tbuckley/cabot-search huggingface dataset:
Involvement of Reactive Oxygen Species in N-(4-Hydroxyphenyl)retinamide-Induced Apoptosis in Cervical Carcinoma Cells
Authors: N. Oridate, S. Suzuki, M. Higuchi, M. F. Mitchell, W. K. Hong, R. Lotan
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: The inhibitory effects of N-(4-Hydroxyphenyl)retinamide (4HPR) on tumorigenesis and tumor growth may result from its ability to induce apoptosis (programmed cell death). Since antioxidants inhibit 4HPR-induced apoptosis, experiments were planned to determine whether the levels of reactive oxygen species increase in cells undergoing apoptosis after exposure to 4HPR. Methods: Cells of the human cervical carcinoma cell line C33A and normal human cervical epithelial cells were treated with 4HPR and analyzed for survival, induction of apoptosis, generation of reactive oxygen species, and expression of the apoptosis-related proteins Bcl-2 and Bax. Results: Treatment with 4HPR decreased C33A cell number by inducing apoptosis in a time- and dose-dependent fashion. DNA fragmentation typical of apoptosis was observed in cells exposed to 4HPR at concentrations of 3 μM or higher for 6–24 hours. The generation of reactive oxygen species was enhanced by 1.85-fold to 4.5-fold after a 1.5-hour treatment with 0.4–10 μM 4HPR. Pyrrolidine dithiocarbamate, an oxygen radical scavenger, suppressed the rate of generation of reactive oxygen species and inhibited 4HPR-induced apoptosis. 4HPR failed to modulate cellular levels of the Bcl-2 and Bax proteins. N-(4-Methoxyphenyl)retinamide, the major 4HPR metabolite, and several other retinoids that bind to nuclear retinoic acid receptors or retinoid X receptors failed to enhance the generation of reactive oxygen species and to induce apoptosis. 4HPR was much less effective in generating reactive oxygen species and in inducing apoptosis in normal human cervical epithelial cells than in C33A cervical carcinoma cells. Conclusions: Enhancement of the generation of reactive oxygen species may be involved in apoptotic pathway induction by 4HPR.
A small molecule approach to engineering vascularized tissue
Authors: Joyce Doorn, Hugo A.M. Fernandes, Bach Q. Le, Jeroen van de Peppel, Johannes P.T.M. van Leeuwen, Margreet R. De Vries, Zeen Aref, Paul H.A. Quax, Ola Myklebost, Daniel B.F. Saris, Clemens A. van Blitterswijk, Jan de Boer
Journal: Biomaterials (2013)
Look back with (some) anger, and a lot of pleasure
Authors: Andrew Bush, Ian Pavord
Journal: Thorax (2015)

This is the last issue put together by the editorial team that has been privileged to look after Thorax for the past five years. We have run out of Adrian Mole book titles, and we have left the seventh age of man for the incoming team to describe us. (For the literary challenged, “Last scene of all, That ends this strange eventful history, Is second childishness and mere oblivion; Sans teeth, sans eyes, sans taste, sans everything”—including the Fowler Cup!) It is time to move on and write our last editorial, in which we want to thank a huge number of people, look back at what we think went well and what did not, and, finally, to pay off some old scores!

First the thanks—we have had a great five years on a personal level, and this as well as any success that may have been achieved is down solely to the efforts of many people. Our deputy editors, Clare Lloyd and Paul Cullinan, have been towers of strength and support, and ensured that our weekly Hanging Committee has always been focused, feisty, and above all, fun. The associate editors have worked tirelessly to bring down decision times to about a third of what they were and guided us with really helpful summaries of the manuscripts. Many hundreds of reviewers have given long hours of valuable and valued time to give us their wisdom and expertise, for zero financial reward and no university or National Health Service recognition; to you all, many thanks, and to all the above, we hope your spouses have not cited us in divorce proceedings. Behind the scenes we have been helped so much by the Thorax staff. Our editorial assistants have always been prompt, efficient, and above all, patient; and the production team have accommodated …
Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: A systematic review and meta-analysis
Authors: Yi-Le Wu, Cai-Yun Hu, Shan-Shan Lu, Feng-Feng Gong, Fang Feng, Zhen-Zhong Qian, Xiu-Xiu Ding, Hui-Yun Yang, Ye-Huan Sun
Journal: Metabolism (2014)
Immune Thrombocytopenic Purpura — From Agony to Agonist
Authors: Robert S. Schwartz
Journal: New England Journal of Medicine (2007)

In the summer of 1950, two hematology fellows working at the Barnes Hospital in St. Louis — William J. Harrington and James W. Hollingsworth — hatched a plan to test their idea that the cause of the idiopathic thrombocytopenic purpura (ITP) in a woman under their care was a factor in the blood that destroyed platelets. They decided that of the two fellows, the one whose blood type matched the patient's would receive 500 ml of her blood. In a flip of the genetic coin, Harrington matched.Within a few hours after receiving the woman's blood, Harrington's platelet count dropped . . .
B<scp>ODY</scp>C<scp>OMPOSITION OF THE</scp>M<scp>ALE AND</scp>F<scp>EMALE</scp>R<scp>EFERENCE</scp>I<scp>NFANTS</scp>
Authors: Samuel J. Fomon, Steven E. Nelson
Journal: Annual Review of Nutrition (2002)

▪ Abstract During infancy, especially early infancy, a substantial proportion of the requirements for energy and specific nutrients are those needed for growth. Knowledge of the body composition of a reference infant (body size and chemical composition at the 50th centile for age) permits an estimate of the growth needs of the infant. In this communication, we review efforts from the 1960s to the present at defining the composition of the male and female reference infants. We and others have demonstrated that accumulation of fat is remarkably rapid during the first 4 or 6 months of life. As a percentage of fat-free mass, water decreases throughout infancy whereas protein and minerals increase. However, the quantitative nature of these changes remains uncertain. After identifying the areas in which further data are needed, we conclude that the single most important area for further work is determining the relation of “bone mineral content” determined by dual energy X-ray absorptiometry to the osseous mineral content of the infant.
Effects of Vibration, Noise and Restraint on Heart Rate, Blood Pressure and Renal Blood Flow in the Pig
Authors: D B Stephens, R D Rader
Journal: Journal of the Royal Society of Medicine (1983)

Pigs and other farm animals are usually transported at least once during their lives; for example, all meat animals are finally taken to the abattoir for slaughter. The vibration, noise and handling associated with such transportation is usually novel to the animals, and therefore constitutes a potential 'stressor'. Such adverse stimuli may trigger physiological and psychological changes which rapidly produce profound changes in blood flow to peripheral organs, particularly the kidney, whose blood vessels are richly supplied with sympathetic nerve fibres. In the present study, ultrasonic techniques have been used with chronically implanted flow sensors for measuring heart rate (HR) and changes in renal blood flow (RBF) in conscious, freestanding and unanaesthetized pigs to monitor their cardiovascular responses to vibration, noise and various handling procedures. In addition, arterial blood pressure (BP) was measured via a catheter placed in the carotid artery. To ensure that vibration and noise could be accurately reproduced, a transport simulator (TS) was constructed in the laboratory. A small decrease of approximately 5% was observed in RBF during the first few minutes of exposure to vibration and noise, but this returned to the control levels monitored in undisturbed animals within a few minutes. Thereafter, RBF became significantly elevated for the remaining period of exposure to vibration and noise. In contrast, HR remained significantly increased throughout. BP was not significantly changed as a result of the experimental manipulation. Restraint and handling of the animals appeared to cause maximal disturbance. HR and BP were more than doubled compared with the resting value, but there was a concomitant marked decrease in RBF.(ABSTRACT TRUNCATED AT 250 WORDS)
Genomic Analyses Reveal Potential Independent Adaptation to High Altitude in Tibetan Chickens
Authors: Ming-Shan Wang, Yan Li, Min-Sheng Peng, Li Zhong, Zong-Ji Wang, Qi-Ye Li, Xiao-Long Tu, Yang Dong, Chun-Ling Zhu, Lu Wang, Min-Min Yang, Shi-Fang Wu, Yong-Wang Miao, Jian-Ping Liu, David M. Irwin, Wen Wang, Dong-Dong Wu, Ya-Ping Zhang
Journal: Molecular Biology and Evolution (2015)

Much like other indigenous domesticated animals, Tibetan chickens living at high altitudes (2,200–4,100 m) show specific physiological adaptations to the extreme environmental conditions of the Tibetan Plateau, but the genetic bases of these adaptations are not well characterized. Here, we assembled a de novo genome of a Tibetan chicken and resequenced whole genomes of 32 additional chickens, including Tibetan chickens, village chickens, game fowl, and Red Junglefowl, and found that the Tibetan chickens could broadly be placed into two groups. Further analyses revealed that several candidate genes in the calcium-signaling pathway are possibly involved in adaptation to the hypoxia experienced by these chickens, as these genes appear to have experienced directional selection in the two Tibetan chicken populations, suggesting a potential genetic mechanism underlying high altitude adaptation in Tibetan chickens. The candidate selected genes identified in this study, and their variants, may be useful targets for clarifying our understanding of the domestication of chickens in Tibet, and might be useful in current breeding efforts to develop improved breeds for the highlands.
STRUCTURAL STUDIES OF HUMAN γG-MYELOMA PROTEINS OF DIFFERENT ANTIGENIC SUBGROUPS AND GENETIC SPECIFICITIES
Authors: B. Frangione, E. C. Franklin, H. H. Fudenberg, M. E. Koshland
Journal: The Journal of Experimental Medicine (1966)

1. Peptide maps of Fc fragments or heavy chains of 36 G myeloma proteins and two "heavy chain disease" proteins belonging to the four gamma-chain subgroups revealed very striking similarities between them. However differences in a few peptides were noted. This was most pronounced for the Ge(gamma(2)d) subgroup which lacked three peptides characteristic of the other three subgroups. While Fc fragments from different proteins belonging to the same subgroup appeared very similar, minor differences in addition to those based on currently recognized Gm factors were occasionally noted. 2. Fc fragments from Gm(a+) We(gamma(2)b) proteins had a peptide previously shown to be characteristic of normal Gm(a+) gammaG-globulins. Fc fragments from Gm(a-) molecules belonging to the We(gamma(2)b), Vi(gamma(2)c), or Ne(gamma(2)a) subgroups, whether Gm(b+), Gm(f+), or Gm(-), had the peptide previously identified in Gm(b+f+) normal gammaG-globulin. This "non-a" peptide was absent in peptide maps from Gm(-) molecules of the Ge(gamma(2)d) subgroup which contained instead another peptide with the same electrophoretic mobility but migrating slightly further on chromatography. 3. Both the "a" and "non-a" peptides were pentapeptides having three amino acids in common, and differing in the other two. The "a" peptide contained one residue of lysine, aspartic acid, threonine, leucine, and glutamic acid. The "non-a" peptides prepared from Gm(b+), Gm(f+), and Gm(-) proteins were identical and contained one residue of lysine, threonine, and methionine sulfone, and two residues of glutamic acid. 4. Several possible mechanisms for the origin of these differences, and their possible role in serologic specificity are discussed.
Abstract IA20: Targeting of microRNAs for therapeutics
Authors: Sakari Kauppinen
Journal: Cancer Research (2012)

Abstract microRNAs act as important post-transcriptional regulators of gene expression by mediating mRNA degradation and translational repression. Moreover, there is ample evidence that perturbations in the levels of individual or entire families of miRNAs are strongly associated with the pathogenesis of a wide range of human diseases. Besides cancer, miRNAs have also been implicated in viral infections, cardiovascular and muscle diseases and CNS disorders. Thus, disease-associated miRNAs represent a potential new class of targets for oligonucleotide-based therapeutics, which may yield patient benefits unobtainable by other therapeutic approaches. LNA is a bicyclic high-affinity RNA analogue, in which the ribose ring is locked in an RNA-like, N-type (C3′-endo) conformation by the introduction of a 2′-O,4′-C methylene bridge. Transfection of LNA-modified antimiR oligonucleotides into cells results in potent and specific inhibition of miRNA function with concomitant derepression of direct target mRNAs. In addition, systemically delivered, unconjugated LNA-antimiRs with a phosphorothioate backbone show high metabolic stability and uptake in many tissues in mice, coinciding with long-term miRNA silencing in vivo. These findings support the utility of LNA-modified antimiR oligonucleotides in the development of therapeutic strategies aimed at pharmacological inhibition of disease-associated miRNAs. We will describe recent progress in targeting of disease-implicated miRNAs for therapeutics using LNA-antimiRs and present an update on the clinical development of antimiR-122 for treatment of hepatitis C virus infection. Citation Format: Sakari Kauppinen. Targeting of microRNAs for therapeutics [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA20.
Abstract 5215: miR-200b/c/429 sub-family negatively regulating Rho/ROCK signaling pathway and suppresses HCC metastasis
Authors: Chun-Ming Wong, Lai Wei, Sandy Leung-Kuen Au, Sandy Leung-Kuen Au, Dorothy Ngo-Yin Fan, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng
Journal: Cancer Research (2014)

Abstract MicroRNAs (miRNAs) are a class of small (∼22 nt) noncoding regulatory RNA molecules that can regulate gene expression by either cleaving or repressing the translation of their mRNA targets. Deregulation of miRNA expression is common in human cancers, including hepatocellular carcinoma (HCC). Recent studies have indicated that the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) negatively regulates epithelial-mesenchymal transition (EMT) and cell motility by targeting E-cadherin repressors, ZEB1 and ZEB2. However, the roles of the miR-200 family in HCC remain elusive. In this study, we found that miR-200 family was frequently down-regulated in human HCC, which was contributed by the frequently CpG hypermethylation of miR-200 promoters. Functionally, although all miR-200 members suppressed ZEB1/2 expression in HCC, only overexpression of miR-200b/c/429 sub-family impeded HCC cell migration. These findings implied that, in addition to ZEB1/2, other yet unidentified miR-200b/c/429 specific targets may play an important role in HCC metastasis. In silico analyses revealed that miR-200b/c/429 sub-family may have a profound role in modulating cell cytoskeletal reorganization. Along with this notion, we further identified RhoA and ROCK2 as down-stream targets of miR-200b/c/429 sub-family. By using immunofluorescence staining, scanning electron microscope and live cell imaging, we demonstrated that overexpression of miR-200b/c/429 subfamily but not miR-200a/141 sub-family suppressed Rho/ROCK signaling mediated stress fiber and focal adhesion formations, which in turn led to a dramatic cell morphology change and loss of cell migration ability. Furthermore, by employed an orthotopic liver implantation model, we showed that overexpression of miR-200b was sufficient to suppress HCC growth and metastasis in nude mice. Our results together suggest that miR-200b/c/429 sub-family functions as a metastatic suppressor in human HCC by negatively regulating Rho/ROCK signaling pathway. Citation Format: Chun-Ming Wong, Lai Wei, Sandy Leung-Kuen Au, Sandy Leung-Kuen Au, Dorothy Ngo-Yin Fan, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng. miR-200b/c/429 sub-family negatively regulating Rho/ROCK signaling pathway and suppresses HCC metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5215. doi:10.1158/1538-7445.AM2014-5215
Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus
Authors: Monique M. Hedderson, Fei Xu, Jeanne A. Darbinian, Charles P. Quesenberry, Sneha Sridhar, Catherine Kim, Erica P. Gunderson, Assiamira Ferrara
Journal: Diabetes Care (2014)

OBJECTIVE Lower levels of sex hormone–binding globulin (SHBG) have been associated with increased risk of diabetes among postmenopausal women; however, it is unclear whether they are associated with glucose intolerance in younger women. We examined whether SHBG concentrations, measured before pregnancy, are associated with risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up examination (1984–1996) and had a subsequent pregnancy (1984–2009). Eligible women were free of recognized diabetes. Case patients were 256 women in whom GDM developed. Two control subjects were selected for each case patient and were matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies. RESULTS Compared with the highest quartile of SHBG concentrations, the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44–2.52]; 2.33 [1.07–5.09]; 4.06 [1.90–8.65]; P for trend &amp;lt; 0.001), after adjusting for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use, prepregnancy weight changes, and homeostasis model assessment of insulin resistance. Having SHBG levels below the median (&amp;lt;64.5 nmol/L) and a BMI ≥25.0 kg/m2 was associated with fivefold increased odds of GDM compared with normal-weight women with SHBG levels at or above the median (5.34 [3.00–9.49]). CONCLUSIONS Low prepregnancy SHBG concentrations were associated with increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.
Development of Tumor-Reactive T Cells After Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant for Chronic Lymphocytic Leukemia
Authors: Tetsuya Nishida, Michael Hudecek, Ana Kostic, Marie Bleakley, Edus H. Warren, David Maloney, Rainer Storb, Stanley R. Riddell
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. Experimental Design: Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8+ T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. Results: Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8+ and CD4+ T cells specific for antigens expressed by CLL. A clonal analysis of the CD8+ T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8+ T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. Conclusions: The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.
End-of-Life Care in the Intensive Care Unit
Authors: Mervyn Koh, Poi Choo Hwee
Journal: JAMA Internal Medicine (2015)

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Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit.
Authors: A Fassi, F Sangalli, R Maffi, F Colombi, E I Mohamed, B M Brenner, G Remuzzi, A Remuzzi
Journal: Journal of the American Society of Nephrology (1998)

It has been suggested that a reduced number of nephrons may predispose to systemic hypertension and glomerular injury. Compensatory hemodynamic changes, due to a low number of glomeruli, might be responsible for glomerular functional and structural changes. It is difficult to evaluate this hypothesis in humans because of limitations in estimating the number of nephrons in the living kidney. The aim of the present study was to estimate nephron number, single glomerular hemodynamics, and glomerular volume in male and female MWF rats, a strain that spontaneously develops systemic hypertension, proteinuria, and glomerulosclerosis. Male and female Wistar rats were used as controls. At 12 to 14 wk of age, male MWF rats developed proteinuria, whereas female MWF and Wistar rats showed normal urinary protein excretion rate. Glomerular number was significantly reduced in male and female MWF rats (13,690+/-1,489 and 12,855+/-1,781 gl/ kidney, respectively) compared with Wistar rats (26,955+/-2,171 and 27,166+/-1,754 gl/kidney, respectively). The mean number of nephrons per unit of body weight was also lower in MWF males (88+/-10) compared with MWF females (139+/-20) and compared with male and female Wistar animals (142+/-14 and 221+/-22 gl/g body wt). Whole-kidney hemodynamic parameters and the number of nephrons were used to calculate single-nephron filtration rate and plasma flow. Both measures were markedly elevated in male MWF rats relative to values obtained in the other three groups. Similarly, glomerular volume was significantly greater in MWF males than in other animals. These results suggest that an inborn deficit of nephrons may be responsible for spontaneous development of later-in-life hypertension and renal dysfunction. The data also indicate the need to investigate the role of this potential pathogenetic factor for human hypertension and kidney disease in humans.