tbuckley/cabot-search huggingface dataset:
Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat.
Authors: S K Wilson
Journal: Circulation Research (1990)

Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure.
Dual Effect of Parity on Breast Cancer Risk in African-American Women
Authors: J. R. Palmer, L. A. Wise, N. J. Horton, L. L. Adams-Campbell, L. Rosenberg
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: In the United States, breast cancer incidence is higher among African-American women than among white women before age 45 but lower at older ages. To explore whether differences in childbearing patterns can explain this observation, we assessed the relation of several childbearing variables to breast cancer risk in a large prospective cohort study of U.S. African-American women. Methods: Black Women's Health Study participants were enrolled in 1995 and were followed by mailed questionnaires every 2 years (in 1997 and 1999). Of the 64 500 women enrolled, 56 725 (88%) completed at least one of the follow-up questionnaires. During 214 862 person-years of follow-up, participants reported 349 breast cancers, of which 128 were among women younger than 45 years and 221 were among women aged 45–70 years. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were derived from age-stratified Cox regression models that adjusted for each of the childbearing variables (parity, age at first birth, and time since last birth). Results: Compared with primiparity, high parity was associated with an increased risk of breast cancer among women younger than 45 years (IRR for four or more births = 2.4, 95% CI = 1.1 to 5.1) and a decreased risk among women aged 45 years and older (IRR = 0.5, 95% CI = 0.3 to 0.9). The IRR for late age at first birth compared with early age was 2.5 (95% CI = 1.1 to 5.8) among the younger women and was not elevated among older women. We found no statistically significant association of time since last birth with breast cancer risk among either younger or older women. Conclusions: Parity has a dual association with breast cancer risk in African-American women; among women younger than 45 years, parity is associated with an increased risk and among women 45 years and older it is associated with a decreased risk. This dual effect may explain some of the observed differences in breast cancer incidence rates among African-American and white women.
Association Between the Connexin37 Polymorphism and Peripheral Arterial Disease in Subjects With Type 2 Diabetes
Authors: Naoto Katakami, Ken'ya Sakamoto, Hideaki Kaneto, Munehide Matsuhisa, Ikki Shimizu, Fukashi Ishibashi, Takeshi Osonoi, Atsunori Kashiwagi, Ryuzo Kawamori, Masatsugu Hori, Yoshimitsu Yamasaki
Journal: Diabetes Care (2009)

Connexin37 is one of the major connexins expressed in the endothelium, monocytes, and macrophages and plays important roles in atherogenesis (1). The COOH-terminus of this protein is a substrate for specific kinase or protein partners and thereby functions as a regulatory domain (2). Because the C-to-T substitution at nucleotide 1019 in the connexin37 gene causes a proline-to-serine substitution in the regulatory COOH-terminus, and affects its function, this polymorphism is likely associated with the pathogenesis of atherosclerosis. Indeed, this polymorphism has been shown to associate with the risk of coronary artery disease (3). In this study, we investigated whether this polymorphism is associated with an ankle-brachial blood pressure index (ABI), …
Minimally Invasive and Robotic Surgery
Authors: Michael J. Mack
Journal: JAMA (2001)

Advances in surgery have focused on minimizing the invasiveness of surgical procedures, such that a significant paradigm shift has occurred for some procedures in which surgeons no longer directly touch or see the structures on which they operate. Advancements in video imaging, endoscope technology, and instrumentation have made it possible to convert many procedures in many surgical specialties from open surgeries to endoscopic ones. The use of computers and robotics promises to facilitate complex endoscopic procedures by virtue of voice control over the networked operating room, enhancement of dexterity to facilitate microscale operations, and development of virtual simulator trainers to enhance the ability to learn new complex operations. Future research will focus on delivery of diagnostic and therapeutic modalities through natural orifices in which investigation is under remote control and navigation, so that truly "noninvasive" surgery will be a reality.
HIV-1 Selection by Epidermal Dendritic Cells during Transmission across Human Skin
Authors: Jeanette C. Reece, Amanda J. Handley, E. John Anstee, Wayne A. Morrison, Suzanne M. Crowe, Paul U. Cameron
Journal: The Journal of Experimental Medicine (1998)

Macrophage tropic HIV-1 is predominant during the initial viremia after person to person transmission of HIV-1 (Zhu, T., H. Mo, N. Wang, D.S. Nam, Y. Cao, R.A. Koup, and D.D. Ho. 1993. Science. 261:1179–1181.), and this selection may occur during virus entry and carriage to the lymphoid tissue. Human skin explants were used to model HIV-1 selection that may occur at the skin or mucosal surface. Macrophage tropic, but not T cell line tropic strains of HIV-1 applied to the abraded epidermis were recovered from the cells emigrating from the skin explants. Dermis and epidermis were separated by dispase digestion after virus exposure to determine the site of viral selection within the skin. Uptake and transmission to T cells of all HIV-1 isolates was found with the dermal emigrant cells, but only macrophage tropic virus was transferred by emigrants from the epidermis exposed to HIV-1, indicating selection only within the epidermis. CD3+, CD4+ T cells were found in both the dermal and epidermal emigrant cells. After cell sorting to exclude contaminating T cells, macrophage tropic HIV-1 was found in both the dermal emigrant dendritic cells and in dendritic cells sorted from the epidermal emigrants. These observations suggest that selective infection of the immature epidermal dendritic cells represents the cellular mechanism that limits the initial viremia to HIV-1 that can use the CCR5 coreceptor.
Do obstetric complications explain high caesarean section rates among women over 30? A retrospective analysis
Authors: Jacqueline S Bell, Doris M Campbell, Wendy J Graham, Gillian C Penney, Mandy Ryan, Marion H Hall
Journal: BMJ (2001)

As a growing proportion of women delay childbearing into their later reproductive years, the risks and costs associated with advancing maternal age become increasingly important. Extensive evidence shows that both obstetric interventions and obstetric complications are more common among older women,1 and it is often assumed that the interventions are a consequence of the complications. Delivery by caesarean section is one such intervention that is associated with maternal age and is of importance for public health. The extent to which the association is explained by obstetric complications is, however, not known. Martel et al showed that an association between maternal age and rates for primary caesarean section persisted after adjustment for induction of labour, epidural anaesthesia, meconium stained amniotic fluid, and fetal distress.2 We aimed to build on this finding by considering a greater number of …
Population response to change in infant feeding guidelines for allergy prevention
Authors: Dean Tey, Katrina J. Allen, Rachel L. Peters, Jennifer J. Koplin, Mimi L.K. Tang, Lyle C. Gurrin, Anne-Louise Ponsonby, Adrian J. Lowe, Melissa Wake, Shyamali C. Dharmage
Journal: Journal of Allergy and Clinical Immunology (2014)
SCG3 Transcript in Peripheral Blood Is a Prognostic Biomarker for REST-Deficient Small Cell Lung Cancer
Authors: Adrian C. Moss, Gregory M. Jacobson, Lauren E. Walker, Neil W. Blake, Ernie Marshall, Judy M. Coulson
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood. Experimental Design: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals. Results: Expression profiling revealed multiple chromogranin transcripts were readily induced on REST depletion, most notably SCG3 was induced &amp;gt;500-fold. The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022). Conclusions: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.
IMP-1 Displays Cross-Talk with K-Ras and Modulates Colon Cancer Cell Survival through the Novel Proapoptotic Protein CYFIP2
Authors: Perry S. Mongroo, Felicite K. Noubissi, Miriam Cuatrecasas, Jiri Kalabis, Catrina E. King, Cameron N. Johnstone, Mark J. Bowser, Antoni Castells, Vladimir S. Spiegelman, Anil K. Rustgi
Journal: Cancer Research (2011)

Insulin-like growth factor 2 mRNA-binding protein-1 (IMP-1) is an oncofetal protein that binds directly to and stabilizes oncogenic c-Myc and regulates, in turn, its posttranscriptional expression and translation. In contrast to normal adult tissue, IMP-1 is reexpressed and/or overexpressed in human cancers. We show that knockdown of c-Myc in human colon cancer cell lines increases the expression of mature let-7 miRNA family members and downregulates several of its mRNA targets: IMP-1, Cdc34, and K-Ras. We further show that loss of IMP-1 inhibits Cdc34, Lin-28B, and K-Ras, suppresses SW-480 cell proliferation and anchorage-independent growth, and promotes caspase- and lamin-mediated cell death. We also found that IMP-1 binds to the coding region and 3'UTR of K-Ras mRNA. RNA microarray profiling and validation by reverse transcription PCR reveals that the p53-inducible proapoptotic protein CYFIP2 is upregulated in IMP-1 knockdown SW480 cells, a novel finding. We also show that overexpression of IMP-1 increases c-Myc and K-Ras expression and LIM2405 cell proliferation. Furthermore, we show that loss of IMP-1 induces Caspase-3- and PARP-mediated apoptosis, and inhibits K-Ras expression in SW480 cells, which is rescued by CYFIP2 knockdown. Importantly, analysis of 228 patients with colon cancers reveals that IMP-1 is significantly upregulated in differentiated colon tumors (P ≤ 0.0001) and correlates with K-Ras expression (r = 0.35, P ≤ 0.0001) relative to adjacent normal mucosa. These findings indicate that IMP-1, interrelated with c-Myc, acts upstream of K-Ras to promote survival through a novel mechanism that may be important in colon cancer pathogenesis.
Reply to J. Lagro et al
Authors: Pierre Soubeyran, Véronique Brouste, Carine Bellera, Muriel Rainfray
Journal: Journal of Clinical Oncology (2012)

We thank Lagro et al 1 for their interest in our recent article 2 and their constructive comments.We indeed agree that gait speed is pre-dictive of various outcomes such as tolerance to treatment.Lagro et al question whether the cutoff of 20 seconds that we applied to determine abnormal scores on the Timed Get Up and Go (GUG) test was the most appropriate cutoff.Indeed, there are multiple thresholds available in the literature according to context of administration, such
Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology.
Authors: M Okamura, Y Kanayama, K Amastu, N Negoro, S Kohda, T Takeda, T Inoue
Journal: Annals of the Rheumatic Diseases (1993)

The correlation between renal histology and class specific (IgG and IgM) antibodies to double stranded DNA (dsDNA) and single stranded DNA (ssDNA) was studied by enzyme linked immunosorbent assay (ELISA) in 40 untreated patients with systemic lupus erythematosus (SLE). The levels of IgG antibodies to dsDNA were significantly higher in patients with World Health Organisation class IV nephritis than in those with class I, class II, or class III nephritis. IgG antibodies to ssDNA were higher in patients with class IV than in those with class II nephritis. IgG antibodies to dsDNA showed a close correlation with the histological activity score and the amount of electron dense deposit. IgG antibodies to ssDNA showed only a weak correlation with the renal histological activity score. IgM antibodies to dsDNA and IgM antibodies to ssDNA were not correlated with renal histological features. Patients with moderate to severe nephritis had a lower ratio of IgM antibodies to dsDNA to IgG antibodies to dsDNA than those with mild nephritis. These results indicate that the measurement of IgG antibodies to dsDNA is predictive in evaluating renal histological activity in patients with SLE.
IgM Contributes to Glomerular Injury in FSGS
Authors: Derek Strassheim, Brandon Renner, Sarah Panzer, Richard Fuquay, Liudmila Kulik, Danica Ljubanović, V. Michael Holers, Joshua M. Thurman
Journal: Journal of the American Society of Nephrology (2013)

Glomerular IgM and C3 deposits frequently accompany idiopathic FSGS and secondary glomerulosclerosis, but it is unknown whether IgM activates complement, possibly contributing to the pathogenesis of these diseases. We hypothesized that IgM natural antibody binds to neoepitopes exposed in the glomerulus after nonimmune insults, triggering activation of the complement system and further injury. We examined the effects of depleting B cells, using three different strategies, on adriamycin-induced glomerulosclerosis. First, we treated wild-type mice with an anti-murine CD20 antibody, which depletes B cells, before disease induction. Second, we evaluated adriamycin-induced glomerulosclerosis in Jh mice, a strain that lacks mature B cells. Third, we locally depleted peritoneal B cells via hypotonic shock before disease induction. All three strategies reduced deposition of IgM in the glomerulus after administration of adriamycin and attenuated the development of albuminuria. Furthermore, we found that glomerular IgM and C3 were detectable in a subset of patients with FSGS; C3 was present as an activation fragment and colocalized with glomerular IgM, suggesting that glomerular IgM may have bound a cognate ligand. Taken together, these results suggest that IgM activates the complement system within the glomerulus in an animal model of glomerulosclerosis. Strategies that reduce IgM natural antibody or that prevent complement activation may slow the progression of glomerulosclerosis.
Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth
Authors: João Ferreira-Martins, Carlos Rondon-Clavo, Derin Tugal, Justin A. Korn, Roberto Rizzi, Maria Elena Padin-Iruegas, Sergio Ottolenghi, Antonella De Angelis, Konrad Urbanek, Noriko Ide-Iwata, Domenico D'Amario, Toru Hosoda, Annarosa Leri, Jan Kajstura, Piero Anversa, Marcello Rota
Journal: Circulation Research (2009)

Rationale : The adult heart possesses a pool of progenitor cells stored in myocardial niches, but the mechanisms involved in the activation of this cell compartment are currently unknown. Objective : Ca 2+ promotes cell growth raising the possibility that changes in intracellular Ca 2+ initiate division of c-kit–positive human cardiac progenitor cells (hCPCs) and determine their fate. Methods and Results : Ca 2+ oscillations were identified in hCPCs and these events occurred independently from coupling with cardiomyocytes or the presence of extracellular Ca 2+ . These findings were confirmed in the heart of transgenic mice in which enhanced green fluorescent protein was under the control of the c-kit promoter. Ca 2+ oscillations in hCPCs were regulated by the release of Ca 2+ from the endoplasmic reticulum through activation of inositol 1,4,5-triphosphate receptors (IP3Rs) and the reuptake of Ca 2+ by the sarco-/endoplasmic reticulum Ca 2+ pump (SERCA). IP3Rs and SERCA were highly expressed in hCPCs, whereas ryanodine receptors were not detected. Although Na + -Ca 2+ exchanger, store-operated Ca 2+ channels and plasma membrane Ca 2+ pump were present and functional in hCPCs, they had no direct effects on Ca 2+ oscillations. Conversely, Ca 2+ oscillations and their frequency markedly increased with ATP and histamine which activated purinoceptors and histamine-1 receptors highly expressed in hCPCs. Importantly, Ca 2+ oscillations in hCPCs were coupled with the entry of cells into the cell cycle and 5-bromodeoxyuridine incorporation. Induction of Ca 2+ oscillations in hCPCs before their intramyocardial delivery to infarcted hearts was associated with enhanced engraftment and expansion of these cells promoting the generation of a large myocyte progeny. Conclusion : IP3R-mediated Ca 2+ mobilization control hCPC growth and their regenerative potential.
Dysregulation of sterol regulatory element binding protein–1c in livers of morbidly obese women is associated with altered suppressor of cytokine signaling–3 and signal transducer and activator of transcription–1 signaling
Authors: Marshall B. Elam, Chandrahasa Yellaturu, George E. Howell, Xiong Deng, George S. Cowan, Poonam Kumar, Edwards A. Park, M. Lloyd Hiler, Henry G. Wilcox, Thomas A. Hughes, George A. Cook, Rajendra Raghow
Journal: Metabolism (2009)
The Efficacy of Epidermal Growth Factor Receptor–Specific Antibodies against Glioma Xenografts Is Influenced by Receptor Levels, Activation Status, and Heterodimerization
Authors: Terrance G. Johns, Rushika M. Perera, Sonja C. Vernes, Angela A. Vitali, Diana X. Cao, Webster K. Cavenee, Andrew M. Scott, Frank B. Furnari
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. Experimental Design: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. Results: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR–expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR–expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. Conclusions: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma.
Genetic and environmental factors in the changing incidence of allergy
Authors: S. Bonini, L. Magrini, G. Rotiroti, M. P. Ronchetti, P. Onorati
Journal: Allergy (1994)

Several studies have indicated that the incidence and prevalence of allergic diseases are increasing. Such data should not be regarded as mere statistical curiosities, but should be analysed to provide information on the factors contributing to allergy and its changing epidemiology. Extensive evidence has been accumulated that allergic diseases are polyfactorial. Data reported in the literature and particularly twin studies have also suggested polyfactorial control of individual allergy variables, such as total serum levels IgE and IgG4, specificity of antibody response, mediator release from inflammatory cells and target organ response. Markers of genetic susceptibility may identify individuals at risk for allergy, while identification of the environmental factors influencing the phenotypic expression of allergy can be useful in evaluating the cost-benefit ratio of taking preventive measures in such individuals.