Inc., San Diego, CA, USA). Subjects from Laval and UBC provided written informed consent and the study was approved by the ethics committees of the respective study sites. At Groningen, the study protocol was consistent with the research code of the University Medical Center Groningen and Dutch national ethical and professional guidelines (“Code of conduct; Dutch federation of biomedical scientific societies”; http://www.federa.org). Prior to the analysis, standard genotyping quality controls and exclusion of patients with disorders that affected lung function (other than COPD) were …