tbuckley/cabot-search huggingface dataset:
Mitochondrial Dysfunction and Apoptosis Underlie the Pathogenic Process in α-B-Crystallin Desmin-Related Cardiomyopathy
Authors: Alina Maloyan, Atsushi Sanbe, Hanna Osinska, Margaret Westfall, Dustin Robinson, Ken-ichi Imahashi, Elizabeth Murphy, Jeffrey Robbins
Journal: Circulation (2005)

Mitochondria and sarcomeres have a well-defined architectural relation that partially depends on the integrity of the cytoskeletal network. An R120G missense mutation in the small heat shock protein alpha-B-crystallin (CryAB) causes desmin-related cardiomyopathy. Desmin-related cardiomyopathy is characterized by the formation of intracellular aggregates containing CryAB and desmin that are amyloid positive, and disease can be recapitulated in transgenic mice by cardiac-specific expression of the mutant protein.To understand the resultant pathology, we explored the acute effects of R120G expression both in vitro and in vivo. In vitro, transfection of adult cardiomyocytes with R120G-expressing adenovirus resulted in altered contractile mechanics. In vivo, as the cytoskeletal network is disturbed but before deficits in organ function can be detected, alterations in mitochondrial organization and architecture occur, leading to a reduction in the maximal rate of oxygen consumption with substrates that utilize complex I activity, alterations in the permeability transition pore, and compromised inner membrane potential. Apoptotic pathways are subsequently activated, which eventually results in cardiomyocyte death, dilation, and heart failure.Cardiac chaperone dysfunction acutely leads to altered cardiomyocyte mechanics, perturbations in mitochondrial-sarcomere architecture, and deficits in mitochondrial function, which can result in activation of apoptosis and heart failure.
An evaluation of the completeness of reporting of childhood tuberculosis
Authors: S. S. S. Teo, M. Alfaham, M. R. Evans, J. M. Watson, A. Riordan, P. Sonnenberg, J. Clark, A. Hayward, M. Sharland, J. Moore-Gillon, V. Novelli, D. Quinn, D. Shingadia
Journal: European Respiratory Journal (2009)

The sensitivity of the Enhanced Tuberculosis Surveillance (ETS) scheme for monitoring tuberculosis in children is unknown. We used the British Paediatric Surveillance Unit (BPSU) reporting scheme to conduct a prospective observational study of tuberculosis in children aged &lt;16 yrs in the UK. Reported cases were then matched with records from the ETS database. A total of 320 cases were reported to the BPSU between January and December 2004. We estimated that there were 557 paediatric cases in England, Wales and Northern Ireland in 2004: 222 (40%) cases reported to both BPSU and ETS, 98 (18%) reported to BPSU but not ETS and 237 (42%) reported to ETS but not BPSU. Children aged &lt;5 yrs were significantly less likely to be reported to ETS compared with older children (p&lt;0.01). There is substantial under-reporting of childhood tuberculosis, especially of children aged &lt;5 yrs. ETS provides a representative picture of the demographics but may miss ∼20% of cases. This should be taken into account when planning training and resource requirements for tuberculosis. Increased efforts are needed to ensure that all paediatric cases are reported to ETS.
Simultaneous presentation of myasthenia gravis and mesothelioma
Authors: D J Thomson
Journal: Journal of the Royal Society of Medicine (2006)

Myasthenia gravis may be a paraneoplastic phenomenon, caused by underlying cancer.1 This case describes the first co-presentation of myasthenia gravis and pleural mesothelioma. If this is a paraneoplastic occurrence, then with the expected increase in incidence of mesothelioma,2 further cases should arise.
Phase I trial of escalating doses of interleukin-1 beta in combination with a fixed dose of interleukin-2.
Authors: P L Triozzi, J A Kim, E W Martin, D C Young, T Benzies, P M Villasmil
Journal: Journal of Clinical Oncology (1995)

PURPOSE Interleukin-1 (IL-1) and IL-2 have synergistic antitumor and myelostimulatory activities. We investigated the clinical and biologic effects of IL-1/IL-2 therapy. PATIENTS AND METHODS Twenty patients with metastatic cancer, divided into five cohorts, were treated with escalating doses of IL-1 beta (0.005 to 0.2 micrograms/kg/d) administered as a 30-minute intravenous (IV) infusion on days 1 to 4, combined with a fixed dose of IL-2 (0.1 mg/m2/d) administered by continuous IV infusion on days 1 to 4. The 4-day cycles were repeated weekly for up to 8 weeks in the absence of toxicity and/or progressive disease. RESULTS Patients tolerated up to 0.2 microgram/kg/d of IL-1 beta in combination with IL-2 without severe adverse effects. Peripheral-blood CD4-to-CD8 ratios and lymphokine-activated killer (LAK) activity were higher at the lower doses (0.005 to 0.05 microgram/kg/d) of IL-1 beta and higher than that of a cohort of patients treated with IL-2 alone. WBC counts, primarily neutrophils, increased significantly with higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d). Platelet counts were not significantly altered. Increases in serum IL-6, interferon gamma (IFN-gamma), and soluble IL-2 receptor levels were observed, but did not vary with IL-1 beta dose. Tumor regressions were observed in patients with colorectal cancer, melanoma, and renal cell carcinoma. CONCLUSION IL-1 beta cancer be administered in combination with IL-2 with acceptable toxicity. Our results suggest that the addition of even low-dose IL-1 beta to IL-2 may be associated with potentially beneficial biologic activity; higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d) may add potentially beneficial hematologic activity.
Preventing Cancer, Cardiovascular Disease, and Diabetes
Authors: Harmon Eyre, Richard Kahn, Rose Marie Robertson, Nathaniel G. Clark, Colleen Doyle, Yuling Hong, Ted Gansler, Thomas Glynn, Robert A. Smith, Kathryn Taubert, Michael J. Thun
Journal: Circulation (2004)

Collectively, cardiovascular disease (including stroke), cancer, and diabetes account for approximately two thirds of all deaths in the United States and about 700 billion dollars in direct and indirect economic costs each year. Current approaches to health promotion and prevention of cardiovascular disease, cancer, and diabetes do not approach the potential of the existing state of knowledge. A concerted effort to increase application of public health and clinical interventions of known efficacy to reduce prevalence of tobacco use, poor diet, and insufficient physical activity-the major risk factors for these diseases-and to increase utilization of screening tests for their early detection could substantially reduce the human and economic cost of these diseases. In this article, the ACS, ADA, and AHA review strategies for the prevention and early detection of cancer, cardiovascular disease, and diabetes, as the beginning of a new collaboration among the three organizations. The goal of this joint venture is to stimulate substantial improvements in primary prevention and early detection through collaboration between key organizations, greater public awareness about healthy lifestyles, legislative action that results in more funding for and access to primary prevention programs and research, and reconsideration of the concept of the periodic medical checkup as an effective platform for prevention, early detection, and treatment.
1076 DIRECT SERUM MARKERS ARE MORE ACCURATE THAN SIMPLE MARKER PANELS FOR THE DETECTION OF FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Authors: S. Tanwar, P.M. Trembling, D. Thorburn, I.N. Guha, J. Parkes, P. Kaye, A. Burt, S.D. Ryder, G. Aithal, C. Day, W.M. Rosenberg
Journal: Journal of Hepatology (2012)
Angiogenic Gene Therapy (AGENT) Trial in Patients With Stable Angina Pectoris
Authors: Cindy L. Grines, Matthew W. Watkins, Greg Helmer, William Penny, Jeffrey Brinker, Jonathan D. Marmur, Andrew West, Jeffery J. Rade, Pran Marrott, H. Kirk Hammond, Robert L. Engler
Journal: Circulation (2002)

Background — The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene. Methods and Results — The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in patients with angina and to select potentially safe and effective doses for subsequent study. Seventy-nine patients with chronic stable angina Canadian Cardiovascular Society class 2 or 3 underwent double-blind randomization (1:3) to placebo (n=19) or Ad5-FGF4 (n=60). Safety evaluations were performed at each visit and exercise treadmill testing (ETT) at baseline and at 4 and 12 weeks. Single intracoronary administration of Ad5-FGF4 seemed to be safe and well tolerated with no immediate adverse events. Fever of &lt;1-day duration occurred in 3 patients in the highest-dose group. Transient, asymptomatic elevations in liver enzymes occurred in 2 patients in lower-dose groups. Serious adverse events during follow-up (mean, 311 days) were not different between placebo and Ad5-FGF4. Overall, patients who received Ad5-FGF4 tended to have greater improvements in exercise time at 4 weeks (1.3 versus 0.7 minutes, P =NS, n=79). A protocol-specified, subgroup analysis showed the greatest improvement in patients with baseline ETT ≤10 minutes (1.6 versus 0.6 minutes, P =0.01, n=50). Conclusions — Results show evidence of favorable anti-ischemic effects with Ad5-FGF4 compared with placebo, and it appears to be safe. Angiogenic gene transfer with Ad5-FGF4 shows promise as a new therapeutic approach to the treatment of angina pectoris.
Comparison of anatomical locations of cutaneous melanoma in men and women: a population‐based study in<scp>F</scp>rance
Authors: V. Chevalier, C. Barbe, A. Le Clainche, G. Arnoult, P. Bernard, E. Hibon, F. Grange
Journal: British Journal of Dermatology (2014)

Identification of differences in melanoma location between the sexes could lead to sex‐specific preventive measures. To compare precise melanoma location and side in men and women. The location of 1542 incident melanomas diagnosed during the period 2004–2011 in the French Champagne‐Ardenne region (1·3 million inhabitants) was recorded using a regional registry and questionnaires sent to physicians. Men and women were compared for frequency of tumours on the head and neck; trunk; upper limb; lower limb; hand and foot. For each location, more precise sublocations were recorded. The laterality (right vs. left) was studied for head/neck and limb tumours. Melanomas predominated on the lower limb in women (32·2% vs. 9·3% in men; P <0·01) and on the trunk in men (41·8% vs. 14·9%; P <0·01), while the proportion of upper limb and head/neck tumours was similar in both sexes. Hand and foot melanomas predominated in women (10·3% vs. 6·3%; P <0·01), with a sex‐related distribution between sublocations. Within the head and neck location, 75·1% of tumours in women were located in the central area vs. 53·7% in the peripheral area in men (P <0·01). Head and neck melanomas were more frequently right‐sided in women and left‐sided in men (P =0·04), with the left/right ratio reaching 1·58 in men vs. 0·61 in women for peripheral tumours (P <0·01). No difference in laterality was observed for other locations. Sex differences in occupational and leisure time ultraviolet exposure, clothing (including shoes), hairstyle, and side and photo exposure in cars could explain these results. General preventive messages could be completed by sex‐specific advice for melanoma prevention.
Osteoarthritis of the hip: agreement between joint space width measurements on standing and supine conventional radiographs
Authors: G.-R. Auleley, B. Rousselin, X. Ayral, R. Edouard-Noel, M. Dougados, P. Ravaud
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To assess the effect of standing position on joint space width (JSW) measurements of the hips with and without osteoarthritis (OA) on pelvic radiographs. <h3>METHODS</h3> Adult patients aged 18 or more had pelvic anteroposterior conventional radiographs standing and supine performed by a single radiologist in the same radiology unit according to standardised guidelines. JSW measurements in mm were made by a single reader blind to patients' identity and type of view, using a 0.1 mm graduated magnifying glass directly laid over the radiograph, at the narrowest point for OA hips or at the vertical joint space for non-OA hips. Agreement of JSW between both views was assessed using the Bland and Altman graphical analysis. <h3>RESULTS</h3> JSW was greater on standing than supine radiographs, for example, 7.1% for OA hips. Mean (SD) differences and limits of agreement (mm) between both views were 0.08 (0.27) and −0.46 to 0.62 for the 70 non-OA hips, 0.02 (0.31) and −0.60 to 0.64 for the 46 OA hips. Corresponding 95% confidence intervals of mean differences were 0.02, −0.14 mm and −0.07, −0.11 mm. <h3>CONCLUSIONS</h3> Measurements of JSW of the hip on pelvic standing and supine radiographs are concordant. Changes less than or equal to 0.64 mm between the two views are similar or inferior to radiological progression of OA.
The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor
Authors: M. Okazaki, K. Yoshimura, Y. Suzuki, G. Uchida, Y. Kitano, K. Harii, G. Imokawa
Journal: British Journal of Dermatology (2003)

The mechanism of the accentuated melanization in café-au-lait macules (CALMs) in patients with neurofibromatosis type 1 (NF1; von Recklinghausen's disease) has not been elucidated.To clarify the mechanism involved in the hyperpigmentation of CALMs in NF1.Using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of cultured cells, we measured the levels of cytokines produced and secreted by keratinocytes and fibroblasts derived from CALMs (group RC: Recklinghausen CALM) skin, compared with cells derived from the skin of normal individuals (group NN: Normal skin of Normal individuals) and cells derived from non-CALM skin of NF1 patients (group RN: Recklinghausen Non-CALM).ELISA revealed that the secretion of hepatocyte growth factor (HGF) and stem cell factor (SCF) by cultured fibroblasts was significantly elevated in group RC compared with groups RN and NN. In parallel, semiquantitative real-time RT-PCR of HGF and SCF mRNAs demonstrated increased expression of both types of transcripts by cultured fibroblasts in group RC compared with group NN. In contrast, the secretion of endothelin-1 and granulocyte/macrophage colony-stimulating factor by cultured keratinocytes occurred at a similar level among all three groups, RC, RN and NN.These findings suggest that increased secretion of HGF and SCF by dermal fibroblasts may be associated with the accentuated epidermal melanization observed in CALMs in the skin of NF1 patients.
Guidelines for ambulatory electrocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Ambulatory Electrocardiography).
Authors: S B Knoebel, M H Crawford, M I Dunn, C Fisch, J S Forrester, A M Hutter, H L Kennedy, R L Lux, L T Sheffield, C Fisch
Journal: Circulation (1989)

It is becoming more apparent each day that despite a strong national commitment to excellence in health care, the resources and personnel are finite.It is, therefore, appropriate that the medical profession examine the impact of developing tech- nology on the practice and cost of medical care.Such analyses, carefully conducted, could potentially impact on the cost of medical care without diminishing the effectiveness of that care.To this end, the American College of Cardiology and the American Heart Association in 1980 established a Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures with the following charge:The Task Force of the American College of Cardiology and the American Heart Association shall define the role of specific noninvasive and invasive procedures in the diagnosis and management of cardiovascular disease.The Task Force shall address, when appropriate, the contribution, uniqueness, sensitivity, specificity, indications, contraindications and costeffectiveness of such specific procedures.The Task Force shall include a Chairman and four members, two representatives from the Amer- ican Heart Association and two representatives from the American College of Cardiology.The Task Force may select ad hoc members as needed upon the approval of the Presidents of both organizations.
Procedural success versus clinical risk status in determining discharge of patients after primary angioplasty for acute myocardial infarction
Authors: Prabhakara S. Heggunje, Kishore J. Harjai, Gregg W. Stone, Rajendra H. Mehta, Dominic L. Marsalese, Judith A. Boura, William W. O'Neill, Cindy L. Grines
Journal: Journal of the American College of Cardiology (2004)
Impact of Hospital Procedure Volume on Surgical Operation and Long-Term Outcomes in High-Risk Curatively Resected Rectal Cancer: Findings From the Intergroup 0114 Study
Authors: Jeffrey A. Meyerhardt, Joel E. Tepper, Donna Niedzwiecki, Donna R. Hollis, Deborah Schrag, John Z. Ayanian, Michael J. O'Connell, Jane C. Weeks, Robert J. Mayer, Christopher G. Willett, John S. MacDonald, Al B. Benson, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2003)

Prior studies have demonstrated superior outcomes after a curative surgical resection of rectal cancer at hospitals where the volume of such surgeries is high. However, because these studies often lack detailed information on tumor and treatment characteristics as well as cancer recurrence, the true nature of this relation remains uncertain.We studied a nested cohort of 1,330 patients with stage II and stage III rectal cancer participating in a multicenter, adjuvant chemoradiotherapy trial. We analyzed differences in rates of sphincter-preserving operations, overall survival, and cancer recurrence by hospital surgical volume.We observed a significant difference in the rates of abdominoperineal resections across tertiles of hospital procedure volume (46.3% for patients resected at low-volume, 41.3% at medium-volume, and 31.8% at high-volume hospitals; P <.0001), even after adjustment for tumor distance from the anal verge. However, this higher rate of sphincter-sparing operations at high-volume centers was not accompanied by any increase in recurrence rates. Hospital surgical volume did not predict overall, disease-free, recurrence-free, or local recurrence-free survival. However, among patients who did not complete the planned adjuvant chemoradiotherapy (270 patients), those who underwent surgery at low-volume hospitals had a significant increase in cancer recurrence (adjusted hazard ratio, 1.94; 95% CI, 1.01 to 3.72; P =.04 for the trend) and a nonsignificant trend toward increased overall mortality (P =.08) and local recurrence (P =.10). In contrast, no significant volume-outcome relation was noted among patients who did complete postoperative therapy.Using prospectively recorded data, we found that hospital surgical volume had no significant effect on rectal cancer recurrence or survival when patients completed standard adjuvant therapy. Sphincter-preserving surgery was more commonly performed at high-volume centers.
A Novel Prodrug of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent
Authors: Kristin R. Landis-Piwowar, Congde Huo, Di Chen, Vesna Milacic, Guoqing Shi, Tak Hang Chan, Q. Ping Dou
Journal: Cancer Research (2007)

Abstract The most abundant and biologically active green tea catechin, (−)-epigallocatechin-3-gallate or (−)-EGCG, has been shown to act as a proteasome inhibitor and tumor cell death inducer. However, (−)-EGCG is unstable under physiologic conditions and has poor bioavailability. Previously, in an attempt to increase the stability of (−)-EGCG, we introduced peracetate protections to its reactive hydroxyl groups and showed that this peracetate-protected (−)-EGCG [Pro-EGCG (1); formerly named compound 1] could be converted into (−)-EGCG under cell-free conditions. In the current study, we provide evidence that when cultured human breast cancer MDA-MB-231 cells were treated with Pro-EGCG (1), (−)-EGCG was not only converted but also accumulated, accompanied by enhanced levels of proteasome inhibition, growth suppression, and apoptosis induction, compared with cells treated with natural (−)-EGCG. To investigate the potential use of Pro-EGCG (1) as a novel prodrug that converts to a cellular proteasome inhibitor and anticancer agent in vivo, MDA-MB-231 tumors were induced in nude mice, followed by treatment with Pro-EGCG (1) or (−)-EGCG for 31 days. Results of this in vivo study showed a significant inhibition of breast tumor growth by Pro-EGCG (1), compared with (−)-EGCG, associated with increased proteasome inhibition and apoptosis induction in tumor tissues. In conclusion, we have shown that Pro-EGCG (1) increases the bioavailability, stability, and proteasome-inhibitory and anticancer activities of (−)-EGCG in human breast cancer cells and tumors, suggesting its potential use for cancer prevention and treatment. [Cancer Res 2007;67(9):4303–10]
Increase in Prefrontal Cortex Serotonin<sub>2A</sub>Receptors Following Estrogen Treatment in Postmenopausal Women
Authors: Akira Kugaya, C. Neill Epperson, Sami Zoghbi, Christopher H. van Dyck, Yankun Hou, Masahiro Fujita, Julie K. Staley, Pradeep K. Garg, John P. Seibyl, Robert B. Innis
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study investigated the effect of estrogen on brain serotonin 2A (5-HT2A) receptors in postmenopausal women and whether there was any correlation of receptor changes with cognition and mood. METHOD: Ten postmenopausal subjects underwent positron emission tomography measurements of 5-HT2A receptor binding with [18F]deuteroaltanserin before and after estrogen replacement therapy. RESULTS: 5-HT2A receptor binding was significantly increased after estrogen replacement therapy in the right prefrontal cortex (right precentral gyrus [Brodmann's area 9], inferior frontal gyrus [Brodmann's area 47], medial frontal gyrus [Brodmann's area 6, 10] and the anterior cingulate cortex [Brodmann's area 32]). In the inferior frontal gyrus [Brodmann's area 44]), receptor up-regulation was correlated with change in plasma estradiol. Verbal fluency and Trail Making Test performance, but not mood, were significantly improved by estrogen without correlation with receptor changes. CONCLUSIONS: Estrogen increases 5-HT2A receptor binding in human prefrontal regions.