tbuckley/cabot-search huggingface dataset:
DEVELOPMENTAL DETERMINANTS OF BLOOD PRESSURE IN ADULTS
Authors: Linda Adair, Darren Dahly
Journal: Annual Review of Nutrition (2005)

▪ Abstract Over the past 20 years a large and varied body of research has attempted to make the case for the developmental origins of elevated adult blood pressure (BP). Experimental animal research has identified plausible biological mechanisms through which fetal nutritional insufficiency may affect adult BP. The majority of human epidemiologic studies demonstrate an inverse association of birth weight (the most commonly used marker of fetal nutrition) with adult BP and higher risk of hypertension among individuals with lower weight at birth. The most adverse BP outcomes occur among individuals who were small at birth but relatively large as adults, a finding that suggests a role for postnatal growth. We critically review the literature on proposed mechanisms and epidemiologic evidence for developmental origins of adult BP and hypertension, considering associations with birth weight, maternal nutrition during pregnancy, child growth patterns, and infant feeding.
SOME PHYSICO-THERAPEUTIC METHODS IN DERMATOLOGY
Authors: Sir MALCOLM MORRIS
Journal: British Journal of Dermatology (1912)

FROM the outburst of inventiveness which recent years have witnessed, medicine has profited not less than other arts, and no branch of medicine more than that of dermatology.I n electro-therapeutics, in actino-therapy, in radio-therapy, more recently in radium-therapy, and most recently of all in the employment of extreme degrees of cold, valuable additions have been made t o the dermatologist's armamentarium.The serviceability of these measures in the treatment of certain benign new growths, of lesions which are the result, directly or indirectly, of inflammatory processes, and in the relief of itching, admits of no dispute.Their usefulness in the treatment of malignant growths, except as palliatives or as auxiliaries of surgery, is less unquestionable.That exaggerated claims have been made in favour of certain of the new methods, and that, a reaction against them has thus been provoked, may a t once be conceded.My aim has always been to hold an even balance between the old and the new, and it is in this spirit that I attempt an estimate, based upon my own experience, of the true place of the new physical agents in dermatological therapeutics.The methods I propose to discuss are the X-rays, the Finsen light, radium, and carbon-dioxide snow ; and it will be convenient to consider them first in connection wit,h the conditions in which they have been most used, beginning with the more serious diseases and passing on to affections of lesser gravity.With regard to growths of a high degree of malignancy, such as
Effect of Supplementation of <i>Coccinia cordifolia</i> Extract on Newly Detected Diabetic Patients
Authors: Rebecca Kuriyan, Ramaswamy Rajendran, Ganapathi Bantwal, Anura V. Kurpad
Journal: Diabetes Care (2008)

Coccinia indica (synonym Coccinia cordifolia), an herb growing abundantly in India, has been used in traditional treatment of diabetes. However, carefully controlled studies of its efficacy are lacking. This study aimed to evaluate the effectiveness of Coccinia cordifolia on blood glucose levels of incident type 2 diabetic patients requiring only dietary or lifestyle modifications.The study was a double-blind, placebo-controlled, randomized trial. Sixty incident type 2 diabetic subjects (aged 35-60 years) were recruited from St. Johns Medical College Hospital, Bangalore, India. The subjects were randomly assigned into the placebo or experimental group and were provided with 1 g alcoholic extract of the herb for 90 days. Anthropometric, biochemical, dietary, and physical activity assessment were carried out at baseline and were repeated at days 45 and 90 of the study. All subjects were provided with standard dietary and physical activity advice for blood sugar control.There was a significant decrease in the fasting, postprandial blood glucose and A1C of the experimental group compared with that of the placebo group. The fasting and postprandial blood glucose levels of the experimental group at day 90 significantly decreased, by 16 and 18%, respectively. There were no significant changes observed in the serum lipid levels.This study suggests that Coccinia cordifolia extract has a potential hypoglycemic action in patients with mild diabetes. However, further studies are needed to elucidate mechanisms of action.
Regulation of PTEN activity by p38δ-PKD1 signaling in neutrophils confers inflammatory responses in the lung
Authors: Arne Ittner, Helena Block, Christoph A. Reichel, Markku Varjosalo, Helmuth Gehart, Grzegorz Sumara, Matthias Gstaiger, Fritz Krombach, Alexander Zarbock, Romeo Ricci
Journal: The Journal of Experimental Medicine (2012)

Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating in acute respiratory distress syndrome (ARDS), a frequent complication with high mortality in humans. Molecular mechanisms underlying recruitment of neutrophils to sites of inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required for recruitment of neutrophils into inflammatory sites. Global and myeloid-restricted deletion of p38δ in mice results in decreased alveolar neutrophil accumulation and attenuation of ALI. p38δ counteracts the activity of its downstream target protein kinase D1 (PKD1) in neutrophils and myeloid-restricted inactivation of PKD1 leads to exacerbated lung inflammation. Importantly, p38δ and PKD1 conversely regulate PTEN activity in neutrophils, thereby controlling their extravasation and chemotaxis. PKD1 phosphorylates p85α to enhance its interaction with PTEN, leading to polarized PTEN activity, thereby regulating neutrophil migration. Thus, aberrant p38δ–PKD1 signaling in neutrophils may underlie development of ALI and life-threatening ARDS in humans.
Expression of Stromelysin-3 in Atherosclerotic Lesions: Regulation via CD40–CD40 Ligand Signaling In Vitro and In Vivo
Authors: Uwe Schönbeck, François Mach, Galina K. Sukhova, Elizabeth Atkinson, Ethan Levesque, Michael Herman, Pierre Graber, Paul Basset, Peter Libby
Journal: The Journal of Experimental Medicine (1999)

Stromelysin-3 is an unusual matrix metalloproteinase, being released in the active rather than zymogen form and having a distinct substrate specificity, targeting serine proteinase inhibitors (serpins), which regulate cellular functions involved in atherosclerosis. We report here that human atherosclerotic plaques (n = 7) express stromelysin-3 in situ, whereas fatty streaks (n = 5) and normal arterial specimens (n = 5) contain little or no stromelysin-3. Stromelysin-3 mRNA and protein colocalized with endothelial cells, smooth muscle cells, and macrophages within the lesion. In vitro, usual inducers of matrix metalloproteinases such as interleukin-1, interferon-γ, or tumor necrosis factor α did not augment stromelysin-3 in vascular wall cells. However, T cell–derived as well as recombinant CD40 ligand (CD40L, CD154), an inflammatory mediator recently localized in atheroma, induced de novo synthesis of stromelysin-3. In addition, stromelysin-3 mRNA and protein colocalized with CD40L and CD40 within atheroma. In accordance with the in situ and in vitro data obtained with human material, interruption of the CD40–CD40L signaling pathway in low density lipoprotein receptor–deficient hyperlipidemic mice substantially decreased expression of the enzyme within atherosclerotic plaques. These observations establish the expression of the unusual matrix metalloproteinase stromelysin-3 in human atherosclerotic lesions and implicate CD40–CD40L signaling in its regulation, thus providing a possible new pathway that triggers complications within atherosclerotic lesions.
Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus
Authors: Masanori Emoto, Katsuhito Mori, Eiko Lee, Naoya Kawano, Yuko Yamazaki, Shoko Tsuchikura, Tomoaki Morioka, Hidenori Koyama, Tetsuo Shoji, Masaaki Inaba, Yoshiki Nishizawa
Journal: Metabolism (2009)
Morphine‐6‐glucuronide: Actions and mechanisms
Authors: Gavin J. Kilpatrick, Terry W. Smith
Journal: Medicinal Research Reviews (2005)

Abstract Morphine‐6‐glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side‐effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the µ‐opioid receptor. The differences for which there is a reasonable consensus in the literature can be summarized as: (1) Morphine has a slightly higher affinity for the µ‐opioid receptor than M6G, (2) M6G shows a slightly higher efficacy at the µ‐opioid receptor, (3) M6G has a lower affinity for the κ‐opioid receptor than morphine, and (4) M6G has a very different absorption, distribution, metabolism, and excretion (ADME) profile from morphine. However, none of these are adequate alone to explain the clinical differences between M6G and morphine. The ADME differences are perhaps most likely to explain some of the differences but seem unlikely to be the whole story. Further work is required to examine further the profile of M6G, notably whether M6G penetrates differentially to areas of the brain involved in pain and those involved in nausea, vomiting, and respiratory control or whether µ‐opioid receptors in these brain areas differ in either their regulation or pharmacology. © 2005 Wiley Periodicals, Inc. Med Res Rev
Revisiting 1-antitrypsin therapy in cystic fibrosis: can it still offer promise?
Authors: S. Brennan
Journal: European Respiratory Journal (2006)

The contribution of the neutrophil-derived serine protease neutrophil elastase (NE) to lung disease in cystic fibrosis (CF) is unquestioned and yet, despite promising preliminary studies in the last 20 yrs to investigate an effective therapy to negate the damaging effect of NE 1, this treatment has failed to take off for patients with CF. This is largely due to the scarcity of clinical trial data relating to this therapy. However, two recent publications 2, 3 signal a renewed interest in the application of treatment with inhaled α1-antitrypsin (AAT) as a panacea for the proteolytic damage occurring in CF lung disease.

NE is released by neutrophils either on the cell membrane during cell migration or into the extracellular space upon stimulation by immune complexes, or by necrotic or apoptotic cells 4. AAT is one of the most important protease inhibitors involved in confining tissue proteolysis during an inflammatory response 5. Secreted by the liver, increased AAT concentrations are stimulated by interleukin (IL)-6 and it acts rapidly in the peripheral tissue to inhibit serine proteases, such as NE, cathepsin G and proteinase 3. While it is believed that AAT secretion is not impaired in CF 6, there are an overwhelming number of activated neutrophils in the lungs, the product of which is an excessive release of NE and other proteases, which cannot be contained by physiological AAT levels.

In the current issue of the European Respiratory Journal Griese et al. 2 present findings on a prospective randomised study of AAT in CF. Griese et al. 2 set out to compare two different deposition patterns of inhaled AAT over a 4-week period to see which of the two provided the best clinical outcome. To achieve this they employed the new technology of …
Effects of an Intravenous Lipid Challenge and Free Fatty Acid Elevation on In Vivo Insulin Sensitivity in African American Versus Caucasian Adolescents
Authors: Stephen F. Burns, Sheryl F. Kelsey, Silva A. Arslanian
Journal: Diabetes Care (2008)

OBJECTIVE—African American youth have lower insulin sensitivity than their Caucasian peers, but the metabolic pathways responsible for this difference remain unknown. Free fatty acids (FFAs) are associated with insulin resistance through the Randle cycle. The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents. RESEARCH DESIGN AND METHODS—Insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp) was evaluated in 22 African American and 21 Caucasian adolescents on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid. RESULTS—During intralipid infusion, fasting insulin and C-peptide concentrations increased while fasting glucose and basal glucose turnover did not change in either group. Insulin sensitivity decreased similarly in African American (normal saline 7.65 ± 0.61 vs. intralipid 5.15 ± 0.52 μmol · kg−1 · min−1 per pmol/l) and Caucasian subjects (normal saline 8.97 ± 0.85 vs. intralipid 5.96 ± 0.56 μmol · kg−1 · min−1 per pmol/l) (P &amp;lt; 0.001). CONCLUSIONS—African American and Caucasian adolescents respond to FFA elevation similarly through increased fasting insulin secretion to maintain fasting glucose homeostasis and reduced peripheral glucose uptake and insulin resistance. Thus, African American adolescents are not more susceptible to FFA-induced insulin resistance than Caucasian youth.
State of the Art in Therapeutic Hypothermia
Authors: Joshua W. Lampe, Lance B. Becker
Journal: Annual Review of Medicine (2010)

Historically, hypothermia was induced prior to surgery to enable procedures with prolonged ischemia, such as open heart surgery and organ transplant. Within the past decade, the efficacy of hypothermia to treat emergency cases of ongoing ischemia such as stroke, myocardial infarction, and cardiac arrest has been studied. Although the exact role of ischemia/reperfusion is unclear clinically, hypothermia holds significant promise for improving outcomes for patients suffering from reperfusion after ischemia. Research has elucidated two distinct windows of opportunity for clinical use of hypothermia. In the early intra-ischemia window, hypothermia modulates abnormal cellular free radical production, poor calcium management, and poor pH management. In the more delayed post-reperfusion window, hypothermia modulates the downstream necrotic, apoptotic, and inflammatory pathways that cause delayed cell death. Improved cooling and monitoring technologies are required to realize the full potential of this therapy. Herein we discuss the current state of clinical practice, clinical trials, recommendations for cooling, and ongoing research on therapeutic hypothermia.
A B Cell Receptor with Two Igα Cytoplasmic Domains Supports Development of Mature But Anergic B Cells
Authors: Amy Reichlin, Anna Gazumyan, Hitoshi Nagaoka, Kathrin H. Kirsch, Manfred Kraus, Klaus Rajewsky, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2004)

B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)α and Igβ a membrane-bound heterodimer. Igα and Igβ are redundant in their ability to support early B cell development, but their roles in mature B cells have not been defined. To examine the function of Igα–Igβ in mature B cells in vivo we exchanged the cytoplasmic domain of Igα for the cytoplasmic domain of Igβ by gene targeting (Igβc→αc mice). Igβc→αc B cells had lower levels of surface IgM and higher levels of BCR internalization than wild-type B cells. The mutant B cells were able to complete all stages of development and were long lived, but failed to differentiate into B1a cells. In addition, Igβc→αc B cells showed decreased proliferative and Ca2+ responses to BCR stimulation in vitro, and were anergic to T-independent and -dependent antigens in vivo.
Nicotine induces cell proliferation by -arrestin-mediated activation of Src and Rb-Raf-1 pathways
Authors: P. Dasgupta
Journal: Journal of Clinical Investigation (2006)

Recent studies have shown that nicotine, a component of cigarette smoke, can stimulate the proliferation of non-neuronal cells. While nicotine is not carcinogenic by itself, it has been shown to induce cell proliferation and angiogenesis. Here we find that mitogenic effects of nicotine in non-small cell lung cancers (NSCLCs) are analogous to those of growth factors and involve activation of Src, induction of Rb-Raf-1 interaction, and phosphorylation of Rb. Analysis of human NSCLC tumors show enhanced levels of Rb-Raf-1 complexes compared with adjacent normal tissue. The mitogenic effects of nicotine were mediated via the alpha7-nAChR subunit and resulted in enhanced recruitment of E2F1 and Raf-1 on proliferative promoters in NSCLC cell lines and human lung tumors. Nicotine stimulation of NSCLC cells caused dissociation of Rb from these promoters. Proliferative signaling via nicotinic acetylcholine receptors (nAChRs) required the scaffolding protein beta-arrestin; ablation of beta-arrestin or disruption of the Rb-Raf-1 interaction blocked nicotine-induced proliferation of NSCLCs. Additionally, suppression of beta-arrestin also blocked activation of Src, suppressed levels of phosphorylated ERK, and abrogated Rb-Raf-1 binding in response to nicotine. It appears that nicotine induces cell proliferation by beta-arrestin-mediated activation of the Src and Rb-Raf-1 pathways.
Prognostic Effects of 25-Hydroxyvitamin D Levels in Early Breast Cancer
Authors: Pamela J. Goodwin, Marguerite Ennis, Kathleen I. Pritchard, Jarley Koo, Nicky Hood
Journal: Journal of Clinical Oncology (2009)

Vitamin D has been linked to breast cancer risk, but prognostic effects are unknown. Such effects are biologically plausible given the presence of vitamin D receptors in breast cancer cells, which act as nuclear transcription factors to regulate gene activity.The study was conducted in a prospective inception cohort of 512 women with early breast cancer diagnosed 1989 to 1996. Vitamin D levels were measured in stored blood. Clinical, pathologic, and dietary data were accessed to examine prognostic effects of vitamin D.Mean age was 50.4 years, mean vitamin D was 58.1 +/- 23.4 nmol/L. Vitamin D levels were deficient (< 50 nmol/L) in 37.5% of patients, insufficient (50 to 72 nmol/L) in 38.5% of patients, and sufficient (> 72 nmol/L) in 24.0% of patients. There was little variation in mean vitamin D levels between summer and winter months. Mean follow-up was 11.6 years; 116 women had distant recurrences, and 106 women died. Women with deficient vitamin D levels had an increased risk of distant recurrence (hazard ratio [HR] = 1.94; 95% CI, 1.16 to 3.25) and death (HR = 1.73; 95% CI, 1.05 to 2.86) compared with those with sufficient levels. The association remained after individual adjustment for key tumor and treatment related factors but was attenuated in multivariate analyses (HR = 1.71; 95% CI, 1.02 to 2.86 for distant recurrence; HR = 1.60; 95% CI, 0.96 to 2.64 for death).Vitamin D deficiency may be associated with poor outcomes in breast cancer.
Web-Based Care Management in Patients With Poorly Controlled Diabetes
Authors: Graham T. McMahon, Helen E. Gomes, Sara Hickson Hohne, Tang Ming-Jye Hu, Betty A. Levine, Paul R. Conlin
Journal: Diabetes Care (2005)

OBJECTIVE—To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes. RESEARCH DESIGN AND METHODS—For this study, 104 patients with diabetes and HbA1c (A1C) ≥9.0% who received their care at a Department of Veterans Affairs medical center were recruited. All participants completed a diabetes education class and were randomized to continue with their usual care (n = 52) or receive web-based care management (n = 52). The web-based group received a notebook computer, glucose and blood pressure monitoring devices, and access to a care management website. The website provided educational modules, accepted uploads from monitoring devices, and had an internal messaging system for patients to communicate with the care manager. RESULTS—Participants receiving web-based care management had lower A1C over 12 months (P &amp;lt; 0.05) when compared with education and usual care. Persistent website users had greater improvement in A1C when compared with intermittent users (−1.9 vs. −1.2%; P = 0.051) or education and usual care (−1.4%; P &amp;lt; 0.05). A larger number of website data uploads was associated with a larger decline in A1C (highest tertile −2.1%, lowest tertile −1.0%; P &amp;lt; 0.02). Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure (P &amp;lt; 0.01). HDL cholesterol rose and triglycerides fell in the web-based group (P &amp;lt; 0.05). CONCLUSIONS—Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes.
Neurological Aspects of Human Glycosylation Disorders
Authors: Hudson H. Freeze, Erik A. Eklund, Bobby G. Ng, Marc C. Patterson
Journal: Annual Review of Neuroscience (2015)

This review presents principles of glycosylation, describes the relevant glycosylation pathways and their related disorders, and highlights some of the neurological aspects and issues that continue to challenge researchers. More than 100 rare human genetic disorders that result from deficiencies in the different glycosylation pathways are known today. Most of these disorders impact the central and/or peripheral nervous systems. Patients typically have developmental delays/intellectual disabilities, hypotonia, seizures, neuropathy, and metabolic abnormalities in multiple organ systems. Among these disorders there is great clinical diversity because all cell types differentially glycosylate proteins and lipids. The patients have hundreds of misglycosylated products, which afflict a myriad of processes, including cell signaling, cell-cell interaction, and cell migration. This vast complexity in glycan composition and function, along with the limited availability of analytic tools, has impeded the identification of key glycosylated molecules that cause pathologies. To date, few critical target proteins have been pinpointed.
Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues
Authors: M. C. Summers, J. D. Biggers
Journal: Human Reproduction Update (2003)

Considerable advances in media development for the culture of preimplantation mammalian embryos have been made since mouse embryos were first cultured and successfully transferred to foster mothers. The purpose of this review is to detail the history of the development of chemically defined media for the culture of preimplantation embryos. Two approaches have been used to determine the composition of chemically defined media: the 'back‐to‐nature' approach and 'let the embryo choose' or empirical optimization approach. Recent developments, including the supplementation of media with amino acids and the use of sequential media for the extended culture of preimplantation embryos, are critically assessed. Importantly, it is recognized that even the best media currently used are not optimal and inevitably cause imbalances and stress to the embryos. Consequently, preimplantation embryos must adapt to the culture environment in order to survive. The adaptations to stress that occur when embryos are placed in a chemically defined environment are reviewed. The implications of these various stresses on the patterns of gene expression in the early embryo and their potential long‐term effects are also emphasized. The scientific and ethical issues raised by the commercialization of human embryo culture media are briefly addressed.