tbuckley/cabot-search huggingface dataset:
Correlation of ventricular area, perimeter, and conotruncal diameter with ventricular mass and function in the chick embryo from stages 12 to 24.
Authors: B B Keller, N Hu, E B Clark
Journal: Circulation Research (1990)

Ventricular form and function are interrelated during cardiovascular development. The study of muscle mechanics requires the real-time measurement of length, area, or volume. Because volume measures are not currently possible in the embryonic heart, we tested the hypothesis that end-diastolic (ED) and end-systolic (ES) ventricular perimeter, area, and conotruncal diameter correlate with ventricular mass and function in the stage 12 to stage 24 white Leghorn chick embryo. Video images of the contracting heart were recorded at 60 Hz on 1/2" videotape and studied with a custom image-analysis workstation. ED and ES video fields were selected by maximum and minimum ventricular area and were planimetered for epicardial ventricular perimeter, area, and conotruncal diameter. Data are reported as (mean +/- SEM, n greater than or equal to 8) and were tested by analysis of variance and regression analysis. Heart rate calculated from cycle length increased from 78 +/- 6 beats/min at stage 12 to 162 +/- 5 beats/min at stage 24. ED and ES area increased geometrically versus stage (y = 0.53 - 0.08x + 0.004x2, r = 0.96, p less than 0.001; and y = 0.60 - 0.09x + 0.004x2, r = 0.98, p less than 0.001, respectively). ED and ES perimeter and conotruncal diameter increased linearly versus stage (r = 0.95, p less than 0.001; r = 0.96, p less than 0.001; and r = 0.93, p less than 0.001; r = 0.93, p less than 0.001, respectively). Shortening fraction for each measurement increased from stage 12 to 16 or 18 then decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial
Authors: Diane K Wherrett, Brian Bundy, Dorothy J Becker, Linda A DiMeglio, Stephen E Gitelman, Robin Goland, Peter A Gottlieb, Carla J Greenbaum, Kevan C Herold, Jennifer B Marks, Roshanak Monzavi, Antoinette Moran, Tihamer Orban, Jerry P Palmer, Philip Raskin, Henry Rodriguez, Desmond Schatz, Darrell M Wilson, Jeffrey P Krischer, Jay S Skyler
Journal: The Lancet (2011)
Most LQT2 Mutations Reduce Kv11.1 (hERG) Current by a Class 2 (Trafficking-Deficient) Mechanism
Authors: Corey L. Anderson, Brian P. Delisle, Blake D. Anson, Jennifer A. Kilby, Melissa L. Will, David J. Tester, Qiuming Gong, Zhengfeng Zhou, Michael J. Ackerman, Craig T. January
Journal: Circulation (2006)

The KCNH2 or human ether-a-go-go related gene (hERG) encodes the Kv11.1 alpha-subunit of the rapidly activating delayed rectifier K+ current (IKr) in the heart. Type 2 congenital long-QT syndrome (LQT2) results from KCNH2 mutations that cause loss of Kv11.1 channel function. Several mechanisms have been identified, including disruption of Kv11.1 channel synthesis (class 1), protein trafficking (class 2), gating (class 3), or permeation (class 4). For a few class 2 LQT2-Kv11.1 channels, it is possible to increase surface membrane expression of Kv11.1 current (IKv11.1). We tested the hypotheses that (1) most LQT2 missense mutations generate trafficking-deficient Kv11.1 channels, and (2) their trafficking-deficient phenotype can be corrected.Wild-type (WT)-Kv11.1 channels and 34 missense LQT2-Kv11.1 channels were expressed in HEK293 cells. With Western blot analyses, 28 LQT2-Kv11.1 channels had a trafficking-deficient (class 2) phenotype. For the majority of these mutations, the class 2 phenotype could be corrected when cells were incubated for 24 hours at reduced temperature (27 degrees C) or in the drugs E4031 or thapsigargin. Four of the 6 LQT2-Kv11.1 channels that had a wild-type-like trafficking phenotype did not cause loss of Kv11.1 function, which suggests that these channels are uncommon sequence variants.This is the first study to identify a dominant mechanism, class 2, for the loss of Kv11.1 channel function in LQT2 and to report that the class 2 phenotype for many of these mutant channels can be corrected. This suggests that if therapeutic strategies to correct protein trafficking abnormalities can be developed, it may offer clinical benefits for LQT2 patients.
Triterpenoid electrophiles (avicins) activate the innate stress response by redox regulation of a gene battery
Authors: Valsala Haridas, Margaret Hanausek, Goshi Nishimura, Holly Soehnge, Amos Gaikwad, Maciej Narog, Erick Spears, Robert Zoltaszek, Zbigniew Walaszek, Jordan U. Gutterman
Journal: Journal of Clinical Investigation (2004)

Avicins are proapoptotic and anti-inflammatory triterpene electrophiles isolated from an Australian desert tree, Acacia victoriae. The presence of two α,β unsaturated carbonyl groups (Michael reaction sites) in the side chain of the avicin molecule prompted us to study its effects on NF-E2–related factor 2 (Nrf2), a redox-regulated transcription factor that controls the expression of a battery of detoxification and antioxidant proteins via its binding to antioxidant response element (ARE). Avicin D–treated Hep G2 cells showed translocation of Nrf2 into the nucleus and a time-dependent increase in ARE activity. These properties were sensitive to DTT, suggesting that avicins affect one or more critical cysteine residues, probably on the Keap1 molecule. Downstream of ARE, an activation of a battery of stress-induced proteins occurred. The implications of these findings were evaluated in vivo in mouse skin exposed to an ancient stressor, UV light. Avicins inhibited epidermal hyperplasia, reduced p53 mutation, enhanced apoptosis, decreased generation of 8-hydroxy-2′-deoxyguanosine, and enhanced expression of NADPH:quinone oxidoreductase 1 and heme oxygenase-1. These data, combined with our earlier published work, demonstrate that avicins represent a new class of plant stress metabolites capable of activating stress adaptation and suppressing proinflammatory components of the innate immune system in human cells by redox regulation. The relevance for treatment of clinical diseases in which stress responses are dysfunctional or deficient is discussed.
Too much or too little
Authors: Fred Charatan
Journal: BMJ (2005)

This study also has limitations.We could assess dementia status only among participants who were still members of the health plan when dementia was diagnosed.However, there were no differences in adiposity or sociodemographic characteristics in those who didn't continue in the health plan.Information on weight cycling, dieting, nutrition, or mid-life measures of cognitive functioning was not collected.A measure of central obesity, such as waist circumference was not collected.As diagnoses of dementia were made during medical visits, some cases of dementia may have been missed in those who did not participate in visits.This would bias results in an underestimation of the effects of obesity on dementia. Mechanisms of effectsAdiposity is one component of the metabolic syndrome, which has also been shown to cause cognitive decline, particularly in those with high levels of inflammation. 8Perhaps adiposity has a direct effect on neuronal degradation.Genetically obese, leptin receptor deficient rodents have impaired performance on spatial memory tasks 9 and long term potentiation of neurones in the hippocampus. 10C reactive protein, an inflammatory marker, is increased in those with greater adiposity 11 and is associated with dementia 12 and cognitive decline. 8 13Recently, obesity in elderly women was shown to be associated with greater cerebral atrophy 14 and white matter hyperintensity. 15 Future studies of cytokines produced in fat cells and neuronal functioning should be useful.Another study found that high skinfold thickness in mid-life was associated with Parkinson's disease. 16 Perhaps adiposity works together with other risk factors to increase neurodegenerative disease.Body mass index predicted dementia more strongly among women.These findings, however, are consistent with the only published prospective study on body mass index and dementia. 3There could be several reasons.There were fewer obese and overweight men, thus the power to detect an effect was reduced.Current body mass index categories may be insensitive indicators of adiposity in men because of less variation in the distribution of visceral fat. 4 Perhaps body mass index and risk of dementia in women is mediated through central obesity, which is highly associated with insulin resistance, cardiovascular disease, increased adipocytokines, and inflammatory markers.All of these conditions could contribute to dementia.Diabetes and cardiovascular disease did not attenuate the effect, though the role of central obesity, inflammation, and adipocytokines on our findings is unknown and should be looked at in future research.
Ginseng Therapy in Non-Insulin-Dependent Diabetic Patients: Effects on psychophysical performance, glucose homeostasis, serum lipids, serum aminoterminalpropeptide concentration, and body weight
Authors: Eero A Sotaniemi, Eila Haapakoski, Arja Rautio
Journal: Diabetes Care (1995)

OBJECTIVE To investigate the effect of ginseng on newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS In this double-blind placebo-controlled study, 36 NIDDM patients were treated for 8 weeks with ginseng (100 or 200 mg) or placebo. Efficacy was evaluated with psychophysical tests and measurements of glucose balance, serum lipids, aminoterminalpropeptide (PIIINP) concentration, and body weight. RESULTS Ginseng therapy elevated mood, improved psychophysical performance, and reduced fasting blood glucose (FBG) and body weight. The 200-mg dose of ginseng improved glycated hemoglobin, serum PIIINP, and physical activity. Placebo reduced body weight and altered the serum lipid profile but did not alter FBG. CONCLUSIONS Ginseng may be a useful therapeutic adjunct in the management of NIDDM.
Proposal for Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials: The STEEP System
Authors: Clifford A. Hudis, William E. Barlow, Joseph P. Costantino, Robert J. Gray, Kathleen I. Pritchard, Judith-Anne W. Chapman, Joseph A. Sparano, Sally Hunsberger, Rebecca A. Enos, Richard D. Gelber, Jo Anne Zujewski
Journal: Journal of Clinical Oncology (2007)

Standardized definitions of breast cancer clinical trial end points must be adopted to permit the consistent interpretation and analysis of breast cancer clinical trials and to facilitate cross-trial comparisons and meta-analyses. Standardizing terms will allow for uniformity in data collection across studies, which will optimize clinical trial utility and efficiency. A given end point term (eg, overall survival) used in a breast cancer trial should always encompass the same set of events (eg, death attributable to breast cancer, death attributable to cause other than breast cancer, death from unknown cause), and, in turn, each event within that end point should be commonly defined across end points and studies.A panel of experts in breast cancer clinical trials representing medical oncology, biostatistics, and correlative science convened to formulate standard definitions and address the confusion that nonstandard definitions of widely used end point terms for a breast cancer clinical trial can generate. We propose standard definitions for efficacy end points and events in early-stage adjuvant breast cancer clinical trials. In some cases, it is expected that the standard end points may not address a specific trial question, so that modified or customized end points would need to be prospectively defined and consistently used.The use of the proposed common end point definitions will facilitate interpretation of trial outcomes. This approach may be adopted to develop standard outcome definitions for use in trials involving other cancer sites.
FL-160 proteins of Trypanosoma cruzi are expressed from a multigene family and contain two distinct epitopes that mimic nervous tissues.
Authors: W C Van Voorhis, L Barrett, R Koelling, A G Farr
Journal: The Journal of Experimental Medicine (1993)

The partial sequence of a gene encoding the COOH terminus of a protein of apparent molecular weight of 160 kD associated with the flagellum of trypomastigotes of Trypanosoma cruzi (FL-160 now renamed to FL-160-1) has been previously reported. The COOH terminus of FL-160-1 has an epitope, defined by 12 amino acids, which molecularly miMics a nervous tissue antigen of 48 kD found in myenteric plexus, sciatic nerve, and a subset of cells in the central nervous system. We now report that FL-160 is a family of highly related genes. The sequence has been determined for the entire open reading frame (ORF) of one of the members of the FL-160 gene family (FL-160-2) and three other partial ORFs. Sequence analysis reveals the various members of the FL-160 gene family to be approximately 80% homologous in the predicted amino acid sequence, but all retain the 12-amino acid molecular mimicry epitope on the COOH terminus. Comparison of the sequence of FL-160-2 to other sequences demonstrates amino acid homology to bacterial sialidase (27%), members of the SA85 gene family (25-30%) and the shed acute-phase antigen/neuraminidase/trans-sialidase gene family (25-30%). Quantitative hybridization at high stringency suggests 750 copies of FL-160 are present in the DNA of each parasite. Reverse transcription and sequence analysis demonstrates that at least five of the members of the FL-160 gene family are transcribed. The NH2 terminus of one of the FL-160 gene products was expressed and antibodies prepared. Antibodies directed to either the COOH or the NH2 terminus of FL-160 bind a 160-kD T. cruzi protein. Both antibodies bind the surface membrane in the flagellar pocket of the trypomastigote. Antibodies to the NH2 terminus bind epineurium and scattered linear densities in sciatic nerve in a pattern distinct from the pattern with antibodies to the COOH terminus. Thus, there are at least two distinct molecular mimicry epitopes on the FL-160 molecule and both mimic epitopes found in nervous tissues. FL-160 may be involved in the generation of autoimmunity to nervous tissues by molecular mimicry, observed in chronic Chagas' disease.
Sclerostin inhibition reverses systemic, periarticular and local bone loss in arthritis
Authors: Xiao-Xiang Chen, Wolfgang Baum, Denise Dwyer, Michael Stock, Kay Schwabe, Hua-Zhu Ke, Marina Stolina, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To test whether inhibition of sclerostin by a targeted monoclonal antibody (Scl-Ab) protects from bone and cartilage damage in inflammatory arthritis. Sclerostin is a potent inhibitor of bone formation and may be responsible for the low level of bone repair in patients with rheumatoid arthritis. <h3>Methods</h3> Human tumour necrosis factor transgenic mice (hTNFtg mice) developing inflammatory arthritis and local and bone loss were administered either vehicle, anti-TNF antibody, Scl-Ab, or a combination of both agents. Inflammation, systemic and periarticular bone loss, bone erosion and cartilage damage were evaluated at baseline (week 8) and after 3 weeks of treatment by clinical assessment, micro-CT and histology. <h3>Results</h3> Scl-Ab did not affect joint swelling or synovitis. Systemic bone loss in the spine and periarticular bone loss in the proximal tibia were completely blocked and partially reversed by inhibition of sclerostin but not by inhibition of TNF. Moreover, Scl-Ab completely arrested the progression of bone erosion in hTNFtg mice and in combination with TNF inhibition even led to significant regression of cortical bone erosions. Protective effects of Scl-Ab were also observed for the articular cartilage. <h3>Conclusions</h3> These data suggest that sclerostin inhibition is a powerful tool to enhance bone repair in inflammatory arthritis.
PRENATAL DIAGNOSIS OF FRAGILE X CHROMOSOME
Authors: LawrenceR. Shapiro, PatrickL. Wilmot, Pauline Brenholz, Alena Leff, Maryann Martino, Gloria Harris, MauriceJ. Mahoney, JohnC. Hobbins, GrantR. Sutherland, PeterB. Jacky
Journal: The Lancet (1982)
Resolution of oral lichenoid lesions after replacement of amalgam restorations in patients allergic to mercury compounds
Authors: JUHANI LAINE, KIRSTI KALIMO, HELI FORSSELL, RISTO-PEKKA HAPPONEN
Journal: British Journal of Dermatology (1992)

The significance of contact allergy in patients with various oral symptoms was studied. Positive patch-test reactions to mercury compounds were found in 21/91 patients. Of these, 18 had lichenoid lesions in oral mucosa in close contact to amalgam fillings, and three patients with contact allergy had neither amalgam fillings in their teeth nor visible oral lesions. Amalgam replacement was carried out in 15/18 symptomatic patients. The fillings were replaced with gold in three cases, composite resin fillings in six, glass ionomer in three and both gold and composite materials in three cases. In 10 patients there was complete replacement and in five it was restricted to the fillings adjacent to the mucosal lesions. After a mean follow-up period of 3.2 years a complete cure was seen in seven patients, each of whom had had all their fillings changed. A marked improvement occurred in six patients, and there was no change in two.
Varying Opinions on the Authenticity of a Human Midgut Carcinoid Cell Line – Letter
Authors: Lee M. Ellis, Shaija Samuel, Eric Sceusi
Journal: Clinical Cancer Research (2010)

In 2007, our laboratory published an article in Clinical Cancer Research reporting on the development of a human midgut carcinoid tumor cell line (1). This cell line has now been shared with over 20 laboratories around the world. Investigators in the field of neuroendocrine tumor research are aware that there are very few human carcinoid cell lines available for use in vitro and for murine studies. At the time of publication of this article, we believed that we had developed the first human midgut carcinoid cell line in North America. These cells expressed dense neurosecretory granules on electron microscopy, VMAT-1/2, and somatostatin receptors (1). Recently, we performed short tandem repeat genotyping of the CNDT cell line, and we were unable to match this cell line to any other cell line in our own database at M.D. Anderson Cancer Center, The John Hopkins database, or the American Type Culture Collection database. This, in some ways, was reassuring as these databases contain data on thousands of cell lines, and we could rule out contamination of our CNDT2 cells by other well-characterized cell lines. However, we then tried to match our cell line with frozen carcinoid specimens in our tissue bank, and unfortunately, we were unable to match our short tandem repeat genotype to the carcinoid tumor that we thought was the source of this cell line. The short tandem repeat data for CNDT2 is listed in Table 1 below:Several investigators who have obtained this cell line have questioned the authenticity of its neuroendocrine background. At the Carcinoid and Neuroendocrine Tumor Scientific Forum 2010, a joint conference sponsored by the Verto Institute, The Raymond and Beverly Sackler Foundation, and The Caring for Carcinoid Foundation, held in Boston, MA, May 7, 2010, there were mixed opinions on the neuroendocrine tumor origin of this cell line, as summarized below. Some of these findings were in contrast with our own findings, whereas other observations were unique from those found in our studies.Researchers are advised to keep in mind the questions and skepticism of investigators in the field regarding the neuroendocrine authenticity of this cell line when reading articles that report on its use.No potential conflicts of interest were disclosed.
Chemotherapy Compared with Bone Marrow Transplantation for Adults with Acute Lymphoblastic Leukemia in First Remission
Authors: Mary M. Horowitz
Journal: Annals of Internal Medicine (1991)

Objective: To compare efficacy of intensive postremission chemotherapy with allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia (ALL) in first remission. Design: Retrospective comparison of two cohorts of patients. Setting: Chemotherapy recipients were treated in 44 hospitals in West Germany in two cooperative group trials; transplants were done in 98 hospitals worldwide. Patients: Patients (484) receiving intensive postremission chemotherapy and 251 recipients of HLA-identical sibling bone marrow transplants for ALL in first remission. Patients ranged from 15 to 45 years of age and were treated between 1980 and 1987. Main Results: Similar prognostic factors predicted treatment failure (non-T-cell phenotype, high leukocyte count at diagnosis, and 8 or more weeks to achieve first remission) of both therapies. After statistical adjustments were made for differences in disease characteristics and time-to-treatment, survival was similar in the chemotherapy and transplant cohorts: Five-year leukemia-free survival probability was 38% (95% Cl, 33% to 43%) with chemotherapy and 44% (Cl, 37% to 52%) with transplant. No specific prognostic group had a significantly better outcome with one treatment compared with the other (6% for the difference; Cl, - 3% to 15%). Causes of treatment failure differed: With chemotherapy, 268 (96%) failures were from relapse and 11 (4%) were treatment-related; with transplants, 43 (32%) failures were from relapse and 92 (68%) were treatment-related. Conclusions: These results suggest that bone marrow transplants currently offer no special advantage over chemotherapy for adults with acute lymphoblastic leukemia in first remission.
Vaccination against HPV-16 Oncoproteins for Vulvar Intraepithelial Neoplasia
Authors: Gemma G. Kenter, Marij J.P. Welters, A. Rob P.M. Valentijn, Margriet J.G. Lowik, Dorien M.A. Berends-van der Meer, Annelies P.G. Vloon, Farah Essahsah, Lorraine M. Fathers, Rienk Offringa, Jan Wouter Drijfhout, Amon R. Wafelman, Jaap Oostendorp, Gert Jan Fleuren, Sjoerd H. van der Burg, Cornelis J.M. Melief
Journal: New England Journal of Medicine (2009)

Vulvar intraepithelial neoplasia is a chronic disorder caused by high-risk types of human papillomavirus (HPV), most commonly HPV type 16 (HPV-16). Spontaneous regression occurs in less than 1.5% of patients, and the rate of recurrence after treatment is high.We investigated the immunogenicity and efficacy of a synthetic long-peptide vaccine in women with HPV-16-positive, high-grade vulvar intraepithelial neoplasia. Twenty women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia were vaccinated three or four times with a mix of long peptides from the HPV-16 viral oncoproteins E6 and E7 in incomplete Freund's adjuvant. The end points were clinical and HPV-16-specific T-cell responses.The most common adverse events were local swelling in 100% of the patients and fever in 64% of the patients; none of these events exceeded grade 2 of the Common Terminology Criteria for Adverse Events of the National Cancer Institute. At 3 months after the last vaccination, 12 of 20 patients (60%; 95% confidence interval [CI], 36 to 81) had clinical responses and reported relief of symptoms. Five women had complete regression of the lesions, and HPV-16 was no longer detectable in four of them. At 12 months of follow-up, 15 of 19 patients had clinical responses (79%; 95% CI, 54 to 94), with a complete response in 9 of 19 patients (47%; 95% CI, 24 to 71). The complete-response rate was maintained at 24 months of follow-up. All patients had vaccine-induced T-cell responses, and post hoc analyses suggested that patients with a complete response at 3 months had a significantly stronger interferon-gamma-associated proliferative CD4+ T-cell response and a broad response of CD8+ interferon-gamma T cells than did patients without a complete response.Clinical responses in women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia can be achieved by vaccination with a synthetic long-peptide vaccine against the HPV-16 oncoproteins E6 and E7. Complete responses appear to be correlated with induction of HPV-16-specific immunity.