bluuebunny/crossref_metadata_2025 huggingface dataset:
EGFL7 participates in regulating biological behavior of growth hormone–secreting pituitary adenomas via Notch2/DLL3 signaling pathway
Authors: Wang Jianpeng , Liu Qian , Gao Hua , Wan Dehong , Li Chuzhong , Li Zhaojian , Zhang Yazhuo
Published: July 2017

Growth hormone–secreting pituitary adenoma accounts for about 20% of the third most common intracranial neoplasm—pituitary adenomas—which makes up 15% of all intracranial tumors. The growth hormone–secreting pituitary adenoma invasion is a key risk factor associated with the operation results and highly correlated with the clinical prognosis. The epidermal growth factor–like domain multiple 7 protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic angiogenesis and enhance the tumor migration and invasion. In this study, for the first time we found that epidermal growth factor–like domain multiple 7 protein expression was markedly higher in invasive growth hormone–secreting pituitary adenoma than non-invasive growth hormone–secreting pituitary adenoma. The tumor volume, histologic subtypes, invasiveness and recurrence of growth hormone–secreting pituitary adenoma were significantly associated with epidermal growth factor–like domain multiple 7 protein expression. Furthermore, we discovered that the histological classification methods of growth hormone–secreting pituitary adenoma according to electron microscopic examination and biological marker classification methods according to epidermal growth factor–like domain multiple 7 protein expression are more valuable in clinical application than the traditional classification methods based on Knosp and Hardy-Wilson grades. In summary, our results indicated epidermal growth factor–like domain multiple 7 protein participates in growth hormone–secreting pituitary adenoma proliferation and invasion regulation via Notch2/DLL3 signaling pathway. These findings raised the possibility that epidermal growth factor–like domain multiple 7 protein might serve as a useful biomarker to assess growth hormone–secreting pituitary adenoma invasion and prognosis or a potential therapeutic target for growth hormone–secreting pituitary adenoma treatment.
Beyond Canterbury: Can Medicine and Law Agree about Informed Consent? And Does It Matter?
Authors: Ginsberg Marc D.
Published: July 2017

Informed consent is central to the law of the physicianpatient relationship, respecting patient autonomy. This paper addresses a conflict between law and medicine in defining informed consent. Additionally, it addresses the possibility that patients prefer not to be “informed“ and would defer decision-making to their physicians.
Public Health and Politics: Using the Tax Code to Expand Advocacy
Authors: Gorovitz Eric
Published: July 2017

Protecting the public's health has always been an inherently political endeavor. The field of public health, however, is conspicuously and persistently absent from sustained, sophisticated engagement in political processes, particularly elections, that determine policy outcomes. This results, in large part, from widespread misunderstanding of rules governing how, and how much, public advocates working in tax-exempt organizations can participate in public policy development.

This article briefly summarizes the rules governing public policy engagement by exempt organizations. It then describes different types of exempt organizations, and how they can work together to expand engagement. Next, it identifies several key mechanisms of policy development that public health advocates could influence. Finally, it suggests some methods of applying the tax rules to increase participation in these arenas.
Differential Item Functioning of the Full and Brief Wisconsin Schizotypy Scales in Asian, White, Hispanic, and Multiethnic Samples and Between Sexes
Authors: Cicero David C. , Martin Elizabeth A. , Krieg Alexander
Published: July 2017

The Wisconsin Schizotypy Scales, including their brief versions, are among the most commonly used self-report measures of schizotypy. Although they have been used extensively in many ethnic groups, few studies have examined their differential item functioning (DIF) across groups. The current study included 1,056 Asian, 408 White, 476 Multiethnic, and 372 Hispanic undergraduates. Unidimensional models of the brief Magical Ideation Scale and Perceptual Aberration Scales fit the data well. For both scales, global tests of measurement invariance provided mixed evidence, but few of the items displayed DIF across ethnicities or between sexes within a multiple indicator multiple causes model. For the full versions of the scales and the brief Revised Social Anhedonia Scale, multiple indicator multiple causes models within an exploratory structural equation modeling framework found that few of the items had DIF. These findings suggest that some of the items may have different psychometric properties across groups, but most items do not.
Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics
Authors: Mitchell Aaron , Muluneh Benyam , Patel Rachana , Basch Ethan
Published: July 2017

Introduction

The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown.

Methods

We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance.

Results

Among 8591 cancer patients, 215 unique patients submitted a total of 478 successful PAP requests for cancer drugs. 40% of PAP-utilizing patients were uninsured, 23% had Medicaid coverage, 20% had Medicare coverage, 2% were dual Medicare/Medicaid eligible, and 14% were commercially insured. Among all cancer patients who received medical treatment, 6.0% required PAP assistance, whereas 10.6% receiving an oral agent required PAP assistance. The proportion receiving PAP assistance varied substantially by drug, ranging from <1% of patients (e.g. carboplatin, methotrexate) to 50% of patients (e.g. ponatinib, temsirolimus). The majority of the retail value obtained was for oral agents, including $1,556,575 of imatinib and $1,449,633 of dasatinib, which were the two drugs with the highest aggregate retail value.

Conclusions

A substantial proportion of cancer patients receive private charitable assistance to obtain standard-of-care treatments. This includes patients with federal and private insurance, suggesting an inability of patients to meet cost-sharing requirements.
Does Adding Information on Toxic Constituents to Cigarette Pack Warnings Increase Smokers’ Perceptions About the Health Risks of Smoking? A Longitudinal Study in Australia, Canada, Mexico, and the United States
Authors: Cho Yoo Jin , Thrasher James F. , Swayampakala Kamala , Lipkus Isaac , Hammond David , Cummings Kenneth Michael , Borland Ron , Yong Hua-Hie , Hardin James W.
Published: July 2017

Background. Health warning labels (HWLs) on cigarette packs in Australia, Canada, Mexico, and the United States include varying information about toxic cigarette smoke constituents and smoking-related health risks. HWL information changed more recently in Australia, Canada, and Mexico than in the United States. Aims. To investigate whether smokers’ knowledge of toxic constituents and perceived smoking-related risks increased after adding this information to HWLs and how knowledge of toxic constituents is associated with perceptions of smoking-related risks. Methods. Data come from a longitudinal, online cohort of 4,621 adult smokers surveyed every 4 months from September 2012 (Wave 1) to January 2014 (Wave 5) in Australia, Canada, and Mexico, with the United States being surveyed from Waves 2 to 5. Generalized estimating equation models estimated the association between perceived smoking-related risk at follow-up and prior wave knowledge of toxic constituents, adjusting for attention to HWLs, sociodemographics, and smoking-related characteristics. Results. Between 2012 and 2014, knowledge of toxic constituents increased in Australia, Canada, and Mexico ( p < .001), but not in the United States. Higher levels of both attention to HWLs and knowledge of toxic constituents were associated with a higher perceived risk of smoking-related conditions at follow-up across all countries except for the United States. Conclusions. Our results suggest that information about toxic constituents on prominent HWLs not only increases smoker’s knowledge of toxic constituents, but that it may also reinforce the effects of HWL messages about specific, smoking-related health outcomes.
CD36-positive B-lymphoblasts Predict Poor Outcome in Children With B-lymphoblastic Leukemia
Authors: Newton Joanna G , Horan John T , Newman Scott , Rossi Michael R , Ketterling Rhett P , Park Sunita I
Published: July 2017

Objective

We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36+ B-LL compared to patients with CD36− B-LL.

Methods

We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts. CD36− control patients were chosen from our leukemia database and matched 2:1 to CD36+ patients for National Cancer Institute (NCI) risk group at diagnosis. We reviewed diagnostic marrow slides for cytoplasmic granules and abstracted clinical data from patient charts. To identify underlying genetic abnormalities, clinical FISH testing and RNA sequencing was performed on 5 of our CD36+ patients, and RNA-seq data from the NIH Therapeutically Applicable Research to Generate Effective Treatments (TARGET) ALL Expansion Phase 2 data set were examined.

Results

Twenty-five of 366 (6.83%) patients diagnosed at our institution in the study period had CD36+ blasts. With a median follow-up of 5.32 years, 5-year event-free survival (EFS) and overall survival (OS) were significantly worse for CD36+ patients compared to CD36− patients who were NCI Standard Risk at diagnosis (EFS: 60% ± 15.49 vs 95% ± 4.87, P = .016; OS: 90% ± 9.5 vs 100%, P = .019). NCI Standard Risk patients whose blasts were both CD36+ and had granules had the worst survival compared to CD36− patients without granules (EFS 25% ± 21.65 vs 95% ± 4.87, P = .0004). From our CD36+ patients and the TARGET database, we found 2 ABL2 mutations, 1 PDGFRB mutation, and 2 NRAS mutations.

Conclusions

For NCI Standard Risk patients, CD36 expression on B-lymphoblasts identifies patients with B-LL who have especially poor outcome. This may be due to underlying genetic abnormalities that may be amenable to targeted therapy.
Distinguishing Epidermolysis Bullosa Acquisita From Bullous Pemphigoid Without Direct Immunofluorescence
Authors: Gardner Kerry M. , Crawford Richard I.
Published: July 2017

Background:

It has been postulated that periodic acid–Schiff staining of basement membrane can predict direct immunofluorescence patterns seen in epidermolysis bullosa acquisita and bullous pemphigoid. It has also been suggested that the type of inflammatory infiltrate or presence of fraying of basal keratinocytes may differentiate these two conditions.

Objective:

In this study, we aimed to confirm these observations.

Methods:

We reviewed 13 cases of direct immunofluorescence-confirmed epidermolysis bullosa acquisita and 19 cases of direct immunofluorescence-confirmed bullous pemphigoid, all with a subepidermal blister in the routinely processed specimen. The gold standard for diagnosis of epidermolysis bullosa acquisita vs bullous pemphigoid was taken to be identification of immune deposits on the dermal side (‘floor’ for epidermolysis bullosa acquisita) or the epidermal side (‘roof’ for bullous pemphigoid) of the salt-split direct immunofluorescence specimen. Our tests to distinguish epidermolysis bullosa acquisita from bullous pemphigoid on the routinely processed biopsy included periodic acid–Schiff basement membrane on the blister roof, neutrophilic infiltrate, lack of eosinophilic infiltrate, and absence of keratinocyte fraying.

Results:

Sensitivity and specificity for each test were as follows: periodic acid–Schiff staining of roof (sensitivity 25%, specificity 95%), neutrophilic infiltrate (sensitivity 54%, specificity 74%), lack of eosinophilic infiltrate (sensitivity 92%, specificity 68%), and absence of keratinocyte fraying (sensitivity 62%, specificity 58%).

Conclusions:

Features in the routinely processed biopsy were unable to reliably distinguish between epidermolysis bullosa acquisita and bullous pemphigoid. Direct immunofluorescence on salt-split skin remains the standard for differentiation.
Old new media: Closed-circuit television and the classroom
Authors: Keeler Amanda
Published: July 2017

This article explores closed-circuit television (CCTV) and its ‘bright promise stage’, as it was contemplated, marketed, and implemented as a low-cost classroom tool. After the Federal Communications Commission issued the 1952 Sixth Report and Order, many schools and communities sought to bring educational television to the classroom. However, this model was financially out of reach for most. CCTV was a more affordable version of educational television that could cater to specific classroom needs and allow schools to create their own in-house network. CCTV represents just one of many new technologies that have been promoted as ideal for classroom instruction over the last century. Using articles and advertisements from popular press magazines, educational journals, books, and archival materials, this article seeks to illuminate the ‘social practices and conflicts’ that contributed to the conversations around CCTV’s classroom utility. It concludes by connecting CCTV’s promotion in the 1950s to more recent new media technologies.
Celebrity enactments of addiction on Twitter
Authors: Dwyer Robyn , Fraser Suzanne
Published: July 2017

Commentators suggest the social media platform, Twitter, might afford challenges to hegemonic knowledge by providing voice to those outside traditional media and by enabling vigorous public discussion and contestation of dominant ideas and concepts. In this article, we ask whether such affordances might be reshaping the culturally charged concept of addiction and, in turn, its accompanying abject and maligned subject, the ‘addict’. To explore this question, we examine Twitter messages about addiction posted by celebrities. These people are among the most highly followed Twitter account holders, meaning their Twitter messages can reach millions of people. Our analysis examines how specific addiction problems, and their solutions, are being constituted through the tweeting practices of celebrities. We also consider the unintentional effects these messages produce. Finally, we examine the ways in which these messages are discussed and contested by the audiences of the celebrities. We find celebrity Twitter activity re-enacts familiar realities of addiction, realities that collapse drug use with harm and addiction, addiction with pathology and death. Abstinence is posed as the only effective and genuine response, and the contradictions in simultaneously individualizing action against addiction and condemning stigmatization are ignored. Despite the ‘revolutionary’ potential of Twitter posited by advocates and some scholars, when it comes to addiction, it seems, the global, uncensored, ‘free’ communication on Twitter serves largely to validate and perpetuate dominant addiction concepts and the stigma and discrimination these concepts evoke.
Thoracic Aortic Aneurysm Repair with Endovascular Stent-Grafts
Authors: Semba Charles P , Mitchell R Scott , Miller D Craig , Kato Noriyuki , Kee Stephen T , Chen Jason T , Dake Michael D
Published: July 2017

The purpose of the study was to describe the clinical experience in using endoluminal stent-grafts for the treatment of thoracic aortic aneurysms in high-risk patients. Patients with aneurysms of the descending thoracic aorta who were considered high surgical risks underwent evaluation for endoluminal repair. The prosthesis was constructed from Z stents covered with polyester fabric using dimensions based upon preprocedural computed tomography scans and angiography. Through a femoral arteriotomy or left retroperitoneal flank incision, a 22–24 Fr delivery catheter was inserted and advanced through the aorta to the target site under fluoroscopic guidance in the operating suite. The stent-graft prosthesis was deployed at the site of the aneurysm.

44 patients (36 male, 8 female; mean age 36 years) underwent stent-graft repair for thoracic aneurysms (mean diameter 6.3 cm). The deployment was technically successful in all cases, with complete aneurysm thrombosis in 88%. The 30-day perioperative mortality rate was 6.8% and 35-month actuarial survival was 82%. There were no cases of stent migration, surgical conversion or intraprocedural death. Paraplegia occurred in two patients who underwent simultaneous surgical infrarenal aortic aneurysm repair immediately followed by stent-graft placement for a coexisting thoracic aneurysm. The conclusion was that placement of endoluminal stent-grafts for repair of thoracic aortic aneurysms is technically feasible in high-risk patients in whom conventional surgery is contraindicated. Long-term studies are needed to determine protection against aneurysm rupture and patient survival.
The lurking punitive threat: The philosophy of necessity and challenges for reform
Authors: Goshe Sonya
Published: July 2017

Despite some encouraging reforms and a new optimism in criminal justice, problematic punishment persists in the USA. In this article, I argue that the difficulties of reform stem, in part, from an ingrained ‘philosophy of necessity’ that places punishment at the core of how to think about crime and social problems, and promotes a worldview that overvalues punishment’s ability to provide safety, provoke change and ensure justice. The philosophy of necessity grants punishment the ‘benefit of the doubt’, even when such confidence is unwarranted, and fosters reliance on punitive norms that encourage excess and abuse. A series of features work together to encourage the philosophy of necessity in the USA: blindness to the history of using punishment to ensure economic and social security for the privileged, ongoing policies that breed high levels of violence, and cultural endorsement of punitive logic as a substitution for social security and substantive justice.
Status moves: Evaluations and effectiveness of status behaviors
Authors: Kim Hee Young , Pettit Nathan C. , Reitman Laura E.
Published: July 2017

This paper examines reactions of in-group members and third-party observers to behaviors people perform to affect the status hierarchy of their group (i.e., status moves). We understand status hierarchies to be “negotiated,” where “status moves” are a means to negotiate the group’s informal order. Results indicate that the valence (positive vs. negative) and context (initiating vs. reacting) of the status move interactively affect observers’ reactions (Studies 1 and 3), and that these reactions are explained by perceptions of the actor’s self- versus group concern (Studies 1–2 and 4) in both experimental as well as more naturalistic contexts. Specifically, initiating status moves elicit stronger reactions, with positive/negative initiating moves resulting in recommendations of greater reward/punishment and status gain/loss for the actor (Studies 1 and 3) than reacting moves. Overall, we offer a first systematic examination of status moves and how people perceive and react to them.
Towards an understanding of early childhood mathematics education: A systematic review of the literature focusing on practicing and prospective teachers
Authors: Linder Sandra M , Simpson Amber
Published: July 2017

This article presents the results of a literature review spanning 15 years (2000–2015), identifying empirical research relating to early childhood mathematics education. A total of 1141 articles were identified and examined in order to determine the current state of research in terms of location, participants, research questions, and the research methodology commonly used in this body of literature. Following a discussion of the overarching view of the literature, the authors present an analysis of a subsection of the literature, focusing on practicing and prospective teachers’ practice.
An Evolutionary Perspective on Mate Rejection
Authors: Kelly Ashleigh J. , Dubbs Shelli L. , Barlow Fiona Kate
Published: July 2017

We argue that mate rejection and ex-partner relationships are important, multifaceted topics that have been underresearched in social and evolutionary psychology. Mate rejection and relationship dissolution are ubiquitous and form integral parts of the human experience. Both also carry with them potential risks and benefits to our fitness and survival. Hence, we expect that mate rejection would have given rise to evolved behavioral and psychological adaptations. Herein, we outline some of the many unanswered questions in evolutionary psychology on these topics, at each step presenting novel hypotheses about how men and women should behave when rejecting a mate or potential mate or in response to rejection. We intend these hypotheses and suggestions for future research to be used as a basis for enriching our understanding of human mating from an evolutionary perspective.
Sexual Regret
Authors: Kennair Leif Edward Ottesen , Bendixen Mons , Buss David M.
Published: July 2017

The current study sought to answer three key questions about explaining the emotion of regret in the domain of casual sex: Are sex differences in sexual regret robust or attenuated in a highly egalitarian culture? What proximate psychological variables might explain sex differences in sexual regret? And what accounts for within-sex variation in experiences of sexual regret about casual sex. We conducted a study of 263 Norwegian students (ages 19–37) who reported how much they regretted having either engaged in, or passed up, their most recent casual sexual experience. Sex differences in sexual regret are not attenuated in this sexually egalitarian culture. The study revealed sex differences in worries about pregnancy, STIs, and reputation; however, these predictors did not succeed in accounting for the sex differences in regret engaging in casual sex. Sexual gratification and socio-sexual orientation both predicted the sex differences in casual sex regret. In contrast, only socio-sexual orientation attenuated the sex difference in regret passing up casual sex. Predictors of within-sex variation in casual sexual regret included worry about sexual reputation, experienced gratification during the encounter, and socio-sexual orientation. Discussion focuses on implications for the psychological design features of this relatively neglected emotion.
Glucocorticoids Inhibit Tetrahydrobiopterin-Dependent Endothelial Function
Authors: Johns Douglas G. , Dorrance Anne M. , Tramontini Nicole L. , Webb R. Clinton
Published: July 2017

Tetrahydrobiopterin (BH4) acts as an important co-factor for endothelial nitric oxide synthase (eNOS). Glucocorticoids have been shown to inhibit expression of the rate-limiting enzyme for tetrahydrobiopterin synthesis, GTP cyclohydrolase, in other cell types. We hypothesized that endothelium-dependent vasodilator responses would be blunted in rats made hypertensive with dexamethasone. Further, we hypothesized that treatment of rat vascular segments with dexamethasone would result in attenuation of endothelial function accompanied by decreased GTP cyclohydrolase expression. We report that endothelium-dependent relaxation responses to the calcium ionophore A23187 are reduced in aortic rings from dexamethasone-hypertensive rats compared with sham values. Dexamethasone incubation abolishes contraction to Nω-nitro-L-arginine (L-NNA, 10–5M) in endothelium-intact aortic rings, and inhibits expression of GTP cyclohydrolase. We conclude that inhibition of BH4 synthesis by glucocorticoid regulation of GTP cyclohydrolase expression may contribute to reduced endothelium-dependent vasodilation characteristic of glucocorticoid-induced hypertension.
Orexin-A Regulates Body Temperature in Coordination with Arousal Status
Authors: Yoshimichi Go , Yoshimatsu Hironobu , Masaki Takayuki , Sakata Toshiie
Published: July 2017

Orexins, hypothalamic neuropeptides, are involved in modulation of food intake and arousal status. To further examine their physiological roles in brain function, the effect of centrally administered orexin-A on body temperature was investigated in rats. Assessed by a telemetry sensor system implanted into the abdominal cavity, infusion of orexin-A into the third cerebroventricle (i3vt) increased body temperature in a dose-responsive manner. Expression of uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT), as a marker for peripheral thermogenesis, failed to increase after the infusion. Expression of UCP3 mRNA in skeletal muscle was up-regulated, whereas UCP2 in white adipose tissue was unchanged after the infusion. The resulting information indicates that orexin neurons regulate body temperature in coordination with arousal status independently of peripheral thermogenesis, which is regulated by BAT UCP1.
Reduced Levels of Thyroid Hormones, Insulin, and Glucose, and Lower Body Core Temperature in the Growth Hormone Receptor/Binding Protein Knockout Mouse
Authors: Hauck Steven J. , Hunter William S. , Danilovich Natasha , Kopchick John J. , Bartke Andrzej
Published: July 2017

The mechanisms that are responsible for the extension of lifespan in the mouse with targeted disruption (knockout [KO]) of the growth hormone (GH) receptor/binding protein (GHR-KO) are unknown. However, in the long-living Ames dwarf mouse, blood glucose and body core temperature (Tco) are consistently lower than in normal mice. In addition, insulin levels are reduced and corticosterone levels are elevated in male dwarfs. These functional alterations, similar to those seen in animals under caloric restriction, have not been proven to be causally related to the extension of lifespan, but they do provide some insight into what traits may be necessary for long life. Therefore, to investigate which of these parameters are similarly affected in two genetically unrelated, yet similarly long-living mouse models, we measured Tco, thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and insulin, in addition to morning and afternoon levels of glucose and corticosterone, in young adult male and/or female GHR-KO mice and their normal siblings. Tco in GHR-KO mice was numerically reduced throughout the 24-hr period; however, these differences were only significant 4 hr prior to lights-off (14:00 hr), immediately after lights-off (18:00 hr), and during the 3 hr preceding lights on (03:00 to 06:00 hr). GHR-KO mice had significantly reduced levels of T3 and T4, while the ratio of these hormones was similar to that in normal mice. Insulin levels in GHR-KO mice were lower than in normal mice; levels in male GHR-KO mice were below the detectable limits of the assay used. Glucose levels in GHR-KO mice (male and females) were lower than in normal mice in measurements taken in both morning and afternoon; however, these differences arose from consistent reductions in males, as morning glucose levels in GHR-KO females were similar to those of normal mice. Corticosterone levels measured in blood plasma collected under basal (nonstressed) conditions showed sex-related alterations. Basal corticosterone levels in female GHR-KO mice were similar to normal females, while those in male GHR-KO mice were higher than in normal males in the afternoon. Corticosterone levels in stressed GHR-KO females were similar to those measured in stressed normal females. These data show that the long-living GHR-KO mouse shares a reduction in glucose, insulin, thyroid hormones, and Tco with the Ames dwarf mouse. Reductions in these parameters may be important to the underlying mechanisms of delayed aging in these animals.
Differential Expression of Na:K:2CI Cotransporter, Glucose Transporter 1, and Aquaporin 1 in Freshly Isolated and Cultured Bovine Corneal Tissues
Authors: Bildin Victor N. , Iserovich Pavel , Fischbarg Jorge , Reinach Peter S.
Published: July 2017

Little is known about whether culturing corneal limiting layers causes changes in the expression of their membrane transporter proteins from those present in fresh tissues. Accordingly, we compared mRNA abundance of three well-described types of transporters: water channel aquaporin 1 (AQP1), glucose transporter (GLUT1), and Na:K:2CI cotransporter (NKCC), as well as NKCC protein levels in fresh bovine corneal epithelium and endothelium with those in their cultured counterparts. Abundance of mRNA encoding AQP1, GLUT1, and NKCC was quantified by a lysate nuclease protection assay. NKCC transcription was further characterized by Northern blotting. All data were normalized to cell DNA and protein contents. In the fresh epithelium, in all three cases mRNA levels were two to four times higher than in the endothelium. Expression of AQP1 and GLUT1 was 10 to 12 times higher than that of NKCC. After the third passage, the endothelial cell mRNA abundance in each case decreased 2- to 3-fold. Passage-dependent decreases were also observed in NKCC protein expression in the epithelial cells. In both corneal layers, there was a qualitative correlation between NKCC mRNA and protein levels. Both in fresh and cultured epithelial and endothelial cells, a shark NKCC1 DNA probe hybridized with mRNAs of two different lengths (about 5.0–5.5 and 7.0–7.5 kb). An anti-NKCC T4 monoclonal antibody recognized two major proteins with apparent molecular masses of 190 to 200 and 150 to 160 kDa. In summary, membrane transporter function in culture may not be always indicative of their role in fresh tissue since in cultured cells AQP1, GLUT1, and NKCC mRNA levels declined. Furthermore, in both epithelial and endothelial cells, there is expression of two different proteins and mRNAs that possibly encode for secretory (NKCC1) and absorptive (NKCC2) isoforms.
Inflammatory Mediators in Gastrointestinal Defense and Injury
Authors: Wallace John L. , Ma Li
Published: July 2017

Inflammation of the mucosal layer of the gastrointestinal (GI) tract is not only a feature almost always associated with ulceration of those tissues, but it also plays an important role in both the production and healing of the lesions. The mediators that coordinate inflammatory responses also have the capability to alter the resistance of the mucosa to injury induced by noxious substances, while others render the mucosa more susceptible to injury. In this article, we provide a review of the inflammatory mediators that modulate GI mucosal defense. Among the mediators discussed are nitric oxide, the eicosanoids (prostaglandins, leukotrienes, and thromboxanes), neuropeptides, cytokines, and proteinases. Many of these mediators are considered potential therapeutic targets for the treatment of ulcerative diseases of the digestive tract.
A Critical Review of Atypical Cerebellum-Type Creutzfeldt-Jakob Disease: Its Relationship to “New Variant” CJD and Bovine Spongiform Encephalopathy
Authors: Narang Harash K.
Published: July 2017

Shortly after the appearance of bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD) was identified in young patients with nonclassical presentation such as difficulty in balancing and ataxia. The classical CJD in older patients starts with dementia. To distinguish between the two types, CJD in young persons has been termed “new variant” (nvCJD). The distinguishing features of classical CJD include initial presentation with dementia, confluent spongiform changes are very unusual in the cerebellum, and PrP plaques are rarely observed. For nvCJD, initially, difficulty with balancing and ataxia occurs, confluent spongiform changes are seen in the cerebellum, and a large number of PrP plaques are seen. The Icelandic observation of sheep scrapie revealed a predominantly ataxic form of scrapie, termed Type II, rather than the itchy form termed Type I. Both types have been known to exist in Europe. Since the clinical signs of Type II scrapie in sheep with trembling and ataxia are similar to those seen in BSE and nvCJD, this suggests that Type II is the cause of BSE and nvCJD. Over 8 years, from 1989 to 1996, I examined the clinical histories of 33 CJD cases aged between the ages of 18 and 84. Six under the age of 40 and 15 over the age of 40 had leading clinical features such as difficulty in balancing and ataxia similar to those seen in the young cases classified as “nvCJD.” Brains were examined from the six of 15 cases over the age of 40, which revealed similar pathology to that seen in young patients classified as “nvCJD.” These findings suggest that all age groups are susceptible to the strain of the agent derived from BSE cattle.
Catechins and Their Oligomers Linked by C4 → C8 Bonds are Major Cacao Polyphenols and Protect Low-Density Lipoprotein from Oxidation In Vitro
Authors: Osakabe Naomi , Yasuda Akiko , Natsume Midori , Takizawa Toshio , Terao Junji , Kondo Kazuo
Published: July 2017

In vitro effects of catechins and their oligomers linked by C4 → C8 bonds are major antioxidative components of chocolate and cocoa. Their effects on the susceptibility of human low-density lipoprotein (LDL) to oxidation were evaluated. The strength of the antioxidative activity was measured using copper ions as the radical generator as compared by weight varied in the following order: (+)-catechin > procyanidin B2 ≥ (–)-eplcatechin ≥ procyanidin C1 > cinnamtannin A2. Using 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrlle) (MeO-AMVN) as the radical generator, the order was (–)-epicatechin ≥ procyanidin B2 ≥ procyanidin C1 > (+)-catechin ≥ cinnamtannin A2. It is suggested that these compounds contribute to the activity of cacao products to protect LDL from oxidation.
Cigarette Smoke Extracts Delay Wound Healing in the Stomach: Involvement of Polyamine Synthesis
Authors: Shin Vivian Y. , Liu Edgar S.L. , Koo Marcel W.L. , Wang Jian Y. , Matsui Hirofumi , Cho Chi H.
Published: July 2017

The association between cigarette smoking and peptic ulcer diseases has been well established. Ornithine decarboxylase (ODC) is crucial for the gastroprotective and mucosal growth promoting effects in gastric ulcer healing. The aim of this study is to elucidate the possible mechanism of how Inhibition of ODC activity is involved in the delay of ulcer healing, if any, by cigarette smoke extracts (CSE). CSE were fractionated into chloroform extract (CE) and ethanol extract (EE). In in vivo study, rats with acetic acid-induced ulcers were given CE or EE intragastrically (2.5 or 5 mg/kg) once daily for 3 days. Ulcer sizes were significantly larger after CE or EE administration, followed by an increase in myeloperoxidase activity and a reduction in cell proliferation. However, both CSE stimulated the number of microvessels following the increase of basic fibroblast growth factor. In In vitro studies, the effect of CE or EE (10, 40, or 100 μg/ml) on cell migration and cell proliferation were measured using an In vitro wound model and [3H]-thymidlne incorporation assay, respectively. Both CSE delayed cell migration and decreased cell proliferation, which were accompanied with a reduction in ODC activity. Exogenous spermidine (5 or 10 μM) could reverse the inhibitory action on cell proliferation and ODC activity induced by CSE. In conclusion, both CSE significantly delayed ulcer healing as a result of reduction in cell proliferation and cell migration. All these effects are, in part, related to the reduction of polyamine synthesis.
Divergent Effects of Leptin on Luteinizing Hormone and Insulin Secretion are Dose Dependent
Authors: Zieba Dorota A. , Amstalden Marcel , Maciel Marlon N. , Keisler Duane H. , Raver Nina , Gertler Arieh , Williams Gary L.
Published: July 2017

We have shown recently that fasting permits leptin to modulate both luteinizing hormone (LH) and insulin secretion in cows. In rodents, leptin causes divergent effects on LH and insulin release that are dose dependent. To test the hypothesis that leptin effects on LH and insulin secretion in fasted cows are dose related, we examined the effects of various doses of recombinant ovine leptin (oleptin) in mature cows. Twenty ovariectomized beef cows, each bearing an estradiol implant to maintain basal estradiol concentrations, were used. All cows were fasted for 60 hr with free access to water and were assigned randomly to one of four groups (n = 5/group): 1) saline control; 2) leptin, 0.2 μg/kg; 3) leptin, 2.0 μg/kg; and 4) leptin, 20 μg/kg body wt. Blood samples were collected at 10-min intervals for 6 hr on Days 0 and 2, with saline or oleptin injected intravenously immediately after the first intensive sample on Day 2 (54 hr). Leptin caused a dose-related increase (P < 0.001) in mean concentrations of circulating LH. Stimulation of LH release by leptin was significant at the lowest (141% of control) and middle (122% of control) doses used, but no increase was observed for the highest dose. Increased mean concentrations of LH appeared to result from an augmentation of basal secretion, as pulse characteristics were not affected. After 54 hr of fasting, plasma insulin concentrations were lowered (P < 0.01) in all treatment groups compared to Day 0. After leptin injections, plasma insulin concentrations increased (P < 0.01) and reached highest concentrations during the first hour of sampling. However, this increase was sustained for several hours only in the intermediate (2.0 μg/kg) dose group. Collectively, our results show that leptin has potent positive effects on both LH and insulin secretion in fasted cows, but the anterior pituitary and endocrine pancreas appear to become downregulated in the presence of excess ligand.
Humic Acid Induces Oxidative DNA Damage, Growth Retardation, and Apoptosis in Human Primary Fibroblasts
Authors: Cheng Mei-Ling , Ho Hung-Yao , Huang Yi-Wen , Lu Fung-Jou , Chiu Daniel Tsun-Yee
Published: July 2017

Humic acid (HA) has been implicated as an etiological factor of Blackfoot disease endemic in the southwest coast of Taiwan. Dysfunction of endothelial cells and vasculopathy have been proposed to explain the onset of ulcerous changes at extremities. However, little is known about the effect of HA on activities of cells in these nonhealing wounds. In the present study, we demonstrate that HA adversely affects the growth properties of fibroblasts, one of the key players in wound repair. HA treatment caused growth arrest and apoptosis in human foreskin fibroblasts (HFF). This was accompanied by a significant increase in the level of 8-hydroxy-2′-deoxyguanosine (8-OHdG) in cellular DNA. The increased fluorescence in dichlorofluorescin (H2DCF)-stained and HA-treated cells suggests the involvement of reactive oxygen species (ROS) in HA-induced biological effects. Conversely, vitamin E pretreatment, which significantly reduced the 8-OHdG formation in HA-treated cells, alleviated the growth-inhibitory and apoptosis-inducing effects of HA. These results indicate that HA initiates oxidative damages to fibroblasts, and leads to their dwindling growth potential and survival. The present study suggests that HA-induced growth retardation and apoptosis of fibroblasts may play a role in the pathogenesis of Blackfoot disease.
Effects of Hypoxia on the Development of Intestinal Enzymes in Neonatal and Juvenile Rats
Authors: Lee Ping C. , Struve Mark , Raff Hershel
Published: July 2017

Hypoxia in the neonate is known to alter the activity of hepatic and pancreatic enzymes involved in lipid and carbohydrate metabolism. The purpose of this study was to evaluate the effect of neonatal hypoxia on the activity of intestinal enzymes, and to determine whether the administration of glucocorticoids to neonates can mimic the effects of hypoxia. Hypoxia in neonatal rats (0–7 days) increased protein content, and lactase and maltase activity in the duodenal and the jejunal segments of the small intestine compared with normoxic controls. Hypoxia in juvenile rats (28–35 days) did not change these enzymes. Two weeks after returning hypoxic (0–7 days) pups to normoxia, their body weight remained lower than the age-matched controls. In the group recovering from hypoxia, sucrase, maltase, and leucine aminopeptidase activities were lower in the duodenal and the jejunal segment. Compared with controls, LDH activity was lower only in the jejunal intestine in the group recovering from hypoxia. All enzyme activities returned to control levels 3 weeks after recovery. Neonatal rats treated with dexamethasone had a decrease in body weight, but increases in sucrase and maltase activity in both the duodenal and the jejunal segment. Hypoxia in newborn rats caused a delayed maturation of small intestinal enzymes. Increases in serum glucocorticoids after hypoxic exposure probably do not play a major role in the delayed maturation of the disaccharidase activity in the small intestine.
Polyamine Concentrations in the Brain of Vitamin B12-Deficient Rats
Authors: Adachi Koshin , Izumi Masayuki , Osano Yutaka , Miura Naofumi , Takatsu Shinobu , Terao Shin-Ichi , Mitsuma Terunori
Published: July 2017

To study the pathophysiology of the neuronal degeneration in vitamin B12 deficiency, we investigated the concentrations of the polyamines putrescine, spermidine, and spermine in brain regions and liver using high-performance liquid chromatography with fluorescence detection. Male Wistar rats were fed either a control or vitamin B12-deficient diet for 20 weeks. No remarkable behavioral changes were observed. Serum vitamin B12 and hepatic methionine concentrations were significantly lower and hepatic homocysteine was elevated in rats fed vitamin B12-deficient diet than in controls. Vitamin B12 deficiency was associated with decreased concentrations of spermidine, spermidine in liver and some regions of brain, although there were no observed abnormalities in behavior. These results suggest that vitamin B12 deficiency may play a role in neuronal degeneration through the disturbance of polyamine concentrations in rat brain.
Influence of Maternal Stress on Uranium-Induced Developmental Toxicity in Rats
Authors: Albina M. Luisa , Belles Montserrat , Gomez Mercedes , Sanchez Domenec J. , Domingo Jose L.
Published: July 2017

It has been demonstrated that uranium is an embryo/fetal toxicant when given orally or subcutaneously to pregnant mice. On the other hand, maternal stress has been shown to enhance the developmental toxicity of a number of metals. In this study, maternal toxicity and developmental effects of a concurrent exposure to uranyl acetate dihydrate (UAD) and restraint stress were evaluated in rats. Four groups of pregnant animals were given subcutaneous injections of UAD at 0.415 and 0.830 mg/kg/day on Days 6 to 15 of gestation. Animals in two of these groups were also subjected to restraint for 2 hr/day during the same gestational days. Control groups included restrained and unrestrained pregnant rats not exposed to UAD. Cesarean sections were performed on gestation Day 20, and the fetuses were weighed and examined for malformations and variations. Maternal toxicity and embryotoxicity were noted at 0.830 mg/kg/day of UAD, while fetotoxicity was evidenced at 0.415 and 0.830 mg/kg/day of UAD by significant reductions in fetal body weight and increases in the total number of skeletally affected fetuses. No teratogenic effects were noted in any group. Maternal restraint enhanced uranium-induced embryo/fetal toxicity only at 0.830 mg/kg/day, a dose that was also significantly toxic to the dams. As in previous studies with other metals, maternal stress enhances uranium-induced developmental toxicity at uranium doses that are highly toxic to the dams; however, at doses that are less acutely toxic the role of maternal stress would not be significant.
Pentameric Procyanidins Isolated from Theobroma cacao Seeds Selectively Downregulate ErbB2 in Human Aortic Endothelial Cells
Authors: Kenny Thomas P. , Keen Carl L. , Jones Paul , Kung Hsing-Jien , Schmitz Harold H. , Gershwin M. Eric
Published: July 2017

Flavonoids isolated from cocoa have biological activities relevant to oxidant defenses, vascular health, tumor suppression, and immune function. The intake of certain dietary flavonoids, along with other dietary substances such as tocopherols, ascorbate, and carotenoids, is epidemiologically associated with a reduced risk of cardiovascular disease. Flavonoids have also been shown to modulate tumor pathology in vitro and in animal models. We took advantage of the conserved sequences found in tyrosine kinases to study the influence of cocoa fractions and controls on gene expression. We report that the pentameric procyanidin (molecular weight of 1442 daltons) fraction isolated from cocoa was a potent inhibitor of tyrosine kinase ErbB2 expression, a receptor important in angiogenesis regulation. Consistent with this primary observation, the cocoa flavonoid fraction also suppressed human aortic endothelial cell (HAEC) growth and decreased expression of two tyrosine kinases responsive to ErbB2 modulation, namely VEGFR-2/KDR and MapK 11/p38β2. These inhibitory effects were observed when HAECs were treated with the flavonol fraction (molecular weight 280 daltons) isolated from cocoa, which comprise the structural subunits from which the procyanidin flavonoid subclass is biosynthetically constructed. Down-regulation of ErbB2 and inhibition of HAEC growth by cocoa procyanidins may have several downstream implications, including reduced vascular endothelial growth factor (VEGF) activity and angiogenic activity associated with tumor pathology. These results suggest specific dietary flavonoids are capable of selectively inhibiting ErbB2 and therefore may offer important insight into the design of therapeutic agents that target tumors overexpressing ErbB2.