tbuckley/cabot-search huggingface dataset:
OBSERVATIONS IN A CASE OF RENAL GLYCOSURIA, DURING AND AFTER PREGNANCY
Authors: HAROLD M. BOWCOCK
Journal: JAMA (1928)

The condition existing in the patient whom we are about to describe is usually referred to in medical literature as renal glycosuria. In addition to this term, the literature contains several designations which have reference to the same symptom-complex. John<sup>1</sup>objects to the term renal glycosuria because "all glycosuria is renal in origin, depending upon the renal threshold as well as the glycemic level"; he suggests the term nondiabetic glycosuria. Umber and Rosenberg<sup>2</sup>speak of renal diabetes or glycosuria innocens. Cyclic renal glycosuria or cyclic glycosuria is a subgroup of renal glycosuria described by Jonas<sup>3</sup>and Faber.<sup>4</sup>Benign glycosuria is a group term including the glycosurias of nondiabetic origin. The diagnosis of renal glycosuria may be made in cases in which there exists a chronic, nonprogressive, apparently harmless glycosuria without the symptoms of diabetes and without hyperglycemia in the fasting or postabsorptive states. The renal threshold
Evidence for a Genetic Component for Substance Dependence in Native Americans
Authors: Cindy L. Ehlers, Ian R. Gizer
Journal: American Journal of Psychiatry (2013)

Although tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans. General population studies have demonstrated that substance dependence has a substantially heritable component (approximately 50% of the risk resulting from genetic influences); however, fewer studies have investigated the role of genetics in the risk for substance dependence in Native Americans.The authors present a literature review of the evidence for a genetic component in the etiology of substance dependence in Native Americans, including studies of heritability, linkage analyses, and candidate genes.Evidence for the heritability of alcohol and drug dependence was found. Linkage analyses revealed that genes influencing risk for substance dependence and related phenotypes, such as body mass index (BMI), drug tolerance, EEG patterns, and externalizing traits, reside on several chromosome regions identified in other population samples. Overlap in the gene locations for substance dependence and BMI suggests that a common genetic substrate may exist for disorders of consumption. Studies of the genes that code for alcohol-metabolizing enzymes have not revealed any risk variants specific to Native American populations, although most Native Americans lack protective variants seen in other populations. Other candidate genes associated with substance dependence phenotypes in Native Americans include OPRM1, CRN1, COMT, GABRA2, MAOA, and HTR3-B.Substance dependence has a substantial genetic component in Native Americans, similar in magnitude to that reported for other populations. The high rates of substance dependence seen in some tribes is likely a combination of a lack of genetic protective factors (metabolizing enzyme variants) combined with genetically mediated risk factors (externalizing traits, consumption drive, and drug sensitivity or tolerance) that combine with key environmental factors (trauma exposure, early age at onset of use, and environmental hardship) to produce an elevated risk for the disorder.
Computational Modeling and Experimental Evaluation of a Novel Prodrug for Targeting the Extracellular Space of Prostate Tumors
Authors: Pavel Pospisil, Ketai Wang, Ayman F. Al Aowad, Lakshmanan K. Iyer, S. James Adelstein, Amin I. Kassis
Journal: Cancer Research (2007)

Abstract We are developing a noninvasive approach for targeting imaging and therapeutic radionuclides to prostate cancer. Our method, Enzyme-Mediated Cancer Imaging and Therapy (EMCIT), aims to use enzyme-dependent, site-specific, in vivo precipitation of a radioactive molecule within the extracellular space of solid tumors. Advanced methods for data mining of the literature, protein databases, and knowledge bases (IT.Omics LSGraph and Ingenuity Systems) identified prostatic acid phosphatase (PAP) as an enzyme overexpressed in prostate cancer and secreted in the extracellular space. Using AutoDock 3.0 software, the prodrug ammonium 2-(2′-phosphoryloxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ2-P) was docked in silico into the X-ray structure of PAP. The data indicate that IQ2-P docked into the PAP active site with a calculated inhibition constant (Ki) more favorable than that of the PAP inhibitor α-benzylaminobenzylphosphonic acid. When 125IQ2-P, the radioiodinated form of the water-soluble prodrug, was incubated with PAP, rapid hydrolysis of the compound was observed as exemplified by formation of the water-insoluble 2-(2′-hydroxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ2-OH). Similarly, the incubation of IQ2-P with human LNCaP, PC-3, and 22Rv1 prostate tumor cells resulted in the formation of large fluorescent IQ2-OH crystals. No hydrolysis was seen in the presence of normal human cells. Autoradiography of tumor cells incubated with 125IQ2-P showed accumulation of radioactive grains (125IQ2-OH) around the cells. We anticipate that the EMCIT approach will enable the active in vivo entrapment of radioimaging and radiotherapeutic compounds within the extracellular spaces of primary prostate tumors and their metastases. [Cancer Res 2007;67(5):2197–205]
Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden
Authors: Leslee J. Shaw, Daniel S. Berman, David J. Maron, G. B. John Mancini, Sean W. Hayes, Pamela M. Hartigan, William S. Weintraub, Robert A. O’Rourke, Marcin Dada, John A. Spertus, Bernard R. Chaitman, John Friedman, Piotr Slomka, Gary V. Heller, Guido Germano, Gilbert Gosselin, Peter Berger, William J. Kostuk, Ronald G. Schwartz, Merill Knudtson, Emir Veledar, Eric R. Bates, Benjamin McCallister, Koon K. Teo, William E. Boden
Journal: Circulation (2008)

Background— Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS). Methods and Results— Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374±50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered ≥10% myocardium. The primary end point was ≥5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (−2.7%; 95% confidence interval, −1.7%, −3.8%) than with OMT (−0.5%; 95% confidence interval, −1.6%, 0.6%; P &lt;0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%; P =0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P =0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction ( P =0.037 [risk-adjusted P =0.26]), particularly if baseline ischemia was moderate to severe ( P =0.001 [risk-adjusted P =0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to ≥10% residual ischemia on follow-up MPS ( P =0.002 [risk-adjusted P =0.09]). Conclusions— In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of ≥5% ischemia reduction with OMT with or without coronary revascularization.
Extracellular Nucleotides and Adenosine Independently Activate AMP-Activated Protein Kinase in Endothelial Cells
Authors: Cleide Gonçalves da Silva, Robert Jarzyna, Anke Specht, Elzbieta Kaczmarek
Journal: Circulation Research (2006)

AMP-activated protein kinase (AMPK) plays a key role in the regulation of energy homeostasis and is activated in response to cellular stress, including hypoxia/ischemia and hyperglycemia. The stress events are accompanied by rapid release of extracellular nucleotides from damaged tissues or activated endothelial cells (EC) and platelets. We demonstrate that extracellular nucleotides (ATP, ADP, and UTP, but not UDP) and adenosine independently induce phosphorylation and activation of AMPK in human umbilical vein EC (HUVEC) by the mechanism that is not linked to changes in AMP:ATP ratio. HUVEC express NTPDases, as well as 5′-nucleotidase; hence, nucleotides can be metabolized to adenosine. However, inhibition of 5′-nucleotidase had no effect on ATP/ADP/UTP-induced phospho- rylation of AMPK, indicating that AMPK activation occurred as a direct response to nucleotides. Nucleotide-evoked phosphorylation of AMPK in HUVEC was mediated by P2Y1, P2Y2, and/or P2Y4 receptors, whereas P2Y6, P2Y11, and P2X receptors were not involved. The nucleotide-induced phosphorylation of AMPK was affected by changes in the concentration of intracellular Ca 2+ and by Ca 2+ /calmodulin-dependent kinase kinase (CaMKK), although most likely it was not dependent on LKB1 kinase. Adenosine-induced phosphorylation of AMPK was not mediated by P1 receptors but required adenosine uptake by equilibrative nucleoside transporters followed by its (intracellular) metabolism to AMP. Moreover, adenosine effect was Ca 2+ and CaMKK independent, although probably associated with upstream LKB1. We hypothesize that P2 receptors and adenosine transporters could be novel targets for the pharmacological regulation of AMPK activity and its downstream effects on EC function.
Telomerase Activation and Rejuvenation of Telomere Length in Stimulated T Cells Derived from Serially Transplanted Hematopoietic Stem Cells
Authors: Richard C. Allsopp, Samuel Cheshier, Irving L. Weissman
Journal: The Journal of Experimental Medicine (2002)

Telomeres shorten in hematopoietic cells, including hematopoietic stem cells (HSCs), during aging and after transplantation, despite the presence of readily detectable levels of telomerase in these cells. In T cells, antigenic stimulation has been shown to result in a marked increase in the level of telomerase activity. We now show that stimulation of T cells derived from serially transplanted HSC results in a telomerase-dependent elongation of telomere length to a size similar to that observed in T cells isolated directly from young mice. Southern analysis of telomere length in resting and anti-CD3/CD28 stimulated donor-derived splenic T cells revealed an increase in telomere size by ∼7 kb for the population as a whole. Stimulation of donor-derived T cells from recipients of HSCs from telomerase-deficient mice did not result in regeneration of telomere length, demonstrating a dependence on telomerase. Furthermore, clonal anti-CD3/CD28 stimulation of donor-derived T cells followed by fluorescent in situ hybridization (FISH) analysis of telomeric signal intensity showed that telomeres had increased in size by ∼50% for all clonal expansions. Together, these results imply that one role for telomerase in T cells may be to renew or extend replicative potential via the rejuvenation of telomere length.
Identification of Epstein-Barr Virus–Induced Gene 3 as a Novel Serum and Tissue Biomarker and a Therapeutic Target for Lung Cancer
Authors: Ryohei Nishino, Atsushi Takano, Hideto Oshita, Nobuhisa Ishikawa, Hirohiko Akiyama, Hiroyuki Ito, Haruhiko Nakayama, Yohei Miyagi, Eiju Tsuchiya, Nobuoki Kohno, Yusuke Nakamura, Yataro Daigo
Journal: Clinical Cancer Research (2011)

This study aims to identify novel biomarkers and therapeutic targets for lung cancer.We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus-induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non-small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.
Control of the differentiation of regulatory T cells and TH17 cells by the DNA-binding inhibitor Id3
Authors: Takashi Maruyama, Jun Li, Jose P Vaque, Joanne E Konkel, Weifeng Wang, Baojun Zhang, Pin Zhang, Brian F Zamarron, Dongyang Yu, Yuntao Wu, Yuan Zhuang, J Silvio Gutkind, WanJun Chen
Journal: Nature Immunology (2010)
THE MOUSE INTESTINAL MICROFLORA WITH EMPHASIS ON THE STRICT ANAEROBES
Authors: Adrian Lee, James Gordon, Chi-Jen Lee, René Dubos
Journal: The Journal of Experimental Medicine (1971)

The various components of the intestinal microflora in the mouse become established according to a definite time sequence; the strict anaerobes are the last groups of bacteria to reach their maximum population levels, 14-16 days after birth. The multiplication of these strict anaerobes in the mouse intestine seems to depend upon the prior multiplication of other bacterial species, and coincides with the ingestion of food other than maternal milk. These two conditioning factors may correspond to the establishment of a suitably reduced Eh potential and to the provision of certain metabolites. Once established, the strict anaerobes constitute by far the largest percentage of the total intestinal microflora; most of them are associated in a viable form with the mucosa. In normal animals they persist at very high levels throughout the life span. However, their populations can be drastically reduced by dietary manipulation of the animal, by administration of vancomycin, or by certain disease processes of the intestine. The strict anaerobic bacteria seem to play an important, and perhaps essential role in the maintenance of the anatomic structures and physiological functions of the intestine. They also seem to hold in check several species of intestinal bacteria, in particular the coliform bacilli.
Protein antigens of the RNA-protein complexes detected by anti-SM and anti-RNP antibodies found in serum of patients with systemic lupus erythematosus and related disorders.
Authors: G E Conner, D Nelson, R Wisniewolski, R G Lahita, G Blobel, H G Kunkel
Journal: The Journal of Experimental Medicine (1982)

Evidence has been obtained previously indicating that the antigens reacting with the anti-Sm and anti-RNP sera are present as a large complex, and similar protein bands are obtained with both types of sera. Inthe present study, it proved possible to break up this complex using SDS treatment before immunoprecipitation. After such treatment, different protein bands were immunoprecipitated by the two antisera; Sm determinants resided, at least partially, in a 19-kd protein. Sequential immunoprecipitation with and without prior SDS treatment provided further evidence for these specificities and suggested that two classes of particles exist in different tissues, one containing proteins immunoreactive with the Sn and RNP antisera and the other containing proteins immunoreactive only with the Sm antisera. The latter particle contained all the bands seen with the first type except for the absence of the 19-kd band. Nitrocellulose blot analyses confirmed the assignment of the 25- and 16-kd polypeptides to Sm antigenic determinants; analyses for RNP proved les informative by this technique. Some differences in the banding patterns were obtained using cells from different species: the 25-kd Sm band was usually double in human cells and single in rat and rabbit tissue. Methods of extraction also caused some differences which was especially true for the rabbit thymus extract widely used for Sm and RNP studies. Additional immunoreactive bands at 68 and 70 kd also were detected when the Sm and RNP antisera were used in nitrocellulose blot analyses. Furthermore, evidence was obtained for a number of other antibodies in lupus sera which have not as yet been detected by serological methods.
Environmental Exposures and the Risk for Alzheimer Disease
Authors: Steven T. DeKosky, Sam Gandy
Journal: JAMA Neurology (2014)

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Zinc-Mediated Reduction of Apoptosis in Cardiac Allografts
Authors: M. H. Kown, T. Van der Steenhoven, F. G. Blankenberg, G. Hoyt, G. J. Berry, J. F. Tait, H. W. Strauss, R. C. Robbins
Journal: Circulation (2000)

Apoptosis is thought to occur during immune-mediated acute rejection of cardiac allografts. In vitro studies have shown that zinc inhibits the activity of the proapoptotic enzyme caspase-3. We hypothesized that ZnCl(2) would reduce acute cardiac rejection in vivo via the blockade of caspase-3-dependent apoptosis. (99m)Tc-labeled annexin V was used to measure apoptosis in cardiac allografts through nuclear imaging. Annexin V binds to phosphatidylserines, which are externalized to the outer membrane of apoptotic cells.Twenty-seven PVG rat hearts were transplanted heterotopically into the abdomen of untreated ACI rats as controls (group 1). Fifteen were scanned and euthanized on postoperative day 4, and 12 were assessed for graft survival. Group 2 and 3 rats (n=15 each) received 1 and 5 mg/kg ZnCl(2) BID IP, respectively. Nine of each of these groups were scanned and euthanized on postoperative day 4, and 6 were studied for allograft survival. Group 4 rats (n=3) received isografts. Region-of-interest analysis demonstrated a dose-dependent reduction in (99m)Tc annexin uptake in ZnCl(2)-treated allografts: 2.43+/-0.37% for group 1, 1. 97+/-0.41% for group 2, 1.21+/-0.47% for group 3, and 0.55+/-0.19% for group 4 (ANOVA, P:=0.001). Graft survival times of 6.4+/-1.7, 9. 3+/-3.0, and 11.5+/-3.4 days for groups 1, 2, and 3, respectively, were also observed (ANOVA, P:=0.001). Caspase-3 activity in the allografts showed a 3.7-fold reduction in group 3 animals compared with group 1 animals (P:=0.004).Apoptosis that occurs in acute cardiac allograft rejection is reduced with ZnCl(2) in a dose-dependent manner via caspase-3 inhibition.
QUANTITATIVE HISTOCHEMISTRY OF THE NEPHRON. V. ALKALINE PHOSPHATASE AND LACTIC DEHYDROGENASE ACTIVITIES IN LUPUS NEPHRITIS*
Authors: Victor E. Pollak, Sjoerd L. Bonting, Robert C. Muehrcke, Robert M. Kark
Journal: Journal of Clinical Investigation (1960)

METHODS Clinical materialA total of 19 kidney specimens was analyzed for alka- line phosphatase and LDH activity.Eighteen specimens were taken by percutaneous renal biopsy (4), and 1 speci- men was obtained at autopsy.Nine specimens were analyzed on 4 patients, studied serially, and a biopsy and autopsy specimen were taken from 1 patient.An independent and detailed histological analysis was made on each specimen according to the methods pre-
The fraud behind the MMR scare
Authors: F. Godlee
Journal: BMJ (2011)

This week we begin a special series of articles by the journalist Brian Deer. It focuses on what may seem a familiar story—the scare linking the MMR vaccine with autism, launched at a press conference in 1998 after the Lancet published a paper by Andrew Wakefield and colleagues describing 12 children with brain and bowel disease.

Deer’s investigation into Wakefield’s work has taken seven years. It led to the UK General Medical Council’s longest ever fitness to practise hearing, after which Wakefield and his senior co-author, John Walker-Smith, were struck off and the paper was retracted. That surely should be the end of the story.

It turns out not to …
Severe hyperphosphatemia and hypocalcemia
Authors: M Sutters, C L Gaboury, W M Bennett
Journal: Journal of the American Society of Nephrology (1996)

In the following report, a case of severe hyperphosphatemia and tetanic hypocalcemia resulting from the inadvertent oral ingestion of a phosphate enema is described. The physiology of serum phosphate regulation and the mechanism by which the elevation of serum phosphate is thought to induce hypocalcemia is discussed, and the treatment of hyperphosphatemia is reviewed. Finally, the potential consequences of the administration of calcium to treat tetany in a patient with severe hyperphosphatemia are considered.
Parallel Loss of Nuclear-Encoded Mitochondrial Aminoacyl-tRNA Synthetases and mtDNA-Encoded tRNAs in Cnidaria
Authors: Karri M. Haen, Walker Pett, Dennis V. Lavrov
Journal: Molecular Biology and Evolution (2010)

Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.