tbuckley/cabot-search huggingface dataset:
Periodate-labile structures at the normal human cutaneous basement membrane zone*
Authors: J. NANCHAHAL, D.J. RICHES
Journal: British Journal of Dermatology (1983)

The distribution of carbohydrates containing 1,2-glycol groups at the basement membrane zones of the dermo-epidermal junction and dermal blood vessels was investigated using the periodic acid-thiosemicarbazide-silver proteinate technique. Controls included pre-incubation with dimedone, dimedone treatment both before and after periodate oxidation, and dimedone treatment followed by thiosemicarbazide and silver proteinate. At the dermo-epidermal junction the anchoring fibrils were stained selectively after both short (45 min) and long (71 h) thiosemicarbazide incubation periods, there being no staining of the lamina densa; however, the lamina densa surrounding blood vessels was labelled. After prolonged treatment with thiosemicarbazide, fibrils were observed traversing the lamina lucida at the dermo-epidermal junction, and collagen fibres were stained faintly. Pre-incubation with dimedone to block aldehyde groups did not affect the staining. However, when periodic acid treatment was omitted, or when sections were incubated with dimedone both before and after periodate oxidation, only melanin granules and the cytoplasm of fibroblasts were stained. Thus, anchoring fibrils are rich in carbohydrates containing 1,2-glycol groups susceptible to periodate oxidation, and correspond to the periodic acid Schiff-positive layer seen at the dermo-epidermal junction. Furthermore, the basement membrane zones of dermal blood vessels and the dermo-epidermal junction differ in their carbohydrate distribution.
F-18 FDG PET/CT Demonstration of an Adrenal Metastasis in a Patient With Anaplastic Thyroid Cancer
Authors: Andrei Iagaru, I Ross McDougall
Journal: Clinical Nuclear Medicine (2006)

An adrenal metastasis was identified on an F-18 FDG PET/CT scan in a patient with anaplastic thyroid cancer. There are very few reports of thyroid cancer, even anaplastic thyroid cancer, metastasizing to the adrenal.
Abstract B46: The role of integrin switching and Deptor in metastatic breast cancer
Authors: Jenny G. Parvani, Molly A. Taylor, William P. Schiemann
Journal: Cancer Research (2013)

Abstract Mammary tumorigenesis converts TGF-β; from a tumor suppressor in normal mammary epithelial cells (MECs) to a tumor promoter in cancerous MECs, likely via Epithelial-Mesenchymal Transiton (EMT). Integrin signaling plays a critical role in this conversion, although the underlying molecular mechanisms remain elusive. Previously, both β1 and β3 integrins have been associated with TGF-β; mediated EMT and metastasis in breast cancer, making both integrins attractive therapeutic targets. Importantly, the interplay and requirement for β1 and β3 integrins in mediating metastatic disease and the downstream effectors that effectuate the malignancy associated with these intergrins have not been fully evaluated. Here, we describe an integrin switching mechanism where functional disruption of β1 integrin mediates compensatory upregulation of β3 integrin expression, which augments TGF-β; signaling and mediates 3D outgrowth of metastatic breast cancer cells. We demonstrate that sole targeting of β1 integrin is insufficient in reducing tumor burden, while sole targeting of β3 integrin significantly alleviates the disease. Furthermore, we identify Deptor, the endogenous inhibitor of mTOR, to be downregulated in β3 integrin expressing cells, suggesting that attenuated Deptor expression may engender the malignancy associated with β3 integrin. Importantly, functional disruption of Deptor in systemically invasive 4T07 cells induces their acquisition of mesenchymal characteristics, while attenuating their ability to proliferate. Collectively, we demonstrate that targeting β1 integrin alone is insufficient in alleviating metastatic breast cancer, while sole targeting of β3 integrin significantly attenuates the disease. Furthermore, our data identifies Deptor as a potential downstream effector in β3 integrin-dependent malignancies. Citation Format: Jenny G. Parvani, Molly A. Taylor, William P. Schiemann. The role of integrin switching and Deptor in metastatic breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B46.
Curvatures of the spine.
Authors: Lawrence C. Parish
Journal: JAMA (1963)

A man who has practiced orthopedic surgery for over four decades is in an enviable position—he has gained an unusual wealth of experience. If, in addition, he has received the best training available in this country and abroad, he may be considered the compleat orthopedist, capable of writing a highly useful monograph. The author of this work has such a background. The main purpose of this book is to describe a conservative approach to the treatment of scoliotic, kyphotic, lordotic, and other curvature problems of the spine. Even if the reader disagrees with the cast and tape method and prefers surgical intervention, he would be rewarded by a study of the extensive collection of photographs and x-rays. In any event, he would have difficulty finding fault with the author's concepts and with his ideas. The chapters are well organized and include sections on terminology, pathology, and clinical signs. The excellent
Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells
Authors: Laura M. Calvi, Olga Bromberg, Yumie Rhee, Jonathan M. Weber, Julianne N. P. Smith, Miles J. Basil, Benjamin J. Frisch, Teresita Bellido
Journal: Blood (2012)
The development of the entire end-systolic pressure-volume and ejection fraction-afterload relations: a new concept of systolic myocardial stiffness.
Authors: I Mirsky, T Tajimi, K L Peterson
Journal: Circulation (1987)

In this study we introduce a new concept of systolic myocardial stiffness that extends the Suga-Sagawa maximum ventricular elastance concept to the myocardium. End-systole is defined as the time of maximum systolic myocardial stiffness (max Eav), which we examined for its load independence and sensitivity to changes in the inotropic state and to heart rate. Seven adult mongrel dogs were instrumented with ultrasonic crystals for measurements of long and short axes and left ventricular wall thickness, and a high-fidelity micromanometer was inserted for measurement of left ventricular pressures. Preload and afterload were altered by inferior vena cava occlusion, nitroprusside, angiotensin II, atropine, propranolol, and various combinations with propranolol. End-systolic stress-strain relations (slope: max Eav) were linear in all seven dogs, implying that end-systolic myocardial stiffness is independent of end-systolic stress. Changes in max Eav (for constant preload and afterload) reflected changes in the ejection fraction; max Eav was also insensitive to propranolol and to changes in heart rate over the range from 120 to 180 beats/min. End-systolic pressure-volume relations (ESPVRs), derived analytically from these stress-strain relations, were nonlinear, and estimates of volume at zero stress (Vom) were always positive. On the other hand, ESPVRs obtained on the basis of the Suga-Sagawa maximum ventricular elastance concept, were linear, and volume at zero pressure (Vop) estimated by linear extrapolation was negative in one case. Based on the concept of systolic myocardial stiffness, the slope of the ESPVR varies with end-systolic volume and attains its maximum value (Emax) at zero end-systolic pressure. Normalization of Emax with Vom demonstrated a close relationship to max Eav. Thus both max Eav and Vom and Emax are ideal variables for assessing changes in myocardial contractility when preload and afterload are constant. Furthermore, Vom and max Eav permit development of the entire ejection fraction-afterload relationship for a given preload, thus providing a method for comparing myocardial contractile states between ventricles.
Re: Gyorgyike Soos, Ioannis Tsakiris, Janos Szanto, Csaba Turzo, P. Gabriel Haas and Balazs Dezso. The Prevalence of Prostate Carcinoma and its precursor in Hungary: An Autopsy Study. Eur Urol 2005;48:739–44
Authors: Balazs Dezso, Gyorgyike Soos, Ioannis Tsakiris, Gabriel P. Haas
Journal: European Urology (2006)
Patients' champion calls for single opt-out clause for all data sharing projects
Authors: M. Limb
Journal: BMJ (2014)

A patients’ group has issued a warning to the UK government over new regional data centres that are meant to provide medical researchers and managers with access to millions of people’s personal medical records.

Healthwatch England said that proposals for so called accredited safe havens risked repeating mistakes made with the controversial care.data programme that ministers had to delay after widespread concerns, including complaints that patients were poorly informed about how the data would be used.

Healthwatch, which speaks on behalf of users of the NHS and social care, said it welcomed the extra assurances given by the secretary of state since the care.data furore about the way GP records will be used and how patients’ right to object to data sharing would be implemented. But these had not been made explicit in rules governing accredited safe havens, demonstrating that lessons had not been learnt, the organisation said.1

Anna Bradley, who chairs Healthwatch …
Ranitidine and sucralfate as maintenance therapy for gastric ulcer disease: endoscopic control and assessment of scarring.
Authors: T Takemoto, M Namiki, M Ishikawa, K Tsuneoka, S Oshiba, K Kawai, N Ogawa
Journal: Gut (1989)

The efficacy of ranitidine (150 mg nocte), and sucralfate (1 g tds) as maintenance therapy to prevent gastric ulcer relapse was evaluated in a 12 month trial in 363 patients. The relapse rates were 8.8% at three months, 14.7% at six months, 18.1% at nine months, and 21.0% at 12 months for the ranitidine group and 14.7%, 21.3%, 29.9%, and 30.2% respectively for the sucralfate group. At nine and 12 months the cumulative relapse rates for the ranitidine group were significantly lower than those for the sucralfate group (p less than 0.05). In both groups ulcers recurred mainly from red scars observed at the endoscopic scarring stage. This indicated the necessity of drug treatment up to the white scar stage. The results suggest that ranitidine is effective in preventing gastric ulcer relapse.
Plasma Renin Activity During Levodopa Therapy
Authors: Jay M. Sullivan
Journal: JAMA (1973)

Plasma renin activity (PRA) was studied in six patients with Parkinson disease under identical conditions of diet and posture before and after seven days of levodopa administration. Significant differences were not found at seven days, nor when the measurement was repeated under similar conditions of sodium excretion after six months of therapy. The PRA responded appropriately to posture before and after therapy. After six months of therapy, sodium restriction resulted in an appropriate response of PRA and aldosterone secretion. A small but significant fall in blood pressure took place seven days after the initiation of levodopa therapy, at which time PRA had not changed significantly. After six months of therapy, blood pressure had returned to control levels. This study suggests that the renin-aldosterone system is not significantly altered by levodopa therapy of Parkinson disease.
Abstract 5318: The breast epithelial stem cell line D492 overexpressing miR200c-141 is resistant to mesenchymal transition.
Authors: Bylgja Hilmarsdottir, Valgardur Sigurdsson, Jon T. Bergthorsson, Franzdottir R. Sigridur, Magnusson K. Magnus, T Gudjonsson
Journal: Cancer Research (2013)

Abstract MicroRNAs (miRs) are highly conserved, small RNA molecules that regulate key biological processes. miRs can act as tumor suppressors or oncogenes and their expression is often deregulated in cancers. The miR200 family is found in two clusters at chromosome 1 (miR200ba-429) and 12 (miR200c-141). Downregulation of the miR200 family has been linked to epithelial to mesenchymal transition (EMT) and recent studies show that members of this family are regulators of epithelial integrity in many tissues. We have recently shown that D492, a breast epithelial cell line with stem cell properties which generates branching structures when cultured in reconstituted basement membrane (rBM), undergoes EMT in coculture with endothelial cells. This is evidenced by formation of a stable spindle-like phenotype, suppression of keratin expression and cadherin switch from E- to N-cadherin (Sigurdsson et al. PLoS ONE 2011). In this study we have mapped the miRNA expressional changes in D492 compared to its mesenchymal-derivative D492M. Among the most profound changes were suppression of the miR200 family. Treatment of D492M with the demethylating agent 5-aza-2′-deoxycytidine reversed the EMT phenotype and reestablished E-cadherin expression. Bisulfite sequencing showed that the promoter region of miR200c-141 was methylated in D492M but not in D492. No methylation was seen in the promoter regions of E-cadherin or miR200ba-429 in either cell line. Overexpression of miR200c-141 in D492M reversed the EMT phenotype resulting in loss of N-cadherin and Snail expression and gain of E-cadherin and EpCAM expression. Interestingly, overexpression of miR200c-141 in D492M failed to reverse keratin expression back to an epithelial phenotype. When cultured in rBM D492M-200c-141 cells form irregular branching and showed no EMT phenotype. Interestingly, overexpression of miR200c-141 in D492M and D492 inhibits endothelial induced mesenchymal transition in rBM. This indicates that silencing of the miR-200c-141 with promoter methylation is associated with endothelial induced-EMT. In conclusion, our data suggests that overexpression of miR-200c-141 in D492 and D492M inhibits and reverses EMT, respectively, and this support the view that miR200c-141 may be a potent tumor suppressor and important regulator of epithelial integrity in the human breast. Citation Format: Bylgja Hilmarsdottir, Valgardur Sigurdsson, Jon T. Bergthorsson, Franzdottir R. Sigridur, Magnusson K. Magnus, T Gudjonsson. The breast epithelial stem cell line D492 overexpressing miR200c-141 is resistant to mesenchymal transition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5318. doi:10.1158/1538-7445.AM2013-5318
Spontaneous Fistula Between a Right Common Iliac Artery and Iliac Vein-Reply
Authors: Dean D. Richards
Journal: JAMA (1984)

<h3>In Reply.—</h3> I am most grateful for the interesting letters received since publication of the case report on spontaneous fistula. Two cases displaying features similar to that case report have come to my attention, including the interesting article by Rubio and Morris<sup>1</sup>as well as a lucid report by George L. Hines, MD et al.<sup>2</sup>Neither case appeared in the extensive MEDLINE search I reviewed in preparation of the original article. I recently searched the<i>Cumulated Index Medicus</i>, volumes 19 (1978), 20 (1979), and 21 (1980), and could find neither of these reports listed or indexed under the appropriate author and subject listings, although they are certainly worthy of such ready access in the medical literature. Also of interest is a case in Dr F. J. Kazmier's<sup>3</sup>series of aortocaval fistulas (case 6), which varies from the aforementioned cases in that a large pseudoaneurysm, which had formed
Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir
Authors: Peter Sillevis Smitt, Maarten Driesse, John Wolbers, Max Kros, Cees Avezaat
Journal: Molecular Therapy (2003)

Between November 1998 and December 2001, we treated 14 patients with advanced recurrent high-grade gliomas with a total dose of 4.6 × 108, 4.6 × 109, 4.6 × 1010, or 4.6 × 1011 viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All patients had recurrence or progression of the tumor 1–24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four patients survived longer than 1 year following gene therapy. One patient is still alive, with histologically confirmed progression of the tumor, 29 months after treatment. Ten patients died within 8 months of treatment, all from progression of the tumor. In 5 patients residual and measurable tumor was visible on the direct (<48 h) postoperative MRI. No objective radiological response was documented on subsequent MRI. None of the patients came to autopsy. In conclusion, the administration of 4.6 × 1011 VP of IG.Ad.MLPI.TK by 50 injections into the wound bed following resection of recurrent malignant glioma, followed by GCV treatment, was well tolerated.
Specific high-affinity binding of high density lipoproteins to cultured human skin fibroblasts and arterial smooth muscle cells.
Authors: R Biesbroeck, J F Oram, J J Albers, E L Bierman
Journal: Journal of Clinical Investigation (1983)

Binding of human high density lipoproteins (HDL, d = 1.063-1.21) to cultured human fibroblasts and human arterial smooth muscle cells was studied using HDL subjected to heparin-agarose affinity chromatography to remove apoprotein (apo) E and B. Saturation curves for binding of apo E-free 125I-HDL showed at least two components: low-affinity nonsaturable binding and high-affinity binding that saturated at approximately 20 micrograms HDL protein/ml. Scatchard analysis of high-affinity binding of apo E-free 125I-HDL to normal fibroblasts yielded plots that were significantly linear, indicative of a single class of binding sites. Saturation curves for binding of both 125I-HDL3 (d = 1.125-1.21) and apo E-free 125I-HDL to low density lipoprotein (LDL) receptor-negative fibroblasts also showed high-affinity binding that yielded linear Scatchard plots. On a total protein basis, HDL2 (d = 1.063-1.10), HDL3 and very high density lipoproteins (VHDL, d = 1.21-1.25) competed as effectively as apo E-free HDL for binding of apo E-free 125I-HDL to normal fibroblasts. Also, HDL2, HDL3, and VHDL competed similarly for binding of 125I-HDL3 to LDL receptor-negative fibroblasts. In contrast, LDL was a weak competitor for HDL binding. These results indicate that both human fibroblasts and arterial smooth muscle cells possess specific high affinity HDL binding sites. As indicated by enhanced LDL binding and degradation and increased sterol synthesis, apo E-free HDL3 promoted cholesterol efflux from fibroblasts. These effects also saturated at HDL3 concentrations of 20 micrograms/ml, suggesting that promotion of cholesterol efflux by HDL is mediated by binding to the high-affinity cell surface sites.
Discordance of Molecular Biomarkers Associated with Epidermal Growth Factor Receptor Pathway between Primary Tumors and Lymph Node Metastasis in Non-small Cell Lung Cancer
Authors: Sarah Park, Alison J. Holmes-Tisch, Eun Yoon cho, Young Mog Shim, Jinkook Kim, Hyo Song Kim, Jeeyun Lee, Yeon Hee Park, Jin Seok Ahn, Keunchil Park, Pasi A. Jänne, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2009)
Alcohol and drug misuse sweeping world, says WHO
Authors: S. Mayor
Journal: BMJ (2001)

<h3>Objective</h3> To assess the impact of pharmacist intervention in reducing prescribing errors in paediatrics, and to analyse the clinical significance and reasons behind the errors detected. <h3>Methods</h3> Cross-sectional epidemiological study analysing the activities of the paediatric pharmacist in a maternity and children9s hospital with 180 paediatric beds, between January 2007 and December 2009. The following variables were analysed: impact of the pharmacist9s recommendation on patient care, reason for the intervention, clinical significance, type of negative outcome associated with the medication, acceptance rate, medication involved, intervention detection date and observations. <h3>Results</h3> A total of 1475 interventions in medical orders for 14 713 paediatric patients were recorded (40 (2.9%) extremely significant interventions and 155 (11.1%) very significant interventions). There were 1357 prescribing errors, 833 of which were dosing errors. 2.2% of the errors detected were potentially fatal (30 cases) and 14.3% (194 cases) were clinically serious. The main reason for interventions was detection of a dosage between 1.5 and 10 times higher than that recommended. The overall rate of acceptance of the pharmacist9s suggestions was 94.3%. The pharmacist carried out an average of 0.019 interventions per patient day throughout the study period. <h3>Conclusion</h3> Interventions by a clinical pharmacist had a major impact on reducing prescribing errors in the study period, thus improving the quality and safety of care provided.