tbuckley/cabot-search huggingface dataset:
Association of Lipoprotein(a) With Puberty in IDDM
Authors: Jennifer J Couper, David J Bates, Robert Cocciolone, Anthea M Magarey, T John C Boulton, James L Penfold, Richard G Ryall
Journal: Diabetes Care (1993)

OBJECTIVE— To determine serum lipoprotein(a) in a large sample of IDDM and control children and to examine a possible association with puberty. RESEARCH DESIGN AND METHODS—Serum lipoprotein(a), apoB-100, and apoA-I were measured under identical conditions in 170 Caucasian children with IDDM aged 12.3 ± 3.59 yr and 233 Caucasian control children aged 13.6 ± 1.12 yr. Patients with persistent microalbuminuria were excluded. Lipoprotein(a), apoB-100, and apoA-I were measured by nephelometry using a specific monoclonal antibody. Pubertal assessment was performed using Tanner staging and testicular volume measurement. RESULTS— Lipoprotein(a) was higher in the IDDM than control group (geometric mean 237 mg/L, 25–75th percentile 134–465 vs. 172 [99–316] mg/L, P = 0.0008). When analyzed according to pubertal stage, only pubertal and postpubertal patients had higher levels than control subjects (265 [148–560] vs. 174 [101–320] mg/L, P = 0.0001), with prepubertal patients showing no difference. Pubertal and postpubertal patients showed both higher lipoprotein(a) (P = 0.01) levels and higher albumin excretion rates (P = 0.02) than prepubertal patients, correcting for the other variable. Lipoprotein(a) was not related to HbA1c, albumin excretion rate, duration, age, sex, mean arterial pressure, or a family history of premature coronary artery disease in the IDDM group. Lipoprotein(a) was not higher in patients with overnight albumin excretion rate above the 95th percentile but below the microalbuminuric range. ApoB-100 did not differ between IDDM and control children. ApoA-I was significantly lower in the IDDM group (1.04 [0.94–1.17] vs. 1.21 [1.10–1.31] g/L; P &amp;lt; 0.0001). CONCLUSIONS— Pubertal and postpubertal IDDM patients have higher serum lipoprotein(a) than Caucasian control subjects. Our findings suggest a rise in lipoprotein(a) may occur during puberty in IDDM. Longitudinal studies are required to clarify the relationship between lipoprotein(a), albumin excretion rate, and puberty.
T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice
Authors: A. von Delwig, D. M Altmann, F. G Charlton, N. McKie, J. D Isaacs, R. Holmdahl, J. H Robinson
Journal: Annals of the Rheumatic Diseases (2006)

<b>Aim:</b> To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine T cell specificity against the arthritogenic CII<sub>259–273</sub> epitope of type II collagen either unmodified or post-translationally glycosylated at Lys<sub>264</sub>. <b>Methods:</b> Arthritis was induced by immunisation with human type II collagen in complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays, using T cell hybridomas specific for the glycosylated and non-glycosylated CII<sub>259–273</sub> epitope. <b>Results:</b> The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non-glycosylated epitope than to the glycosylated CII<sub>259–273</sub>. Most of the T cell hybridomas generated from CII-immunised mice recognised the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells. <b>Conclusion:</b> This study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC-II, which could contribute to the pathogenicity of autoimmune arthritis.
Zinc supplementation during pregnancy: a double blind randomised controlled trial.
Authors: K. Mahomed, D. K. James, J. Golding, R. McCabe
Journal: BMJ (1989)

OBJECTIVE--To see whether zinc supplementation during pregnancy improves maternal and fetal outcome. DESIGN--Prospective study started at booking and continued till discharge of mother and baby from the maternity hospital. Mothers were randomly assigned to receive zinc supplementation or placebo in a double blind trial. SETTING--Mothers booking at one hospital. PATIENTS--Women booking before 20 weeks of gestation who agreed to take part in the study. 494 Mothers were followed up till the end of pregnancy. There was no difference between the groups given zinc and placebo in their social or medical backgrounds. INTERVENTIONS--Mothers in the active treatment group received one capsule of 20 mg elemental zinc daily and those in the placebo treated group a capsule identical in appearance and taste with the active capsule but which contained inert substances. MAIN OUTCOME MEASURE--Various adverse outcomes were tested, including maternal bleeding, hypertension, complications of labour and delivery, gestational age, Apgar scores, and neonatal abnormalities. The main outcome measure was birth weight. RESULTS--There were no differences whatsoever between mothers given a zinc supplement and those given a placebo. CONCLUSION--Zinc supplementation in pregnancy in the United Kingdom does not seem to offer any benefits to the mother or her fetus.
Differential expression of cyclooxygenase 2 in human colorectal cancer
Authors: J Dimberg, A Samuelsson, A Hugander, P Soderkvist
Journal: Gut (1999)

Experimental, clinical, and epidemiological studies have implicated mitogenic metabolites of arachidonic acid such as prostaglandin E(2) (PGE(2)) in colorectal carcinogenesis. Recently, cyclooxygenase 2 (COX-2) which catalyses the conversion of arachidonic acid to PGE(2), has displayed increased levels in human colorectal cancer.To evaluate whether there is differential COX-2 expression from different locations (caecum, ascending, transverse, descending, or sigmoid colon, and rectum) in human colorectal cancer.Protein levels of COX-2 were determined by western blot analysis in tumours and adjacent normal mucosa of 39 patients with colorectal cancer.There was a notable overexpression of COX-2 protein in tumours located in the rectum (p<0.001) compared with other locations in the colon. Rectal tumours revealed elevated COX-2 protein levels in 18/20 cases compared with 4/19 colonic cases. No association between enhanced COX-2 protein expression in tumour tissue and Dukes's stages was found.Results suggest that the differential COX-2 expression may be due to differences in gene regulatory factors affecting COX-2 expression and/or reflect secondary changes in tumour progression which may have clinical implications.
Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy
Authors: Christoph Stein, Halina Machelska
Journal: Pharmacological Reviews (2011)

The concept that the immune system can communicate with peripheral sensory neurons to modulate pain is based mostly on documented interactions between opioid ligands and receptors. Such findings may have broad implications for the development of safer pain medication. Innovative strategies take into account that analgesics should be particularly active in pathological states rather than producing a general suppression of the central nervous system, as with conventional morphine- or cannabinoid-like drugs. Inflammation of peripheral tissue leads to increased functionality of opioid receptors on peripheral sensory neurons and to local production of endogenous opioid peptides. In addition, endocannabinoids were detected in leukocytes, but their role in pain modulation has yet to be addressed. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing immune cells to sites of painful injury, and the augmentation of peripheral ligand and receptor synthesis (e.g., by gene therapy). Similar approaches may be pursued for cannabinoids. The ultimate goal is to avoid detrimental side effects of currently available analgesics such as respiratory depression, cognitive impairment, addiction, gastrointestinal bleeding, and thromboembolic complications.
Predicting prognosis of breast cancer with gene signatures: are we lost in a sea of data?
Authors: Takayuki Iwamoto, Lajos Pusztai
Journal: Genome Medicine (2010)

A large number of prognostic and predictive signatures have been proposed for breast cancer and a few of these are now available in the clinic as new molecular diagnostic tests. However, several other signatures have not fared well in validation studies. Some investigators continue to be puzzled by the diversity of signatures that are being developed for the same purpose but that share few or no common genes. The history of empirical development of prognostic gene signatures and the unique association between molecular subsets and clinical phenotypes of breast cancer explain many of these apparent contradictions in the literature. Three features of breast cancer gene expression contribute to this: the large number of individually prognostic genes (differentially expressed between good and bad prognosis cases); the unstable rankings of differentially expressed genes between datasets; and the highly correlated expression of informative genes.
Selective Electrical Interfaces with the Nervous System
Authors: Wim L. C. Rutten
Journal: Annual Review of Biomedical Engineering (2002)

To achieve selective electrical interfacing to the neural system it is necessary to approach neuronal elements on a scale of micrometers. This necessitates microtechnology fabrication and introduces the interdisciplinary field of neurotechnology, lying at the juncture of neuroscience with microtechnology. The neuroelectronic interface occurs where the membrane of a cell soma or axon meets a metal microelectrode surface. The seal between these may be narrow or may be leaky. In the latter case the surrounding volume conductor becomes part of the interface. Electrode design for successful interfacing, either for stimulation or recording, requires good understanding of membrane phenomena, natural and evoked action potential generation, volume conduction, and electrode behavior. Penetrating multimicroelectrodes have been produced as one-, two-, and three-dimensional arrays, mainly in silicon, glass, and metal microtechnology. Cuff electrodes circumvent a nerve; their selectivity aims at fascicles more than at nerve fibers. Other types of electrodes are regenerating sieves and cone-ingrowth electrodes. The latter may play a role in brain-computer interfaces. Planar substrate-embedded electrode arrays with cultured neural cells on top are used to study the activity and plasticity of developing neural networks. They also serve as substrates for future so-called cultured probes.
Activation and Involvement of Ral GTPases in Colorectal Cancer
Authors: Timothy D. Martin, Jonathan C. Samuel, Elizabeth D. Routh, Channing J. Der, Jen Jen Yeh
Journal: Cancer Research (2011)

Current approaches to block KRAS oncogene function focus on inhibition of K-Ras downstream effector signaling. We evaluated the antitumor activity of selumetinib (AZD6244, ARRY-142886), a potent and selective MEK1/2 inhibitor, on a panel of colorectal carcinoma (CRC) cells and found no inhibition of KRAS mutant CRC cell anchorage-independent growth. Although AKT activity was elevated in KRAS mutant cells, and PI3K inhibition did impair the growth of MEK inhibitor-insensitive CRC cell lines, concurrent treatment with selumetinib did not provide additional antitumor activity. Therefore, we speculated that inhibition of the Ral guanine exchange factor (RalGEF) effector pathway may be a more effective approach for blocking CRC growth. RalGEFs are activators of the related RalA and RalB small GTPases and we found activation of both in CRC cell lines and patient tumors. Interfering RNA stable suppression of RalA expression reduced CRC tumor cell anchorage-independent growth, but surprisingly, stable suppression of RalB greatly enhanced soft agar colony size and formation frequency. Despite their opposing activities, both RalA and RalB regulation of anchorage-independent growth required interaction with RalBP1/RLIP76 and components of the exocyst complex. Interestingly, RalA interaction with the Exo84 but not Sec5 exocyst component was necessary for supporting anchorage-independent growth, whereas RalB interaction with Sec5 but not Exo84 was necessary for inhibition of anchorage-independent growth. We suggest that anti-RalA-selective therapies may provide an effective approach for KRAS mutant CRC.
The removal of amateur tattoos by salabrasion
Authors: ALEXANDRA M.M. STRONG, IAN T. JACKSON
Journal: British Journal of Dermatology (1979)

Due to the recent upsurge in self-inflicted tattoos in teenagers it was decided to employ for their removal the method of salabrasion, i.e. abrasion with table salt. This technique was recently used by Manchester (1973, 1974) for the removal of commercial tattoos. Fourteen patients with twenty-eight tattoo or only tiny flecks of pigment remaining visible; eleven showed a fair response, i.e. the tatoo, although much lighter in colour, was still legible but the patient was satisfied with the result; three showed a poor response, i.e. the tattoo appeared as if untreated; four (two patients) defaulted. In general, as could be expected, the darker the tattoo the more difficult was its removal and those on fingers were particularly resistant.
Co-expression of eotaxin-2 and IL-5 in double transgenic mice leads to eosinophil degranulation and the development of pulmonary pathologies*1
Authors: S.I. Ochkur, T.L. Biechele, B. McElhinney, C.A. Protheroe, R.S. Pero, M.T. Borchers, K.R. O'Neill, D.C. Colbert, M.P. McGarry, Y. Janssen-Heininger, C.R. Irvin, H.H. Shen, N.A. Lee, J.J. Lee
Journal: Journal of Allergy and Clinical Immunology (2004)
A Second Leukotriene B4 Receptor, Blt2
Authors: Takehiko Yokomizo, Kazuhiko Kato, Kan Terawaki, Takashi Izumi, Takao Shimizu
Journal: The Journal of Experimental Medicine (2000)

Leukotriene B4 (LTB4) is a potent chemoattractant and activator of both granulocytes and macrophages. The actions of LTB4 appear to be mediated by a specific G protein–coupled receptor (GPCR) BLT1, originally termed BLT (Yokomizo, T., T. Izumi, K. Chang, Y. Takuwa, and T. Shimizu. 1997. Nature. 387:620–624). Here, we report the molecular cloning of a novel GPCR for LTB4, designated BLT2, which binds LTB4 with a Kd value of 23 nM compared with 1.1 nM for BLT1, but still efficiently transduces intracellular signaling. BLT2 is highly homologous to BLT1, with an amino acid identity of 45.2%, and its open reading frame is located in the promoter region of the BLT1 gene. BLT2 is expressed ubiquitously, in contrast to BLT1, which is expressed predominantly in leukocytes. Chinese hamster ovary cells expressing BLT2 exhibit LTB4-induced chemotaxis, calcium mobilization, and pertussis toxin–insensitive inhibition of adenylyl cyclase. Several BLT1 antagonists, including U 75302, failed to inhibit LTB4 binding to BLT2. Thus, BLT2 is a pharmacologically distinct receptor for LTB4, and may mediate cellular functions in tissues other than leukocytes. BLT2 provides a novel target for antiinflammatory therapy and promises to expand our knowledge of LTB4 function. The location of the gene suggests shared transcriptional regulation of these two receptors.
Abnormal visceral autonomic innervation in neurogenic faecal incontinence.
Authors: C T Speakman, M A Kamm
Journal: Gut (1993)

Changes of denervation in the anal sphincter striated and smooth muscle in patients with neurogenic faecal incontinence are well established. This study aimed to determine if there is also a more proximal visceral autonomic abnormality. Thirty women with purely neurogenic faecal incontinence (prolonged pudendal nerve latencies and an intact sphincter ring) and 12 patients with neuropathic changes together with an anatomical disruption were studied. Two control groups consisted of 18 healthy volunteer women and 17 women with normal innervation but an anatomically disrupted sphincter. Rectal sensation was assessed using balloon distension and electrical mucosal stimulation, and anal sensation by electrical stimulation. Rectal compliance was studied to determine whether sensory changes were primary or caused by altered rectal wall viscoelastic properties. Anal canal pressure changes in response to both rectal distension and rectal electrical stimulation were measured to assess the intrinsic innervation of the internal anal sphincter. Patients with neurogenic incontinence alone had impaired rectal sensation to distension (53.1 v 31.5 ml, p &lt; 0.05, neurogenic v controls) and to electrical stimulation (24.4 v 14.8 mA, p &lt; 0.005). Patients with neurogenic incontinence and sphincter disruption also showed impaired sensation compared with healthy controls (55.8 ml v 31.5 ml, p &lt; 0.05 and 22.9 mA v 14.8 mA, p &lt; 0.05). Patients with only a disrupted sphincter had normal visceral sensation to both types of testing. Both rectal compliance and the response of the internal anal sphincter to rectal distension and electrical stimulation were normal in all patient groups. This study suggests that there is a visceral sensory abnormality in patients with neurogenic incontinence which is not caused by altered rectal compliance. As evaluated in this study the intrinsic innervation of the internal anal sphincter is not affected in this process.
Preoperative Therapy in Invasive Breast Cancer: Reviewing the State of the Science and Exploring New Research Directions
Authors: Julie R. Gralow, Jo Anne Zujewski, Eric Winer
Journal: Journal of Clinical Oncology (2008)

InMarch2007,theNationalCancerInstitute(NCI)sponsoredaState oftheScienceConferenceonPreoperativeTherapyinInvasiveBreast Cancer. The major goals of the conference were to review current clinical standards and to identify opportunities for future research. The conference did not seek to develop a consensus statement or a clinical guideline, but it did attempt to characterize appropriate clinical care. Importantly, an additional conference objective was to explore how research in the preoperative setting could be used to accelerate progress in the development of new and more effective treatments for individuals with breast cancer. In patients with operable breast cancer, randomized trials have demonstratedthatpreoperativeandpostoperativechemotherapy(us
M. Biot on a Means of Detecting Sugar in Urine by an Optical Instrument
Authors: M. Biot
Journal: BMJ (1841)

M. MANDL having inquired of me wlhether the rotatory power* inight not be employed to detect the presence of sugar in diabetic urine, I uindertook the investig,ation, the results of which I now submikit to the Academy of Sciences.Diabetes, as is well known, manifests itself chiefly by an increased secretion of urine, which is capable of undergoing alcoholic fermentationi.Ir 1806, M. Thenard extracted from diabetic urine a solid, insipid matter; but though in1-* When a ray of polarized light is made to pass through a tube con- taining a solution of sugar, and received on a peculiar kind of prism, a double disc is perceived; but on turning the prism the second disc dis- appears.The extent of rotationi of thie prism indicates, with the utmost precision, the quantity of sugar containied in any fluid.M. Biot terms this the "rotatory power."We have briefly described the instrument in our last number.-EDS.
A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target
Authors: Anjan Debnath, Derek Parsonage, Rosa M Andrade, Chen He, Eduardo R Cobo, Ken Hirata, Steven Chen, Guillermina García-Rivera, Esther Orozco, Máximo B Martínez, Shamila S Gunatilleke, Amy M Barrios, Michelle R Arkin, Leslie B Poole, James H McKerrow, Sharon L Reed
Journal: Nature Medicine (2012)
Combined Haploinsufficiency for ATM and RAD9 as a Factor in Cell Transformation, Apoptosis, and DNA Lesion Repair Dynamics
Authors: Lubomir B. Smilenov, Howard B. Lieberman, Stephen A. Mitchell, Ronald A. Baker, Kevin M. Hopkins, Eric J. Hall
Journal: Cancer Research (2005)

Loss of function of oncogenes, tumor suppressor genes and DNA damage processing genes has been implicated in the development of many types of cancer, but for the vast majority of cases, there is no link to specific germ line mutations. In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined. The results show that cells having low levels of both ATM and RAD9 proteins are more sensitive to transformation by radiation, have different DNA double-strand break repair dynamics and are less apoptotic when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. Our conclusions are that under stress conditions, the efficiency and capacity for DNA repair mediated by the ATM/RAD9 cell signaling network depend on the abundance of both proteins and that, in general, DNA repair network efficiencies are genotype-dependent and can vary within a specific range.
In vivo uptake of inhaled particles by airway phagocytes is enhanced in patients with mild asthma compared with normal volunteers
Authors: J C Lay, N E Alexis, K L Zeman, D B Peden, W D Bennett
Journal: Thorax (2008)

<h3>Background:</h3> The uptake of inhaled particulate matter by airway phagocytes is an important defence mechanism contributing to the clearance of potentially toxic substances, including aeroallergens, from the lung. Since airway monocytes and macrophages can also function as antigen presenting cells, their ability to engulf materials deposited on the airway surface is of particular interest in patients with allergic asthma. To determine whether airway mononuclear phagocytes of patients with allergic asthma might have enhanced phagocytic activity, the in vivo uptake of inhaled radiolabelled particles was compared in 10 patients with mild allergic asthma and 8 healthy (non-allergic) individuals. <h3>Methods:</h3> Phagocyte function was assessed by quantifying the proportion of radioactivity associated with cellular and supernatant fractions of induced sputum 2 h after inhalation of radiolabelled sulfur colloid particles. All subjects were pretreated with albuterol before sputum induction. A standardised breathing pattern was used to target aerosol deposition in the bronchial airways. <h3>Results:</h3> In vivo particle uptake by airway cells was significantly greater in patients with asthma than in healthy volunteers (57.2% (95% CI 46.5% to 67.9%) vs 22.3% (95% CI 4.9% to 39.6%), p&lt;0.01), as was in vitro phagocytosis of opsonised zymosan-A bioparticles. There was also a significant correlation (r = 0.85, p&lt;0.01) between the percentage of sputum mononuclear phagocytes and the percentage uptake of particles in the patients with asthma but not in the control subjects. <h3>Conclusions:</h3> In vivo particle uptake by airway macrophages is enhanced in persons with mild asthma. Enhanced uptake and processing of particulate antigens could contribute to the pathogenesis and progression of allergic airways disease and may contribute to the increased risk of disease exacerbation associated with particulate exposure.