tbuckley/cabot-search huggingface dataset:
Nail dystrophy in chronic sarcoidosis
Authors: N.H. COX, D.J. GAWKRODGER
Journal: British Journal of Dermatology (1988)

We report details of five patients with nail dystrophy associated with sarcoidosis. All had bone cysts in the underlying terminal phalanx and had a chronic course of the disease. Radiological examination is indicated in patients with sarcoidosis and nail dystrophy as bone cysts are frequently asymptomatic.
Effects of Bradykinin on the Systemic and Coronary Vascular Bed of the Intact Dog
Authors: G. M. MAXWELL, R. B. ELLIOTT, G. M. KNEEBONE
Journal: Circulation Research (1962)

Bradykinin, in the circumstances of this study, increased heart rate, cardiac output, and coronary blood flow. Systemic, pulmonary, and coronary vascular resistances decreased; these changes were not entirely due to the decrease in systemic and pulmonary arterial pressures. The changes in myocardial oxygen and carbon dioxide metabolism were mostly related to the increase in coronary blood flow. Bradykinin was found to be associated with a decrease in cardiac efficiency.
Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.
Authors: U Diczfalusy, B F Kase, S E Alexson, I Björkhem
Journal: Journal of Clinical Investigation (1991)

We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to beta-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [3H]prostaglandin F2 alpha to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK C18 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2 alpha metabolite from the Zellweger patient was identified as an omega-oxidized C20-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin F2 alpha metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal beta-oxidation is of major importance for in vivo chain shortening of prostaglandins.
Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
Authors: Akiko Hayashi-Takagi, Manabu Takaki, Nick Graziane, Saurav Seshadri, Hannah Murdoch, Allan J Dunlop, Yuichi Makino, Anupamaa J Seshadri, Koko Ishizuka, Deepak P Srivastava, Zhong Xie, Jay M Baraban, Miles D Houslay, Toshifumi Tomoda, Nicholas J Brandon, Atsushi Kamiya, Zhen Yan, Peter Penzes, Akira Sawa
Journal: Nature Neuroscience (2010)
Ultrasound-guided cutting-needle biopsy for diagnosing pleural disease: Experience in Oxford
Authors: R.J. Hallifax, J.P. Corcoran, H. Rostom, N.M. Hassan, M. Nagendran, A. Manuel, N.M. Rahman
Journal: European Respiratory Journal (2013)

Introduction:  Definitive diagnosis of pleural disease (particularly malignancy) depends upon histological proof obtained via pleural biopsy. Image-guided sampling is now standard practice. Local anaesthetic thoracoscopy has a high diagnostic yield for pleural disease. Thoracoscopy is not always possible in frail patients, if pleural fluid is heavily loculated, or where lung is adherent to the chest wall. Such cases can be converted “on the table” to cutting-needle biopsy.  Aim:  The present study was conducted to determine the diagnostic yield of a physician-lead service in both planned biopsies and cases of failed thoracoscopy.  Methods:  Retrospective review of all ultrasound-guided cutting-needle biopsies performed in the Pleural Unit between January 2010 and November 2012. The histological results were assessed for the yield of pleural tissue.  Results:  A total of 32 biopsies were undertaken. Overall, 29 (90.6%) successfully obtained sufficient tissue for histological diagnosis. 14 of 32 were biopsies conducted after failed thoracoscopy (6.8% of 205 the attempted thoracoscopies): 12/14 (85.7%) obtained sufficient tissue. 8/29 (27.6%) demonstrated pleural malignancy on histology (despite previous negative cytology), while 21/29 (72.4%) were benign. Of the benign cases, six were pleural tuberculosis (TB), two were pleural sarcoidosis and the remaining thirteen were benign pleural thickening/fibrosis. All were “true negatives” (at an average of 17 months of follow-up).  Conclusion:  Ultrasound-guided cutting needle pleural biopsy in the hands of physicians obtains pleural tissue successfully in a high proportion of cases, including those of failed thoracoscopy.
Evolution of ionic channels of biological membranes.
Authors: F Franciolini, A Petris
Journal: Molecular Biology and Evolution (1989)

This paper presents a view of the evolution and phylogenetic distribution of ionic channels of biological membranes. The view is based on the assumptions that ionic channels (1) appeared very early in the history of life, (2) have evolved from a common ancestor, and (3) have been subjected to evolutionary pressure to reach precision and high speed of signaling. We propose that Ca2+ was the intracellular messenger and modulator of the most primitive biological systems, which implies that the first channel to appear may have been a calcium channel. Then, very soon the entire group of potassium channels evolved from the calcium channel to improve the shape of signals and to restore initial conditions. Sodium channels probably appeared relatively late, diversifying from calcium channels in the early metazoan groups. Mainly because Na+ ions do not interfere with cellular metabolism (thus allowing the inward current--and, consequently, the speed of conduction--to be greatly increased), sodium channels probably proved advantageous in the generation of the action potential, and selection replaced calcium channels with sodium channels in this function. Finally, with the acquisition of multicellularity, channels responsible for synaptic transmission appeared. The case of the acetylcholine receptor channel is briefly discussed.
Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing
Authors: Giovanni A Rossi, Andrew A Colin
Journal: European Respiratory Journal (2014)

There is evidence that respiratory viruses play a key role in the development and exacerbation of obstructive respiratory diseases in children. This review attempts to juxtapose the separate profiles and prototypes of pathogenenetic mechanisms represented by the two most common amongst such viruses: respiratory syncytial virus (RSV) and human rhinovirus (HRV). RSV represents the most common agent of severe airway disease in infants and young children, and is predominant in winter months. Large epidemiological studies have revealed an unequivocal relationship between RSV infection and subsequent wheezing into childhood, thought to be related to long-term changes in neuroimmune control of the airways rather than allergic sensitisation. HRV is a highly diverse group of viruses that affect subjects of all ages, is ubiquitous and occurs year-round. In contrast to RSV, infections with HRV cause minimal cytotoxicity but induce a rapid production of cytokines and chemokines with amplification of the inflammatory response. The susceptibility to HRV-induced bronchiolitis and subsequent wheezing appears to be linked to individual predisposition since it is often associated with a family or personal history of asthma/atopy. Thus, RSV probably serves as an “inducer” rather than a “trigger”. Conversely, HRVs seem to serve as a “trigger” rather than an “inducer” in predisposed individuals.
“Sufficient Life Expectancy”: An Amazing Inclusion Criterion in Cancer Phase II-III Trials
Authors: Nicolas Penel, Stéphanie Clisant, Jean-Louis Lefebvre, Antoine Adenis
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: A tremendous change in eligibility criteria has been observed during the past two decades in the majority of clinical trials. The number of eligibility criteria has notably increased and they are more and more factual. They may include the biologic signature of the tumor. For example, some ongoing studies investigating HER or KIT antagonists consider only patients without k-ras or with specific KIT (D816H/V) mutations. In such a context of sophistication of eligibility criteria, the concept of sufficient life expectancy (SLE) appears as an amazing and rather subjective eligibility criterion. With this in mind, we reviewed all the study protocols of phase II or III trials (n 123) carried out in our institution between 1991 and 2008. We assessed how frequently the SLE criterion was requested and which types of studies required it. Eighty-four studies (68%) were phase II trials, and 81 (66%) were industry sponsored. In one study protocol, the SLE criterion coexisted with 51 other eligibility criteria. The primary end points were response rate (86 trials; 70%), survival (19 trials; 16%), and quality-of-life measurements (18 trials; 14%). The most frequent tumors were breast cancers (27 trials; 22%), sarcomas (13 trials; 10%), and colorectal cancers (10 trials; 8%). The SLE criterion was required in 75 of 123 trials (61%). The most frequent SLE cut-offs were 4 and 6 months (24% and 33%, respectively). All these 75 study protocols required both the SLE criteria and a “good performance status.” None of them provided any tool or relevant reference that could enlighten the investigator in properly assessing the SLE. Overall, the SLE criterion was significantly more frequent in industrysponsored studies (odds ratio [OR], 6.1; range, 2.7 to 13.8), in trials
Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region
Authors: T FUJII
Journal: Cardiovascular Research (2004)

Catechol O-methyltransferase (COMT) is believed to exert degradative action at high norepinephrine (NE) levels. Although COMT exists in cardiac tissues, the contribution of cardiac COMT activity to regional NE kinetics, particularly in ischemia-induced NE accumulation, remains unclear. We investigated the role of cardiac COMT in NE kinetics in the ischemic region.We implanted a microdialysis probe into the left ventricular myocardium of anesthetized rabbits and induced myocardial ischemia by 60-min coronary artery occlusion. We monitored myocardial interstitial levels of NE and its metabolites in the presence and absence of a COMT inhibitor. We intraperitoneally administered entacapone (10 mg/kg) 120 min before control sampling.In control, entacapone increased interstitial dihydroxyphenylglycol (DHPG, intraneuronal NE metabolite by monoamine oxidase (MAO)) levels and decreased interstitial normetanephrine (NMN, extraneuronal NE metabolite by COMT) and 3-methoxy-4-hydroxyphenylglycol (MHPG, extraneuronal DHPG metabolite by COMT) levels, but did not change interstitial NE levels. Coronary occlusion increased NE levels to 165+/-48 nM at 45-60 min of occlusion. This increase was accompanied by increases in DHPG and NMN levels (11.3+/-1.1 and 9.3+/-1.3 nM at 45-60 min of occlusion). Entacapone augmented the ischemia-induced NE and DHPG responses (333+/-51 and 22.9+/-2.4 nM at 45-60 min of occlusion). In contrast, the ischemia-induced NMN response was suppressed by entacapone (2.0+/-0.4 nM at 45-60 min of occlusion). Reperfusion decreased interstitial NE levels and increased interstitial DHPG and NMN levels. Entacapone suppressed changes in NE and NMN levels, but augmented the increase in dialysate DHPG.Myocardial ischemia evoked increases in myocardial interstitial NE and NMN levels. COMT inhibition augmented the increase in NE (substrate of COMT) levels and suppressed the increase in NMN (metabolite by COMT) levels. In the ischemic heart, COMT contributes to the removal of accumulated NE in the myocardium.
Baby steps on the path to understanding intentions
Authors: Amrisha Vaish, Amanda Woodward
Journal: Behavioral and Brain Sciences (2005)

Tomasello et al. lay out a three-step ontogenetic pathway for infants' understanding of intentional action. By this account, before 9 months, infants do not understand actions as being goal directed. However, we caution against drawing strong conclusions from negative findings, and, based on recent findings, propose that a key aspect of goal knowledge is present well before 9 months.
On the Evolution of Some Endoscopic Light Delivery Systems for Photodynamic Therapy
Authors: H. van den Bergh
Journal: Endoscopy (1998)

Progress in photodynamic therapy (PDT) depends on the development of: (1) photosensitizers, (2) optical devices among which are lasers and light delivery systems, and (3) clinical procedure. The light delivery systems which are the focus of this article are fiberoptic devices developed in Lausanne, Switzerland* for use in the endoscopic treatment of cancer or precancerous lesions in the bronchi, the esophagus, the uterus, the cervix, the upper aerodigestive tract and thoracic cavity. Light delivery systems for both surface and interstitial application are presented, together with some of the physical principles on which they are based. Incorporation in these devices of the possibility for in-situ measurement of reflected therapeutic light and/or fluorescence emitted by endogenous and/or exogenous dyes allows for improved light and drug dosimetry, as well as the measurement of photobleaching, local oxygenation and other tissue properties. The necessity of information on tissue optical parameters, as well as the use of simple mathematical models and tissue phantoms, for optimizing light distributing devices is underlined.
Systemic administration of a TLR7 ligand leads to transient immune incompetence due to peripheral-blood leukocyte depletion
Authors: Matthias Gunzer, Helge Riemann, Yasmin Basoglu, Anja Hillmer, Carsten Weishaupt, Sandra Balkow, Bernd Benninghoff, Beat Ernst, Meike Steinert, Thomas Scholzen, Cord Sunderkötter, Stephan Grabbe
Journal: Blood (2005)
Phase II Study of Irinotecan Plus Cisplatin Induction Followed by Concurrent Twice-Daily Thoracic Irradiation With Etoposide Plus Cisplatin Chemotherapy for Limited-Disease Small-Cell Lung Cancer
Authors: Ji-Youn Han, Kwan Ho Cho, Dae Ho Lee, Hyae Young Kim, Eun-A Kim, Sung Young Lee, Jin Soo Lee
Journal: Journal of Clinical Oncology (2005)

Purpose Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-naïve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). Patients and Methods Between November 2001 and May 2003, 35 chemotherapy-naïve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m 2 and irinotecan 80 mg/m 2 intravenously (IV) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m 2 IV on days 43 and 64, and etoposide 100 mg/m 2 IV on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. Results All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. Conclusion IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.
Insulin-Like Growth Factor-1 Attenuates the Detrimental Impact of Nonocclusive Coronary Artery Constriction on the Heart
Authors: Baosheng Li, Manabu Setoguchi, Xiaowei Wang, Anna Maria Andreoli, Annarosa Leri, Ashwani Malhotra, Jan Kajstura, Piero Anversa
Journal: Circulation Research (1999)

Coronary artery narrowing (CAN) induces tissue injury, which may involve myocyte necrosis and apoptosis. Insulin-like growth factor (IGF)-1 may counteract cell death, modifying the detrimental effects of myocardial ischemia. On this basis, CAN was produced in female FVB.Igf+/- mice and nontransgenic littermates, and the animals were euthanized 7 days later. CAN consisted of an 82% reduction in the vessel luminal cross-sectional area in both groups of mice. Severe left ventricular dysfunction was present in CAN nontransgenic and transgenic mice, but heart and left ventricular weights increased more in littermates than in FVB.Igf+/- mice. Similarly, the changes in chamber volume and diastolic wall stress were greater in nontransgenic mice. Subacute tissue injury, represented by foci of replacement fibrosis, was 2.6-fold higher in CAN littermates than in FVB.Igf+/- mice. Ongoing myocyte necrosis was 5-fold greater in nontransgenic mice, whereas apoptosis was low and did not differ in the 2 groups of mice. In CAN nontransgenic mice, myocyte necrosis was 12-fold more frequent than apoptosis but, in CAN transgenic mice, these 2 types of cell death were comparable. alpha-Myosin and beta-myosin isoform mRNAs were affected by CAN, but alpha-myosin mRNA was reduced more in nontransgenic mice. In conclusion, myocyte necrosis and replacement fibrosis are the prevailing forms of myocardial damage induced by CAN. Constitutive overexpression of IGF-1 attenuates myocyte necrosis and tissue injury, having no effect on cell apoptosis. These factors limit ventricular dilation, myocardial loading, cardiac hypertrophy, and alterations in alpha- and beta-myosin isoform expression.
Allergic Pulmonary Inflammation Promotes the Recruitment of Circulating Tumor Cells to the Lung
Authors: Anna G. Taranova, David Maldonado, Celine M. Vachon, Elizabeth A. Jacobsen, Hiam Abdala-Valencia, Michael P. McGarry, Sergei I. Ochkur, Cheryl A. Protheroe, Alfred Doyle, Clive S. Grant, Joan Cook-Mills, Lutz Birnbaumer, Nancy A. Lee, James J. Lee
Journal: Cancer Research (2008)

Abstract Allergen-induced respiratory inflammation facilitates and/or elicits the extravasation of proinflammatory leukocytes by well-understood mechanisms that mediate the movement of multiple cell types. The nonspecific character of these pathways led us to hypothesize that circulating cancer cells use similar mechanisms, promoting secondary tumor formation at distal sites. To test this hypothesis, the frequency of metastasis to the lung as a function of allergic pulmonary inflammation was assessed following the i.v. injection of B16-F10 melanoma cells in mice. These studies showed that allergen-induced pulmonary inflammation resulted in a &amp;gt;3-fold increase in lung metastases. This increase was dependent on CD4+ T-cell activities; however, it occurred independent of the induced eosinophilia associated with allergen provocation. Interventional strategies showed that existing therapeutic modalities for asthma, such as inhaled corticosteroids, were sufficient to block the enhanced pulmonary recruitment of cancer cells from circulation. Additional mechanistic studies further suggested that the ability of circulating cancer cells to extravasate to surrounding lung tissues was linked to the activation of the vascular endothelium via one or more Gαi-coupled receptors. Interestingly, a survey of a clinical breast cancer surgical database showed that the incidence of asthma was higher among patients with lung metastases. Thus, our data show that allergic respiratory inflammation may represent a risk factor for the development of lung metastases and suggest that amelioration of the pulmonary inflammation associated with asthma will have a direct and immediate benefit to the 7% to 8% of breast cancer patients with this lung disease. [Cancer Res 2008;68(20):8582–9]
Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas
Authors: Jian‐Hua Luo, Baoguo Ren, Sergei Keryanov, George C. Tseng, Uma N. M. Rao, Satdarshan P. Monga, Steven Strom, Anthony J. Demetris, Michael Nalesnik, Yan P. Yu, Sarangarajan Ranganathan, George K. Michalopoulos
Journal: Hepatology (2006)

This study analyzed gene expression patterns and global genomic alterations in hepatocellular carcinomas (HCC), hepatoblastomas (HPBL), tissue adjacent to HCC and normal liver tissue derived from normal livers and hepatic resections. We found that HCC and adjacent non-neoplastic cirrhotic tissue have considerable overlap in gene expression patterns compared to normal liver. Several genes including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under-expressed gene. HCC can be subdivided into three clusters based on gene expression patterns. HCC and HPBL have clearly different patterns of gene expression, with genes IGF2, Fibronectin, DLK1, TGFb1, MALAT1 and MIG6 being over-expressed in HPBL versus HCC. In addition, specific areas of the genome appear unstable in HCC, with the same regions undergoing either deletion or increased gene dosage in all HCC. In conclusion, a set of specific genes and areas of genomic instability are found across the board in liver neoplasia. (HEPATOLOGY 2006.)
Next stage of RA treatment: is TNF inhibitor-free remission a possible treatment goal?
Authors: Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2012)

Biological agents targeting tumour necrosis factor (TNF) have revolutionised the treatment of rheumatoid arthritis (RA) and clinical remission has become a realistic treatment goal. Discontinuing anti-TNF therapy after sustained remission has emerged as an important area of investigation in rheumatology from the risk-benefit point of view, including health economic considerations. However, there is little information as to whether 'biologic-free remission' is possible after sustained remission following intensive treatment with TNF inhibitors in RA. European studies such as BeSt and OPTIMA in patients with early RA and Japanese studies such as remission induction by remicade in patients with RA and HONOR in patients with long-standing RA encountered during routine clinical practice have shown that, after a reduction in disease activity to clinical remission or low disease activity by infliximab or adalimumab in combination with methotrexate, patients can successfully remain in clinical remission without TNF inhibitors with no radiological and functional damage progression of articular destruction. Experimental findings in TNF-deficient mouse models suggest that TNF inhibitors may change the disease process of RA and bring about the potential of immunological remission, raising the possibility of a 'treatment holiday' of TNF inhibitors after intensive treatment.