tbuckley/cabot-search huggingface dataset:
Predominance of Heart Failure in the Heart of Soweto Study Cohort
Authors: Simon Stewart, David Wilkinson, Craig Hansen, Vinesh Vaghela, Robert Mvungi, John McMurray, Karen Sliwa
Journal: Circulation (2008)

There is a paucity of data to describe the clinical characteristics of heart failure (HF) in urban African communities in epidemiological transition.Chris Hani Baragwanath Hospital services the 1.1 million black African community of Soweto, South Africa. Of 1,960 cases of HF and related cardiomyopathies in 2006, we prospectively collected detailed demographic and clinical data from all 844 de novo presentations (43%). Mean age was 55 +/- 16 years, and women (479 [57%]) and black Africans (739 [88%]) predominated. Most (761 [90%]) had > or =1 cardiovascular risk. Mean left ventricular ejection fraction was 45 +/- 18%. Overall, 180 patients (23%) had isolated diastolic dysfunction, 234 (28%) tricuspid regurgitation, 121 (14%) isolated right HF, and 100 (12%) mitral regurgitation. The most common diagnoses were hypertensive HF (281 [33%]), idiopathic dilated cardiomyopathy (237 [28%]), and, surprisingly, right HF (225 [27%]). Black Africans had less ischemic cardiomyopathy (adjusted odds ratio, 0.12; 95% CI, 0.07 to 0.20) but more idiopathic and other causes of cardiomyopathy (adjusted odds ratio, 4.80; 95% CI, 2.57 to 8.93). Concurrent renal dysfunction, anemia, and atrial fibrillation were found in 172 (25%), 72 (10%), and 53 (6.3%) cases, respectively.These contemporary data highlight the multiple challenges of preventing and managing an increasing and complex burden of HF in urban Africa. In addition to tackling antecedent hypertension, a predominance of young women and a large component of right HF predicate the development of tailored therapeutic strategies.
Occupational dust or gas exposure and prevalences of respiratory symptoms and asthma in a general population
Authors: P Bakke, GE Eide, R Hanoa, A Gulsvik
Journal: European Respiratory Journal (1991)

The relationship of occupational airborne, exposure to respiratory symptoms and asthma was examined using a self-administered questionnaire in a cross-sectional survey of a random sample (n = 4,992 subjects) of the general population aged 15-70 yrs of Hordaland county, Norway. The response rate was 90%. Twenty nine percent of the population had a history of occupational dust or gas exposure, 5% reported having been exposed to asbestos at work, and 4% reported quartz exposure. A history of occupational dust or gas exposure was associated with morning cough, chronic cough, phlegm when coughing, breathlessness on exercise, occasional wheezing and a physician's diagnosis of asthma after adjusting for sex, age, smoking habits and urban-rural area of residence. The adjusted relative odds ratios for the respiratory disorders in subjects exposed to dust or gas ranged from 1.6-1.9. The population attributable risk of occupational dust or gas exposure for the respiratory disorders ranged from 11-19%. The study indicates that respiratory disorders are independently associated with occupational airborne exposure in a Norwegian general population sample.
The New Infectious Disease.
Authors: L. K. Hirshberg.
Journal: JAMA (1907)

Baltimore, Feb.6, 1907. <h3>To the Editor:</h3> —Dr. Sheffield takes a very unkind attitude toward the simple announcement of an undifferentiated infectious disease. Far be it from me to claim anything that justly belongs to another. So far as I can find, there has been no claim made by me of "discovery." Nor do I wish any honor or credit for publishing observations, strictly objective. If the cases described in the several papers by me are the same as Dr. Sheffield's, there will be honor enough for me in having called the attention of the medical world to his paper of eleven years ago. But as his own letter points out a few of the many differences between his cases and mine, I shall briefly repeat them: When I mentioned lack of data, I referred only to additional methods of examination which have crept into our technic in the intervening eleven years.
Antigen presentation by renal tubular epithelial cells.
Authors: V E Rubin-Kelley, A M Jevnikar
Journal: Journal of the American Society of Nephrology (1991)

The interaction between immune effector cells such as T lymphocytes and parenchymal cells in organ-specific immune injury is dynamic. It is now appreciated that the specificity, intensity, and eventual destructive effects of such interactions can be greatly influenced by responses of the target issue. Renal tubular cells are particularly well suited to participate in such immune collaborations. (1) They are exposed to innumerable potentially immunogenic peptides from blood and glomerular filtrate and have pathways to further process these peptides; (2) they express surface molecules which facilitate their engagement to T cells; and (3) they can produce proinflammatory cytokines. In the models of immune-mediated tubulointerstitial injury that are currently studied, there has been a great interest in defining the T lymphocytes that initiate, accelerate, or suppress disease. Surprisingly, there has been relatively little attention on defining the tubular cell responses that regulate these immune-mediated processes. This review will therefore focus on this intriguing aspect of immune tubular injury and relate what is known about antigen presentation by tubular cells in autoimmune renal disease.
Lapatinib, a Dual EGFR and HER2 Kinase Inhibitor, Selectively Inhibits HER2-Amplified Human Gastric Cancer Cells and is Synergistic with Trastuzumab <i>In vitro</i> and <i>In vivo</i>
Authors: Zev A. Wainberg, Adrian Anghel, Amrita J. Desai, Raul Ayala, Tong Luo, Brent Safran, Marlena S. Fejzo, J. Randolph Hecht, Dennis J. Slamon, Richard S. Finn
Journal: Clinical Cancer Research (2010)

HER2 amplification occurs in 18% to 27% of gastric and gastroesophageal junction cancers. Lapatinib, a potent ATP-competitive inhibitor simultaneously inhibits both EGFR and HER2. To explore the role of HER family biology in upper gastrointestinal cancers, we evaluated the effect of lapatinib, erlotinib, and trastuzumab in a panel of molecularly characterized human upper gastrointestinal cancer cell lines and xenografts.EGFR and HER2 protein expression were determined in a panel of 14 human upper gastrointestinal cancer cell lines and HER2 status was assessed by fluorescent in situ hybridization. Dose-response curves were generated to determine sensitivity to lapatinib, erlotinib, and trastuzumab. In HER2-amplified cells, the combination of trastuzumab and lapatinib was evaluated using the median effects principal. The efficacy of lapatinib, trastuzumab, or the combination was examined in HER2-amplified xenograft models.Lapatinib had concentration-dependent antiproliferative activity across the panel with the greatest effects in HER2-amplified cells. There was no association between EGFR protein expression and sensitivity to any of the HER-targeted agents. Cell cycle analysis revealed that lapatinib induced G(1) arrest in sensitive lines and phosphorylated AKT and phosphorylated ERK were decreased in response to lapatinib as well. The combination of lapatinib and trastuzumab was highly synergistic in inhibiting cell growth with a combination index of <1. The combination also induced greater decreases in AKT and ERK activation, G(0)-G(1) cell cycle arrest, and increased rates of apoptosis. In vivo studies showed that the combination of lapatinib and trastuzumab had greater antitumor efficacy than either drug alone.Together, these data suggest that lapatinib has activity in HER2-amplified upper gastrointestinal cancer and supports the ongoing clinical investigation of lapatinib in patients with HER2-amplified disease.
Cigarette Smoking Increases Sympathetic Outflow in Humans
Authors: Krzysztof Narkiewicz, Philippe J.H. van de Borne, Martin Hausberg, Ryan L. Cooley, Michael D. Winniford, Diane E. Davison, Virend K. Somers
Journal: Circulation (1998)

Background —It is generally accepted that smoking increases blood pressure and inhibits muscle sympathetic nerve activity (SNA). The decrease in muscle SNA with cigarette smoking might be secondary to baroreflex responses to the pressor effect of smoking, thus obscuring a sympathetic excitatory effect of smoking. We tested the hypothesis that smoking increases sympathetic outflow. Methods and Results —We examined the effects of sham smoking, cigarette smoking, and cigarette smoking in combination with nitroprusside on muscle (baroreflex-dependent) SNA in 10 healthy habitual smokers. The 3 sessions were performed in random order, each study on a separate day. In an additional study, we also investigated the effects of sham smoking and cigarette smoking on skin (baroreflex-independent) SNA in 9 subjects. Compared with sham smoking, cigarette smoking alone increased blood pressure and decreased muscle SNA. When the blood pressure increase in response to smoking was blunted by nitroprusside infusion, there was a striking increase in muscle SNA. Muscle SNA increased up to 3-fold the levels seen before smoking ( P &lt;0.001), accompanied by an increase in heart rate of up to 37±4 bpm. Cigarette smoking also induced a 102±22% increase in skin SNA ( P =0.03). Conclusions —These data provide the first direct evidence that cigarette smoking increases sympathetic outflow.
Medical School Libraries
Authors: Susan Crawford
Journal: JAMA (1977)

To the Editor.—  To my article  School Libraries in the United States, 1960 through 1975 (237:464, 1977) I wish to add data and references, received subsequent to publication, to complete the historical record.  Table 2, which provides data on support to health sciences libraries by the National Library of Medicine (NLM), does not cover the period immediately succeeding passage of the Medical Library Assistance Act in 1965. During the first five years of the Act's existence (1965 to 1970), a total of $40.8 million were expended for 604 projects. For the period 1965 to 1976, therefore, NLM has expended a total of $81 million for 1250 projects (M. Corning, Assistant Director for International Programs, National Library of Medicine, personal communication).  In addition to the references cited, I wish to include the following four significant studies, emanating from the medical community, which documented the need for improved bio-medical communication:
Systemic Delivery of scAAV9 Expressing SMN Prolongs Survival in a Model of Spinal Muscular Atrophy
Authors: Chiara F. Valori, Ke Ning, Matthew Wyles, Richard J. Mead, Andrew J. Grierson, Pamela J. Shaw, Mimoun Azzouz
Journal: Science Translational Medicine (2010)

Spinal muscular atrophy is one of the most common genetic causes of death in childhood, and there is currently no effective treatment. The disease is caused by mutations in the survival motor neuron gene. Gene therapy aimed at restoring the protein encoded by this gene is a rational therapeutic approach to ameliorate the disease phenotype. We previously reported that intramuscular delivery of a lentiviral vector expressing survival motor neuron increased the life expectancy of transgenic mice with spinal muscular atrophy. The marginal efficacy of this therapeutic approach, however, prompted us to explore different strategies for gene therapy delivery to motor neurons to achieve a more clinically relevant effect. Here, we report that a single injection of self-complementary adeno-associated virus serotype 9 expressing green fluorescent protein or of a codon-optimized version of the survival motor neuron protein into the facial vein 1 day after birth in mice carrying a defective survival motor neuron gene led to widespread gene transfer. Furthermore, this gene therapy resulted in a substantial extension of life span in these animals. These data demonstrate a significant increase in survival in a mouse model of spinal muscular atrophy and provide evidence for effective therapy.
Eosinophilia in D-penicillamine therapy.
Authors: D H Smith, D L Scott, G C Zaphiropoulos
Journal: Annals of the Rheumatic Diseases (1983)

Cross-sectional and longitudinal studies have been carried out to determine the incidence and clinical significance of eosinophilia in patients taking penicillamine for rheumatoid arthritis. In a cross-sectional study of 204 patients eosinophilia was found with equal frequency during treatment with penicillamine, gold, and nonsteroidal anti-inflammatory drugs. A longitudinal study of 89 patients treated with penicillamine showed no consistent relationship between eosinophilia and adverse reactions to the drug. It is concluded that routine monitoring of eosinophil counts is unlikely to be of value in the management of patients taking penicillamine.
GPCR agonist-induced transactivation of the EGFR upregulates MLC II expression and promotes hypertension in insulin-resistant rats
Authors: Prabhakara Reddy Nagareddy, Kathleen M. MacLeod, John H. McNeill
Journal: Cardiovascular Research (2010)

The presence of metabolic abnormalities such as insulin resistance and elevated levels of various vasoconstrictor G-protein-coupled receptor (GPCR) agonists contributes to the development of hypertension. Recent studies have suggested a link between disease progression and activation of growth factor receptor signalling pathways such as the epidermal growth factor receptor (EGFR) by matrix metalloproteinases (MMPs). We hypothesized that excessive stimulation of GPCRs such as α1-adrenergic receptors activates MMP-dependent EGFR transactivation and contributes to the development of hypertension by promoting increased synthesis of contractile proteins in vascular smooth muscle (VSM). We tested this concept in experiments using insulin-resistant VSM cells (VSMCs) and fructose hypertensive rats (FHRs), a model of acquired systolic hypertension and insulin resistance. We found that insulin resistance and agonist stimulation increased the expression and activity of MMPs (MMP-2 and MMP-7), the EGFR, contractile proteins such as myosin light chain kinase and MLC II, and their transcriptional activators including P90 ribosomal kinase (P90RSK) and serum response factor, possibly via the activation of extracellular signal-regulated kinase (ERK1/2) in VSMCs. Further, in insulin-resistant VSMCs and arteries from FHRs, disruption of MMP-EGFR signalling either by a pharmacological or small interfering RNA approach normalized the increased expression and activity of contractile proteins and their transcriptional activators and prevented the development of hypertension in FHRs. Our data suggest that the MMP-EGFR pathway could be a potential target in the treatment of hypertension in insulin resistance and/or hyperglycaemic conditions such as type 2 diabetes.
Serum Soluble Vascular Cell Adhesion Molecule-1: Role as a Surrogate Marker of Angiogenesis
Authors: G. J. Byrne, A. Ghellal, J. Iddon, A. D. Blann, V. Venizelos, S. Kumar, A. Howell, N. J. Bundred
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Angiogenesis, the development of new blood vessels from pre-existing vasculature, is a prerequisite for tumor growth and metastasis. Surrogate markers for angiogenesis would be useful for studying the effectiveness of antiangiogenesis drugs. We examined the potential of three serum glycoproteins—vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin (E-selectin), and von Willebrand factor (VWF)—to serve as markers for angiogenesis. Methods: Preoperative serum levels of VCAM-1, E-selectin, and VWF were measured by enzyme-linked immunosorbent assay in 93 women with early breast cancer and were compared with microvessel density in each tumor, histologic features, and recurrence after surgery. Serum samples were taken from 55 women with advanced breast cancer who were commencing hormonal therapy, both immediately before therapy and 3 months later. Changes in serum levels of VCAM-1, E-selectin, and VWF were compared with the response of the disease to hormonal therapy assessed 6 months after the start of hormone therapy or at disease progression. All P values are two-sided. Results: In women with early breast cancer, serum levels of VCAM-1 (but not of E-selectin or VWF) correlated closely with microvessel density in tumors (r = .65; P<.001), and women who developed early recurrence had higher preoperative levels of serum VCAM-1 than those who remained disease free (P = .01). Serum VCAM-1 levels rose in women with advanced breast cancer whose disease progressed (P<.001) but remained unchanged or fell in women with advanced breast cancer whose disease remained stable or showed a partial response to hormonal therapy. Conclusion: Serum VCAM-1 appears to be a surrogate marker of angiogenesis in breast cancer. Its measurement may, therefore, help in the assessment of antiangiogenesis drugs currently in phase II trials.
Detection of Residual Subclinical Ovarian Carcinoma after Completion of Adjuvant Chemotherapy
Authors: Mory Nouriani, Afshin Bahador, Jonathan S. Berek, Joan P. Cheng, Dennis S. Chi, William A. Cliby, Giuseppe Del Priore, Mark K. Dodson, Bridgette D. Duggan, David M. Gershenson, Scott E. Lentz, Richard T. Penson, William R. Robinson, Mildred Rodriguez, Lynda D. Roman, Mimi C. Yu, Karen Zempolich, Louis Dubeau
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma. Experimental Design: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings. Results: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings. Conclusions: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity.
The binding of surface proteins from Staphylococcus aureus to human bronchial mucins
Authors: D Trivier, N Houdret, RJ Courcol, G Lamblin, P Roussel, M Davril
Journal: European Respiratory Journal (1997)

Colonization by Staphylococcus aureus is frequently observed in obstructive lung diseases, particularly in cystic fibrosis. It has been shown that the bacteria bind to mucins, the main constituent of bronchial secretions. The binding mechanism, however, remains unclear. We have investigated the interactions of two strains of S. aureus, one mucoid and one nonmucoid, with human bronchial mucins. Using a solution phase assay, the binding capacity of the two strains to radiolabelled bronchial mucins was assessed. The bacterial constituents were released by lysostaphin lysis and the surface components of the nonmucoid strain were extracted with the use of a detergent (3-([3-cholamidopropyl] dimethylammonio)-1-propane sulphonate (CHAPS)). All were analysed for mucin-binding using an overlay assay. The amount of mucins bound to the nonmucoid strain was threefold greater than that of the mucoid strain. In the lysostaphin extract from the mucoid strain, only a 57 kDa protein faintly bound 125I-labelled mucins, whereas three mucin-binding proteins (52, 57 and 71 kDa) were identified from the nonmucoid strain. Two surface proteins, one major at 60 kDa and one minor at 71 kDa, bound radiolabelled bronchial mucins and their binding was almost completely inhibited by ovine submaxillary mucin. These results indicate: 1) differences in the mucin-binding capacity from one strain of S. aureus to another; and 2) the presence of external and internal adhesins binding to human respiratory mucins in the nonmucoid strain.
Dysphagia in Behcet's syndrome
Authors: S. Arma, K. S. Habibulla, J. J. Price, J. L. Collis
Journal: Thorax (1971)

The association of dysphagia and Behçet9s syndrome is described. Care has been taken to establish the exact cause for the dysphagia, and autonomic nervous system abnormalities were demonstrated. The local condition appears to be similar to but not identical with achalasia. In view of this similarity a Heller9s myotomy was performed with a satisfactory result.
Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy
Authors: Shimako Yamamoto, Guiping Yang, Daniela Zablocki, Jing Liu, Chull Hong, Song-Jung Kim, Sandra Soler, Mari Odashima, Jill Thaisz, Ghassan Yehia, Carlos A. Molina, Atsuko Yatani, Dorothy E. Vatner, Stephen F. Vatner, Junichi Sadoshima
Journal: Journal of Clinical Investigation (2003)

Activation of mammalian sterile 20–like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity–dependent manner. In vivo, cardiac-specific overexpression of Mst1 in transgenic mice results in activation of caspases, increased apoptosis, and dilated cardiomyopathy. Surprisingly, however, Mst1 prevents compensatory cardiac myocyte elongation or hypertrophy despite increased wall stress, thereby obscuring the use of the Frank-Starling mechanism, a fundamental mechanism by which the heart maintains cardiac output in response to increased mechanical load at the single myocyte level. Furthermore, Mst1 is activated by ischemia/reperfusion in the mouse heart in vivo. Suppression of endogenous Mst1 by cardiac-specific overexpression of dominant-negative Mst1 in transgenic mice prevents myocyte death by pathologic insults. These results show that Mst1 works as both an essential initiator of apoptosis and an inhibitor of hypertrophy in cardiac myocytes, resulting in a previously unrecognized form of cardiomyopathy.