tbuckley/cabot-search huggingface dataset:
Cutaneous innervation before and after one treatment period of acupuncture
Authors: C.P. Carlsson, F. Sundler, J. Wallengren
Journal: British Journal of Dermatology (2006)

Background The effect of acupuncture on nociceptive pain is well documented, but effects on nociceptive itch have been contradictory. Objectives To evaluate possible effects of acupuncture on the occurrence, distribution and function of sensory nerve fibres in human skin. Methods Ten subjects were treated by inserting 10 acupuncture needles subcutaneously at the upper lateral aspect of one buttock. The subjects were recruited from an acupuncture clinic and were undergoing specific acupuncture treatment for their disorders. The needles were stimulated (rotated to and fro) twice during the twice-weekly 25-min sessions over 5 weeks. Skin biopsies, diameter 3 mm, were taken before and 3–6 days after local acupuncture. Antibodies to the pan-neuronal marker protein gene product 9·5 (PGP 9·5), calcitonin gene-related peptide (CGRP), vanilloid receptor 1 (VR1) and μ- and δ-opioid receptors were employed to study sensory unmyelinated nerve fibres that transmit nociceptive pain and itch. A histamine prick test using planimetry was used to record experimental itch after acupuncture on the treated area and on the corresponding control skin, and a visual analogue scale was used to evaluate itch. Results The mean ± SEM number of CGRP-immunoreactive nerve fibres per biopsy section was reduced from 36·0 ± 3·3 to 21·3 ± 4·0 (P = 0·05) after the treatment. PGP 9·5-immunoreactive nerve fibres were found both in the epidermis and in the subpapillary dermis. The mean ± SEM total number of PGP 9·5-immunoreactive nerve fibres decreased from 249·8 ± 16·7 to 211·8 ± 12·0 (P = 0·03). The PGP 9·5-immunoreactive nerve fibres occurring in the dermis appeared more fragmented after the acupuncture compared with pretreatment. VR1 immunoreactivity was found both in the free nerve fibres and in kite-like formations, possibly mast cells, throughout the dermis, sometimes occurring around hair follicles. The mean ± SEM number of VR1-immunoreactive elements was not significantly influenced by acupuncture, at 33·5 ± 4·6 vs. 43·0 ± 4·4 (P = 0·09). No immunoreactivity was found in the skin against μ- and δ-opioid receptors with the antibodies used in this study. Neither histamine-induced itch nor cutaneous responses were influenced by acupuncture. Conclusions The present data indicate an effect of acupuncture on neuropathic itch but not histamine-mediated itch. Our findings support the opinion that the pain-relieving effects of acupuncture partly depend on its effect on the peripheral innervation.
Neurexin-Neuroligin Transsynaptic Interaction Mediates Learning-Related Synaptic Remodeling and Long-Term Facilitation in Aplysia
Authors: Yun-Beom Choi, Hsiu-Ling Li, Stefan R. Kassabov, Iksung Jin, Sathyanarayanan V. Puthanveettil, Kevin A. Karl, Yang Lu, Joung-Hun Kim, Craig H. Bailey, Eric R. Kandel
Journal: Neuron (2011)
Postmortem Cardiovascular Magnetic Resonance Imaging in Fetuses and Children
Authors: Andrew M. Taylor, Neil J. Sebire, Michael T. Ashworth, Silvia Schievano, Rosemary J. Scott, Angie Wade, Lyn S. Chitty, Nikki Robertson, Sudhin Thayyil
Journal: Circulation (2014)

Background— Perinatal and pediatric autopsies have declined worldwide in the past decade. We compared the diagnostic accuracy of postmortem, cardiovascular magnetic resonance (CMR) imaging with conventional autopsy and histopathology assessment in fetuses and children. Methods and Results— We performed postmortem magnetic resonance imaging in 400 fetuses and children, using a 1.5-T Siemens Avanto magnetic resonance scanner before conventional autopsy. A pediatric CMR imager reported the CMR images, masked to autopsy information. The pathologists were masked to the information from CMR images. The institutional research ethics committee approved the study, and parental consent was obtained. Assuming a diagnostic accuracy of 50%, 400 cases were required for a 5% precision of estimate. Three cases were excluded from analysis, 2 with no conventional autopsy performed and 1 with insufficient CMR sequences performed. Thirty-eight CMR data sets were nondiagnostic (37 in fetuses ≤24 weeks; 1 in a fetus &gt;24 weeks). In the remaining 359 cases, 44 cardiac abnormalities were noted at autopsy. Overall sensitivity and specificity (95% confidence interval) of CMR was 72.7% (58.2–83.7%) and 96.2% (93.5–97.8%) for detecting any cardiac pathology, with positive and negative predictive values of 72.7% (58.2–83.7%) and 96.2% (93.5–97.8%), respectively. Higher sensitivity of 92.6% (76.6–97.9%), specificity of 99.1% (97.4–99.7%), positive predictive value of 89.3% (72.8–96.3%), and negative predictive value of 99.4% (97.8–99.8%) were seen for major structural heart disease. Conclusions— Postmortem CMR imaging may be a useful alternative to conventional cardiac autopsy in fetuses and children for detecting cardiac abnormalities. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01417962.
Brown pigment gallstones: The role of bacterial hydrolases and another missed opportunity
Authors: Jorge J. Gumucio, Donald J. Ostrow
Journal: Hepatology (1991)

The bile acids in brown pigment stones and gallbladder bile were fractionated into free acids, glycine and taurine conjugates, and sulfates, using diethylamino-hydroxypropyl-Sephadex LH-20 (DEAPLH-20) column chromatography, and were quantitated by gas chromatography. Twenty-eight cases of brown pigment stones were studied and divided into two groups: those with and those without bacteria possessing bile acid-deconjugating activity. In the former, free bile acid amounted to 62 ± 34% of the total bile acid, while in the latter, only 0.1% of total bile acid was free bile acid. The fraction of total bile acid made up of free bile acids was found to be consistently higher in brown pigment stones than in the corresponding bile, irrespective of the presence or absence of biliary infection. Free bile acid is present in negligible amounts in normal bile. Total bile acid concentration in the bile of patients with brown pigment stones was significantly less than that of controls (13 vs. 50 mg/ml). Biliary infection is almost always present in cases with brown pigment stones. These findings suggest that bacterial infection is present at the initiation of brown pigment stone formation as well as during the period of ensuing stone growth.
The history of oral hygiene products: how far have we come in 6000 years?
Authors: S L Fischman
Journal: Periodontology 2000 (1997)

How far have we come in the past six millennia? Numerous dental epidemiological studies indicate that people are keeping their teeth longer than over before in this century. Agents and devices have evolved, by custom and by research, to enable people, with professional assistance, to maintain good oral health. Our diets, our lifestyles and our professional colleagues have "conspired" as pathogenic influences on oral health. The profession has met the challenge by developing and perfecting a myriad of devices and agents to thwart these pathogenic factors. Patient motivation and professional acceptance of preventive dentistry procedures still remain challenges. We certainly eat well, speak well, look fine and "smell fresh"--but we also have plaque, gingivitis and dental caries. The reader can determine how much progress has been made by reflecting on his or her personal oral health status!
The Therapeutic Efficacy of Anti–Vascular Endothelial Growth Factor Antibody, Bevacizumab, and Pemetrexed against Orthotopically Implanted Human Pleural Mesothelioma Cells in Severe Combined Immunodeficient Mice
Authors: Qi Li, Seiji Yano, Hirokazu Ogino, Wei Wang, Hisanori Uehara, Yasuhiko Nishioka, Saburo Sone
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Malignant pleural mesothelioma (MPM) is an aggressive malignancy, which has a poor prognosis with a median survival of less than 1 year. The vascular endothelial growth factor (VEGF) has been reported to be an ideal therapeutic target, and a multitargeted antifolate, pemetrexed, has been clinically used for the treatment of MPM. Experimental Design: We examined the therapeutic efficacy of the antihuman VEGF neutralizing antibody, bevacizumab, in combination with pemetrexed against two different human MPM cells, EHMES-10 and MSTO-211H, orthotopically inoculated into severe combined immunodeficient mice. Results: Bevacizumab inhibited a VEGF-induced proliferation of the human endothelial cells in a dose-dependent manner, but it had no effect on the proliferation of the two MPM cell lines in vitro. The orthotopically inoculated EHMES-10 cells (VEGF high expressing) produced thoracic tumors and a large volume of bloody pleural effusion, whereas the MSTO-211H cells (VEGF low expressing) produced thoracic tumors and a small volume of bloody effusions. Treatment with bevacizumab effectively inhibited the production of thoracic tumors and dramatically prevented the production of pleural effusion by the EHMES-10 cells but not the MSTO-211H cells. Treatment with bevacizumab reduced the number of enlarged tumor-associated vessels and proliferating tumor cells. Moreover, treatment with bevacizumab in combination with pemetrexed more effectively suppressed the formation of the pleural effusion and prolonged the survival compared with the control and monotherapy in the EHMES-10 cell–bearing severe combined immunodeficient mice. Conclusions: These results suggest that the combined use of bevacizumab and pemetrexed may therefore be promising for controlling the progression of MPM highly expressing VEGF.
Treatment of the arthropathy of familial hypercholesterolaemia.
Authors: G J Carroll, C E Bayliss
Journal: Annals of the Rheumatic Diseases (1983)

A 29-year-old woman suffering from the arthropathy of familial hypercholesterolaemia was treated with a fat-modified low-cholesterol diet and colestipol. Symptomatic improvement occurred in association with a moderate reduction in the plasma cholesterol concentration. The pathogenesis of the musculoskeletal features of this disease is reviewed, and the implications of this patient's therapeutic response are explored.
Communicating <i>BRCA1</i> and <i>BRCA2</i> Genetic Test Results
Authors: Dorothea Gadzicki, Luzie U. Wingen, Birgitta Teige, Denise Horn, Kristin Bosse, Friedmar Kreuz, Timm Goecke, Dieter Schäfer, Theda Voigtländer, Barbara Fischer, Ursula Froster, Brigitte Welling, Irmgard Debatin, Bernard H. F. Weber, Ines Schönbuchner, Irmgard Nippert, Brigitte Schlegelberger
Journal: Journal of Clinical Oncology (2006)

German colleagues 1 and to note that their sample characteristics and findings were similar to ours. 2 It is rewarding to see that cultural differences do not diminish the strength of the relationships we observed in patterns of family communication following BRCA1 and BRCA2 testing.While our study did not include the informing of second-degree relatives, the data Gadzicki et al 1 report is similar to findings in other studies 3,4 and they offer several interesting hypotheses to explain their results.Another possible rationale about the reluctance of tested individuals to inform second-degree relatives has been described in the context of families with hereditary nonpolyposis colorectal cancer mutations. 5 This hypothesis is that within families there are rules, probably often unspoken, about who has the right to inform certain relatives about weighty matters.A rule may be that only parents have the right to inform their children, whether the children are minors or
1127 HEPATITIS B VIRUS INDUCES LOSS OF CIAPl AND SENSITIVITY TO TNF-ALPHA IN PRIMARY HEPATOCYTES
Authors: U. Nachbur, R. Chin, M. Nguyen, A. Bankovacki, L. Earnest-Silveira, C.-T. Bock, J. Silke, J. Torresi
Journal: Journal of Hepatology (2011)
<i>Rip2</i> Deficiency Leads to Increased Atherosclerosis Despite Decreased Inflammation
Authors: Malin C. Levin, Pernilla Jirholt, Anna Wramstedt, Maria E. Johansson, Anna M. Lundberg, Maria Gustafsson Trajkovska, Marcus Ståhlman, Per Fogelstrand, Mikael Brisslert, Linda Fogelstrand, Zhong-Qun Yan, Göran K. Hansson, Harry Björkbacka, Sven-Olof Olofsson, Jan Borén
Journal: Circulation Research (2011)

Rationale: The innate immune system and in particular the pattern-recognition receptors Toll-like receptors have recently been linked to atherosclerosis. Consequently, inhibition of various signaling molecules downstream of the Toll-like receptors has been tested as a strategy to prevent progression of atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, including Toll-like receptors, and is therefore an interesting potential target for pharmaceutical intervention. Objective: We hypothesized that inhibition of Rip2 would protect against development of atherosclerosis. Methods and Results: Surprisingly, and contrary to our hypothesis, we found that mice transplanted with Rip2 −/− bone marrow displayed markedly increased atherosclerotic lesions despite impaired local and systemic inflammation. Moreover, lipid uptake was increased whereas immune signaling was reduced in Rip2 −/− macrophages. Further analysis in Rip2 −/− macrophages showed that the lipid accumulation was scavenger-receptor independent and mediated by Toll-like receptor 4 (TLR4)–dependent lipid uptake. Conclusions: Our data show that lipid accumulation and inflammation are dissociated in the vessel wall in mice with Rip2 −/− macrophages. These results for the first time identify Rip2 as a key regulator of cellular lipid metabolism and cardiovascular disease.
Electrode radius predicts lesion radius during radiofrequency energy heating. Validation of a proposed thermodynamic model.
Authors: D E Haines, D D Watson, A F Verow
Journal: Circulation Research (1990)

Myocardial heating by transcatheter delivery of radiofrequency (RF) energy has been proposed as an effective means of arrhythmia ablation. A thermodynamic model describing the radial temperature gradient at steady state during RF-induced heating is proposed. If one assumes that RF power output is adjusted to maintain a constant electrode-tissue interface temperature at all times, then this thermodynamic model predicts that the radius of the RF-induced lesion will be directly proportional to the electrode radius. A total of 76 RF-induced lesions were created in a model of isolated canine right ventricular free wall perfused and superfused with oxygenated Krebs-Henseleit buffer. Electrode radius was varied between 0.75 and 2.25 mm. RF energy (500 kHz) was delivered for 90 seconds, and the power output was adjusted to maintain a constant electrode-tissue interface temperature of 60 degrees C. A strong linear correlation was observed between electrode radius and lesion radius in two dimensions: transverse (p = 0.0001, r = 0.85) and transmural (p = 0.0001, r = 0.89). With these data, the temperature correlation with irreversible myocardial injury in this model was calculated at 46.6-48.8 degrees C. Therefore, the proposed thermodynamic model closely predicts the observed relation between electrode radius and lesion size during RF myocardial heating.
Overweight and changes in weight status during childhood in relation to asthma symptoms at 8 years of age
Authors: Salome Scholtens, Alet H. Wijga, Jacob C. Seidell, Bert Brunekreef, Johan C. de Jongste, Ulrike Gehring, Dirkje S. Postma, Marjan Kerkhof, Henriette A. Smit
Journal: Journal of Allergy and Clinical Immunology (2009)
Assessing Rates of Hypoglycemia as an End Point in Clinical Trials
Authors: Douglas B. Muchmore, Lutz Heinemann, William Tamborlane, Xionghua W. Wu, Alexander Fleming
Journal: Diabetes Care (2015)

The American Diabetes Association (ADA) recently convened a working group to assess the impact of hypoglycemia and to provide guidance about how this information should be used in practice (1), but the methods used to assess hypoglycemia in clinical trials have received less attention.

The widely accepted definitions of hypoglycemia include severe, documented symptomatic, asymptomatic, and probable symptomatic hypoglycemia and pseudohypoglycemia (1). Severe hypoglycemia is the most robust end point for clinical trials. Unfortunately, from the clinical trial perspective, it is relatively rare, occurring at a rate of about 13.5 episodes per 100 patient-years in type 1 diabetes trials (2). This calls for a very large sample size (Table 1) to adequately power a study. In small populations (e.g., insulin pump users), a study comparing severe hypoglycemia …
Memories of David Denison
Authors: Andrew Bush
Journal: Thorax (2014)

In 1980, 2 years postqualification, flushed with the recent acquisition of the MRCP, I saw an advertisement in the BMJ for a research fellow post in clinical physiology at the Brompton. I came up to look around and be interviewed for a job which (rightly) I did not get, and first met David Denison, the professor and head of department. First impressions (subsequently confirmed and reconfirmed) were of a man with an incredibly sharp and original mind, lively in debate and with a great sense of fun, but who was also totally devoid of any pomposity or ‘side’, to use an old-fashioned phrase. We shared a love for many things, including Jaroslav Hasek's immortal creation, the Good Soldier Schwek (who subsequently appeared on my slides for my first ever BTS presentation, typically drawn by David—nothing was too much trouble if it tickled his fancy!). David clearly hugely enjoyed life, and enjoyed finding things out. Physiology was obviously an endless fascination to him, and these were the heydays of physiology. Incredibly now, the consolation prize for another unsuccessful candidate at the interview was a research job in a wet lab. I left the interview determined to make it back again.

During a subsequent registrar job, I did a physiology project in the department (which became the Schwek presentation, and a Clinical Science paper) and, subsequently, had a call from David offering me a research fellowship. I accepted with alacrity, and stayed for more than 4 years, obtaining an MD and having my career launched into a new direction, paediatrics, largely by Elliott Shinebourne. I met many fellows there who went on to great things—the current BTS president and the current Respiratory Tsar, to name but two. They were great years⇓.



Professor David Denison. 7 March 1933–8 February 2014 



David inspired huge …
Altered DNA Methylation: A Secondary Mechanism Involved in Carcinogenesis
Authors: Jay I. Goodman, Rebecca E. Watson
Journal: The Annual Review of Pharmacology and Toxicology (2002)

This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?
Spinal adrenergic mechanisms regulating sympathetic outflow to blood vessels.
Authors: D G Taylor, M J Brody
Journal: Circulation Research (1976)

The role of descending spinal catecholamine (CA)-containing fibers in cardiovascular regulation was examined. Monoamine-containing fibers were visualized by fluorescence histochemical methods at the cervical, thoracic, and lumbar spinal segments. Two major groups of descending CA-containing axons were located in the lateral funiculus at the midcervical spinal level. At the thoracolumbar spinal segments CA-containing terminals were concentrated mostly around cells of the intermediolateral nucleus. In addition a distinct CA-containing fasciculus was observed at the level of the sympathetic nucleus which appeared to course toward the opposite site of the cord. To evaluate the role of the efferent CA-containing fibers, changes in heart rate, arterial pressure, femoral blood flow, and calculated peak vascular resistance were elicited by electrical stimulation of selected sites in the midcervical spinal cord. Although changes in femoral flow and arterial pressure were evoked from many midcervical sites, there was a distinct correlation between the magnitude of peak femoral resistance elevation and density of CA-containing axons activated. Furthermore, efferent spinal vasoconstrictor outflow to the hindlimbs crosses below the cervical level. This observation is in good agreement with fluorescence microscopy studies revealing CA-containing fibers which appear to decussate. Pharmacological studies also were undertaken to evaluate transmission in spinal vasopressor pathways. In these studies alpha-adrenergic receptor antagonists and agonists were perfused into the spinal subarachnoid space. Heart rate, arterial pressure, femoral flow, and femoral resistance responses elicited from efferent spinal pathways were significantly attenuated following superfusion of the spinal cord with the alpha-antagonists BE-2254 (HEAT) and phentolamine. It was shown that inhibition of the centrally evoked responses was due to actions of the alpha-antagonists at a spinal locus and not due to peripheral vascular alpha-receptor blockade. Spinal perfusion with the alpha-receptor agonist norepinephrine potentiated cardiovascular responses. Likewise, loading with the norepinephrine precursor 3,4-dihydroxy-L-phenylalanine (L-dopa) enhanced vasoconstrictor responses evoked in the cross-perfused hindlimb of p-chlorophenylalanine-pretreated cats. These observations support the idea that bulbospinal CA-containing fibers relay excitatory impulses to preganglionic vasoconstrictor neurons and that spinal alpha-adrenergic receptor activation is necessary for transmission of this information.
Plasma Levels of Soluble Tie2 and Vascular Endothelial Growth Factor Distinguish Critical Limb Ischemia From Intermittent Claudication in Patients With Peripheral Arterial Disease
Authors: Clarence M. Findley, Robert G. Mitchell, Brian D. Duscha, Brian H. Annex, Christopher D. Kontos
Journal: Journal of the American College of Cardiology (2008)