tbuckley/cabot-search huggingface dataset:
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis
Authors: Armin Schneider, Carola Krüger, Tobias Steigleder, Daniela Weber, Claudia Pitzer, Rico Laage, Jaroslaw Aronowski, Martin H. Maurer, Nikolaus Gassler, Walter Mier, Martin Hasselblatt, Rainer Kollmar, Stefan Schwab, Clemens Sommer, Alfred Bach, Hans-Georg Kuhn, Wolf-Rüdiger Schäbitz
Journal: Journal of Clinical Investigation (2005)

G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases.
The introduction of successful treatment of diabetes mellitus with insulin
Authors: Charilaos Stylianou, Christopher Kelnar
Journal: Journal of the Royal Society of Medicine (2009)

The introduction of insulin for treating patients with diabetes mellitus must rate as Canada's earliest contribution to the welfare of humankind. The report by Banting and his colleagues1 has been included in the James Lind Library because it provides an example of the kind of treatment effect that is so dramatic that there is no need for the very carefully controlled research which is needed to provide reliable evidence about the effects of most treatments.2 What led to Banting's important study, and what evidence was published subsequently confirming that a major advance in treatment had been discovered?
Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage☆
Authors: Y ABDALLAH, A GKATZOFLIA, D GLIGORIEVSKI, S KASSECKERT, G EULER, K SCHLUTER, M SCHAFER, H PIPER, C SCHAFER
Journal: Cardiovascular Research (2006)

Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the underlying mechanisms are still unknown. In this study, we investigated in isolated rat cardiomyocytes subjected to hypoxia and reoxygenation whether administration of insulin during reoxygenation reduces reoxygenation-induced hypercontracture, a hallmark of acute reperfusion injury. The effects of insulin on potential pro-survival kinases, i.e., PI 3-kinase, NO synthase (eNOS), and cGMP-dependent protein kinase (PKG), and on cytosolic Ca2+ control in reoxygenated cardiomyocytes were investigated.Administration of insulin (10 mU/L) during reoxygenation protected cardiomyocytes against hypercontracture development (cell length as % of end-hypoxic length: control 61.6+/-3.2; insulin 76.3+/-2.9; n=26; p<0.05 vs. control). Cytosolic [Ca2+] recovery during the first 2 min of reoxygenation was accelerated (fura-2 ratio after 2 min of reoxygenation; control 1.01+/-0.05; insulin 0.79+/-0.04; n=26; p<0.05 vs. control). The beneficial effects of insulin on cytosolic [Ca2+] recovery and hypercontracture were suppressed in the presence of inhibitors of PI 3-kinase (LY294002, 1 microM), eNOS (L-NMMA, 100 microM), PKG (KT 5823, 1 microM), or sarcoplasmic reticulum Ca2+ pump (SERCA) (thapsigargin, 150 nM). Insulin increased phosphorylation and activity of eNOS and augmented phospholamban phosphorylation in reoxygenated cardiomyocytes. Correlated with phospholamban phosphorylation, insulin also augmented SR Ca2+ load.Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture. This is due to acceleration of cytosolic [Ca2+] recovery by enhanced Ca2+ sequestration into the sarcoplasmic reticulum via SERCA activation. This protective mechanism is activated through the survival pathway consisting of PI 3-kinase, eNOS, and PKG.
Amniotic Membrane Transplantation in Acute Phase of Toxic Epidermal Necrolysis with Severe Corneal Involvement
Authors: Akira Kobayashi, Tsuyoshi Yoshita, Kazuhisa Sugiyama, Kengo Miyashita, Yo Niida, Shoichi Koizumi, Scheffer C.G. Tseng
Journal: Ophthalmology (2005)
Acidosis-Sensing Glutamine Pump SNAT2 Determines Amino Acid Levels and Mammalian Target of Rapamycin Signalling to Protein Synthesis in L6 Muscle Cells
Authors: Kate Evans, Zeerak Nasim, Jeremy Brown, Heather Butler, Samira Kauser, He[Combining Acute Accent]le[Combining Grave Accent]ne Varoqui, Jeffrey D. Erickson, Terence P. Herbert, Alan Bevington
Journal: Journal of the American Society of Nephrology (2007)

Wasting of lean tissue as a consequence of metabolic acidosis is a serious problem in patients with chronic renal failure. A possible contributor is inhibition by low pH of the System A (SNAT2) transporter, which carries the amino acid L-glutamine (L-Gln) into muscle cells. The aim of this study was to determine the effect of selective SNAT2 inhibition on intracellular amino acid profiles and amino acid-dependent signaling through mammalian target of rapamycin in L6 skeletal muscle cells. Inhibition of SNAT2 with the selective competitive substrate methylaminoisobutyrate, metabolic acidosis (pH 7.1), or silencing SNAT2 expression with small interfering RNA all depleted intracellular L-Gln. SNAT2 inhibition also indirectly depleted other amino acids whose intracellular concentrations are maintained by the L-Gln gradient across the plasma membrane, notably the anabolic amino acid L-leucine. Consequently, SNAT2 inhibition strongly impaired signaling through mammalian target of rapamycin to ribosomal protein S6 kinase, ribosomal protein S6, and 4E-BP1, leading to impairment of protein synthesis comparable with that induced by rapamycin. It is concluded that even though SNAT2 is only one of several L-Gln transporters in muscle, it may determine intracellular anabolic amino acid levels, regulating the amino acid signaling that affects protein mass, nucleotide/nucleic acid metabolism, and cell growth.
Two way push videoenteroscopy in investigation of small bowel disease
Authors: Y Bouhnik, A Bitoun, B Coffin, R Moussaoui, A Oudghiri, J C Rambaud
Journal: Gut (1998)

Aims —To evaluate the diagnostic yield and safety of a new push type videoenteroscope (PVE) for diagnosis of small bowel disease. Methods —Three hundred and thirteen patients were referred for one or two way PVE from December 1993 to June 1996. Indications for PVE were: an unexplained iron deficiency anaemia with or without clinically evident gastrointestinal bleeding; or a complementary investigation for suspected small bowel disease, after a small bowel barium follow through (SBBFT) considered as normal or abnormal, but without a definite diagnosis. Results —A jejunoscopy and a retrograde ileoscopy were carried out in 306 and 234 patients, respectively. In patients with isolated anaemia (n=131) and those with clinically evident gastrointestinal bleeding associated anaemia (n=72), PVE provided a diagnosis in 26 (19.8%) and 22 (30.5%) cases, respectively. Lesions found were located in the jejunoileum in 30 (14.7%) patients and in the gastroduodenum or the colon in 18 (8.8%) patients—that is, within the reach of the conventional gastroscope/colonoscope. In patients with normal (n=54) or abnormal (n=56) SBBFT, PVE provided a diagnosis in 17 (31%) and 27 (48%) cases, respectively. In 25% of cases, the abnormal appearance of SBBFT was not confirmed. The site of the radiological abnormality was not reached in 27% of cases. Lesions were located at the jejunum and the ileum in 59 (64%) and 33 (36%) cases, respectively. Conclusions —PVE is useful in around 30% of cases of unexplained anaemia or after an SBBFT which failed to provide an accurate aetiological diagnosis. Use of retrograde videoenteroscopy increases diagnostic yield by one third.
Cancer plan for Scotland will cost 40m
Authors: B. Christie
Journal: BMJ (2001)

Doctors and other health workers in Scotland are to be given a key role in deciding how cancer services develop, as part of a £40m ($56m) strategy designed to improve the treatment and prevention of the disease.

The Scottish health department has decided to place the people who are delivering the care at the heart of the planning process by charging them with determining priorities for investment and change. Three regional cancer advisory groups are to be set up around the …
The High Prevalence of Autoantibodies to Tissue Transglutaminase in First-Degree Relatives of Patients With Type 1 Diabetes Is Not Associated With Islet Autoimmunity
Authors: Alistair J. K. Williams, Alastair J. Norcross, Robert J. Lock, David J. Unsworth, Edwin A. M. Gale, Polly J. Bingley
Journal: Diabetes Care (2001)

OBJECTIVE—To determine the extent of celiac autoimmunity in type 1 diabetic patients and the overlap between islet and celiac autoimmunity in their nondiabetic relatives. RESEARCH DESIGN AND METHODS—IgA antibodies to tissue transglutaminase were determined in serum taken from 433 type 1 diabetic patients and 1,442 nondiabetic first-degree relatives. Samples with transglutaminase antibodies above the 97.5th percentile of 347 schoolchildren were also assayed for IgA anti-endomysial antibodies (EMAs). Markers of islet autoimmunity (islet cell antibodies and autoantibodies to insulin, glutamate decarboxylase, and protein tyrosine phosphatase IA-2) had previously been measured in all relatives. RESULTS—In the absence of known celiac disease, the prevalence of transglutaminase antibody levels above the 97.5th percentile of the schoolchildren was 13.4% in diabetic patients and 7.0% in nondiabetic relatives. EMAs were found in addition to transglutaminase antibodies in 2.6% of probands and in 1.9% of first-degree relatives, but none of the schoolchildren. Transglutaminase antibodies were found to persist in 10 of 30 patients and in 30 of 59 relatives with follow-up samples taken at least 2 years after the initial sample. Of 186 nondiabetic relatives with islet autoantibodies, only 10 also had transglutaminase antibodies. CONCLUSIONS—We found a high prevalence of celiac autoimmunity in patients and first-degree relatives of children with type 1 diabetes, but we found limited overlap between islet and celiac autoimmunity in nondiabetic relatives. The high prevalence of celiac autoimmunity may be explained by shared genetic susceptibility and identifies a population within which screening for the disease may be justified.
Laennec's stethoscope--the Welsh connection
Authors: J. S Morris
Journal: Journal of the Royal Society of Medicine (2004)

In the twenty-first century the Necker Hospital in Paris is a large hospital of over 800 beds providing specialist care for children and some adults.The hospital, a mixture of new and old buildings set in 22 acres, was founded in 1778 by Madam Necker a writer, philanthropist and wife of Jacques Necker who was director of finances to Louis XVI.The French physician Rene ´The ´ophile Hyacinth Laennec, from Quimper in Brittany, became chef de service at the Necker Hospital in 1816 and it was there that he described the stethoscope.He used the stethoscope in his practice and correlated his clinical findings with those he found at post mortem examinations. 1In 1819 he published his findings in his book Traite ´de l'Auscultation Me ´diate.Laennec was acknowledged as an innovator and teacher and over three hundred foreign students studied with him. 2 Three of the foreign students had a strong Welsh connection and their contributions to the introduction of the stethoscope to the UK are the subject of this report.The three doctors were Charles James Blasius Williams, Thomas Davies and Thomas Prestwood Lucas.Of the three, Williams made the greatest contribution to the science and art of auscultation.
M265 Daily Activity Monitoring In Idiopathic Pulmonary Fibrosis
Authors: M. Crooks, S. Hart
Journal: Thorax (2014)

<h3>Introduction</h3> Idiopathic pulmonary fibrosis (IPF) is an incurable chronic progressive lung disease with a poor prognosis. Decline in forced vital capacity (FVC) is the primary outcome measure in most clinical trials. However, slowing lung function decline does not translate into patients feeling better. We investigated the acceptability of activity monitoring as a patient centred outcome measure in IPF and correlated results with lung function and quality of life (QoL) measures. <h3>Methods</h3> IPF Subjects underwent activity monitoring 23 h a day for a minimum of 8 days using the SenseWear armband (Bodymedia, Philadelphia). Monitoring data from the first and last monitored days were discarded to prevent clinic visits impacting the results. Participants completed the St George’s Respiratory Questionnaire (SGRQ) as a QoL measure. Lung function measurements performed within 3 months were collected and correlations assessed using Pearsons correlation coefficient. Data are presented as mean±SD. <h3>Results</h3> 17 IPF subjects (Age 76 ± 6.3, 82% males, FVC%predicted 82.3 ± 16.1%, TLCO% predicted 48.3 ± 13.3%) were monitored. There was excellent compliance – armbands were worn for an average of 23 h and 9 min per day (range: 22 h and 10 min to 24 h) for 6.2 ± 0.6 complete days. Activity levels measured in METs were 1.25 ± 0.2 with a daily step count of 3364 ± 2504. IPF subjects were physically active (METs &gt;3) for 83.8 ± 57.4 min per day. Mean daily METs inversely correlated with SGRQ score (r=-0.64, p = &lt;0.01). Mean daily METs correlated with FVC (% predicted) (r = 0.50, p = 0.04) but there was no correlation with TLCO (% predicted) (r = 0.39, p = 0.13). Conversely TLCO inversely correlated with SGRQ score (r=-0.55, p = 0.03) but FVC did not (r=-0.29, p = 0.26). <h3>Conclusion</h3> Activity monitoring is an acceptable, well tolerated means of measuring functional status in IPF patients. Mean daily activity level correlates well with QoL measures and FVC. Neither individual lung function measurement performed as well in terms of correlation with QoL and activity level. A larger longitudinal study is required to further evaluate the role of activity monitoring in IPF and identify its utility in prognostication.
Mortality in the 4-Year Trial of Tiotropium (UPLIFT) in Patients with Chronic Obstructive Pulmonary Disease
Authors: Bartolome Celli, Marc Decramer, Steven Kesten, Dacheng Liu, Sunil Mehra, Donald P. Tashkin
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

In the 4-year UPLIFT trial, tiotropium improved lung function and health-related quality of life and decreased exacerbations compared with usual respiratory medications except inhaled anticholinergics in patients with chronic obstructive pulmonary disease (COPD). Mortality and its causes was a secondary endpoint in UPLIFT.We describe the effect of tiotropium on survival and analyze differences between mortality during treatment and during follow-up of discontinued patients.This study involved a randomized, double-blind trial comparing tiotropium with placebo in patients with COPD (>or=40 yr of age; postbronchodilator FEV(1) <or=70%; FEV(1)/FVC <or=70%). Mortality was evaluated during treatment and with follow-up of discontinued patients. Cause of death was adjudicated by an endpoint committee.A total of 5,993 patients were randomized, 3,006 to placebo and 2,987 to tiotropium. While patients were receiving treatment, there were 792 deaths, with a lower risk in the tiotropium group (hazard ratio, 0.84; 95% confidence interval [CI], 0.73-0.97). Statistical significance was observed at the end of the protocol-defined treatment period (P = 0.034) but not 30 days thereafter (P = 0.086). Adjustment by GOLD stage, sex, age, baseline smoking behavior, and baseline respiratory medications subgroups did not alter the results of the analysis. The most common causes of death adjudicated by an independent end-point committee were lower respiratory, cancer, general disorders, and cardiac disorders. The hazard ratios for lower respiratory and cardiac mortality during treatment were 0.86 (95% CI, 0.68-1.09) and 0.86 (95% CI, 0.75-0.99), respectively.Treatment with tiotropium over 4 years is associated with decreased mortality, with the effect being most prominent in the cardiac and respiratory systems.
ASSESSMENT OF POSTURAL STABILITY IN SUBJECTS WITH LUMBAR DISC HERNIATION
Authors: Zdenek Svoboda, Miroslav Janura, Eva Filipiova
Journal: British Journal of Sports Medicine (2013)

Background Chronic spinal disc disease leads to disorders in postural movement coordination and deteriorates postural stability. 1 Recent studies suggest that subjects with lumbar disc herniation (LDH) develop visual compensation mechanisms for underlying sensory–motor deficits. In subjects with unilateral disease, using two separate force plates, enable the balance evaluation of each limb. The aim of this study was to assess postural stability in LDH subjects on both the affected and the unaffected limbs. Methods The experimental group consisted of ten (6 males, 4 females) LDH subjects (L4/L5 or L5/S1 level) with an age of 41±8 years, weight 79±15 kg and height 177±6 cm. The treatment was only conservative (with no surgical intervention). The control group was composed of eleven healthy subjects (6 males, 5 female) with an age 40±9 years, weight 73±12 kg and height 174±9 cm. Postural sways (center of pressure movement) were evaluated using two force plates Kistler (Kistler Instrumente AG, Switzerland). All participants carried out three 30 s balance tasks: stance with opened eyes (EO), stance with closed eyes (EC) and stance with narrow base of support (NBS). In each test mean loading, medial lateral (ML) and anterior posterior sways (standard deviations of COP coordinates) were evaluated. Statistical analyses were performed by two-way ANOVA with Tukey's post hoc test (Statistica 9.0, independent variables: limb, group). Results There was no significant difference in limb loading for both the experimental and the control group and total ML sway and AP sway. In the EO and EC conditions, there was no significant difference between postural sway of limbs of LDH subjects and limbs of controls. In the NBS conditions, the ML sway was greater in affected limb compared to dominant (p&lt;0.01) and non-dominant (p&lt;0.05) limbs of controls. Discussion/Conclusions The results suggest that the balance evaluation of each limb independently can be useful in assessment of groups of subjects with unilateral disease. The LDH subjects showed increased ML postural sway on the affected limb during NBS conditions. Similar findings reported Mientjes and Frank 2 for chronic low back pain patients. They found an increase in the ML postural sway of these patients compared to healthy controls when the task involved increased complexity and removal of visual information.
A review of paediatric tuberculosis in Denmark: 10-year trend, 2000-2009
Authors: Camilla Ingrid Hatleberg, Julie B. Prahl, Jeppe Nørgaard Rasmussen, Peter Henrik Andersen, Stephanie Bjerrum, Vibeke Østergaard Thomsen, Isik Somuncu Johansen
Journal: European Respiratory Journal (2013)

Paediatric tuberculosis (TB) is a key indicator for recent transmission and presents a reservoir for the disease. We describe trends in epidemiology, microbiological characteristics and treatment outcome in Denmark between 2000 and 2009. Data were retrieved from the national TB surveillance system and the International Reference Laboratory of Mycobacteriology. In total, 323 TB cases were reported in children aged &lt;15 years, accounting for 7.6% of all notified cases in Denmark. The overall incidence rate of childhood TB declined from 4.1 per 100 000 to 1.9 per 100 000 in the study period. Immigrant children comprised 79.6% of all cases, with the highest incidence rate of 94.1 per 100 000 children in 2001. In contrast to immigrant children, the majority of Danish children were aged &lt;5 years and had a known exposure to TB. Pulmonary TB was the commonest presentation. Only half of the cases were culture confirmed. We observed an overall decreasing trend in the child to adult notification ratio, but a slight increase in the ratio when calculated specifically for ethnic Danes. Childhood TB needs continuous attention with a special focus on risk groups. Emphasis on improving early TB case detection, contact tracing and further implementation of preventive treatment is necessary.
The Treatment of Alcoholism in a Comprehensive Community Mental Health Center
Authors: WILLIAM T. HART
Journal: American Journal of Psychiatry (1970)

The author believes that alcoholism is an emotional illness and should be treated like any other emotional illness. At present, prejudice toward the alcoholic often hides this fact and hinders his care. After outlining psychotherapeutic strategies and the minimum essential network of community services, the author describes how alcoholism services are delivered in a comprehensive community mental health center in Rochester, N. Y.
Role of microRNAs in stem/progenitor cells and cardiovascular repair
Authors: P. Jakob, U. Landmesser
Journal: Cardiovascular Research (2011)

MicroRNAs (miRNAs), small non-coding RNAs, play a critical role in differentiation and self-renewal of pluripotent stem cells, as well as in differentiation of cardiovascular lineage cells. Several miRNAs have been demonstrated to repress stemness factors such as Oct4, Nanog, Sox2 and Klf4 in embryonic stem cells, thereby promoting embryonic stem cell differentiation. Furthermore, targeting of different miRNAs promotes reprogramming towards induced pluripotent stem cells. MicroRNAs are critical for vascular smooth muscle cell differentiation and phenotype regulation, and miR-143 and miR-145 play a particularly important role in this respect. Notably, these miRNAs are down-regulated in several cardiovascular disease states, such as in atherosclerotic lesions and vascular neointima formation. MicroRNAs are critical regulators of endothelial cell differentiation and ischaemia-induced neovascularization. miR-126 is important for vascular integrity, endothelial cell proliferation and neovascularization. miR-1 and miR-133 are highly expressed in cardiomyocytes and their precursors and regulate cardiomyogenesis. In addition, miR-499 promotes differentiation of cardiomyocyte progenitor cells. Notably, miRNA expression is altered in cardiovascular disease states, and recent studies suggest that dysregulated miRNAs may limit cardiovascular repair responses. Dysregulation of miRNAs may lead to an altered function and differentiation of cardiovascular progenitor cells, which is also likely to represent a limitation of autologous cell-based treatment approaches in these patients. These findings suggest that targeting of specific miRNAs may represent an interesting novel opportunity to impact on endogenous cardiovascular repair responses, including effects on stem/progenitor cell differentiation and functions. This approach may also serve to optimize cell-based treatment approaches in patients with cardiovascular disease.
Retinal Neovascularization and Endogenous Fungal Endophthalmitis in Intravenous Drug Users
Authors: Thuy Doan, Gurunadh A. Vemulakonda, Deana Choi, C. Dirk Keene, Lakshmi Akileswaran, Russell N. Van Gelder, Jennifer R. Chao
Journal: Ophthalmology (2014)