tbuckley/cabot-search huggingface dataset:
Commission warns against selling genetic tests direct to the public
Authors: L. Eaton
Journal: BMJ (2003)

Genetic testing kits, which allow individuals to find out their long term risk of certain diseases, should not be sold direct to the public, the United Kingdom's Human Genetics Commission has recommended in a report to the government.

The growing number of tests available and the rapid technological developments in the area make it impossible to take an overall decision to accept the tests en masse, says the report. But it stops short of a complete ban on …
Clinical Lecture on Colles's Fracture of the Radius
Authors: G. H. B. Macleod
Journal: BMJ (1879)

GENTLEMEN,-Here is an elderly female who has just been admitted into my clinical wards, and who has sustained an injury of the left fore- arm.She tells us that her feet slipped on " a slide", and that she fell backwards and towards the left side, putting her hand down obliquely behind her.She fell with violence, the "hilt" of her hand coming into contact with the ground; and her hand was violently extended and bent backwards on the forearm.She was much shaken.She was conscious that something had snapped in her forearm, and she found that she had lost the use of it.She also suffered much pain.You will observe how she nurses the injured arm with her right one, and holds it across her body; how she inclines her body to the left side; how her pained limb is held between pronation and supination; and how, when I ask her to supinate it, she turns the whole extremity from the shoulder, and that evidently with pain.We will make her sit down and place her arm on her knee, so as to examine it more care- fully and with less inconvenience to her.The fingers are bent; the wrist-joint is round (as you see by comparing it with its fellow); the back of the hand and wrist rise up unnaturally in a rounded mass, and no longer retain, as on the other hand, the level of the back of the fore- arm.
Chronic subdural haematoma after snowboard head injury
Authors: M Uzura, Y Taguchi, M Matsuzawa, H Watanabe, S Chiba
Journal: British Journal of Sports Medicine (2003)

Two cases of chronic subdural haematoma following a snowboard head injury are reported. Although such cases are rare in sport, the risk in snowboarders is higher than expected. Evaluation of a snowboarder with a history of head injury, albeit mild, who complains of headaches should include computed tomography or magnetic resonance imaging to allow rapid identification of any intracranial pathology.
Involvement of Guanosine Triphosphatases and Phospholipase C-γ2 in Extracellular Signal–regulated Kinase, c-Jun NH2-terminal Kinase, and p38 Mitogen-activated Protein Kinase Activation by the B Cell Antigen Receptor
Authors: Ari Hashimoto, Hidetaka Okada, Aimin Jiang, Mari Kurosaki, Steven Greenberg, Edward A. Clark, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (1998)

Mitogen-activated protein (MAP) kinase family members, including extracellular signal–regulated kinase (ERK), c-Jun NH2-terminal kinase ( JNK), and p38 MAP kinase, have been implicated in coupling the B cell antigen receptor (BCR) to transcriptional responses. However, the mechanisms that lead to the activation of these MAP kinase family members have been poorly elucidated. Here we demonstrate that the BCR-induced ERK activation is reduced by loss of Grb2 or expression of a dominant-negative form of Ras, RasN17, whereas this response is not affected by loss of Shc. The inhibition of the ERK response was also observed in phospholipase C (PLC)-γ2–deficient DT40 B cells, and expression of RasN17 in the PLC-γ2–deficient cells completely abrogated the ERK activation. The PLC-γ2 dependency of ERK activation was most likely due to protein kinase C (PKC) activation rather than calcium mobilization, since loss of inositol 1,4,5-trisphosphate receptors did not affect ERK activation. Similar to cooperation of Ras with PKC activation in ERK response, both PLC-γ2–dependent signal and GTPase are required for BCR-induced JNK and p38 responses. JNK response is dependent on Rac1 and calcium mobilization, whereas p38 response requires Rac1 and PKC activation.
Abstract 4959: High-resolution MALDI imaging mass spectrometry demonstrated the correlation between phosphatidylinositol profiles and invasion/metastasis in human breast cancer
Authors: Masahiro Kawashima, Nobuko Kawaguchi-Sakita, Masahiro Sugimoto, Taka-Aki Sato, Koichi Tanaka, Masakazu Toi
Journal: Cancer Research (2014)

Abstract High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI IMS) is an emerging application for lipid research that provides a detailed histological distribution of ionized lipids within tissue section. Phosphatidylinositol (PI) is one of the major classes of membrane phospholipid. The cellular membrane fluidity and signal transduction activity could be modulated by the alteration of fatty acid composition of PIs. Especially, PI-3kinase pathway, which can be activated by the phosphorylation of PIs, has become a great concern in breast cancer treatment. Although the amount of PIs is known to increase in human breast cancer tissues, it remains unclear how PIs are distributed in cancerous tissues. In this study, we investigated the detailed spatial distribution of PIs in breast tissues obtained from 24 patients, including 23 invasive ductal carcinoma (IDC), 4 ductal carcinoma in situ (DCIS), and 4 fibrocystic change lesions by using HR-MALDI IMS. The distribution of PIs was visualized at the resolution of 10um. 10 PIs with different fatty acid composition were detected in breast tissues. High-resolution analysis revealed the fatty acid composition of PIs was altered specifically in cancer cell clusters compared to stromal cells and non-malignant epithelia. PIs carrying monounsaturated fatty acid (MUFA) and PIs carrying polyunsaturated fatty acid (PUFA) showed the specific localization to cancer cell clusters. However, the proportion of PIs carrying MUFA and PIs carrying PUFA showed a clear inverse correlation in cancer cells. When we compared the PI profiles of IDC, DCIS, and FC, it was suggested that the accumulation of PIs carrying PUFA was occurred during the step of invasion. Moreover, lymph node metastasis well correlated with the accumulation of PIs carrying PUFA in cancer cells. HR-MALDI IMS firstly demonstrated the possible association between the PI profiles of breast cancer cells and their invasion/metastasis ability. Although this is a preliminary study, HR-MALDI IMS could be a useful modality to visualize the reprogramming of the lipid metabolism which reflects the cancer cell phenotype. Citation Format: Masahiro Kawashima, Nobuko Kawaguchi-Sakita, Masahiro Sugimoto, Taka-Aki Sato, Koichi Tanaka, Masakazu Toi. High-resolution MALDI imaging mass spectrometry demonstrated the correlation between phosphatidylinositol profiles and invasion/metastasis in human breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4959. doi:10.1158/1538-7445.AM2014-4959
Restricted diet rescues rat enteric motor neurones from age related cell death
Authors: T Cowen
Journal: Gut (2000)

<h3>BACKGROUND</h3> Alone among autonomic neurones, enteric neurones are known to be vulnerable to age related cell death; over 50% may be lost in aging rodents. A previous study demonstrated unexpectedly that neurones of the myenteric plexus from rats fed a restricted diet appeared not to suffer from extensive cell death in contrast with previous studies of ad libitum fed animals. <h3>AIMS</h3> To compare myenteric neurone numbers in the ileum of young and aging male Sprague-Dawley rats fed either ad libitum or a restricted diet. <h3>METHODS</h3> Neurones were counted in whole mount preparations of rat ileum stained immunohistochemically for the pan-neuronal marker PGP9.5, for choline acetyltransferase, or for nitric oxide synthase, or with NADH or NADPH histochemistry. <h3>RESULTS</h3> Neurone numbers in the rat myenteric plexus were substantially affected by the dietary regimen: ad libitum feeding (50–60 g per day of standard rat chow) resulted in the death of about 50% of myenteric neurones in 24 month Sprague-Dawley rats, while numbers were unchanged when the daily dietary intake was halved between the ages of six and 24 months. Animals fed a double restricted diet (15 g per day) showed no cell loss at 30 months, as well as the predicted increase in longevity. Neurone loss was largely complete by 16 months in ad libitum fed animals. Numbers of cholinergic (possibly motor) neurones, as demonstrated by choline acetyltransferase immunohistochemistry, were substantially reduced in ad libitum fed aging rats but not in animals fed a restricted diet. Loss of cholinergic neurones after ad libitum feeding was confirmed by reduced numbers of neurones of a size range matching that of cholinergic neurones. <h3>CONCLUSIONS</h3> Ad libitum feeding of adult rats has adverse effects on the survival of myenteric neurones, neurone loss commencing before 16 months of age. Cholinergic neurones appear to be particularly vulnerable to the effects of diet. Restricting dietary intake from six months of age prevents neurone loss almost entirely up to 30 months of age in these rats.
Comparison of first degree relatives and spouses of people with chronic tension headache
Authors: S. Ostergaard, M. B. Russell, L. Bendtsen, J. Olesen
Journal: BMJ (1997)

The extraordinary diversity of excitatory synapse sizes is commonly attributed to activity-dependent processes that drive synaptic growth and diminution. Recent studies also point to activity-independent size fluctuations, possibly driven by innate synaptic molecule dynamics, as important generators of size diversity. To examine the contributions of activity-dependent and independent processes to excitatory synapse size diversity, we studied glutamatergic synapse size dynamics and diversification in cultured rat cortical neurons (both sexes), silenced from plating. We found that in networks with no history of activity whatsoever, synaptic size diversity was no less extensive than that observed in spontaneously active networks. Synapses in silenced networks were larger, size distributions were broader, yet these were rightward-skewed and similar in shape when scaled by mean synaptic size. Silencing reduced the magnitude of size fluctuations and weakened constraints on size distributions, yet these were sufficient to explain synaptic size diversity in silenced networks. Model-based exploration followed by experimental testing indicated that silencing-associated changes in innate molecular dynamics and fluctuation characteristics might negatively impact synaptic persistence, resulting in reduced synaptic numbers. This, in turn, would increase synaptic molecule availability, promote synaptic enlargement, and ultimately alter fluctuation characteristics. These findings suggest that activity-independent size fluctuations are sufficient to fully diversify glutamatergic synaptic sizes, with activity-dependent processes primarily setting the scale rather than the shape of size distributions. Moreover, they point to reciprocal relationships between synaptic size fluctuations, size distributions and synaptic numbers mediated by the innate dynamics of synaptic molecules as they move in, out and between synapses. <b>SIGNIFICANCE STATEMENT</b> Sizes of glutamatergic synapses vary tremendously, even when formed on the same neuron. This diversity is commonly thought to reflect the outcome of activity-dependent forms of synaptic plasticity, yet activity-independent processes might also play some part. Here we show that in neurons with no history of activity whatsoever, synaptic sizes are no less diverse. We show that this diversity is the product of activity-independent size fluctuations, which are sufficient to generate a full repertoire of synaptic sizes at correct proportions. By combining modeling and experimentation we expose reciprocal relationships between size fluctuations, synaptic sizes and synaptic counts, and show how these phenomena might be connected through the dynamics of synaptic molecules as they move in, out and between synapses.
Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack
Authors: Jamie A. Lopez, Olivia Susanto, Misty R. Jenkins, Natalya Lukoyanova, Vivien R. Sutton, Ruby H. P. Law, Angus Johnston, Catherina H. Bird, Phillip I. Bird, James C. Whisstock, Joseph A. Trapani, Helen R. Saibil, Ilia Voskoboinik
Journal: Blood (2013)
An introduction to modern work on the Bowditch phenomenon
Authors: M. I M NOBLE
Journal: Cardiovascular Research (1988)

Journal Article An introduction to modern work on the Bowditch phenomenon Get access MARK I M NOBLE MARK I M NOBLE From King Edward VII Hospital, Midhurst, Sussex Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 8, August 1988, Page 586, https://doi.org/10.1093/cvr/22.8.586 Published: 01 August 1988
Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin
Authors: K. Jung, F. Linse, R. Heller, C. Moths, R. Goebel, Ch. Neumann
Journal: Allergy (1996)

In the skin of normal and atopic individuals, the expression of E-selectin (ELAM-1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals (n = 17), the healthy-appearing skin of patients with atopic dermatitis (n = 10), and their acute (n = 5) and chronic (n = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was found to be significantly increased in nonlesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1, and ELAM-1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy-appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM-1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin-4 from cells which reside in atopic skin. The question of whether the inherent upregulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.
Comparison of Cost-Effectiveness and Utility of Exercise ECG, Single Photon Emission Computed Tomography, Positron Emission Tomography, and Coronary Angiography for Diagnosis of Coronary Artery Disease
Authors: Randolph E. Patterson, Robert L. Eisner, Steven F. Horowitz
Journal: Circulation (1995)

Background To compare cost-effectiveness and utility of four clinical algorithms to diagnose obstructive coronary atherosclerotic heart disease (CAD), we compared exercise ECG (ExECG), stress single photon emission computed tomography (SPECT), positron emission tomography (PET), and coronary angiography. Methods and Results Published data and a straightforward mathematical model based on Bayes’ theorem were used to compare strategies. Effectiveness was defined as the number of patients with diagnosed CAD, and utility was defined as the clinical outcome, ie, the number of quality-adjusted life years (QALY) extended by therapy after the diagnosis of CAD. Our model used published values for costs, accuracy, and complication rates of tests. Analysis of the model indicates the following results. (1) The direct cost (fee) for each test differs considerably from total cost per ΔQALY. (2) As pretest likelihood of CAD (pCAD) in the population increases, there is a linear increase in cost per patient tested but a hyperbolic decrease in cost per effect and cost per utility unit, ie, increased cost-effectiveness and decreased cost per utility unit. (3) At pCAD&lt;0.70, analysis of the model indicates that stress PET is the most cost-effective test, with the lowest cost per utility, followed by SPECT, ExECG, and angiography, in that order. (4) Above a threshold value of pCAD of 0.70 (for example, middle-aged men with typical angina), proceeding directly to angiography as the first test showed the lowest cost per effect or utility. This quantitative model has the advantage of estimating a threshold value of pCAD (0.70) at which the rank order of cost-effectiveness and cost per utility unit change. The model also allows substitution of different values for any variable as a way to account for the uncertainties of clinical data, ie, changing costs, test accuracy and risk, etc. This procedure, called sensitivity analysis, showed that the rank order of cost-effectiveness did not change despite changes in several variables. Conclusions (1) Estimation of total costs of diagnostic tests for CAD requires consideration not only of the direct cost of the test per se (eg, test fees) but also of the indirect and induced costs of management algorithms based on the test (eg, cost/ΔQALY). (2) It is essential to consider the clinical history (pCAD) when selecting the clinical algorithm to make a diagnosis with the lowest cost per effect or cost per utility unit. (3) Stress PET shows the lowest cost per effect or cost per utility unit in patients with pCAD&lt;0.70. (4) Angiography shows the lowest cost per effect or cost per utility unit in patients with pCAD&gt;0.70.
Plasma Osmolality and Feeding Practices of Healthy Infants in First Three Months of Life
Authors: D. P. Davies
Journal: BMJ (1973)

Plasma osmolality was measured in 60 healthy infants aged 1 to 3 months. The mean plasma osmolality in the 14 breast-fed infants (group A) was 284.3 mOsm/1. Nine infants fed artificial milk formulae alone (group B) had a mean value of 293.8 mOsm/1.; 37 infants already receiving solid foods in addition to artificial milk formulae (group C) had a mean value of 297.1 mOsm/1. The number of individual observations in the hyperosmolar range (more than 300 mOsm/1.) in groups A, B, and C were 0, 1, and 15, accounting respectively for 0%, 11.1%, and 40.5% of the total number of observations in each group.These results suggest that the early introduction to solid foods and the widespread use of artificial milk formulae at the expense of breast-feeding during the first three months of life result in an excessive dietary solute intake. This considerably stretches the ability of the immature kidney to maintain normal plasma tonicity. Minimal loss of water could precipitate a dangerous situation for babies with hyperosmolar plasma.
Vascular Permeability Factor (Vascular Endothelial Growth Factor) Expression and Angiogenesis in Cervical Neoplasia
Authors: Anthony.J Guidi, G. Abu-Jawdeh, B. Berse, Robert.W Jackman, K. Tognazzi, Harold.F Dvorak, L. F. Brown
Journal: JNCI Journal of the National Cancer Institute (1995)

Background : Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms reponsible for angiogenesis in cervical neoplasia, however, are not well defined. Purpose: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. Methods: Sixtysix cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIIIrelated antigen were evaluated quantitatively for microvessel density and for the presence of epithelial stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. Results: VPF mRNA expression, epithelial stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with lowgrade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. Conclusions: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia. [J Natl Cancer Inst 87:1237-1245,1995]
Iain Cran McLean
Authors: G. Purdie
Journal: BMJ (2009)

After gaining a degree in embryology, Iain Cran McLean worked briefly in cancer research and then in new drug developments for Napp Laboratories. In 1982, he started his medical studies in Aberdeen, undertaking his general practice training in Dumfries. This was followed by his first partnership in Fraserburgh in 1990. He returned to practise in the south west …
High Expression Levels of X-Linked Inhibitor of Apoptosis Protein and Survivin Correlate with Poor Overall Survival in Childhood <b> <i>de Novo</i> </b> Acute Myeloid Leukemia
Authors: Ingo Tamm, Stephan Richter, Doreen Oltersdorf, Ursula Creutzig, Jochen Harbott, Frank Scholz, Leonid Karawajew, Wolf-Dieter Ludwig, Christian Wuchter
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare. Experimental Design: Using flow cytometry and Western blot analysis, we, therefore, investigated 45 leukemic cell samples from children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins [CD95, Bcl-2, Bax, Bcl-xL, procaspase-3, X-linked inhibitor of apoptosis protein (XIAP), cellular inhibitor of apoptosis protein–1 (cIAP-1), survivin]. Results: XIAP (P &amp;lt; 0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by French-American-British (FAB) morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (P &amp;lt; 0.01) and Bcl-xL (P &amp;lt; 0.01) expression was lower in patients with favorable rather than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP [30 (n = 10) versus 41 months (n = 34); P &amp;lt; 0.05] and survivin [27 (n = 10) versus 41 months (n = 34); P &amp;lt; 0.05]. Conclusions: We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups, and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics, and poor overall survival should be confirmed within prospective pediatric AML trials.