tbuckley/cabot-search huggingface dataset:
Microtubule Depolymerization Normalizes In Vivo Myocardial Contractile Function in Dogs With Pressure-Overload Left Ventricular Hypertrophy
Authors: Masaaki Koide, Masayoshi Hamawaki, Takahiro Narishige, Hiroshi Sato, Shintaro Nemoto, Gilberto DeFreyte, Michael R. Zile, George Cooper, Blase A. Carabello
Journal: Circulation (2000)

Background —Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction. Methods and Results —In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152±16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro. Conclusions —These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload–induced cardiac hypertrophy.
Abstract LB-347: Identify signaling responses to MEK inhibitor AZD6244 in lung cancer cells with proteomics reverse phase protein array
Authors: Bingbing Dai, Wenbin Liu, John V. Heymach, Lauren A. Byers, Jing Wang, Kevin R. Coombes, Bingliang Fang, Jack A. Roth
Journal: Cancer Research (2012)

Abstract AZD6244 is small-molecule inhibitor that targets the MAPK pathway, and is currently in phase I/II clinical evaluation. While some efficacy of these agents has been observed in phase I/II clinical trials, one of the hurdles of targeted therapy is the intrinsic and acquired resistance mediated by complex feedback pathways. Identifying downstream effectors required for cellular response to MEK inhibitors will help us understand the mechanism of resistance, possibly leading to the development of direct therapeutic targets. Explore the signaling responses after treatment with MEK inhibitors will also allow us to identify signaling feedback loops and cross talks. We used reverse phase protein array (RPPA) technology to determine which downstream effectors of MEK/ERK pathways critical for cell growth inhibition or apoptosis induced by MEK inhibitors, and to identify which signaling pathways are inhibited or activated when the pathways is blocked. RPPA is a antibody-based quantitative assay used to analyze nanoliter amounts of sample for 200 proteins to determine expression levels and protein modifications such as phosphorylation or cleavage. Experiments were carried out in 5 resistant and 5 sensitive cell lines with the MEK inhibitor, AZD6244. Cells were treated at different time points (0, 6, 12, 24, 48, and 72 hours) and with various dosages (0, 0.3, 1, 3 and 10 µM). Cell lysates were collected and quantified for RPPA assays. The data was analyzed for the presence of clusters based on differential protein expression by using available methods with a statistical software package (StatSoft, Tulsa, OK). Significantly changed proteins were analyzed with Ingenuity Pathway Analysis (IPA). Proteins Data from RPPA was further validated by using Western blotting with the same antibody used in the RPPA assay. The results showed that inhibition of MEK/ERK could activate multiple signaling pathways including AKT, SRC, STAT3 and IGF1R. Activation of those signaling pathway through signaling cross talk and feedbacks may involved in the intrinsic and acquitted resistance to MEK inhibitor. We also indentified a penal of molecules, such as BIM, P27, p53 and JNK were specifically induced only in the sensitive cells. Those molecules might be the mediators of MEK inhibitor induced cell apoptosis. The results will be helpful in understanding of the signaling cross talks and feedbacks and in the exploration of mechanisms of sensitivity and resistance to the treatment with MEK inhibitors in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-347. doi:1538-7445.AM2012-LB-347
Increased Incidence of Gestational Diabetes in Women Receiving Prophylactic 17α-Hydroxyprogesterone Caproate for Prevention of Recurrent Preterm Delivery
Authors: Andrei Rebarber, Niki B. Istwan, Karen Russo-Stieglitz, Jane Cleary-Goldman, Debbie J. Rhea, Gary J. Stanziano, Daniel H. Saltzman
Journal: Diabetes Care (2007)

OBJECTIVE—Progesterone has a known diabetogenic effect. We sought to determine whether the incidence of gestational diabetes mellitus (GDM) is altered in women receiving weekly 17α-hydroxyprogesterone caproate (17P) prophylaxis for the prevention of recurrent preterm birth. RESEARCH DESIGN AND METHODS—Singleton gestations in women having a history of preterm delivery were identified from a database containing prospectively collected information from women receiving outpatient nursing services related to a high-risk pregnancy. Included were patients enrolled for outpatient management at &amp;lt;27 weeks' gestation with documented pregnancy outcome and delivery at &amp;gt;28 weeks. Patients with preexisting diabetes were excluded. The incidence of GDM was compared between patients who received prophylactic intramuscular 17P (250-mg weekly injection initiated between 16.0 and 20.9 weeks' gestation) and those who did not. RESULTS—Maternal BMI and age were similar. The incidence of GDM was 12.9% in the 17P group (n = 557) compared with 4.9% in control subjects (n = 1,524, P &amp;lt; 0.001; odds ratio 2.9 [95% CI 2.1–4.1]). CONCLUSIONS—The use of 17P for the prevention of recurrent preterm delivery is associated with an increased risk of developing GDM. Early GDM screening is appropriate for women receiving 17P prophylaxis.
Increased arterial stiffness in children with cystic fibrosis: Table 1–
Authors: Tobias Buehler, Markus Steinmann, Florian Singer, Nicolas Regamey, Carmen Casaulta, Martin H. Schoeni, Giacomo D. Simonetti
Journal: European Respiratory Journal (2012)

To the Editors:

The survival of patients with cystic fibrosis (CF) is increasing and, therefore, there is a need to focus on extrapulmonary comorbidities that could affect their length and quality of life [1]. Diseases with a systemic inflammatory state are associated with increased arterial stiffness, an independent risk factor for cardiovascular diseases [2, 3]. This premature ageing of the vasculature has been demonstrated in CF adults, but it is not known whether it begins in childhood [4]. We hypothesised that arterial stiffness is increased in CF children compared with healthy controls and that it is related to the degree of systemic inflammation.

Digital volume pulse (DVP) analysis, with the computation of the stiffness index (SIDVP) and pulse wave velocity between the carotid and femoral arteries (PWVcf) were determined in 31 CF children (13 females; median age 12.2 yrs, interquartile range (IQR) 9.3–14.8 yrs) and in 48 healthy controls, matched for sex and age (19 female; median age 10.9 yrs, IQR 9.7–13.4 yrs). Office blood pressure was taken as the mean of three measurements obtained from the supine child after 10 min of rest with a validated oscillometric device (Dinamap XL; Criticon Inc., Tampa, FL, USA). The Pulse Trace PWV …
A Chemotherapy-Radiotherapy Rx Regimen For Children With Stage III Hodgkin's Disease
Authors: M. P. Sullivan, L. M. Fuller
Journal: CA A Cancer Journal for Clinicians (1973)

Long-term survival, often tantamount to cure, is now being obtained following energetic therapy in adults with Stage III, A and B, Hodgkin's disease.In chil dren, over eight years of age, the disease and the tolerance of therapy appear simi lar to that of adults.Long-term survival should, therefore, be possible in chil dren despite the fact that late effects of irradiation and even chemotherapy may necessitate some modification of the adult treatment plans.As approximately one third of children with Hodgkin's dis ease present with Stage III disease, the potential for cure makes it imperative that these children be identified and, in particular, that they be considered separately from children with Stage IV disease. Liver scanSpleen scan Bone scan Immunologic studies Skin hypersensitivity Lymphocyte transformation *celiotomy & splenectomy (age 2-5 yrs.)
Abstract 5107: Notch3 Signaling in Macrophages Promotes Obesity and Atherosclerosis in Hypercholesterolemic Mice
Authors: Tetsuro Miyazaki, Hiroyuki Yamazaki, Kunio Morishige, Elena Aikawa, Masanori Aikawa
Journal: Circulation (2009)

Background: Macrophage activation participates in the pathogenesis of atherosclerosis and obesity, major components of the cardiometabolic syndrome. The Notch signaling pathway involves four receptors (Notch1– 4) and regulates various biological processes during development. We previously demonstrated that Notch signaling induces proinflammatory responses in macrophages in vitro. However, the role of each receptor in macrophage activation remains unclear. The present study has determined the reality in vivo of our in vitro findings by exploring whether Notch3 expression in macrophages promotes cardiometabolic disorders. Methods and Results: We established macrophage-selective transgenic mice for the Notch3 intercellular domain (a constitutively active form) under control of the scavenger receptor A promoter/enhancer (Notch3tg). In vitro studies demonstrated that peritoneal macrophages of Notch3tg mice expressed higher levels of various molecules associated with inflammation (e.g., IL-1 β , iNOS) and arterial remodeling and calcification (MMP-8/collagenase-2, MMP-13/collagenase-3, BMP-4 and BMP-7) than wild-type macrophages (p&lt;0.05). To assess the in vivo role of macrophage activation via Notch3 in visceral obesity and atherosclerosis, we generated compound mutant mice by crossing Notch3tg with Ldlr−/− mice, a model of atherosclerosis and the metabolic syndrome. After high fat feeding for 24 weeks, the weight of epididymal fat in Notch3tg:Ldlr−/− mice (n=10) was greater than that of Ldlr−/− littermates (n=10, p&lt;0.05). Notch3tg:Ldlr−/− epididymal fat expressed higher RNA levels of leptin and lower levels of hormone sensitive lipase, a key regulator of lipolysis in fat tissue, consistent with visceral fat accumulation. In addition, N3tg:Ldlr−/− mice showed increased plaque size in atherosclerotic aortas (p&lt;0.05). The aorta of N3tg:Ldlr−/− mice further exhibited more advanced calcification than Ldlr−/− mice (p&lt;0.05) in association with higher levels of the osteogenesis inducer BMP-7 (p&lt;0.01). Conclusion: These data indicate that macrophage activation through Notch3 signaling promotes obesity and atherosclerosis and provide new insight into the pathogenesis of chronic inflammatory diseases.
US Preterm Births: “D” Is for Dismal
Authors: Rebecca Voelker
Journal: JAMA (2010)

who took finasteride experienced a 24% reduction in prostate cancer incidence compared with men taking placebo (Thompson IM et al. N Engl J Med. 2003;349[3]:215-224). Preliminary results presented earlier this year from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial indicate that dutasteride reduces the incidence of prostate cancer in men older than age 50 years by 23% compared with placebo. “Current studies are attempting to define what population of men would most benefit from these cancer preventive drugs,” said Brown. Brown noted that because clinicians still lack a thorough understanding of individuals’ susceptibility to cancer and their response to various agents, they cannot properly screen populations or predict who will benefit from different drugs. “Future preclinical and clinical studies should focus on developing accurate cancer risk assessment tools and testing next-generation targeted agents singly and in combination for their toxicity and ability to prevent cancer,” he said.
Serum aluminium concentration and aluminium deposits in bone in patients receiving haemodialysis.
Authors: S A Charhon, P M Chavassieux, P J Meunier, M Accominotti
Journal: BMJ (1985)

Serum aluminium concentrations and biopsy specimens of bone were examined in 56 patients with end stage chronic renal failure receiving maintenance haemodialysis. Deposits of aluminium in bone specimens were often associated with low bone formation with or without osteomalacia. Serum aluminium concentrations of greater than 3.7 mumol/l (10 micrograms/100 ml) indicated a high probability of deposits of aluminium in bone specimens, although high serum concentrations did not predict the type of renal bone disease. Biopsy of the bone is the best method of detecting aluminium intoxication of bone. A serum aluminium concentration of 3.7 mumol/l should be the threshold beyond which bone biopsy should be performed to confirm an overload of aluminium and identify histological bone changes induced by aluminium.
Gene expression profiling of ATL patients: compilation of disease-related genes and evidence for TCF4 involvement in BIRC5 gene expression and cell viability
Authors: Cynthia A. Pise-Masison, Michael Radonovich, Kathleen Dohoney, John C. Morris, Deirdre O'Mahony, Min-Jung Lee, Jane Trepel, Thomas A. Waldmann, John E. Janik, John N. Brady
Journal: Blood (2009)
Paradoxical effects of cyclosporin A on collagen arthritis in rats.
Authors: N Kaibara, T Hotokebuchi, K Takagishi, I Katsuki
Journal: The Journal of Experimental Medicine (1983)

The effect of the immunosuppressive agent cyclosporin A (CS-A) on collagen arthritis in Sprague-Dawley rats is investigated. A 14-d course of CS-A treatment at doses of 15 mg/kg per day or more, begun on the same day as type II collagen immunization, suppressed the development of arthritis as well as humoral and delayed-type hypersensitivity (DTH) skin test responses to type II collagen, possibly by interfering with helper T cells. Additional studies demonstrated that CS-A treatment only during the induction phase of immunity proved to be successful. When CS-A treatment was started only during the immediately preclinical phase of arthritis or after the disease onset, a significant enhancement of the disease was obtained in a dose-dependent manner. This enhancement was accompanied by an augmentation of DTH skin reactions, while antibody responses were either suppressed or unaffected. These results appear to be attributable at least in part to a suppressive effect of CS-A on a population of suppressor T cells, thus resulting in a T cell-mediated helper effect. It is therefore reasonable to assume that the paradoxical effects of CS-A on collagen arthritis in rats might be caused by an altering of the sensitive balance of the two regulatory subpopulations of T cells. It is also possible that cell-mediated immune responses may play an important role in influencing the course of the disease.
N-acetyl cysteine directed detoxification of 2-hydroxyethyl methacrylate by adduct formation
Authors: Giuseppina Nocca, Vincenzo D'Antò, Claudia Desiderio, Diana Valeria Rossetti, Rosa Valletta, Adriana Marquez Baquala, Helmut Schweikl, Alessandro Lupi, Sandro Rengo, Gianrico Spagnuolo
Journal: Biomaterials (2009)
A Survey of the Availability of Primary Bioinformatics Web Resources
Authors: Trias Thireou, George Spyrou, Vassilis Atlamazoglou
Journal: Genomics Proteomics & Bioinformatics (2007)

Abstract The explosive growth of the bioinformatics field has led to a large amount of data and software applications publicly available as web resources. However, the lack of persistence of web references is a barrier to a comprehensive shared access. We conducted a study of the current availability and other features of primary bioinformatics web resources (such as software tools and databases). The majority (95%) of the examined bioinformatics web resources were found running on UNIX/Linux operating systems, and the most widely used web server was found to be Apache (or Apache-related products). Of the overall 1,130 Uniform Resource Locators (URLs) examined, 91% were highly available (more than 90% of the time), while only 4% showed low accessibility (less than 50% of the time) during the survey. Furthermore, the most common URL failure modes are presented and analyzed.
The Pathology of Congenital Heart Disease: A Personal Experience With More Than 6300 Congenitally Malformed Hearts
Authors: Frederick J. Schoen
Journal: JAMA (1996)

As leaders in a small cadre of cardiovascular clinicians and pathologists with a comprehensive understanding of and experience in the morphology of congenital heart disease, Dr Bharati (over 25 years) and the late Dr Lev (over 60 years) have made immense contributions. This impressive, informative, and richly illustrated two-volume work of more than 1500 pages summarizes their experience with the evaluation of over 6300 hearts. The book has two major sections. The first, only 64 pages long, has nine chapters describing general concepts of external and internal cardiac functional anatomy, embryology, terminology, and methods of examination. The second section has approximately 40 chapters of varying length and complexity, nearly all devoted to specific disease entities. The initial and largest disease-oriented chapter, on tetralogy of Fallot, has 66 pages and 154 illustrations, describing both simple and complex, acyanotic and cyanotic types, with individual consideration of the aorta, pulmonary tract, ventricular septal
Obesity in Developing Nations and US Weight Guidelines
Authors: Walid Aldoori
Journal: JAMA (1995)

To the Editor.  —In the article by Dr Willett and colleagues, 1 the authors voiced their concern that the current US weight guidelines may be falsely reassuring US women older than 35 years regarding their risk of coronary heart disease. Although the current guidelines are meant for US women, their impact will be felt in other countries. It is my experience that such guidelines will be followed almost blindly in many developing countries. This is mainly due to two factors. First, the perception is that weight guidelines or almost all guidelines dealing with different health aspects that are recommended for the US population represent the truth or the gold standard to be followed. Second, many developing countries have a limited ability to evaluate and formulate their individual guidelines because of financial and/or scientific constraints.
Atopic Dermatitis—A New Therapeutic Regimen
Authors: Samuel Ayres
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The<i>Primer on Allergic and Immunologic Diseases</i>(1982; 248:2611) of Nov 26, 1982, discusses atopic dermatitis as an allergic manifestation, which is contrary to a recent statement in the seventh edition of<i>Andrews'Diseases of the Skin</i>, edited by Domonkos and colleagues,<sup>1</sup>published in 1982. According to the opinion of these authoritative dermatologists regarding atopic dermatitis: "Identification of the allergens, their elimination, and hyposensitization to the offending substances, have been the principal methods of study and management of this disease. Clinically this approach has been remarkably unrewarding." My own personal experience coincides with this statement. A revolution in the etiologic concept and therapeutic management of atopic dermatitis occurred at the October 1963 meeting of the Los Angeles Dermatological Society when Jud R. Scholtz, MD, introduced a new regimen based on findings by Sulzberger and associates<sup>2,3</sup>that atopic dermatitis was associated with a defect in the patient's
<i>Mind and its Disorders. A Text-Book for Students and Practitioners of Medicine</i>. By W. H. B. Stoddard, M. D., F. R. C. P.,<i>Lecturer on Mental Diseases, St. Thomas's Hospital Medical School, State Resident Physician and Medical Superintendent Bethlem Royal Hospital, etc. Third Edition with illustrations. (Philadelphia: P. Blakiston's Son Co., 1919.</i>)
Authors: M W. Peck
Journal: American Journal of Psychiatry (1920)
The Treatment of Typhoid Fever.
Authors: J. Sanderson Christison
Journal: JAMA (1898)

Chicago, Sept. 10, 1898. <h3>To the Editor:</h3> —While much, of late, has been written on the treatment of typhoid fever, I feel that a brief statement of my experience may be of some value to others, especially as I seem to have met with greater success than anyone else whose reports I have read. I have thus far hesitated to relate my experience, because of the fact that when I changed my location several years ago, to adopt a more exclusive practice, I destroyed some of my records. However, I can recall at least twenty-eight cases in my last four years of general practice, and I think there were more in that period. But one can easier recall deaths than cases. Two deaths occurred among my typhoid fever cases during the four years in question, but one of these two cases was moribund when I first saw it. It was
Ultrasound scanning in the detection of hepatic fibrosis and steatosis.
Authors: S H Saverymuttu, A E Joseph, J D Maxwell
Journal: BMJ (1986)

Hepatic steatosis and fibrosis produce abnormal echo patterns on ultrasound scanning, but the potential of ultrasound scanning for diagnosing these conditions in routine clinical practice is uncertain. A prospective comparative study of 85 patients with histologically assessed liver conditions was performed, and specificity was assessed in 76 patients with functional bowel disease who were presumed to have normal livers. Histological examination showed steatosis ranging from mild to severe in 48 patients and fibrosis ranging from increased fibrous tissue to established cirrhosis in 35 patients. Ultrasound scanning accurately identified steatosis, recognising 45 cases (sensitivity 94%) with a specificity of 84%. Fibrosis was less reliably detected (sensitivity 57% and specificity 88%). Of the 50 patients with alcoholic liver disease, 47 (94%) yielded abnormal results on scanning. In the 76 patients with functional bowel disease there was only one false positive result, giving a specificity of 99% in this group. As hepatic steatosis is the earliest change in alcoholic liver disease and seems to be of prognostic importance for the development of cirrhosis, ultrasound scanning provides an effective screening procedure, particularly in the occult alcoholic, who often presents with non-specific gastrointestinal complaints.