tbuckley/cabot-search huggingface dataset:
The Prognostic Significance of Altered Cyclin-Dependent Kinase Inhibitors in Human Cancer
Authors: J. Tsihlias, MD, FRCSC, L. Kapusta, MD, FRCPC, J. Slingerland, MD, FRCPC, PhD
Journal: Annual Review of Medicine (1999)

Progression through the cell cycle is governed by cyclin-dependent kinases (cdks), whose activity is inhibited by the cdk inhibitors. Cyclins, cdks, and cdk inhibitors are frequently deregulated in cancers. This chapter reviews the prognostic significance of alterations in cdk inhibitors. Loss of p27 protein provides independent prognostic information in breast, prostate, colon, and gastric carcinomas, and immunohistochemical (IHC) staining for p27 may eventually become part of routine histopathologic processing of cancers. Loss of IHC staining for p21 may be prognostic in certain cancers but conflicting results are reported in breast cancer. Reports on homozygous deletion of p16 and p15 genes suggest the value of larger, prospective studies with standardized treatment protocols to definitively establish the prognostic utility of p15/p16 deletions in acute leukemias. Larger trials and the development of a consensus on methods for deletion analysis, IHC staining, and tumor scoring will be needed to move these molecular assays from bench to bedside.
Fasting Plasma C-Peptide and Micro- and Macrovascular Complications in a Large Clinic-Based Cohort of Type 1 Diabetic Patients
Authors: Francesco Panero, Giulia Novelli, Chiara Zucco, Paolo Fornengo, Massimo Perotto, Olivia Segre, Giorgio Grassi, Paolo Cavallo-Perin, Graziella Bruno
Journal: Diabetes Care (2008)

OBJECTIVE—A protective effect of residual β-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications. RESEARCH DESIGN AND METHODS—We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994–2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated. RESULTS—Residual β-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (β = 0.02; P &amp;lt; 0.0001) and triglycerides (β = 0.20; P = 0.05) and inversely associated with diabetes duration (β = −0.03; P &amp;lt; 0.0001) and HDL cholesterol (β = −0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (&amp;lt;0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37–0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38–1.58]). CONCLUSIONS—Our study shows an independent protective effect of residual β-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest β-cell function over time.
Reflex suppression of renin secretion during distention of cardiopulmonary receptors in dogs.
Authors: J E Zehr, J A Hasbargen, K D Kurz
Journal: Circulation Research (1976)

We studied the effect of brief periods of left atrial-pulmonary vein distention on the rate of renin secretion in sodium-restricted dogs anesthetized with chloralose and breathing spontaneously. Series 1 consisted of 32 trials in seven dogs with intact renal nerves and intact vagi. Renin secretion, calculated as the product of renal venous minus arterial renin activity (radioimmunoassay) times renal plasma flow (electromagnetic flowmeter), was depressed to 56% of control during atrial distention despite no change in arterial pressure, central venous pressure, or renal blood flow. Series 2 consisted of 58 trials in 12 dogs which had undergone unilateral renal denervation several days prior to the studies. Simultaneous, bilateral determinations indicated that renin secretion from the innervated kidney was depressed to 58% of control during atrial distention; secretion from the denervated kidney was unchanged. Series 3 consisted of 30 trials in six dogs with bilateral cervical vagotomy. Atrial distention evoked no changes in renin secretion. We conclude that left atrial distention reflexly reduces the rates of renin secretion via vagal afferent and renal sympathetic efferent pathways.
Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation
Authors: P le Coutre, H Meisel, J Hofmann, C Rocken, G L Vuong, S Neuburger, P G Hemmati, B Dorken, R Arnold
Journal: Gut (2009)

Hepatitis E virus (HEV) is the major cause of several outbreaks of waterborne hepatitis in tropical and subtropical countries and of sporadic cases of viral hepatitis in endemic and industrialised countries. Generally, HEV causes an acute self-limiting hepatitis. The clinical course is characterised by transient viraemia and transaminasaemia followed by a full hepatic recovery. Recent studies describe prolonged and chronic HEV infections in some immunosuppressed patients after solid organ transplantation. Here, an indigenous acute limited hepatitis E in a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia prior to allogeneic stem cell transplantation is reported. Fourteen weeks after stem cell transplantation, reappearance of HEV viraemia was observed, with increasing viral load and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed a reactivation of endogenous HEV genotype 3, indicating viral persistence after recovery from acute hepatitis E.
Adenosine produces pulmonary vasoconstriction in sheep. Evidence for thromboxane A2/prostaglandin endoperoxide-receptor activation.
Authors: I Biaggioni, L S King, N Enayat, D Robertson, J H Newman
Journal: Circulation Research (1989)

Adenosine, an intermediate product in the metabolism of ATP, is thought to produce vasodilation in all vascular beds with the exception of the kidney. Due to its theoretical potential as a pulmonary vasodilator, we studied the hemodynamic effects of adenosine in the pulmonary vasculature of chronically instrumented awake sheep. Adenosine produced significant pulmonary vasoconstriction instead of the expected vasodilatation. Bolus injections of adenosine into the superior vena cava produced a dose-dependent increase in pulmonary artery pressure that was entirely due to an increase in vascular resistance, since cardiac output decreased slightly. This effect is produced via activation of specific cell surface adenosine receptors, since it was blocked by the adenosine-receptor antagonists theophylline and dipropylsulfophenylxanthine. The cell type involved in adenosine-induced pulmonary vasoconstriction appears to be located within the lung, since vasoconstriction was blunted when adenosine was infused into the left atrium, distal to the lung. However, adenosine does not directly vasoconstrict the pulmonary vasculature, because its effect could be completely abolished by cyclooxygenase inhibition with either indomethacin or ibuprofen and by a thromboxane A2/prostaglandin endoperoxide-receptor antagonist (SQ 29,548). Adenosine-induced vasoconstriction was also greatly reduced after inhibition of thromboxane synthesis. Thus, adenosine produced pulmonary vasoconstriction through generation of a thromboxane/endoperoxide product. Whether endogenous adenosine is involved in the generation of pulmonary vasoconstriction seen in pathophysiological states remains to be determined. To our knowledge, this is the first clear evidence for adenosine-induced vasoconstriction outside the kidney and for an interaction between adenosine and eicosanoid mechanisms.
Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Severe Aortic Valve Stenosis
Authors: Hans Gustav Hørsted Thyregod, Daniel Andreas Steinbrüchel, Nikolaj Ihlemann, Henrik Nissen, Bo Juel Kjeldsen, Petur Petursson, Yanping Chang, Olaf Walter Franzen, Thomas Engstrøm, Peter Clemmensen, Peter Bo Hansen, Lars Willy Andersen, Peter Skov Olsen, Lars Søndergaard
Journal: Journal of the American College of Cardiology (2015)
Trafficking of NMDA Receptors
Authors: Robert J. Wenthold, Kate Prybylowski, Steve Standley, Nathalie Sans, Ronald S. Petralia
Journal: The Annual Review of Pharmacology and Toxicology (2003)

The NMDA receptor (NMDAR) plays a central role in the function of excitatory synapses. Recent studies have provided interesting insights into several aspects of the trafficking of this receptor in neurons. The NMDAR is not a static resident of the synapse. Rather, the number and composition of synaptic NMDARs can be modulated by several factors. The interaction of PDZ proteins, generally thought to occur at the synapse, appears to occur early in the secretory pathway; this interaction may play a role in the assembly of the receptor complex and its exit from the endoplasmic reticulum. This review addresses recent advances in our understanding of NMDAR trafficking and its synaptic delivery and maintenance.
Fertility in men with primary ciliary dyskinesia presenting with respiratory infection.
Authors: N C Munro, D C Currie, K S Lindsay, T A Ryder, A Rutman, A Dewar, M A Greenstone, W F Hendry, P J Cole
Journal: Thorax (1994)

BACKGROUND--Primary ciliary dyskinesia is characterised by chronic rhinosinusitis, chronic bronchial sepsis (usually with bronchiectasis), dextrocardia in approximately 50% of cases, and male infertility. The latter, described in patients attending infertility clinics, results from immotile but viable spermatozoa. Experience in a respiratory clinic suggests that infertility in men is not invariable. METHODS--The seminal fluid of 12 men with primary ciliary dyskinesia, six with dextrocardia, who presented consecutively with upper and lower respiratory tract sepsis was examined. Nasal ciliary beating was dyskinetic or absent in all cases, and nasal ciliary ultrastructure was abnormal in those 11 patients examined. RESULTS--Viable but immotile spermatozoa with abnormal tail ultrastructure were found in the ejaculate of only two patients. Two other patients had apparently fathered children; seminology in both these cases showed a normal spermatozoa count, one with normal spermatozoal motility and normal ultrastructure, the other with moderately reduced spermatozoal motility and abnormal ultrastructure (dynein arm deficiency on the peripheral microtubule doublets). A further two patients had normal spermatozoa counts, normal spermatozoa tail ultrastructure, and normal or only moderately reduced motility of spermatozoa. The spermatozoa of one patient were normally motile but there was severe oligozoospermia, and five patients were azoospermic. CONCLUSIONS--Not all men with primary ciliary dyskinesia have immotile spermatozoa. Seminal analysis is recommended in men with primary ciliary dyskinesia so that accurate counselling about reproductive capability may be given.
TRPA1 Agonists Evoke Coughing in Guinea Pig and Human Volunteers
Authors: Mark A. Birrell, Maria G. Belvisi, Megan Grace, Laura Sadofsky, Shoaib Faruqi, David J. Hele, Sarah A. Maher, Véronique Freund-Michel, Alyn H. Morice
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Cough is the most frequent reason for consultation with a family doctor, or with a general or respiratory physician. Treatment options are limited and one meta-analysis concluded that over-the-counter remedies are ineffective. There is also increasing concern about their use in children. Environmental irritants such as air pollution and cigarette smoke are thought to evoke cough by stimulating airway sensory nerves; however, how this occurs is not fully understood.We hypothesized that the TRPA1 (transient receptor potential cation channel, subfamily A, member 1) receptor may have a role as a novel target for tussive agents given that many potential irritants have been shown to activate this channel.We investigated the effect of TRPA1 ligands on vagal sensory nerve activity in vitro and in guinea pig and human tussive challenge models.We demonstrated that TRPA1 agonists such as acrolein activate cloned human TRPA1 channels in HEK293 cells and also vagal sensory nerves in murine, guinea pig, and human tissues. A role for TRPA1 was confirmed, using specific inhibitors and tissue from Trpa1(-/-) gene-deleted animals. Finally, TRPA1 ligands evoked reproducible tussive responses in both a guinea pig model and normal volunteers.This study identifies the TRPA1 receptor as a promiscuous receptor, activated by a wide range of stimuli, making it a perfect target for triggering cough and as such one of the most promising targets currently identified for the development of antitussive drugs.
Mutation of the mouse hepatocyte nuclear factor/forkhead homologue 4 gene results in an absence of cilia and random left-right asymmetry.
Authors: J Chen, H J Knowles, J L Hebert, B P Hackett
Journal: Journal of Clinical Investigation (1998)

Winged helix transcription factors play important roles in cellular differentiation and cell-specific gene expression. To define the role of the winged helix factor hepatocyte nuclear factor/forkhead homologue (HFH)-4, a targeted mutation was created in the mouse hfh-4 gene. No expression of HFH-4 was detected in hfh-4(-)/- mice by RNA blot analysis, in situ hybridization, or RT-PCR. hfh-4(-)/- mice were noted to have abnormalities of organ situs consistent with random determination of left-right asymmetry. In addition, a complete absence of cilia was noted in hfh-4(-)/- mice. The hfh-4 gene is thus essential for nonrandom determination of left-right asymmetry and development of ciliated cells. Homozygous mutant mice also exhibited prenatal and postnatal growth failure, perinatal lethality and, in some cases, hydrocephalus. RT-PCR revealed an absence of left-right dynein (lrd) expression in the embryonic lungs of hfh-4(-)/- mice, suggesting that HFH-4 may act by regulating expression of members of the dynein family of genes. The abnormalities in ciliary development and organ situs in hfh-4(-)/- mice are similar to those observed in human congenital syndromes such as Kartagener syndrome. Targeted mutation of hfh-4 thus provides a model for elucidating the mechanisms regulating ciliary development and determination of left-right asymmetry.
Teaching Atlas of Nuclear Medicine
Authors: John B. Selby
Journal: Clinical Nuclear Medicine (2000)

Professor Emeritus, Radiology Medical University of South Carolina Charleston, South Carolina CLINICAL NUCLEAR MEDICINE publishes in each issue a section of references to articles of interest to its readers taken from the world medical literature. Articles below were selected from listings received through October 20, 2000. Slavic and Oriental language articles have English summaries unless marked with an asterisk after language abbreviation.
High calcium concentration in bones promotes bone metastasis in renal cell carcinomas expressing calcium-sensing receptor
Authors: Elke Joeckel, Tobias Haber, Dirk Prawitt, Kerstin Junker, Christian Hampel, Joachim W Thüroff, Frederik C Roos, Walburgis Brenner
Journal: Molecular Cancer (2014)

Abstract Background The prognosis for renal cell carcinoma (RCC) is related to a high rate of metastasis, including 30% of bone metastasis. Characteristic for bone tissue is a high concentration of calcium ions. In this study, we show a promoting effect of an enhanced extracellular calcium concentration on mechanisms of bone metastasis via the calcium-sensing receptor (CaSR) and its downstream signaling molecules. Methods Our analyses were performed using 33 (11/category) matched specimens of normal and tumor tissue and 9 (3/category) primary cells derived from RCC patients of the 3 categories: non-metastasized, metastasized into the lung and metastasized into bones during a five-year period after nephrectomy. Expression of CaSR was determined by RT-PCR, Western blot analyses and flow cytometry, respectively. Cells were treated by calcium and the CaSR inhibitor NPS 2143. Cell migration was measured in a Boyden chamber with calcium (10 μM) as chemotaxin and proliferation by BrdU incorporation. The activity of intracellular signaling mediators was quantified by a phospho-kinase array and Western blot. Results The expression of CaSR was highest in specimens and cells of patients with bone metastases. Calcium treatment induced an increased migration (19-fold) and proliferation (2.3-fold) exclusively in RCC cells from patients with bone metastases. The CaSR inhibitor NPS 2143 elucidated the role of CaSR on the calcium-dependent effects. After treatment with calcium, the activity of AKT, PLCγ-1, p38α and JNK was clearly enhanced and PTEN expression was almost completely abolished in bone metastasizing RCC cells. Conclusions Our results indicate a promoting effect of extracellular calcium on cell migration and proliferation of bone metastasizing RCC cells via highly expressed CaSR and its downstream signaling pathways. Consequently, CaSR may be regarded as a new prognostic marker predicting RCC bone metastasis.
The significance of the squeeze test to identify arthritis was underestimated or not?
Authors: Wei Luo, Chao Zeng, Hongbo He
Journal: Annals of the Rheumatic Diseases (2015)

We read with deep interest the article by van den Bosch et al 1 related to the diagnostic accuracy of the squeeze test to identify arthritis. This cross-sectional cohort study suggested that a positive squeeze test is associated with local joint inflammation with a very low sensitivity, indicating a high percentage of swollen joints with a negative squeeze test. Doctors should ‘keep in mind’ the characteristics of this test when performing in daily practice. We really appreciate the work that has been done by the authors. The findings help clinicians understand the effect of the squeeze test to identify arthritis. However, there are some worthwhile issues that need to be explored.

The squeeze test is an easy, rapid and cheap method to identify arthritis in metacarpophalangeal (MCP) and metatarsophalangeal joints for general practitioners (GPs) as promoted by some experts and societies.2–4 We agree with …
Anthropometric assessment of youth national championship basketball players in relation to playing position
Authors: J Viswanathan, A S Nageswara, S Baskar
Journal: British Journal of Sports Medicine (2010)

Profiling can be a valuable means of identifying talent, strengths and weaknesses, assigning player positions and helping in the optimal design of training programmes. The objective of this study was to provide anthropometric profile of elite national basketball players. A squad of youth national championship basketball players (n = 44) provided informed consent to participate in this study. Using ISAK (International Society of Advancement of Kinanthropometry) accredited methods, a total of 22 measurements (sectioned as: skinfolds, girths, lengths and breadths) were made for each player. The procedure involved three measures at each site to calculate a mean value and an acceptable technical error margin. All data collection was performed by an ISAK level-2 accredited anthropometrist. Performance ability of the players were assessed by using FIBA Live Stat basketball software in terms of offensive and defensive rebounds, shots made versus missed, assist, steel and blocked. Significant differences were found between players playing positions for some anthropometric characteristics (height, weight, arm span, hip-waist ratio, percentage body fat) and strong correlations were noted between playing ability with anthropometrical variables as height, percentage of body fat and breadth measurements (r = 0.62–0.81; p &lt; 0.01). The study shows that the centre players have superior values in all anthropometric parameters followed by forwards and then the guards. High successive shooting percentage was observed among the forward players followed by the centre players and then the guards.
The effect of pulmonary rehabilitation on exercise tolerance pulmonary function dyspnea and quality of life in patients with idiopathic pulmonary fibrosis
Authors: Baruch Vainshelboim, Jose Oliveira, Liora Yohoshua, Israela Weis, Benjamin Fox, Mordechai Kramer
Journal: European Respiratory Journal (2013)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal lung disease with worse prognosis and no effective treatment. IPF characterized by restriction, impaired gas exchange, dyspnea, exercise intolerance and poor quality of life (QOL). However, little is known regarding the effect of pulmonary rehabilitation (PR) on IPF. The aim of the study was to examine the effect of PR on exercise tolerance, pulmonary function, dyspnea and QOL in IPF patients.   Methods:  A randomized controlled trial was conducted. Thirty-two IPF patients aged 67±8 years were allocated to PR group (n=15) or control group (n=17). PR group participated in 12-week outpatient pulmonary rehabilitation program, consisting of twice weekly 60-minute exercise training, while control group continued with regular medical treatment. Pulmonary function test, cardiopulmonary exercise test, 6MWT, dyspnea and QOL questionnaires were assessed at baseline and after 12-week intervention.   Results:  VO 2  peak and 6MWT increased significantly by 2.1 ml/kg/min p=0.002 and 70 m p   Conclusions:  PR in patients with IPF improves exercise tolerance, pulmonary and ventilatory capacities, dyspnea and quality of life. PR effectively reversed several disease manifestations, which have an important clinical significance for IPF patients. We suggest considering include PR for all IPF patient as a standard comprehensive treatment.
Aquaporin 2 Promotes Cell Migration and Epithelial Morphogenesis
Authors: Ying Chen, William Rice, Zhizhan Gu, Jian Li, Jianmin Huang, Michael B. Brenner, Alfred Van Hoek, Jianping Xiong, Gregg G. Gundersen, Jim C. Norman, Victor W. Hsu, Robert A. Fenton, Dennis Brown, Hua A. Jenny Lu
Journal: Journal of the American Society of Nephrology (2012)

The aquaporin 2 (AQP2) water channel, expressed in kidney collecting ducts, contributes critically to water homeostasis in mammals. Animals lacking or having significantly reduced levels of AQP2, however, have not only urinary concentrating abnormalities but also renal tubular defects that lead to neonatal mortality from renal failure. Here, we show that AQP2 is not only a water channel but also an integrin-binding membrane protein that promotes cell migration and epithelial morphogenesis. AQP2 expression modulates the trafficking and internalization of integrin β1, facilitating its turnover at focal adhesions. In vitro, disturbing the interaction between AQP2 and integrin β1 by mutating the RGD motif led to reduced endocytosis, retention of integrin β1 at the cell surface, and defective cell migration and tubulogenesis. Similarly, in vivo, AQP2-null mice exhibited significant retention of integrin β1 at the basolateral membrane and had tubular abnormalities. In summary, these data suggest that the water channel AQP2 interacts with integrins to promote renal epithelial cell migration, contributing to the structural and functional integrity of the mammalian kidney.