tbuckley/cabot-search huggingface dataset:
ON BECOMING A NUTRITIONAL BIOCHEMIST
Authors: Donald B. McCormick
Journal: Annual Review of Nutrition (2004)

Much of the science underlying nutrition has come from biochemical studies. This certainly is true in our understanding of the metabolism and function of such micronutrient cofactors as vitamins and metal ions. My own interest stems from an early desire to understand the molecular events in an organism and ultimately to know the fate of those nutrients that are needed to maintain life. My training in chemistry, biochemistry, and nutrition was helpful in gaining knowledge about the interface among these disciplines. My interests followed an understandable trail, beginning with those factors that cause plant galls and continuing through carbohydrate metabolism to vitamins. After all, from studying such pentitols as ribitol with Professor Touster at Vanderbilt University through indoctrination with enzymes, vitamins, and coenzymes with Professor Snell at the University of California-Berkeley, it was rational to begin my independent academic life investigating the enzymes that convert a ribityl-containing vitamin, namely riboflavin, to its operational flavocoenzymes. While at Cornell University, I encountered Professor Wright, who shared an interest in biotin. My realization that there was a similar need to determine the metabolism of lipoate followed logically. Interactions with inorganic chemists such as Professor Sigel at Basel University, as well as inorganic chemists at Cornell, led to an interest in metal ions. As summarized in this article, my colleagues and I are pleased to have contributed to both basic knowledge about cofactors and to have utilized much of this information in extensions to applications. Along the way, I have served by teaching, researching, and administrating at the universities that provided my positions in academe, and I have worked to share the load of numerous public and professional duties that are summarized herein. Altogether it has been an enjoyable career to be a nutritional biochemist. I recommend it for those who follow.
MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1α/HIF-1β
Authors: Paul Cao, Zhiyong Deng, Meimei Wan, Weiwei Huang, Scott D Cramer, Jianfeng Xu, Ming Lei, Guangchao Sui
Journal: Molecular Cancer (2010)

Abstract Background In prostate cancer (PCa), the common treatment involving androgen ablation alleviates the disease temporarily, but results in the recurrence of highly aggressive and androgen-independent metastatic cancer. Therefore, more effective therapeutic approaches are needed. It is known that aberrant epigenetics contributes to prostate malignancy. Unlike genetic changes, these epigenetic alterations are reversible, which makes them attractive targets in PCa therapy to impede cancer progression. As a histone methyltransferease, Ezh2 plays an essential role in epigenetic regulation. Since Ezh2 is overexpressed and acts as an oncogene in PCa, it has been proposed as a bona fide target of PCa therapy. MicroRNAs (miRNAs) regulate gene expression through modulating protein translation. Recently, the contribution of miRNAs in cancer development is increasingly appreciated. In this report, we present our study showing that microRNA-101 (miR-101) inhibits Ezh2 expression and differentially regulates prostate cancer cells. In addition, the expression of miR-101 alters upon androgen treatment and HIF-1α/HIF-1β induction. Result In our reporter assays, both miR-101 and miR-26a inhibit the expression of a reporter construct containing the 3'-UTR of Ezh2. When ectopically expressed in PC-3, DU145 and LNCaP cells, miR-101 inhibits endogenous Ezh2 expression in all three cell lines, while miR-26a only decreases Ezh2 in DU145. Ectopic miR-101 reduces the invasion ability of PC-3 cells, while restored Ezh2 expression rescues the invasiveness of PC-3 cells. Similarly, miR-101 also inhibits cell invasion and migration of DU145 and LNCaP cells, respectively. Interestingly, ectopic miR-101 exhibits differential effects on the proliferation of PC-3, DU-145 and LNCaP cells and also causes morphological changes of LNCaP cells. In addition, the expression of miR-101 is regulated by androgen receptor and HIF-1α/HIF-1β. While HIF-1α/HIF-1β induced by deferoxamine mesylate (DFO) decreases miR-101 levels, the overall effects of R-1881 on miR-101 expression are stimulatory. Conclusions This study indicates that miR-101 targets Ezh2 and decreases the invasiveness of PCa cells, suggesting that miR-101 introduction is a potential therapeutic strategy to combat PCa. MiR-101 differentially regulates prostate cell proliferation. Meanwhile, the expression of miR-101 is also modulated at different physiological conditions, such as androgen stimulation and HIF-1α/HIF-1β induction.
Dual‐Wavelength Irradiation and Dox Delivery for ­Cancer Cell Ablation with Photocatalytic Pr Doped TiO<sub>2</sub>/NGO ­Hybrid Nanocomposite
Authors: Hongje Jang, Myung‐Ho Choi, Yeajee Yim, Young‐Kwan Kim, Dal‐Hee Min
Journal: Advanced Healthcare Materials (2015)

Herein, hybrid nanocomposite of praseodymium doped TiO 2 nanocrystals and graphene oxide nanosheets are prepared by facile hydrothermal treatment. As‐synthesized Pr‐TiO 2 /NGO hybrid nanocomposite exhibits enhanced photocatalytic activity under visible light irradiation by the intact graphene oxide and doped lanthanide mediated band gap narrowing compared to TiO 2 . Moreover, high payload and controlled release of doxorubicin by charge reversal of hybrid nanocomposite at endosomal pH and near‐infrared irradiation mediated efficient photothermal conversion provide highly favorable features in therapeutic applications. Through the combination of these three distinctive therapeutic modalities, highly efficient trimodal cancer cell ablation is demonstrated.
CLONED POTASSIUM CHANNELS FROM EUKARYOTES AND PROKARYOTES
Authors: Lily Yeh Jan, Yuh Nung Jan
Journal: Annual Review of Neuroscience (1997)

▪ Abstract Potassium channels contribute to the excitability of neurons and signaling in the nervous system. They arise from multiple gene families including one for voltage-gated potassium channels and one for inwardly rectifying potassium channels. Features of potassium permeation, channel gating and regulation, and subunit interaction have been analyzed. Potassium channels of similar design have been found in animals ranging from jellyfish to humans, as well as in plants, yeast, and bacteria. Structural similarities are evident for the pore-forming α subunits and for the β subunits, which could potentially regulate channel activity according to the level of energy and/or reducing power of the cell.
Cardiac arrhythmias after chronic embolization of the sinus node artery: alterations in parasympathetic pacemaker control.
Authors: J M Loeb, D E Euler, W C Randall, J F Moran, G Brynjolfsson
Journal: Circulation (1980)

Embolization of the sinus node artery was accomplished in dogs by injecting rapidly hardening vinyl latex into the sinus node artery. Embolization immediately shifted the pacemaker to a junctional focus; however, with time postoperatively, the pacemaker shifted to an atrial site. Variable episodes of pacemaker failure, sinoatrial block, junctional rhythm, wandering atrial pacemaker and idioventricular escape rhythms were commonly observed on Holter monitor in isolation but only rarely when the dog was in the laboratory. Severe bradycardia (38.9 +/- 3.7 beats/min) was the predominant rhythm by 3-6 months postoperatively. In addition, these same dogs had a greater overall increase in heart rate after atropine than normal dogs (17.5 +/- 13.5 vs 116.6 +/- 15.9 beats/min above control; p less than 0.02). Responses to vagal stimulation in this group were abnormal, as long periods of asystole and bradycardia were observed after stimulation was terminated. These data suggest an alteration in parasympathetic pacemaker control after chronic embolization of the sinus node artery.
The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO)
Authors: R. Manchanda, M. Godfrey, L.A. Wong-Taylor, M.J. Halaska, M. Burnell, J.P. Grabowski, M. Gultekin, D. Haidopoulos, I. Zapardiel, B. Vranes, V. Kesic, P. Zola, N. Colombo, R. Verheijen, M. Bossart, J. Piek
Journal: Annals of Oncology (2012)
The effect of percutaneously absorbed steroids on hypothalamic-pituitary adrenal function after intensive use in in-patients*
Authors: D. D. MUNRO
Journal: British Journal of Dermatology (1976)

Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function.
Predictive value of oocyte morphology in human IVF: a systematic review of the literature
Authors: Laura Rienzi, Gábor Vajta, Filippo Ubaldi
Journal: Human Reproduction Update (2010)

Non-invasive selection of developmentally competent human oocytes may increase the overall efficiency of human assisted reproduction and is regarded as crucial in countries where legal, social or religious factors restrict the production of supernumerary embryos. The purpose of this study was to summarize the predictive value for IVF success of morphological features of the oocyte that can be obtained by light or polarized microscopic investigations.Studies about oocyte morphology and IVF/ICSI outcomes were identified by using a systematic literature search.Fifty relevant articles were identified: 33 analysed a single feature, 9 observed multiple features and investigated the effect of these features individually, 8 summarized the effect of individual features. Investigated structures were the following: meiotic spindle (15 papers), zona pellucida (15 papers), vacuoles or refractile bodies (14 papers), polar body shape (12 papers), oocyte shape (10 papers), dark cytoplasm or diffuse granulation (12 papers), perivitelline space (11 papers), central cytoplasmic granulation (8 papers), cumulus-oocyte complex (6 papers) and cytoplasm viscosity and membrane resistance characteristics (2 papers). None of these features were unanimously evaluated to have prognostic value for further developmental competence of oocytes.No clear tendency in recent publications to a general increase in predictive value of morphological features was found. These contradicting data underline the importance of more intensive and coordinated research to reach a consensus and fully exploit the predictive potential of morphological examination of human oocytes.
Early captopril treatment inhibits DNA synthesis in endothelial cells and normalization of maximal coronary flow in infarcted rat hearts
Authors: H Nelissen-Vrancken
Journal: Cardiovascular Research (1998)

Objectives: Cardiac remodeling due to myocardial infarction (MI) includes myocyte hypertrophy, collagen deposition, a rise in DNA synthesis, and normalization of initially diminished maximal coronary bloodflow. Previously, we demonstrated that early captopril treatment can prevent the rise in total DNA synthesis, collagen deposition and hypertrophy. In the present experiments, we investigated the effects of captopril or perindoprilat treatment on cardiac endothelial cell proliferation and maximal coronary flow. Methods: MI was induced by ligation of the left coronary artery in Wistar rats. Sham-operated and infarcted rats were treated with captopril (12 mg/kg.d s.c.) from either day 0–21 (early) or day 21–35 (late) after surgery. In isolated retrogradely perfused rat hearts, maximal coronary flow was determined following maximal dilatation with nitroprusside and adenosine (1 mM each). In separate groups, sections of hearts of sham-operated and MI rats treated with BrdU (day 7–14) and either captopril or perindoprilat (1 mg/kg.d s.c.; day 0–14) were double stained with a monoclonal anti-BrdU antibody and the lectin GSI. The total fraction of DNA synthesizing cells and its proportion of endothelial cells was determined. Results: Maximal coronary flow was completely normalized in MI hearts within three weeks after surgery. Early captopril, but not late captopril, inhibited the normalization of maximal coronary flow in MI hearts (Early: sham, 27.4±1.0; MI, 21.2±1.4 ml/min; P<0.05; mean±SEM) without affecting the hypertrophic response. The total fraction of DNA synthesizing cells was significantly increased in MI hearts (sham: 7.6±1.9; MI: 14.9±2.2%). The proportion of endothelial cells, however, was comparable in sham-operated and infarcted hearts (sham: 30±3; MI: 33±3%). Both early captopril and perindoprilat treatment inhibited total DNA synthesis in MI hearts. Only in captopril pre-treated hearts, this inhibition was associated with a disproportionate inhibition of the endothelial cell proliferation (10.3±2.0%). Conclusion: Early captopril treatment inhibits endothelial cell proliferation and coronary vessel growth following MI, which seems to be partly due to inhibition of the renin angiotensin system.
Estimated numbers and prevalence of PI*S and PI*Z alleles of 1-antitrypsin deficiency in European countries
Authors: I. Blanco
Journal: European Respiratory Journal (2005)

The current study focuses on developing estimates of the numbers of individuals carrying the two most common deficiency alleles, PI*S and PI*Z, for alpha1-antitrypsin deficiency (AT-D) in Europe. Criteria for selection of epidemiological studies were: 1) AT phenotyping performed by isoelectrofocusing or antigen-antibody crossed electrophoresis; 2) rejection of "screening studies"; 3) statistical precision factor score of > or = 5 for Southwest, Western and Northern Europe, > or = 4 for Central Europe, > or = 3 for Eastern Europe; and 4) samples representative of the general population. A total of 75,390 individuals were selected from 21 European countries (one each from Austria, Belgium, Latvia, Hungary, Serbia-Montenegro, Sweden and Switzerland; two each from Denmark, Estonia and Lithuania; three each from Portugal and the UK; four each from Finland, The Netherlands, Norway and Spain; five each from Russia and Germany; six from Poland; eight from Italy; and nine from France). The total AT-D populations of a particular phenotype in the countries selected were: 124,594 ZZ; 560,515 SZ; 16,323,226 MZ; 630,401 SS; and 36,716,819 MS. The largest number of ZZ (5,000-15,000) were in Italy, Spain, Germany, France, the UK, Latvia, Sweden and Denmark, followed by Belgium, Portugal, Serbia-Montenegro, Russia, The Netherlands, Norway and Austria (1,000-2,000), with < 1,000 in each of the remaining countries. A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found.
N-Acetyl-β-D-Glucosaminidase Does Not Enhance Prediction of Cardiovascular or All-Cause Mortality by Albuminuria in a Low-Risk Population
Authors: Marit D. Solbu, Ingrid Toft, Maja-Lisa Løchen, Ellisiv B. Mathiesen, Bjørn O. Eriksen, Toralf Melsom, Inger Njølstad, Tom Wilsgaard, Trond G. Jenssen
Journal: Journal of the American Society of Nephrology (2015)

Albuminuria is a well known risk factor for cardiovascular disease and mortality, but focus on renal tubular dysfunction as a potential risk factor is growing also. The association between the urinary activity of N-acetyl-β-D-glucosaminidase (NAG) and cardiovascular risk has been assessed mostly in cross-sectional studies. We studied the cross-sectional associations between urinary NAG and cardiovascular risk factors and the longitudinal associations between NAG, cardiovascular disease, and all-cause mortality in a general population. Urinary NAG/creatinine ratio (NAG ratio) and albumin/creatinine ratio (ACR) were measured in 6834 participants of the Tromsø Study in 1994-1995. During the median 17.5 years of follow-up, 958 myocardial infarctions, 726 ischemic strokes, and 2358 deaths were registered. In multivariable analyses adjusted for albuminuria and cardiovascular risk factors, a baseline NAG ratio in the highest quartile was associated with an increased risk of myocardial infarction (hazard ratio [HR], 1.43; 95% confidence interval [95% CI], 1.16 to 1.76), ischemic stroke (HR, 1.41; 95% CI, 1.10 to 1.80), and all-cause mortality (HR, 1.60; 95% CI, 1.39 to 1.84). Combined, ACR and NAG ratio above median associated with a 48%-80% increased risk for the three end points. However, the NAG ratio did not add significantly to the baseline risk-prediction models when assessed by area under the receiver operating characteristics curve or net reclassification improvement. In conclusion, the nonsignificant improvement of risk prediction does not support the clinical use of NAG ratio in cardiovascular risk assessment in a low-risk group.
Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial
Authors: Nan Shan Zhong, Tieying Sun, Chao Zhuo, George D'Souza, Sang Haak Lee, Nguyen Huu Lan, Chi-Huei Chiang, David Wilson, Fang Sun, Joseph Iaconis, David Melnick
Journal: The Lancet Infectious Diseases (2014)
Role of thyrotrophin releasing hormone and corticotrophin releasing factor in stress related alterations of gastrointestinal motor function
Authors: C Beglinger, L Degen
Journal: Gut (2002)

There is a growing body of experimental and clinical evidence to indicate that stress influences gastrointestinal motility. The most common pattern of gastrointestinal motor alterations induced by a variety of different stress factors is that of delayed gastric emptying and accelerated colonic transit. Central administration of corticotrophin releasing factor mimics both of these effects. This review focuses on the effects of two centrally acting peptides known to influence gastrointestinal motility and transit in experimental animals: thyrotrophin releasing hormone and corticotrophin releasing factor. The biological actions of these peptides are discussed in relation to the motility changes and pathways involved in their actions.
<i>Chlamydia pneumoniae</i> and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation
Authors: Sebastian Sasu, David LaVerda, Nilofer Qureshi, Douglas T. Golenbock, Debbie Beasley
Journal: Circulation Research (2001)

An early component of atherogenesis is abnormal vascular smooth muscle cell (VSMC) proliferation. The presence of Chlamydia pneumoniae in many atherosclerotic lesions raises the possibility that this organism plays a causal role in atherogenesis. In this study, C pneumoniae elementary bodies (EBs) rapidly activated p44/p42 mitogen-activated protein kinases (MAPKs) and stimulated proliferation of VSMCs in vitro. Exposure of VSMCs derived from human saphenous vein to C pneumoniae EBs (3×10 7 inclusion forming units/mL) enhanced bromodeoxyuridine (BrdU) incorporation 12±3-fold. UV- and heat-inactivated C pneumoniae EBs also stimulated VSMC proliferation, indicating a role of direct stimulation by chlamydial antigens. However, the mitogenic activity of C pneumoniae was heat-labile, thus excluding a role of lipopolysaccharide. Chlamydial hsp60 (25 μg/mL) replicated the effect of C pneumoniae , stimulating BrdU incorporation 7±3-fold. Exposure to C pneumoniae or chlamydial hsp60 rapidly activated p44/p42 MAPK, within 5 to 10 minutes of exposure. In addition, PD98059 and U0126, which are two distinct inhibitors of upstream MAPK kinase 1/2 (MEK1/2), abolished the mitogenic effect of C pneumoniae and chlamydial hsp60. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the p44/p42 MAPK pathway. Human VSMCs were shown to express TLR4 mRNA and protein, and a TLR4 antagonist abolished chlamydial hsp60–induced VSMC proliferation and attenuated C pneumoniae –induced MAPK activation and VSMC proliferation. Together these results indicate that C pneumoniae and chlamydial hsp60 are potent inducers of human VSMC proliferation and that these effects are mediated, at least in part, by rapid TLR4-mediated activation of p44/p42 MAPK.
Circulating Follicular Helper–Like T Cells in Systemic Lupus Erythematosus: Association With Disease Activity
Authors: Jin‐Young Choi, John Hsi‐en Ho, Sandra G. Pasoto, Viviane Bunin, Sang Taek Kim, Solange Carrasco, Eduardo F. Borba, Celio R. Gonçalves, Priscila R. Costa, Esper G. Kallas, Eloisa Bonfa, Joseph Craft
Journal: Arthritis & Rheumatology (2015)

Objective To assess circulating follicular helper T (Tfh)–like CD4+ T cells in patients with systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods Blood samples from patients with SLE, as well as blood samples from patients with Behçet's disease (BD) and healthy individuals as controls, were analyzed. In all samples, circulating Tfh‐like cells were enumerated by flow cytometry, using, as markers, expression of CXCR5, inducible T cell costimulator (ICOS), and programmed death 1 (PD‐1) protein, as well as secretion of interleukin‐21 (IL‐21). The frequency of circulating Tfh‐like cells was compared to that of circulating plasmablasts (CD19+IgD−CD38+). In addition, the possible association of circulating Tfh‐like cells with the SLE Disease Activity Index (SLEDAI) was evaluated. Results The subset of circulating Tfh‐like T cells, identified as CXCR5 high ICOS high PD‐1 high , was expanded in the blood of SLE patients compared to controls. Circulating Tfh‐like cells were found to produce IL‐21 and had lower expression of CCR7 as compared to that in circulating CXCR5 high central memory T cells, thereby enabling their distinction. Expression of PD‐1, but not ICOS or CXCR5, was significantly elevated in circulating Tfh‐like cells from SLE patients compared to controls. PD‐1 expression among CXCR5 high circulating Tfh‐like cells correlated with the SLEDAI, frequency of circulating plasmablasts, and anti–double‐stranded DNA antibody positivity, but not with disease duration or past organ injury; rather, this cell profile appeared to be a reflection of current active disease. Conclusion Circulating Tfh‐like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T cell–B cell collaboration, with a causal relationship that is central to disease pathogenesis. These findings also suggest that circulating Tfh‐like cells provide a surrogate for aberrant germinal center activity in SLE, and that their PD‐1 expression offers a tool for measuring disease activity and monitoring the response to therapies.