tbuckley/cabot-search huggingface dataset:
Diet-Induced Hyperhomocysteinemia Exacerbates Neointima Formation in Rat Carotid Arteries After Balloon Injury
Authors: Hiroyuki Morita, Hiroki Kurihara, Shigetaka Yoshida, Yuichiro Saito, Takayuki Shindo, Yoshio Oh-hashi, Yukiko Kurihara, Yoshio Yazaki, Ryozo Nagai
Journal: Circulation (2001)

Background —Increasing evidence indicates that elevated plasma homocysteine levels are associated with an increased risk of atherosclerosis and endothelial dysfunction, although little specific information on the mechanisms responsible for the atherogenic effects of homocysteine or on the in vivo contribution made by hyperhomocysteinemia to atherosclerosis is currently available. Because homocysteine is known to exert a direct inhibitory effect on endothelial cell growth in vitro, we hypothesized that this effect contributes to the progression of atherosclerotic lesions initiated by endothelial damage caused by mechanical injury. Methods and Results —We prepared diet-induced hyperhomocysteinemic rats in which neointima formation after balloon injury to the common carotid artery was assessed. Moderate hyperhomocysteinemia (plasma homocysteine levels 3- to 4-fold higher than control) significantly exacerbated neointima formation. Oral administration of folate, which had a homocysteine-lowering effect, diminished neointima formation induced by moderate hyperhomocysteinemia. Furthermore, the attenuation of reendothelialization was shown in diet-induced hyperhomocysteinemic rats with Evans blue staining. Conclusions —Diet-induced hyperhomocysteinemia, even mild to moderate, exacerbates neointima formation after denuding injury, making hyperhomocysteinemia a likely risk factor for postangioplasty restenosis. It may be mediated through an inhibitory effect of homocysteine on reendothelialization. Homocysteine lowering with folate supplementation can effectively ameliorate the detrimental effects of moderate hyperhomocysteinemia. Clinical trials would seem to be warranted.
Effects of low dose corticosteroids on bone mass in rheumatoid arthritis: a longitudinal study.
Authors: P N Sambrook, M L Cohen, J A Eisman, N A Pocock, G D Champion, M G Yeates
Journal: Annals of the Rheumatic Diseases (1989)

Low dose corticosteroids are effective in suppressing synovitis in rheumatoid arthritis (RA), but there remains concern about their side effects, particularly osteoporosis. To examine the effects of low dose corticosteroids on bone loss in RA bone mineral density (BMD) was measured in the lumbar spine and hip for up to two years in 15 patients treated with these agents (mean dose prednis(ol)one 6.6 mg/day). 15 patients not receiving them, and 15 age matched controls. The initial BMD at both skeletal sites was significantly reduced in both patient groups compared with controls. The mean change in bone density was 0.2, 0.1, and -0.1% a year in the spine and -2.0, -1.9, and -1.0% a year in the hip respectively for the three groups. These rates of bone loss were not significantly different between groups at either site. These findings suggest that low dose corticosteroid treatment in RA is not associated with an increased risk of osteoporosis.
Longitudinal assessment in COPD patients: multidimensional variability and outcomes
Authors: Ciro Casanova, Armando Aguirre-Jaíme, Juan P. de Torres, Victor Pinto-Plata, Rebeca Baz, Jose M. Marin, Miguel Divo, Elizabeth Cordoba, Santiago Basaldua, Claudia Cote, Bartolomé R. Celli
Journal: European Respiratory Journal (2013)

The value and timing of multidimensional assessments in chronic obstructive pulmonary disease (COPD) remains unclear because there is little information about their variability and relationship to outcome. The aim of this study was to determine the progression of COPD using clinical and spirometric variability over time with mortality as the outcome. We determined the annual intra-individual variability of forced expiratory volume in 1 s (FEV1) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index in 403 patients with at least five measurements. The pattern was defined as "stable" if the annual change remained constant in ≥66% of the observations and "unstable" if it did not meet that threshold. We explored the minimum number of yearly observations that related to mortality in the 704 patients of the cohort. The "unstable" pattern of FEV1 was seen in 53% and 40% of patients using a threshold of 40 mL·year(-1) and 100 mL·year(-1), respectively. There was a slightly more "stable" pattern in the BODE index (62% for 1 point). A profile associated with mortality was defined by a baseline measurement followed by annual measurements for 2 years of the BODE index, but not its individual components, including FEV1 (p<0.001). Progression of COPD measured using FEV1 is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better assesses disease progression.
Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain.
Authors: E Puré, K Inaba, M T Crowley, L Tardelli, M D Witmer-Pack, G Ruberti, G Fathman, R M Steinman
Journal: The Journal of Experimental Medicine (1990)

Two prior studies with a small number of T cell lines have shown that the presentation of native protein antigens by epidermal Langerhans cells (LC) is regulated. When freshly isolated, LC are efficient antigen-presenting cells (APC), but after a period of culture LC are inefficient or even inactive. The deficit in culture seems to be a selective loss in antigen processing, since cultured LC are otherwise rich in major histocompatibility complex (MHC) class II products and are active APC for alloantigens and mitogens, which do not require processing. We have extended the analysis by studying presentation to bulk populations of primed lymph node and a T-T hybrid. Only freshly isolated LC can be pulsed with the protein antigens myoglobin and conalbumin, but once pulsed, antigen is retained in an immunogenic form for at least 2 d. The acquisition of antigen, presumably as MHC-peptide complexes, is inhibited if the fresh LC are exposed to foreign protein in the presence of chloroquine or cycloheximide. The latter, in contrast, improves the efficacy of antigen pulsing in anti-Ig-stimulated B blasts. In additional studies of mechanism, we noted that both fresh and cultured LC endocytose similar amounts of an antigen, rhodamineovalbumin, into perinuclear granules. However, freshly isolated LC synthesize high levels class II MHC molecules and express higher amounts of the class II-associated invariant chain. Fresh LC are at least 5-10 times more active than many other cells types in the level of biosynthesis of MHC class II products. These findings provide a physiologic model in which newly synthesized MHC class II molecules appear to be the principal vehicle for effective antigen processing by APC of the dendritic cell lineage. Another APC, the B lymphoblast, does not appear to require newly synthesized MHC class II molecules for presentation.
Involvement of macrophages in the pathology of toxic epidermal necrolysis
Authors: J.C. ROUJEAU, L. DUBERTRET, SYLVIANE MORITZ, HELENE JOUAULT, MICHELE HESLAN, J. REVUZ, R. TOURAINE
Journal: British Journal of Dermatology (1985)

In toxic epidermal necrolysis (TEN), as in the 'epidermal type' of erythema multiforme, the necrotic epidermis is infiltrated with mononuclear cells. We studied the epidermal infiltrate in seven cases of TEN. About half the cells obtained from pieces of cleaved epidermis dissociated by trypsin were non-epithelial. On cytologic analysis, 80% of these foreign cells exhibited markers of macrophages, 15% were granulocytes and only 5% were lymphocytes (almost exclusively OKT8 T lymphocytes). Semi-thin sections of early prenecrotic lesions showed exocytosis of mononuclear cells within the epidermis with features of satellite cell necrosis and formation of colloid bodies. Almost all these mononuclear cells were macrophages as evidenced by endogenous peroxidase-positive granules. These findings suggest that some kind of macrophage-mediated cytotoxicity may play a role in the necrosis of epidermal cells during TEN.
Termination of Cardiac Ca <sup>2+</sup> Sparks
Authors: Aleksey V. Zima, Eckard Picht, Donald M. Bers, Lothar A. Blatter
Journal: Circulation Research (2008)

Ca 2+ release from cardiac sarcoplasmic reticulum (SR) via ryanodine receptors (RyRs) is regulated by dyadic cleft [Ca 2+ ] and intra-SR free [Ca 2+ ] ([Ca 2+ ] SR ). Robust SR Ca 2+ release termination is important for stable excitation–contraction coupling, and partial [Ca 2+ ] SR depletion may contribute to release termination. Here, we investigated the regulation of SR Ca 2+ release termination of spontaneous local SR Ca 2+ release events (Ca 2+ sparks) by [Ca 2+ ] SR , release flux, and intra-SR Ca 2+ diffusion. We simultaneously measured Ca 2+ sparks and Ca 2+ blinks (localized elementary [Ca 2+ ] SR depletions) in permeabilized ventricular cardiomyocytes over a wide range of SR Ca 2+ loads and release fluxes. Sparks terminated via a [Ca 2+ ] SR -dependent mechanism at a fixed [Ca 2+ ] SR depletion threshold independent of the initial [Ca 2+ ] SR and release flux. Ca 2+ blink recovery depended mainly on intra-SR Ca 2+ diffusion rather than SR Ca 2+ uptake. Therefore, the large variation in Ca 2+ blink recovery rates at different release sites occurred because of differences in the degree of release site interconnection within the SR network. When SR release flux was greatly reduced, long-lasting release events occurred from well-connected junctions. These junctions could sustain release because local SR Ca 2+ release and [Ca 2+ ] SR refilling reached a balance, preventing [Ca 2+ ] SR from depleting to the termination threshold. Prolonged release events eventually terminated at a steady [Ca 2+ ] SR , indicative of a slower, [Ca 2+ ] SR -independent termination mechanism. These results demonstrate that there is high variability in local SR connectivity but that SR Ca 2+ release terminates at a fixed [Ca 2+ ] SR termination threshold. Thus, reliable SR Ca 2+ release termination depends on tight RyR regulation by [Ca 2+ ] SR .
Photodynamic Diagnosis Using 5-Aminolevulinic Acid for the Detection of Positive Surgical Margins during Radical Prostatectomy in Patients with Carcinoma of the Prostate: A Multicentre, Prospective, Phase 2 Trial of a Diagnostic Procedure
Authors: Christoph Adam, Georg Salomon, Sebastian Walther, Dirk Zaak, Wael Khoder, Armin Becker, Oliver Reich, Andreas Blana, Roman Ganzer, Stefan Denzinger, Gralf Popken, Ronald Sroka, Ruth Knüchel-Clarke, Jens Köllermann, Guido Sauter, Arndt Hartmann, Simone Bertz, Markus Graefen, Hartwig Huland, Wolf Wieland, Christian G. Stief
Journal: European Urology (2009)
Nodular prurigo—a clinicopathological study of 46 patients
Authors: C.M.E. ROWLAND PAYNE, J.D. WILKINSON, P.H. MCKEE, W. JURECKA, M.M. BLACK
Journal: British Journal of Dermatology (1985)

In a study of 46 patients with nodular prurigo (NP), potential metabolic causes of pruritus, such as anaemia, hepatic dysfunction, uraemia and myxoedema, were present in 50%. Focal causes of pruritus were important in 37% and included insect bites, venous stasis, folliculitis and nummular eczema. Psycho‐social disorders were recorded in over 50% of patients and were considered relevant in 33%. Clinical and histological appearances ranged from classical NP to chronic lichenified eczema. Neural hyperplasia was not a prominent feature.
Inappropriate elevation of serum leptin levels in children with chronic renal failure. European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood.
Authors: M Daschner, B Tönshoff, W F Blum, P Englaro, A M Wingen, F Schaefer, E Wühl, W Rascher, O Mehls
Journal: Journal of the American Society of Nephrology (1998)

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.
Belonging to a network—microRNAs, extracellular vesicles, and the glioblastoma microenvironment
Authors: Jakub Godlewski, Anna M. Krichevsky, Mark D. Johnson, E. Antonio Chiocca, Agnieszka Bronisz
Journal: Neuro-Oncology (2014)

The complexity of glioblastoma multiforme (GBM) and its distinct pathophysiology belong to a unique brain microenvironment and its cellular interactions. Despite extensive evidence of a role for microRNAs in GBM cells, little is known about microRNA-dependent communication between different cellular compartments of the microenvironment that may contribute to the tumor phenotype. While the majority of microRNAs are found intracellularly, a significant number of microRNAs have been observed outside of cells, often encapsulated in secreted extracellular vesicles (EVs). The function of these circulating/secreted microRNAs has not been explored in the context of the brain tumor microenvironment. Establishing how microRNAs are involved in the regulation of oncogenic signaling networks between tumor cells and stroma is likely to add a needed additional layer of complexity to the tumor network, consisting of intercellular communication. More importantly, microRNA/EV signaling may provide an additional therapeutic target for this deadly disease.
Microtubule Disruption by Colchicine Reversibly Enhances Calcium Signaling in Intact Rat Cardiac Myocytes
Authors: B. G. Kerfant, G. Vassort, A. M. Gómez
Journal: Circulation Research (2001)

Abstract —Using the whole-cell patch-clamp configuration in rat ventricular myocytes, we recently reported that microtubule disruption increases calcium current ( I Ca ) and [Ca 2+ ] i transient and accelerates their kinetics by adenylyl cyclase activation. In the present report, we further analyzed the effects of microtubule disruption by 1 μmol/L colchicine on Ca 2+ signaling in cardiac myocytes with intact sarcolemma. In quiescent intact cells, it is possible to investigate ryanodine receptor (RyR) activity by analyzing the characteristics of spontaneous Ca 2+ sparks. Colchicine treatment decreased Ca 2+ spark amplitude (F/F 0 : 1.78±0.01, n=983, versus 1.64±0.01, n=1660, recorded in control versus colchicine-treated cells; P &lt;0.0001) without modifying the sarcoplasmic reticulum Ca 2+ load and enhanced their time to peak (in ms: 6.85±0.09, n=1185, versus 7.33±0.13, n=1647; P &lt;0.0001). Microtubule disruption also induced the appearance of Ca 2+ sparks in doublets. These alterations may reflect RyR phosphorylation. To further investigate Ca 2+ signaling in cardiac myocytes with intact sarcolemma, we analyzed [Ca 2+ ] i transient evoked by field stimulation. Cells were loaded with the fluorescence Ca 2+ indicator, Fluo-3 cell permeant, and stimulated at 1 Hz. [Ca 2+ ] i transient amplitude was greater and its decay was accelerated in colchicine-treated, field-stimulated myocytes. This effect is reversible. When colchicine-treated myocytes were placed in a colchicine-free solution for 30 minutes, tubulin was repolymerized into microtubules, as shown by immunofluorescence, and the increase in [Ca 2+ ] i transient was reversed. In summary, we demonstrate that microtubule disruption by colchicine reversibly modulates Ca 2+ signaling in cardiac cells with intact sarcolemma. The full text of this article is available at http://www.circresaha.org.
A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme
Authors: Kenneth E. Bernstein, Frank S. Ong, Wendell-Lamar B. Blackwell, Kandarp H. Shah, Jorge F. Giani, Romer A. Gonzalez-Villalobos, Xiao Z. Shen, Sebastien Fuchs
Journal: Pharmacological Reviews (2012)

Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors.
THE IMPORTANCE OF DEXTROSE IN THE MEDIUM OF TISSUE CULTURES
Authors: Margaret Reed Lewis
Journal: The Journal of Experimental Medicine (1922)

It is not advisable to enter into a discussion of these findings at the present time, owing to the lack of experimental evidence as to the exact nature of the vacuoles. Regardless of the nature of these bodies or of what factors produce them, they are structures abnormal to the connective tissue cells. The lack of dextrose in the medium of tissue cultures leads to some condition distinctly detrimental to the cells, resulting in their vacuolation and death, even when the medium contains abundant protein material. The addition of small amounts (0.5 to 1 per cent) of dextrose to the medium delays the formation of vacuoles and prolongs the life of the culture. The addition of large amounts (2 to 5 per cent) prevents vacuolation of the cells, but so much dextrose usually leads to a change in the hydrogen ion concentration of the culture resulting in an acid condition which arises coincidentally with the degeneration of the cells.
Impact of Incident Venous Thromboembolism on Risk of Arterial Thrombotic Diseases
Authors: Caroline Lind, Linda E. Flinterman, Kristin F. Enga, Marianne T. Severinsen, Søren R. Kristensen, Sigrid K. Brækkan, Ellisiv B. Mathiesen, Inger Njølstad, Suzanne C. Cannegieter, Kim Overvad, John-Bjarne Hansen
Journal: Circulation (2013)

Growing evidence supports an association between venous thromboembolism (VTE) and arterial thrombotic diseases (ie, myocardial infarction and ischemic stroke). We aimed to study the association between VTE and future arterial events and to determine the population attributable risk of arterial events by VTE in a large prospective cohort recruited from the general population.In 1994 to 1995 and 1993 to 1997, 81 687 subjects were included in the Tromsø Study and in the Diet, Cancer and Health Study and followed up to the date of incident venous and arterial events (myocardial infarction or ischemic stroke), death or migration, or to the end of the study period (2010 and 2008, respectively). There were 1208 cases of VTE and 90 subsequent arterial events during a median follow-up of 12.2 years. An association between VTE and future arterial events was found in all women and men aged <65 years but not in men aged >65 years. Women <65 years old with VTE had 3.3-fold higher risk of arterial disease (adjusted hazard ratio, 3.28; 95% confidence interval, 1.69-6.35) compared with women of the same age without VTE. The corresponding hazard ratio in men aged <65 years was 2.06 (95% confidence interval, 1.32-3.20). Only 0.9% of the arterial events were attributed to VTE, and the VTE explained 63.8% of the risk of arterial events among VTE patients.Our findings imply that women and young men with VTE have higher risk of arterial thrombotic disease than those without VTE. However, only 1% of the arterial thrombotic events in the population are attributed to VTE.
Optimal Cut Points of Waist Circumference for the Clinical Diagnosis of Metabolic Syndrome in the Japanese Population
Authors: Yuka Matoba, Toyoshi Inoguchi, Shigeru Nasu, Shizu Suzuki, Toshihiko Yanase, Hajime Nawata, Ryoichi Takayanagi
Journal: Diabetes Care (2008)

In 2005, the International Diabetes Federation (IDF) and the Japanese Committee for the Diagnostic Criteria of Metabolic Syndrome (Japanese definition) proposed metabolic syndrome definitions for the Japanese population (1,2). Both definitions included waist circumference as an essential component and adopted cut points of 85 cm for men and 90 cm for women based on the relationship between waist circumference and visceral fat area by computed tomography (3). However, those cut points have been in dispute because of their suboptimal sensitivity and specificity (4–6). Recently, the IDF proposed common cut points for the whole Asian population including the Japanese: 90 cm for men and 80 cm for women (7). In this study, we investigated optimal waist cut points to identify subjects with multiple risk factors in the Japanese population and verified the cut points to predict carotid intima-media thickening in metabolic syndrome subjects as a surrogate marker of early atherosclerosis and cardiovascular disease (8–10).

We reviewed cross-sectional data from 1,658 men and 1,116 women (aged 48.8 ± 9.8 and 46.8 ± 10.4 years, respectively) who had annual medical checkup services provided by their employers. The medical checkup took place from May 2005 to November 2006 at the Human Dry Dock Center Wellness in Fukuoka, Japan. Subjects on antihypertensive and/or antidiabetic medications were included as individuals with hypertension and/or diabetes, respectively. We excluded 158 subjects on medications for dyslipidemia because we were unable to determine …