tbuckley/cabot-search huggingface dataset:
The energetic cost of contraction is higher in the myocardium of patients with hypertrophic cardiomyopathy
Authors: J. S. Ingwall
Journal: Cardiovascular Research (2014)

This editorial refers to ‘Gene-specific increase in the energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations’ by E.R. Witjas-Paalberends et al. , doi:10.1093/cvr/cvu127. 

Hypertrophic cardiomyopathy (HCM) is a disease characterized by a hypertrophied left ventricle (LV) in the absence of any overt cause and by an increased incidence of arrhythmias and cardiac sudden death. The subset of HCM patients with familial hypertrophic cardiomyopathy (FHC) displays a highly variable phenotype ranging from no symptoms to overt cardiomyopathy with early onset sudden cardiac arrest. This variability has made it difficult to identify any unifying mechanism that would lead to designing new approaches for diagnosis and therapy.

Most of the several hundred mutations associated with HCM/FHC occur in sarcomeric proteins, and roughly half of them reside in two proteins: myosin and cardiac myosin-binding protein C (cMyBP-C). One hypothesis for a unifying mechanism underlying HCM/FHC is that the energetic cost of contraction is higher in the myocardium of HCM/FHC patients: the free energy released from the hydrolysis of ATP by myosin is used less efficiently to generate force at the whole heart level. The article by Witjas-Paalberends and Guclu (co-first authors) and their colleagues appearing in this issue1 makes a significant contribution supporting this hypothesis. Before commenting on their results, we will briefly review the properties of myosin and cMyBP-C and their history in the HCM/FHC literature.

Myosin has many functions: …
Lymphoma: An Analysis of 460 Cases from the Ellis Fischel State Cancer Hospital.
Authors: A. McChesney Evans
Journal: Annals of Internal Medicine (1965)

s1 May 1965Lymphoma: An Analysis of 460 Cases from the Ellis Fischel State Cancer Hospital.A. McChesney Evans, M.D., F.A.C.P.A. McChesney Evans, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1094_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOne-hundred per cent follow-up of patients comprising 24 years of experience offers a unique opportunity to investigate epidemiologic factors and the details of the natural history of the lymphomas. The majority of these patients are rural permanent residents and are classed in the standard histologic groups: Hodgkin's granuloma, Hodgkin's sarcoma, small cell lymphosarcoma, reticulum cell sarcoma, lymphoblastic lymphosarcoma; an additional 126 cases of chronic lymphoid leukemia and 24 cases of acute lymphoid leukemia diagnosed during this period were also investigated. By means of advanced statistical analysis and modern computer techniques including cluster analysis, the date of symptom onset and place... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: A. McChesney Evans, M.D., F.A.C.P.Affiliations: Columbia, Missouri PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1094-1094KeywordsAcute lymphoblastic leukemiaComputersEpidemiologyHodgkin lymphomaLymphocytesLymphocytic leukemiaLymphomaPrecursor cellsSarcoma ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
Serial Analysis of Gene Expression in Progressing and Regressing Mouse Tumors Implicates the Involvement of RANTES and TARC in Antitumor Immune Responses
Authors: Yukoh Nakazaki, Hidenori Hase, Hiroyuki Inoue, Yoshihito Beppu, Xin K. Meng, Gaku Sakaguchi, Ryo Kurita, Shigetaka Asano, Yusuke Nakamura, Kenzaburo Tani
Journal: Molecular Therapy (2006)

Previously we demonstrated that gene transduction of the granulocyte–macrophage colony stimulating-factor (GM-CSF) gene into mouse tumor cells eliminated tumorigenicity in vivo. The rejection process of the subcutaneous tumor was as follows: transient tumor growth peaked around 10 days after tumor injection, then the tumors were rejected within a week. In this paper, we analyzed the gene expression of the transiently established tumor masses by the serial analysis of gene expression method to identify molecules associated with the antitumor effect. We then screened those genes that were differentially expressed between the parental and the GM-CSF-transduced tumors and identified a group of genes that are suggested to have a relationship with tumor rejection, including a cytokine receptor, adhesion molecules, chemokines, cytotoxicity-related molecules, and others. Focusing on the chemokine genes TARC and RANTES, which were preferentially expressed in the GM-CSF-transduced tumors, their forced expression on mouse tumor cells showed moderate suppression of tumor formation. Transduction of GM-CSF in combination with either the TARC or the RANTES gene into tumor cells profoundly inhibited tumor establishment. Histological findings suggested the significant contribution of CD4+ T cells to tumor regression in both TARC/GM-CSF- and RANTES/GM-CSF-transduced tumor cells, in excess of that seen with GM-CSF transduction alone.
Peripheral Arterial Disease in Diabetic and Nondiabetic Patients
Authors: Edward B. Jude, Samson O. Oyibo, Nicholas Chalmers, Andrew J.M. Boulton
Journal: Diabetes Care (2001)

OBJECTIVE—The aim of this study was to quantify the distribution of peripheral arterial disease in the diabetic and nondiabetic population attending for angiography and to compare severity and outcome between both groups of patients. RESEARCH DESIGN AND METHODS—Randomly selected lower-extremity angiograms were examined according to the Bollinger system. Patient demographics and medical history were recorded and case notes were examined to determine which patients later underwent a revascularization procedure or amputation and which patients had died. RESULTS—A total of 136 arteriograms obtained between 1992 and 1996 were analyzed. The age (mean ± SD) of the patients was 64.7 ± 10.8 years. Diabetic patients (43%) and nondiabetic patients were of similar age (63.9 ± 10.4 vs. 65.3 ± 11.1 years, P = 0.43), with a similar history of smoking (81.0 vs. 76.9%, P = 0.26), ischemic heart disease (41.4 vs. 37.2%, P = 0.54), and hypercholesterolemia (24.4 vs. 30.8%, P = 0.48). However, there were a greater proportion of hypertensive patients in the diabetic group (63.8 vs. 39.7%, P = 0.006). Diabetic patients had greater severity of arterial disease in the profunda femoris and all arterial segments below the knee (P = 0.02). A greater number of amputations occurred in the diabetic group: diabetic patients were five times more likely to have an amputation (41.4 vs. 11.5%, odds ratio [OR] 5.4, P &amp;lt; 0.0001). Mortality was higher in the diabetic group (51.7 vs. 25.6%, OR 3.1, P = 0.002), and diabetic patients who died were younger at presentation than nondiabetic patients (64.7 ± 11.4 vs. 71.1 ± 8.7 years, P = 0.04). CONCLUSIONS—In patients with peripheral arterial disease, diabetic patients have worse arterial disease and a poorer outcome than nondiabetic patients.
The Blessings of Co-operation.
Authors: Jas. Osbourne De Courcy
Journal: JAMA (1894)

St. Libory, Ill., Sept. 28, 1894. <h3>To the Editor:</h3> —I congratulate you and theJournal of the American Medical Associationupon entering your new quarters on Fifth Avenue, where room, conveniences and surroundings will be much more desirable. I would like to see the day when every worthy physician of America shall become a member of theAmerican Medical Association, and theJournalmaking weekly visits to each office. If there is any good reason why any member of the fraternity should withhold his name, himself and his skill, knowledge and influence from theAssociationI can not imagine what it is. The one thing above all others, so much needed in the profession is coöperation. If the faculty throughout the country will come into theAssociation, the long felt need of coöperation will be established, and the means of communication through theJournalwill be perfect. Thus once united,
SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer
Authors: George T. Budd, William E. Barlow, Halle C.F. Moore, Timothy J. Hobday, James A. Stewart, Claudine Isaacs, Muhammad Salim, Jonathan K. Cho, Kristine J. Rinn, Kathy S. Albain, Helen K. Chew, Gary V. Burton, Timothy D. Moore, Gordan Srkalovic, Bradley A. McGregor, Lawrence E. Flaherty, Robert B. Livingston, Danika L. Lew, Julie R. Gralow, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2014)

To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer.A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome.Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor-negative/human epidermal growth factor receptor 2 (HER2) -negative tumors (P = .067), with no differences seen with hormone receptor-positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40).Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor-negative/HER2-negative tumors.
TCT-662 Age-related Effect of Smoking on Coronary Artery Disease Assessed by Grayscale and Virtual histology Intravascular Ultrasound
Authors: Soo-Jin Kang, Bernard De Bruyne, Akiko Maehara, Roxana Mehran, Gary S. Mintz, LeRoy Rabbani, Patrick W. Serruys, Stefan Verheye, Giora Weisz, Ke Xu
Journal: Journal of the American College of Cardiology (2013)
Exosomes Derived from Genetically Modified DC Expressing FasL Are Anti-inflammatory and Immunosuppressive
Authors: Seon Hee Kim, Nicole Bianco, Rajasree Menon, Eric R. Lechman, William J. Shufesky, Adrian E. Morelli, Paul D. Robbins
Journal: Molecular Therapy (2005)

We previously have demonstrated the ability of primary murine bone marrow-derived DC (BM-DC), genetically modified by adenoviral infection to express FasL, to inhibit progression of established collagen-induced arthritis (CIA) following systemic delivery. Here we demonstrate that exosomes derived from genetically modified BM-DC expressing FasL are able to inhibit inflammation in a murine footpad model of delayed-type hypersensitivity (DTH). Local administration of exosomes derived from DC expressing FasL (Exo/FasL) as well as the parental DC/FasL resulted in a significant reduction in swelling in both the treated and the untreated distal paw. However, both the DC/FasL and the Exo/FasL were unable to suppress the DTH response in lpr (Fas-deficient) mice. Gene transfer of FasL to BM-DC from gld (FasL-deficient) mice resulted in restoration of the ability of DC as well as DC-derived exosomes to suppress DTH. The ability of DC-derived exosomes and DC to suppress DTH responses was antigen specific and MHC class II dependent, but class I independent. The injected exosomes were found to be internalized into CD11c+ cells at the site of injection and in the draining popliteal lymph node. Systemic injection of exosome/FasL into mice with established CIA resulted in significant disease amelioration. These results demonstrate that both systemic and local administration of exosomes derived from FasL-expressing DC are able to suppress antigen-specific immune responses through an MHC class II-dependent pathway, resulting in effective and sustained treatment of established collagen-induced arthritis and suppression of the DTH inflammatory response. These results suggest that DC/FasL-derived exosomes could be used clinically for the treatment of inflammatory and autoimmune diseases.
Studies of immune functions of patients with systemic lupus erythematosus. T-cell subsets and antibodies to T-cell subsets.
Authors: T Sakane, A D Steinberg, J P Reeves, I Green
Journal: Journal of Clinical Investigation (1979)

Antibodies to T cells present in the plasma of patients with active systemic lupus erythematosus (SLE) plus complement are able to eliminate concanavalin A-induced suppressor function for the proliferative responses of T cells to allogeneic lymphocytes (MLR) and of B cells to pokeweed mitogen (PWM). Such antibodies were found to be effective in eliminating suppressor function only when T cells were treated before activation; there was no effect when treatment was performed after activation. These studies indicate that the antibodies preferentially interact with a T cell necessary for the generation of suppressor cells, rather than with mature, activated suppressor cells. Studies of individual SLE patients indicate that the same defects observed in SLE T cells were induced in normal T cells by plasma from that patient. Such observations suggest that many T-cell defects associated with active SLE may not be intrinsic T-cell abnormalities, but, rather, secondary effects of anti-T-cell antibodies. Studies of the T-cell subpopulations responsible for suppression of the MLR and PWM responses indicate that only T gamma cells (T cells bearing receptors for the Fc portion of immunoglobulin [Ig]G) acted as precursors of suppressor cells for the MLR, whereas both T gamma and T non-gamma cells (T cells not bearing receptors for the Fc portion of IgG) could be activated to suppress the PWM response. Consistent with this observation, SLE anti-T-cell antibodies that preferentially killed T gamma cells preferentially eliminated suppressor cells for the MLR.
Prompting Asthma Intervention in Rochester–Uniting Parents and Providers (PAIR-UP)
Authors: Jill S. Halterman, Maria Fagnano, Paul J. Tremblay, Susan G. Fisher, Hongyue Wang, Cynthia Rand, Peter Szilagyi, Arlene Butz
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> A disproportionate number of impoverished and minority children have asthma and receive suboptimal preventive care. <h3>Objective</h3> To evaluate whether the Prompting Asthma Intervention in Rochester–Uniting Parents and Providers (PAIR-UP) intervention, administered in primary care offices, improves the delivery of preventive care and reduces morbidity for urban children with asthma. <h3>Design, Setting, and Participants</h3> Cluster randomized trial in which 12 urban primary care practices were matched based on size and type and randomly allocated to the PAIR-UP intervention or usual care (UC). We enrolled 638 children aged 2 to 12 years with persistent or poorly controlled asthma in the waiting room prior to a visit with a clinician for any reason from October 2009 to January 2013. Blinded interviewers called caregivers within 2 weeks to inquire about preventive measures taken at the visit and called them 2 and 6 months later to assess symptoms. <h3>Interventions</h3> Children enrolled at PAIR-UP practices received prompts for the caregiver and clinician at the time of the visit that outlined the child’s asthma severity or control as well as specific guideline-based recommendations to enhance preventive care. These practices also received educational resources and periodic feedback on their asthma care performance. The UC practices received copies of the asthma guidelines. <h3>Main Outcomes and Measures</h3> The primary outcome was symptom-free days (SFDs) per 2 weeks at the 2-month follow-up. <h3>Results</h3> We enrolled 638 children (participation rate of 80%; 36% were black, 36% were Hispanic, and 68% had Medicaid insurance). Groups were similar in demographic characteristics and asthma severity at baseline. At the index visit, more children in the PAIR-UP group received a preventive medication action (new medication, increased dose, recommendation to restart preventive medication) than in the UC group (58% vs 33%; odds ratio [OR] = 2.8; 95% CI, 1.9 to 3.9). More children in the PAIR-UP group than in the UC group received an asthma action plan (61% vs 23%; OR = 8.3; 95% CI, 3.7 to 18.7), discussions regarding asthma (93% vs 78%; OR = 4.5; 95% CI, 2.8 to 7.2), and secondhand smoke counseling (80% vs 63%; OR = 2.6; 95% CI, 1.2 to 5.5). At the 2-month follow-up, children in the PAIR-UP group had more SFDs per 2 weeks than those in the UC group (mean difference, 0.78 days; 95% CI, 0.29 to 1.27). At 6 months, the improvement in SFDs was no longer statistically significant (mean difference, 0.56; 95% CI, −0.14 to 1.25). <h3>Conclusions and Relevance</h3> The PAIR-UP intervention improved the delivery of preventive asthma care and reduced asthma morbidity for high-risk urban children with persistent asthma at 2 months, but the improvement in SFDs was no longer significant at 6 months. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01105754
Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis
Authors: Daniel E. Spratt, Elizabeth A. Gordon Spratt, Shenhong Wu, Antonio DeRosa, Nancy Y. Lee, Mario E. Lacouture, Christopher A. Barker
Journal: Journal of Clinical Oncology (2014)

To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases.MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I(2) tests.After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients.Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed.
Licensing Parents: Can We Prevent Child Abuse and Neglect?
Authors: David L. Chadwick
Journal: JAMA (1995)

As Judge Charles D. Gill of Connecticut points out in the foreword to this work, the subject of licensing parents is often discussed in a facetious manner. We may think about our state department of motor vehicles and conclude that governmental agencies cannot be capable of managing such a complicated task. Or we may simply think that licensing parents is politically impossible in a democracy where having babies is the one validating achievement still possible for just about anyone in the reproductive age group. But Dr Westman's book takes this subject out of the comic context and forces its serious consideration. Westman develops his arguments through 12 tightly written chapters. He first examines the deteriorating quality of life in the United States and the social problems that are causing the deterioration. He points out the benefits and calculates the financial value of competent parenting and then thoroughly and carefully describes
Cancer-associated molecular signature in the tissue samples of patients with cirrhosis
Authors: Jin Woo Kim, Qinghai Ye, Marshonna Forgues, Yidong Chen, Anuradha Budhu, Jessica Sime, Lorne J. Hofseth, Rashmi Kaul, Xin Wei Wang
Journal: Hepatology (2004)

Several types of aggressive cancers, including hepatocellular carcinoma (HCC), often arise as a multifocal primary tumor. This suggests a high rate of premalignant changes in noncancerous tissue before the formation of a solitary tumor. Examination of the messenger RNA expression profiles of tissue samples derived from patients with cirrhosis of various etiologies by complementary DNA (cDNA) microarray indicated that they can be grossly separated into two main groups. One group included hepatitis B and C virus infections, hemochromatosis, and Wilson's disease. The other group contained mainly alcoholic liver disease, autoimmune hepatitis, and primary biliary cirrhosis. Analysis of these two groups by the cross-validated leave-one-out machine-learning algorithms revealed a molecular signature containing 556 discriminative genes (P <.001). It is noteworthy that 273 genes in this signature (49%) were also significantly altered in HCC (P <.001). Many genes were previously known to be related to HCC. The 273-gene signature was validated as cancer-associated genes by matching this set to additional independent tumor tissue samples from 163 patients with HCC, 56 patients with lung carcinoma, and 38 patients with breast carcinoma. From this signature, 30 genes were altered most significantly in tissue samples from high-risk individuals with cirrhosis and from patients with HCC. Among them, 12 genes encoded secretory proteins found in sera. In conclusion, we identified a unique gene signature in the tissue samples of patients with cirrhosis, which may be used as candidate markers for diagnosing the early onset of HCC in high-risk populations and may guide new strategies for chemoprevention. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
733 REACTIVATION OF OVERT AND OCCULT HBV INFECTION IN IMMUNOSUPPRESSIVE SETTINGS
Authors: N. Coppola, G. Tonziello, M. Pisaturo, M. Fiore, V. Iodice, S. Guastrafierro, C. Sagnelli, N. Capoluongo, V. Messina, G. Pasquale, E. Sagnelli
Journal: Journal of Hepatology (2010)
Rehabilitation after Cardiac Illness
Authors: B. M. Groden, A. I. Cheyne
Journal: BMJ (1972)

Though the total number of patients with cardiac illness referred to a work classification clinic was relatively small (57), the results obtained in terms of patients at work in the year after assessment is encouraging. It is suggested that a comparatively simple method can help in the rehabilitation of patients, often by removing minor anxieties, and by improving communication among the various agencies interested in the welfare and employment of the individual patient.