tbuckley/cabot-search huggingface dataset:
E2F-1 Overexpression in U2OS Cells Increases Cyclin B1 Levels and cdc2 Kinase Activity and Sensitizes Cells to Antimitotic Agents
Authors: Angelo J. Russo, Pellegrino G. Magro, Zhen Hu, Wei-Wei Li, Rowayda Peters, Jennifer Mandola, Debabrata Banerjee, Joseph R. Bertino
Journal: Cancer Research (2006)

The E2F transcription factors play a critical role in coordinating transcription of specific genes essential for G1-S transition. In early G1, the retinoblastoma protein (pRB) becomes phosphorylated by cyclin-dependent kinases, disrupting pRB binding to E2F-1-3, allowing "free" E2F to regulate genes involved in proliferation. In the present study, we used a tetracycline E2F-1 inducible U2OS osteosarcoma cell line to investigate the effect of increasing levels of E2F-1 on the cytotoxicity of various chemotherapeutic drugs. Upon overexpression of E2F-1, there was no detectable change in cytotoxicity to doxorubicin, cisplatin, 5-fluorouracil, or etoposide. In contrast, overexpression of E2F-1 resulted in a marked increase in sensitivity to vinblastine and paclitaxel, drugs that are known to be more effective against cells in M phase. Therefore, we investigated the effect of E2F-1 overexpression on proteins regulating the G2-M transition and M phase, in particular cyclin B1 and cdc2 kinase. Cyclin B1 mRNA and protein levels increased within 24 hours of E2F1 induction together with an increase in associated cdc2 kinase activity. Overexpression of cyclin B1 also resulted in a specific increase in sensitivity to paclitaxel and an increase in the cellular growth rate. Knockdown of cyclin B1 using an RNA interference oligo resulted in a slower cellular growth rate and an increase in resistance to paclitaxel. These studies add support to recent reports that show E2F regulates genes involved in mitotic entry and exit and allow the suggestion that mitotic inhibitors may have selective effects in tumors that overexpress E2F-1.
Alexithymia and Obesity
Authors: M. Clerici, S. Albonetti, R. Papa, G. Penati, G. Invernizzi
Journal: Psychotherapy and Psychosomatics (1992)

Many authors consider alexithymia a predisposing factor to psychosomatic and somatopsychic pathologies. In this study we investigated the presence of alexithymic characteristics in a group of 106 massive obese patients who requested a surgical intervention. 6 Rorschach alexithymia variables in the protocols of patients and a non-patient reference group (n = 600) were studied. Findings supported the presence of a striking alexithymic element among severely obese patients in comparison with their lean counterparts.
A Case of Laparoscopically Detected Cholangiocarcinoma of a Few Millimeters in Size, with Portal Fibrosis
Authors: M. Watanabe, Y. Shimada, S. Nagaoka, S. Fukumoto, H. Hirakawa, K. Nishimura
Journal: Endoscopy (1987)

A 54-year-old male with no subjective complaints was admitted to our hospital with fatty liver and low echoic lesion of 3 X 4 cm, thereafter revealed to be a hemangioma. A white lesion of few millimeters in size was detected in the left lobe of the liver at laparoscopic examination, and histologically diagnosed in an aimed biopsy as cholangiocarcinoma. Another 5 lesions (three white spots, a white longitudinal protrusion and a white lesion with a lacy pattern) suggestive of malignancy were also selectively biopsied, but all proved histologically negative. Microwave coagulation was applied to all biopsied sites as anti-cancer therapy.
Foxp3+ Regulatory T Cells Promote T Helper 17 Cell Development In Vivo through Regulation of Interleukin-2
Authors: Yi Chen, Christopher J. Haines, Ilona Gutcher, Kristin Hochweller, Wendy M. Blumenschein, Terrill McClanahan, Günter Hämmerling, Ming O. Li, Daniel J. Cua, Mandy J. McGeachy
Journal: Immunity (2011)
Chronic intermittent hypoxia: A breath of fresh air in the understanding of NAFLD pathogenesis
Authors: Maud Lemoine, Lawrence Serfaty
Journal: Journal of Hepatology (2011)

Obesity and its comorbidities have reached dramatic worldwide epidemic proportions over the last decade leading to a growing attention raised by the politics and the medical community. Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome is widely observed in obese subjects. NAFLD encompasses a large spectrum of liver injuries ranging from simple steatosis to steatohepatitis (NASH) and cirrhosis with a risk of hepatocellular carcinoma [1]. In this setting, NAFLD has emerged as a major public health issue all over the world. However, its pathogenesis is still poorly understood and its relative treatments remain insufficient. Obstructive sleep apnea (OSA) that consists of upper airway obstruction leading to intermittent hypoxia (IH), affects 25–50% of the obese individuals [2]. Its severity is usually assessed by the level of apnea-hypopnea index (AHI) and the cumulative percentage of study time spent below a SaO2 of 90%. Correction of hypoxia with nasal continuous positive airway pressure (CPAP) is the standard non-surgical treatment. Through hypoxia and effects on insulin sensitivity, lipid metabolism and inflammation, OSA might play a role in the development of NAFLD/NASH and has received growing interest in the management of obesity. Several human studies have suggested a role of OSA and its hypoxia-relative consequences in the development of NAFLD [3–7]. In a large cohort of patients with OSA, Tanne et al. reported severe OSA as a risk factor of elevated transaminases independent of body mass index (BMI) [3]. Liver biopsy performed in a subgroup of patients with abnormal liver tests revealed NASH in 67% and positive relationship between the severity of liver injury and OSA. There was also a strong relationship independent of BMI, between OSA and insulin resistance assessed by HOMA index, a central actor in the development of NAFLD. Because of the limited number of patients with liver biopsy, we were unable
Integration of Occidental and Oriental Psychosomatic Treatments
Authors: Yujiro Ikemi, Hitoshi Ishikawa
Journal: Psychotherapy and Psychosomatics (1979)

The Oriental approach to life can contribute to the development of psychosomatic medicine in three major ways, revolving around its realization of the illusion of mind-body dualism, its development of practical somatopsychic techniques for learning self-control, and its orientation towards realizing our true nature. In our department we are currently exploring the use of both standard psychosomatic as well as a variety of somatopsychic techniques, with the ultimate goal of providing a meaningful integration of these approaches. While working to realize the integration of these varied approaches, we feel we are discovering some important clinical principles.
Multilocular giant epidermal cyst
Authors: M. Fujiwara, Y. Nakamura, T. Ozawa, A. Kitoh, T. Tanaka, A. Wada, G. Honjo, K. Nose
Journal: British Journal of Dermatology (2004)

Sir, Epidermal cysts are common benign lesions. They are generally small, and giant epidermal cysts with a diameter of 5 cm or more are rare.1, 2 An epidermal cyst is usually a unilocular lesion.1–3 To our knowledge, all of the giant subcutaneous epidermal cysts reported in the English language literature have been unilocular, except for one lesion reported by Shibata et al.4 (a lobulated mass). However, they did not explain the significance of the lobulation.4 Because a large soft tissue tumour with multiple lobulation may reflect a malignancy, the lack of reports of a high frequency of multiple lobulation in giant epidermal cysts leads to diagnosis of these tumours as possibly malignant subcutaneous tumours. We report four patients (patients 1–4) with multilocular giant epidermal cysts (MGEC) presenting as multiple nodules and showing septa inside the cyst cavity, and four patients (patients 5–8) with unilocular giant epidermal cysts (UGEC). In each case, the tumour gradually enlarged to become a soft and domed mass. The mean diameter of the MGEC was 12 cm, and that of the UGEC was 8·5 cm. The female : male ratio of the former was 1 : 3, and that of the latter was 3 : 1. There were no differences, except for the mean diameter and the sex ratio, between the patients with MGEC and those with UGEC (Table 1).
Toxicity of platinum (IV) salts for cells of pulmonary origin.
Authors: M D Waters, T O Vaughan, D J Abernethy, H R Garland, C C Cox, D L Coffin
Journal: Environmental Health Perspectives (1975)

The acute toxicity of tetravalent platinum was studied in vitro by use of rabbit alveolar macrophages and human lung fibroblasts (strain WI-38). Alveolar macrophages were exposed in tissue culture for 20 hr to platinum dioxide (PtO2) or platinum tetrachloride (PtCl4). There was no evidence of dissolution of PtO2 and no decrease in viable cells at concentrations as high as 500 mug/ml. PtCl4 was soluble in the macrophage system and after a 20-hr exposure, resulted in loss of viability in 50% of the cells originally present at a concentration of 0.30mM (59 mug Pt/ml). After a 20-hr exposure, rapidly growing human lung fibroblasts were rendered nonviable by PtCl4 at comparable concentrations. A decrease in total cellular ATP was observed at lower concentrations in macrophages and fibroblasts along with a reduction in phagocytic activity of macrophages as compared to controls. With the fibroblasts, a 50% decrease in incorporation of 14C-thymidine was observed after a 22-hr exposure to PtCl4 at a concentration of 0.007mM; higher concentrations were required to inhibit the incorporation of 14C-uridine and 14C-leucine. Time-course studies indicated that the inhibition of 14C-thymidine incorporation was nearly complete (90%) after 7 hr in the presence of 0.06mM PtCl4. Under the same conditions, there was little inhibition (15%) of 14C-leucine incorporation and moderate inhibition (50%) of 14C-uridine incorporation. Higher concentrations of PtCl4 were required to inhibit 14C-thymidine incorporation into the acid-soluble fraction than were required to inhibit incorporation into the acid-precipitable fraction. Hence, the preferential inhibition of DNA synthesis by PtCl4 may result from an impairment of the incorporation process.
Abstract LB-210: A multiplexed serum biomarker immunoassay panel discriminates clinical lung cancer patients from cancer-free high-risk subjects in a CT-screened cohort
Authors: William L. Bigbee, Vanathi Gopalakrishnan, Sanja Dacic, Milos Hauskrecht, Joel L. Weissfeld, David O. Wilson, Jill M. Siegfried, Anna E. Lokshin
Journal: Cancer Research (2010)

Abstract Clinical decision making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk subjects with indeterminate pulmonary nodules commonly found by screening. The specificity and sensitivity needed to improve interpretation of CT images in the setting of a suspicious pulmonary nodule would be less stringent than those needed for lung cancer screening in the general population. As a first step in identifying and characterizing serum protein biomarkers to more accurately identify individuals with lung cancer in populations of high-risk tobacco-exposed individuals, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary lung cancer diagnosed in a clinical setting and sera from 56 age-, sex- and smoking-matched CT-screened controls. These controls are drawn from a cohort of participants in the Pittsburgh Lung Screening Study (PLuSS) who have undergone CT screening and are known to be cancer-free after a minimum of 3 years follow-up. We found a profile of 8 biomarkers - PRL, TTR, THSP, SELE, CCL5, MIF, and SERPINE1 and ERBB2 - that distinguished lung cancer from controls in the training set with a sensitivity (SN) of 92.9% and specificity (SP) of 87.5%. The balanced accuracy (average of SN and SP) from 20-fold internal cross-validation of the training set was 82.5% ± 4.8%. We then applied this 8 biomarker model to an independent test set of 10 additional clinically detected lung cancer cases and 83 randomly selected PLuSS participants who were known to be cancer-free. These PLuSS controls in the test set included subjects with and without CT-detected pulmonary nodules and a range of airflow obstruction and radiographic emphysema. The biomarker model classified these test set cases and controls with a balanced accuracy of 83.6% (90.0% SN and 77.1% SP). Importantly, the misclassified PLuSS controls in the test set displayed no significant association with airway function variables or level of suspicion of pulmonary nodule. Taken together, these data suggest that the 8 biomarker panel classified lung cancer independently of pulmonary function abnormalities and the presence of non-cancerous pulmonary nodules, and thus may provide clinical utility in ruling out lung cancer in tobacco-exposed individuals screened by CT imaging. [Supported by NCI SPORE in Lung Cancer P50 CA090440 (JMS) and NCI Early Detection Research Network Biomarker Discovery Laboratory U01 CA084968 (WLB)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-210.
Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia
Authors: Shilpa Gandre-Babbe, Prasuna Paluru, Chiaka Aribeana, Stella T. Chou, Silvia Bresolin, Lin Lu, Spencer K. Sullivan, Sarah K. Tasian, Julie Weng, Helene Favre, John K. Choi, Deborah L. French, Mignon L. Loh, Mitchell J. Weiss
Journal: Blood (2013)
The Thinker's Sign
Authors: Herbert J. Rothenberg
Journal: JAMA (1963)

To the Editor:  —Repeated pressure on and friction of the epidermis results in a characteristic hyperkeratotic plaque known as a callus. Production of these lesions requires chronic intermittent stimulation, such as might be a feature of certain occupations—hence, the well-known lesions on the shoulders of hod-carriers, the hands of mechanics, the lips of trumpeters, and the thumbs of leather buffers. There seems to be less appreciation of the fact that certain chronic disease states might result in the widespread adoption of characteristic postures, satisfying the mechanical requirements for callus formation, and consequently resulting in lesions as specific for the disease state as the lesions named are for the corresponding occupations. An example of just such an occurrence is herein described.  Bilateral discrete calluses are frequently observed in the suprapatellar areas of patients suffering from chronic pulmonary disease with advanced respiratory insufficiency. The characteristic posture instinctively assumed by patients attempting to
Slovakian doctors promise further action to secure affordable healthcare
Authors: J. Feinmann
Journal: BMJ (2012)

Slovakian doctors have pledged to continue to take industrial action to defend affordable healthcare in the former Communist country—after claiming victory in the latest battle over pay for healthcare staff and what they have condemned as government attempts to privatise Slovak healthcare.

Just before Christmas, the Slovak parliament voted to halt moves to turn the country’s public hospitals into joint stock companies—as well as approving a staged pay rise for doctors. The turnabout occurred after a mass resignation of 1600 doctors, including seven out of 10 surgeons and anaesthetists, from Slovak hospitals on 1 December—with a further threat on 16 December that they would refuse to return to …
Retrospective study of influence of deprivation on uptake of cardiac rehabilitation
Authors: J. Pell, A. Pell, C. Morrison, O. Blatchford, H. Dargie
Journal: BMJ (1996)

Table 1-Association between road traffic noise level and psychiatric disorder.Values are mean (SE) score on general health questionnaire (GHQ) unless otherwise stated Road traffic noise level (dB(A)) 51-55 dB 5640 dB
Senile keratotic patches and topical vitamin A.
Authors: J Cleland
Journal: BMJ (1969)

The following summer, during the routine examination of school " leavers," a girl aged 15 years was seen with a rash of typical distribution thought to be scabies.She was asked, largely by chance, if there were any starlings' nests at her home, and she replied that the loft was full of them.A visit to the house confirmed that this was so, the birds having gained access to the loft through a missing tile in the roof.The loft communicated directly with the girl's bedroom by an open ventilator in the ceiling.Nesting material was collected, and the presence of Dermanyssus gallinae again confirmed.Similar measures to the loft and bedroom coincided with early and complete recovery of the patient.Though not perhaps common, it is of some importance to identify these creatures cor- rectly, since infestation may recur despite treatment, as it did in two of our patients, if nesting material is not destroyed.Spontaneous recovery, however, should normally occur if the source of the mites is removed.-We are, etc.,
Intracardiac conduction intervals in children with congenital heart disease: comparison of His bundle studies in 41 normal children and 307 patients with congenital cardiac defects.
Authors: A R Levin, J I Haft, M A Engle, K H Ehlers, A A Klein
Journal: Circulation (1977)

His bundle electrograms were recorded in 348 patients aged 2 months to 24 years following routine diagnostic cardiac catheterization. Among 41 children found to be free of anatomic or hemodynamic abnormality the following mean values were obtained: P-H interval, 93.4 +/- 15.3 msec; P-A time, 21.2 +/- 7.1 msec; A-H interval, 72.2 +/- 15.9 msec; and H-V interval, 39.8 +/- 5.2 msec. The remaining 307 patients were analyzed by diagnosis of congenital heart disease. The mean P-H interval was found to be significantly increased in both ostium primum and secundum atrial septal defect (ASD) with A-H prolongation in primum ASD and P-A prolongation in secundum ASD. The mean H-V interval was significantly prolonged in ostium primum ASD and in patients with severe aortic stenosis, aortic insufficiency. and mitral regurgitation. Grouping of the patients physiologically revealed that patients with moderate-to-severe right ventricular volume overload had P-H prolongation, and patients with severe left ventricular volume or pressure overload had H-V prolongation. The clinical implications of these findings are discussed.
Recognition of Thyroid Disease in the Fetus
Authors: Robert D. Utiger
Journal: New England Journal of Medicine (1991)

Newborn infants may have hyperthyroidism or hypothyroidism. Hyperthyroidism is usually recognized in newborns, not only because of its clinical manifestations, but also because it occurs in a setting in which it may be anticipated — namely, when the mother has or has had hyperthyroidism due to Graves' disease. Hypothyroidism is less often recognized clinically in neonates, 1 both because they may have few or no signs of the disorder and because there is usually no reason to anticipate it. Its most common cause is thyroid dysgenesis, which is not related to any maternal thyroid disease and for which no risk factors . . .
Development and Validation of a Multiple-Choice Question Paper in Basic Colonoscopy
Authors: S. Thomas-Gibson, B. P. Saunders
Journal: Endoscopy (2005)

Factual knowledge underpins competence in all clinical skills. A multiple-choice question paper (MCQ) was designed as part of an accelerated colonoscopy training week (ACTW). In the United Kingdom, there are no validated methods of assessing core knowledge in colonoscopy. The aims of this study were to develop an MCQ paper, to demonstrate its construct validity, and to establish whether the ACTW improved core knowledge.Two 30-question MCQ papers (A and B) were designed. Delegates attending the British Society of Gastroenterology (BSG) 2004 meeting responded either to MCQ paper A or B. Demographic data were collected on their experience in colonoscopy. Doctors attending the ACTW completed either MCQ paper A or B before the course, and the other paper after the course.Seventy-eight delegates at the BSG meeting completed the MCQ. There was a significant difference in the scores between those who had carried out less than 200 colonoscopies (mean 32.5 %) and those who had performed more than 200 (mean 58.4 %; P < 0.0001). Seventeen doctors attending the ACTW completed the MCQ. The mean score for papers A and B increased significantly following the course--57.2 % before the ACTW, 67 % after it ( P = 0.003).This MCQ is capable of differentiating between endoscopists with different levels of experience in colonoscopy. Doctors attending an ACTW significantly improve their knowledge in colonoscopy. A validated MCQ such as this could be used as part of the assessment process to ascertain competence in colonoscopy.
Llewellyn Charles Rutter
Authors: Michael Rutter
Journal: BMJ (2004)

General practitioner Wolverhampton 1937-63 and regional medical officer Nottingham 1964-72 (b Newcastle 1907; q Birmingham 1930; DObst RCOG), died from prostate cancer on 17 January 2004.​2004.




Figure 1




Llewellyn turned down the opportunity of a hospital career to spend four years (1932-36) running a Friends (Quaker) hospital in the Lebanon. On his return, he took up general practice. He was active in local medical affairs and was a founder member of the Royal College of General Practitioners. In 1964 he moved to Nottingham to take up the post of regional medical officer. In his younger days he was a keen field hockey player. He was a lifelong member of the Society of Friends and a fellow of the BMA. He leaves a wife, Winifred (now aged 100); four children; and six grandchildren.
Interferon-γ release assay for tuberculosis in patients with psoriasis treated with tumour necrosis factor antagonists:<i>in vivo</i>and<i>in vitro</i>analysis
Authors: I. Sauzullo, F. Mengoni, R. Marocco, C. Potenza, N. Skroza, T. Tieghi, M. Lichtner, V. Vullo, C.M. Mastroianni
Journal: British Journal of Dermatology (2013)

Background Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers. Objectives To investigate the longitudinal changes of interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens by serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing in patients with psoriasis during long-term anti-TNF therapy. The direct in vitro effect of adalimumab on IFN-γ secretion was also evaluated. Methods In total, 148 patients with psoriasis designated to start anti-TNF treatment were enrolled. We performed a tuberculin skin test at screening, and QFT-GIT at baseline and serially for 24 months after TNF antagonist onset. Results At screening, QFT-GIT was positive in 22·3% of the patients, negative in 73·6% and indeterminate in 4%. The IFN-γ response following isoniazid therapy declined and became QFT-GIT negative in 8% of 26 patients with LTBI; in 69% of subjects with LTBI the QFT-GIT remained persistently positive with a significant increase of IFN-γ levels during the follow-up, even if no cases of active tuberculosis were found. Variations of IFN-γ levels were observed also in 7% of 27 patients without LTBI who switched to positive QFT-GIT after 12 or 18 months of biologic therapy, suggesting a new occurrence or reactivation of LTBI. In vitro data showed that in the presence of adalimumab the IFN-γ levels were significantly reduced in a dose-dependent manner (P < 0·05). Conclusions Fluctuations of IFN-γ release may occur in patients with psoriasis treated with TNF antagonists. The clinical use of repeated blood tests and the correct interpretation of individual IFN-γ changes could be useful in identifying possible cases of LTBI reactivation or newly acquired tuberculosis infection during long-term anti-TNF treatment.
STROMAL CELL-DERIVED FACTOR-1, GRANULOCYTE COLONY STIMULATING FACTOR, FIBROBLAST, VASCULAR ENDOTHELIAL AND HEPATOCYTE GROWTH FACTORS ARE INCREASED IN HYPOXIA/ANOXIA CONDITIONED BONE MARROW-DERIVED STEM CELL MEDIUM
Authors: Sharad Rastogi, Michael S. Sabbah, Hani N. Sabbah
Journal: Journal of the American College of Cardiology (2010)