tbuckley/cabot-search huggingface dataset:
Treatment of lichen sclerosus with carbon dioxide laser vaporization
Authors: M. KARTAMAA, S. REITAMO
Journal: British Journal of Dermatology (1997)

We have treated 10 patients (five women and five men) with lichen sclerosus (LS), verified by histopathological studies from skin biopsies, with CO2 laser vaporization. All men studied had LS of the penile skin, of the women, three had extragenital lesions and two LS of the perineal skin. The mean follow-up time was 32 months (range 3-79 months). One man had both penile and urethral LS. All penile lesions of the five men were clinically cured by laser treatment: however, urethral lesions of one patient recurred despite three separate treatments. The two women with perineal LS improved after laser treatment. However, LS recurred on the treated are in one and on the margins of the treated area in another. Two women with LS on the skin of the breast became asymptomatic after treatment. One woman had several lesions on the skin of the trunk that improved after treatment but were not cured completely. The present study suggests that carbon dioxide vaporization may be an effective treatment of skin lesions in LS.
Lymphocytic oesophagitis, a condition in search of a disease?: Table 1
Authors: Jukka Ronkainen, Marjorie M Walker, Pertti Aro, Tom Storskrubb, Nicholas J Talley, Zohreen B Ahmed, Victoria Salter, Michael Vieth, Lars Agréus
Journal: Gut (2012)

The secretion of IL-9, initially recognized as a Th2 cytokine, was recently attributed to a novel CD4 T cell subset termed Th9 in the murine system. However, IL-9 can also be secreted by mouse Th17 cells and may mediate aspects of the proinflammatory activities of Th17 cells. Here we report that IL-9 is secreted by human naive CD4 T cells in response to differentiation by Th9 (TGF-β and IL-4) or Th17 polarizing conditions. Yet, these differentiated naive cells did not coexpress IL-17 and IL-9, unless they were repeatedly stimulated under Th17 differentiation-inducing conditions. In contrast to the naive cells, memory CD4 T cells were induced to secrete IL-9 by simply providing TGF-β during stimulation, as neither IL-4 nor proinflammatory cytokines were required. Furthermore, the addition of TGF-β to the Th17-inducing cytokines (IL-1β, IL-6, IL-21, IL-23) that induce memory cells to secrete IL-17, resulted in the marked coexpression of IL-9 in IL-17 producing memory cells. The proinflammatory cytokine mediating TGF-β–dependent coexpression of IL-9 and IL-17 was identified to be IL-1β. Moreover, circulating monocytes were potent costimulators of IL-9 production by Th17 cells via their capacity to secrete IL-1β. Finally, to determine whether IL-9/IL-17 coproducing CD4 cells were altered in an inflammatory condition, we examined patients with autoimmune diabetes and demonstrated that these subjects exhibit a higher frequency of memory CD4 cells with the capacity to transition into IL-9<sup>+</sup>IL-17<sup>+</sup> cells. These data demonstrate the presence of IL-17<sup>+</sup>IL-9<sup>+</sup> CD4 cells induced by IL-1β that may play a role in human autoimmune disease.
Prognostic significance of thrombocytosis in patients with primary lung cancer
Authors: LM Pedersen, N Milman
Journal: European Respiratory Journal (1996)

In patients with malignancies, thrombocytosis has previously been related to disease stage, histological type, and survival. In the present study, the prevalence of thrombocytosis and the prognostic information provided by platelet counts were analysed in a large cohort of patients with primary lung cancer. At the time of diagnosis, pretreatment platelet counts were retrospectively recorded in 1,115 consecutive patients with histologically proven primary lung cancer. All patients were reviewed regarding histological type, tumour, node, metastasis (TNM) classification stage and survival. The prevalence of thrombocytosis in patients with lung cancer was compared with that in a series of 550 consecutive out-patients with benign lung disorders. In 269 surgically resected patients, postoperative platelet counts were recorded 1-3 months after resection of the tumour. In the follow-up period, thromboembolic episodes diagnosed either clinically or at autopsy were recorded. The overall prevalence of thrombocytosis (&gt; 400 x 10(9) platelets.L-1) in the patients with lung cancer was 32%. The frequency of thrombocytosis was significantly higher compared with the control subjects (32 vs 6%; p &lt; 0.0001). Platelet counts differed significantly among subgroups defined by the TNM classification, with the proportion of patients with &gt; 400 x 10(9) platelets.L-1 greatest in the more advanced TNM stages (stage I and II 23% vs stage III and IV 37%; p &lt; 0.0001). Patients with thrombocytosis had a significantly poorer survival than patients with normal platelet counts (p &lt; 0.0001). In a multivariate survival analysis (Cox model), thrombocytosis continued to correlate strongly with poor survival even when adjusted for histological type, sex, age, and TNM stage (p &lt; 0.001). In surgically resected patients, the frequency of preoperative and postoperative thrombocytosis differed significantly (23.0 vs 8.9%; p &lt; 0.0001). Survival rate was significantly reduced in patients with preoperative thrombocytosis (p = 0.005). Thrombocytosis was not associated with an increased incidence of thromboembolism. In conclusion, thrombocytosis is an independent prognostic factor of survival in patients with primary lung cancer. We suggest that platelet counts should be included in future multivariate analyses of survival in patients with lung cancer.
Autophagy activation by rapamycin reduces severity of experimental osteoarthritis
Authors: Beatriz Caramés, Akihiko Hasegawa, Noboru Taniguchi, Shigeru Miyaki, Francisco J Blanco, Martin Lotz
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Osteoarthritis is associated with cell death and extracellular matrix degradation in articular cartilage. Autophagy is an essential cellular homeostasis mechanism that was found to be deficient in ageing and osteoarthritic cartilage. This study determined whether pharmacological inhibition of the mammalian target of rapamycin (mTOR), a key inhibitor of autophagy, has disease-modifying activity in experimental osteoarthritis. <h3>Methods</h3> Experimental osteoarthritis was induced by transection of the medial meniscotibial ligament and the medial collateral ligament in 2-month-old C57Bl/6 mice (n=36). Rapamycin (1 mg/kg weight/day) (n=18 mice) or dimethyl sulphoxide vehicle control (n=18 mice) was administered intraperitoneally for 10 weeks. Histopathological changes in articular cartilage and synovium were examined by using semiquantitative scoring systems. Rapamycin effects on mTOR signalling, autophagy, cartilage homeostasis and inflammation were analysed by immunohistochemistry and immunofluorescence staining. <h3>Results</h3> Rapamycin affected the mTOR signalling pathway in mouse knee joints as indicated by the inhibition of ribosomal protein S6 phosphorylation, a target of mTOR and activation of LC3, a main marker of autophagy. The severity of cartilage degradation was significantly (p&lt;0.01) reduced in the rapamycin-treated group compared with the control group and this was associated with a significant (p&lt;0.05) decrease in synovitis. Rapamycin treatment also maintained cartilage cellularity and decreased ADAMTS-5 and interleukin-1β expression in articular cartilage. <h3>Conclusions</h3> These results suggest that rapamycin, at least in part by autophagy activation, reduces the severity of experimental osteoarthritis. Pharmacological activation of autophagy may be an effective therapeutic approach for osteoarthritis.
CDC25B Involvement in the Centrosome Duplication Cycle and in Microtubule Nucleation
Authors: Rose Boutros, Valérie Lobjois, Bernard Ducommun
Journal: Cancer Research (2007)

Abstract Centrosome amplification is frequently reported in human cancers, although the molecular mechanisms that are responsible for this remain unclear. There is significant evidence to support a role for cyclin-dependent kinase (CDK)–cyclin complexes in centrosome duplication. The activities of CDK-cyclin complexes are, in turn, regulated by the CDC25 family of phosphatases in a strict spatiotemporal manner, and we have recently reported that CDC25B localizes to the centrosomes from early S phase. In the present study, we have investigated the role of centrosomally localized CDC25B in centrosome duplication. We first observed that overexpression of CDC25B under an inducible promoter in S phase results in centrosome overduplication. We found that forced expression of wild-type but not phosphatase-inactive CDC25B at the centrosomes results in centrosome amplification, aberrant microtubule organization, and abnormal accumulation of γ-tubulin. In contrast, inhibition of CDC25B phosphatase activity inhibits the assembly of interphase microtubules and the centrosomal localization of γ-tubulin. We propose that CDC25B is part of the pathway that controls the localization of γ-tubulin to the centrosomes, thereby regulating centrosome duplication during S phase and the nucleation of microtubules. We speculate that abnormal expression of CDC25B in numerous human tumors might therefore have a critical role in centrosome amplification and genomic instability. [Cancer Res 2007;67(24):11557–64]
Cauda equina syndrome
Authors: C. Lavy, A. James, J. Wilson-MacDonald, J. Fairbank
Journal: BMJ (2009)

#### Summary points 

An understanding of cauda equina syndrome is important not only to orthopaedic surgeons and neurosurgeons but also to general practitioners, emergency department staff, and other specialists to whom these patients present. Recognition of the syndrome by all groups of clinicians is often delayed as it presents with bladder, bowel, and sexual problems, which are common complaints and have a variety of causes. Patients may not mention such symptoms because of embarrassment or because the onset is slow and insidious. 

Cauda equina syndrome is a clinical area that attracts a high risk of litigation. Although symptoms have poor predictive value on their own for the syndrome, it is important to document the nature and timing of bladder, bowel, and sexual symptoms (along with any associated clinical findings), particularly if they are new, especially in those with a history of back pain and associated leg pain, and to make a timely referral for appropriate investigation and expert treatment.

This review aims to highlight cauda equina syndrome as a possible clinical diagnosis, review the evidence for an emergency surgical approach, and maintain an awareness of the medicolegal issues that surround the condition.

Cauda equina syndrome results from the dysfunction of multiple sacral and lumbar nerve roots in the lumbar vertebral canal. Such root dysfunction can cause a combination of clinical features, but the term cauda equina syndrome is used only when these include impairment of bladder, bowel, or sexual …
Bone scintigraphy in chronic knee pain: comparison with magnetic resonance imaging
Authors: T. Boegard, O. Rudling, J. Dahlstrom, H. Dirksen, I. F Petersson, K. Jonsson
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To compare increased bone uptake of <sup>99</sup>Tc<sup>m</sup>-MDP and magnetic resonance (MR) detected subchondral lesions, osteophytes, and cartilage defects in the knee in middle aged people with longstanding knee pain. <h3>METHODS</h3> Fifty eight people (aged 41–58 years, mean 50) with chronic knee pain, with or without radiographic knee osteoarthritis, were examined with bone scintigraphy. The pattern and the grade of increased bone uptake was assessed. On the same day, a MR examination on a 1.0 T imager was performed. The presence and the grade of subchondral lesions, osteophytes, and cartilage defects were registered. <h3>RESULTS</h3> The κ values describing the correlation between increased bone uptake and MR detected subchondral lesions varied between 0.79 and 0.49, and between increased bone uptake and MR detected osteophytes or cartilage defects the values were &lt;0.54. The κ values describing the correlation between the grade of bone uptake and the grade of the different MR findings was &lt;0.57. <h3>CONCLUSIONS</h3> Good agreement was found between increased bone uptake and MR detected subchondral lesion. The agreement between increased bone uptake and osteophytes or cartilage defects was in general poor as well as the agreement between the grade of bone uptake and the grade of the MR findings.
Sympathetic response to oral carbohydrate administration. Evidence from microelectrode nerve recordings.
Authors: C Berne, J Fagius, F Niklasson
Journal: Journal of Clinical Investigation (1989)

Microneurography was used to measure sympathetic outflow in human muscle nerves (MSA) for up to 90 min after the ingestion of 100 g D-glucose, 75.8 g D-xylose, intravenous D-glucose (0.35 g/kg), and 300 ml water. 19 healthy subjects were examined using a microelectrode positioned in the right peroneal nerve. MSA increased from 21 +/- 0.9 bursts/min at rest to 36.9 +/- 4.3 bursts/min 30 min after ingestion of D-glucose and from 18.9 +/- 2.9 to 26.3 +/- 3.4 bursts/min 30 min after D-xylose. The increase in MSA was already significant by 15 min. MSA had not returned to the basal level after 90 min. Neither intravenous D-glucose nor water intake enhanced MSA. MSA increased in parallel with plasma norepinephrine, and a significant correlation (r = 0.55; P less than 0.001) was observed between the plasma insulin concentration and MSA after D-glucose ingestion. In three subjects the outflow of sympathetic nerve activity to the skin was examined after oral D-glucose and no change was observed, emphasizing the differentiated nature of the sympathetic nerve response to carbohydrate. Multiple factors such as insulin alone, hemodynamic adjustment to splanchnic vasodilation, and gastrointestinal distension are probably involved in the increased muscle nerve sympathetic outflow after carbohydrate ingestion.
MUCUS IN INTESTINAL CONTENTS OF GERMFREE RATS
Authors: Göran Lindstedt, Sven Lindstedt, Bengt E. Gustafsson
Journal: The Journal of Experimental Medicine (1965)

The fecal excretion of total nitrogen and of total hexosamines has been determined in germfree and conventional rats. Germfree rats excreted more hexosamines than the conventional rats, while no difference in the nitrogen excretion was found. Infection of the germfree rats with a normal flora resulted in a temporarily increased excretion of hexosamines and nitrogen over a period of 2 to 3 days after which they reached the level of the conventional animals. The contents of the germfree cecum contained 65 to 137 mg of hexosamines and 57 to 127 mg of nitrogen as compared to 1.2 to 5.3 and 7.4 to 23 mg in conventional animals. The high figures for hexosamines were due to an increase in the total amount of contents in the cecum and to a fivefold increase in the concentration of hexosamine-containing material. Studies on the distribution of hexosamine-containing cecal contents between sediment and supernatant after centrifugation at 20,000 g for 2 hours demonstrated that 5 to 10 per cent of the hexosamines occurred in the sediment in the germfree rats, while 75 to 85 per cent was found in this fraction in the conventional rats. The soluble part of the cecal contents in germfree as well as in the conventional rats contained 70 per cent of hexosamines in molecules with a molecular weight above approximatively 100,000 as found by gel filtration experiments on sephadex gels. The higher weight of the germfree cecal wall was reflected in a high total amount of nitrogen and hexosamines. Isolated strains of bacteria capable of reducing the cecal size in vivo did not show any capacity to degrade the mucus in vitro in a test system, where a full intestinal flora was highly active.
Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study
Authors: A J Welton, M R Vickers, J A Cooper, T W Meade, T M Marteau
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective</b>: To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women9s stated willingness to participate. <b>Design</b>: Quasirandomised, interview based study. <b>Setting</b>: 10 group practices in the Medical Research Council9s General Practice Research Framework. <b>Participants</b>: 436 postmenopausal women aged 45-64 who had not had a hysterectomy. <b>Main outcome measures</b>: Stated willingness to enter a trial and reasons for the decisions made. <b>Results</b>: Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health. <b>Conclusion</b>: For preventive trials the inclusion of a placebo arm may reduce patients9 willingness to participate.
What is Fitts' law about?
Authors: Herbert Heuer
Journal: Behavioral and Brain Sciences (1997)

Movement time and accuracy, as defined by Plamondon &amp; Alimi, do not conform to empirical definitions. When definitions are used that conform better to empirical ones, the original predictions of the kinematic theory are no longer valid – as is demonstrated by simulations. Thus the theoretically derived quadratic law and the successful empirical quadratic law seem to be independent of each other.
Cell adhesion regulates platelet-derived growth factor–induced MAP kinase and PI-3 kinase activation in stellate cells
Authors: Vinicio Carloni, Raffaella M. S. DeFranco, Alessandra Caligiuri, Alessandra Gentilini, Silvia Cappadona Sciammetta, Elisabetta Baldi, Benedetta Lottini, Paolo Gentilini, Massimo Pinzani
Journal: Hepatology (2002)

The biologic effects of growth factors are dependent on cell adhesion, and a cross talk occurs between growth factors and adhesion complexes. The aim of the present study was to evaluate the influence of cell adhesion on the major intracellular signaling pathways elicited by platelet-derived growth factor (PDGF) in hepatic stellate cells (HSC). PDGF signaling was investigated in an experimental condition characterized by lack of cell adhesion for different intervals of time. Basal and PDGF-induced focal adhesion kinase (FAK) tyrosine phosphorylation was maintained in a condition of cell suspension for 2, 4, and 6 hours, whereas it was completely lost after 12 and 24 hours. We examined MAP kinase activity at 2 and 24 hours, corresponding to the higher and lower levels of FAK phosphorylation. In these experiments, MAP kinase activity correlated with FAK phosphorylation. Stimulation with PDGF was able to cause Ras-GTP loading only in adherent cells. The ability of PDGF to induce phosphatidylinositol 3-kinase (PI 3-K) activity was abrogated in cells maintained in suspension. The Ser473 phosphorylation of Akt was only marginally affected by the lack of cell adhesion. We then evaluated the association of FAK with c-Src. This association was found to be cell adhesion dependent, and it did not appear to be dependent from phosphorylated FAK. These changes in PDGF-induced intracellular signaling were associated with a remarkable reduction of PDGF-proliferative potential in nonadherent cells, although no marked differences in the apoptotic rate were observed. In conclusion, these results suggest that cell adhesion differentially regulates major signaling pathways activated by PDGF in HSC.
Neuregulin/ErbB Signaling Regulates Cardiac Subtype Specification in Differentiating Human Embryonic Stem Cells
Authors: Wei-Zhong Zhu, Yiheng Xie, Kara White Moyes, Joseph D. Gold, Bardia Askari, Michael A. Laflamme
Journal: Circulation Research (2010)

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) exhibit either a "working" chamber or a nodal-like phenotype. To generate optimal hESC-CM preparations for eventual clinical application in cell-based therapies, we will need to control their differentiation into these specialized cardiac subtypes.To demonstrate intact neuregulin (NRG)-1β/ErbB signaling in hESC-CMs and test the hypothesis that this signaling pathway regulates cardiac subtype abundance in hESC-CM cultures.All experiments used hESC-CM cultures generated using our recently reported directed differentiation protocol. To support subsequent action potential phenotyping approaches and provide a higher-throughput method of determining cardiac subtype, we first developed and validated a novel genetic label that identifies nodal-type hESC-CMs. Next, control hESC-CM preparations were compared to those differentiated in the presence of exogenous NRG-1β, an anti-NRG-1β neutralizing antibody, or the ErbB antagonist AG1478. We used 3 independent approaches to determine the ratio of cardiac subtypes in the resultant populations: direct action potential phenotyping under current-clamp, activation of the aforementioned genetic label, and subtype-specific marker expression by RT-PCR. Using all 3 end points, we found that inhibition of NRG-1β/ErbB signaling greatly enhanced the proportion of cells showing the nodal phenotype.NRG-1β/ErbB signaling regulates the ratio of nodal- to working-type cells in differentiating hESC-CM cultures and presumably functions similarly during early human heart development. We speculate that, by manipulating NRG-1β/ErbB signaling, it will be possible to generate preparations of enriched working-type myocytes for infarct repair, or, conversely, nodal cells for potential use in a biological pacemaker.