tbuckley/cabot-search huggingface dataset:
SPECIAL ARTICLE
Authors: ROBERT L. REPLOGLE, HERBERT J. MEISELMAN, EDWARD W. MERRILL
Journal: Circulation (1967)

Blood viscosity is dependent on the shear rate at which it is measured. Reversible red cell aggregation is largely a function of fibrinogen-red cell interaction at normal hematocrits. Red cell aggregation is the basis for the anomalous rheological behavior of blood, since a considerable fraction of the shear stress applied to blood flowing at low shear rates is required to break up the aggregates accounting for the greater shear stress required to produce a given shear rate of low magnitude. Erythrocyte sedimentation rate is also a measure of red cell aggregation and has been used as an indicator of the "suspension stability" of blood. The tendency for red cell aggregation is greatest during periods of low flow states and is maximum when the blood is standing still. At such times, a certain shear stress, the yield stress, must be applied to overcome the reversible red cell-fibrinogen bond, causing the blood to "yield" or begin to flow. Manipulation of blood viscosity and yield shear stress, by hemodilution or fibrinogen dilution are readily accomplished, and experimental studies indicate that these rheological alterations have circulatory and metabolic significance.
Acquisition of mitogenic responsiveness by nonresponding lymphocytes upon insertion of appropriate membrane components.
Authors: A Jakobovits, N Sharon, I Zan-Bar
Journal: The Journal of Experimental Medicine (1982)

The effect of insertion of plasma membrane components from lymphocytes responding to mitogens into the membranes of nonresponding cells using Sendai virus envelopes as vehicles was examined. T cells modified by B membranes were stimulated by lipopolysaccharide (LPS) to proliferate as well as to produce interleukin-2 activity. B cells modified by T membranes were stimulated by concanavalin A to proliferate and to produce interleukin-2 activity. B cells derived from C3H/HeJ LPS-nonresponder strain of mice, when modified by B membranes derived from the LPS-responder C3H/eb strain, acquired LPS responsiveness. These findings indicate that the inability of either T or B cells to respond to specific mitogens is due to the lack of suitable plasma membrane constituents and that by changing the membrane composition the lymphocytes can be endowed with new functions.
Uses of blood gas estimations.
Authors: G. D. Walker
Journal: BMJ (1968)

MWCA JOURNALI units of insulin daily.She attended regularly, usually well controlled, though during a cold in 1964 the blood sugar reached 290 mg./100 ml., with considerable ketosis.Chest x-rays in 1963 and 1964 were normal.There were no further admissions until November 1967 at the age of 17.She then needed 36 units Soluble+ 36 units P.Z.insulin daily, and developed a precomatose state after an emotional crisis.She again had basal crepita- tions and, now, tenderness in the left hypo- chondrium.Later in the day a localized "rub" developed in the left 4th and 5th interspaces, thought at first to be pericardial friction.The blood sugar was 350 mg./100 ml., and there was considerable ketosis.X-ray again showed emphysema at the root of the neck on the right, and in a thin line outside the heart shadow.She made a good recovery, and, still fit, attends the clinic regularly.
Clinical Outcomes of Pregnancies Complicated by Mild Gestational Diabetes Mellitus Differ by Combinations of Abnormal Oral Glucose Tolerance Test Values
Authors: Mary Helen Black, David A. Sacks, Anny H. Xiang, Jean M. Lawrence
Journal: Diabetes Care (2010)

OBJECTIVE To examine the association between levels of hyperglycemia, determined by each prenatal oral glucose tolerance test (OGTT) value (fasting, 1 and 2 h), and maternal and perinatal outcomes and to determine whether the risk for these outcomes differs for women whose value(s) equaled or exceeded the thresholds for gestational diabetes mellitus (GDM) established by the International Association of Diabetes in Pregnancy Study Groups (IADPSG). RESEARCH DESIGN AND METHODS This article discusses a retrospective study of 8,711 women, delivering at ≥20 weeks' gestation, who had a prenatal 2-h 75-g OGTT without a prior 50-g challenge and were not treated with insulin, glyburide, diet, and/or exercise during pregnancy. Associations between adverse outcomes and elevated OGTT values are reported. RESULTS After excluding treated women, 19.4% of the remaining women had IADPSG-defined GDM. Continuous fasting, 1- and 2-h OGTT measures, and GDM (yes/no) were significantly associated with most adverse outcomes. However, the magnitude and significance of risk for these outcomes differed by various combinations of abnormal glucose values. Women with normal fasting and elevated postload values were at higher risk for preterm delivery, gestational hypertension, and having an infant with hyperbilirubinema, whereas women with elevated fasting and normal postload values were at higher risk of having a large-for-gestational-age infant, compared with women without GDM. CONCLUSIONS Risks for different adverse outcomes vary depending on which single or combined IADPSG-defined OGTT thresholds are equaled or exceeded. Prospective studies are needed to determine whether changing pre- and postprandial glucose targets during pregnancy will more uniformly reduce adverse outcomes.
Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA
Authors: Hirotsugu Tabata, Marcy Silver, Jeffrey M Isner
Journal: Cardiovascular Research (1997)

Objective: Previous studies have demonstrated that arterial gene transfer of naked DNA encoding for a secreted protein may permit modulation of the host phenotype despite a low transfection efficiency. Acidic fibroblast growth factor (aFGF) is an angiogenic growth factor, but is not secreted by intact cells. In the current study, we investigated the hypothesis that addition of a hydrophobic leader sequence to achieve active secretion of the gene product would permit therapeutic angiogenesis following arterial gene transfer of naked DNA encoding for aFGF. Methods: Ten days following surgical induction of unilateral hindlimb ischemia, New Zealand white rabbits were randomized to intra-arterial gene transfer with one of three plasmids: p267 (encoding non-secreted aFGF, n = 10), pMJ35 (encoding secreted aFGF) (n = 10), or 500 μg of pGSVLacZ (control, n = 10) (500 μg each). All animals were studied at 30 days post-gene transfer for evidence of therapeutic angiogenesis. Results: pMJ35 transfectants had more angiographically visible collaterals (angiographic score=0.76±0.02) than either p267 (0.55±0.02, p<0.01) or LacZ (0.47±0.02, p<0.001). Limb blood pressure ratio for pMJ35 was 0.88±0.02 vs. 0.68±0.04 for p267 (p<0.01) and 0.57±0.04 for LacZ (p<0.001). Vascular resistance was significantly lower in the pMJ35 group, compared with that in pGSVLacZ group, both in resting state (3.2±0.4 vs. 7.4±1.4 respectively, p<0.05) and after the administration of nitroprusside. Capillary density (per mm2) was also superior in pMJ35 group (274±10) vs. p267 (204±9, p<0.01) and LacZ (177±6, p<0.001). Conclusion: The paracrine effects of a secreted gene product may obviate the need for adjunctive vectors in strategies of arterial gene therapy.
Phase I Study of Temozolomide and Irinotecan for Recurrent Malignant Gliomas in Patients Receiving Enzyme-Inducing Antiepileptic Drugs: A North American Brain Tumor Consortium Study
Authors: Monica E. Loghin, Michael D. Prados, Patrick Wen, Larry Junck, Frank Lieberman, Howard Fine, Karen L. Fink, Minesh Metha, John Kuhn, Kathleen Lamborn, Susan M. Chang, Timothy Cloughesy, Lisa M. DeAngelis, Ian H. Robins, Kenneth D. Aldape, W.K. Alfred Yung
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. Design: Patients with recurrent malignant glioma received a fixed dose of temozolomide (150 mg/m2) daily for 5 days from days 1 to 5 every 28 days, and an i.v. infusion of irinotecan on days 1 and 15 of each cycle. The starting dose of irinotecan was 350 mg/m2, which was escalated to 550 mg/m2 in 50-mg/m2 increments. The plasma pharmacokinetics of irinotecan and its active metabolite, SN-38, were determined during the infusion of irinotecan on cycle 1, day 1. Results: Thirty-three patients were enrolled into the study and treated. Thirty-one patients were evaluable for both tumor response and toxicity and two patients were evaluable for toxicity only. Common toxicities included neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose for irinotecan was determined to be 500 mg/m2. Conclusions: The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m2, administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan.
Novel Mechanism of MDA-7/IL-24 Cancer-Specific Apoptosis through SARI Induction
Authors: Rupesh Dash, Praveen Bhoopathi, Swadesh K. Das, Siddik Sarkar, Luni Emdad, Santanu Dasgupta, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2013)

Abstract Subtraction hybridization combined with induction of cancer cell terminal differentiation in human melanoma cells identified melanoma differentiation–associated gene-7/interleukin-24 (mda-7/IL-24) and SARI (suppressor of AP-1, induced by IFN) that display potent antitumor activity. These genes are not constitutively expressed in cancer cells and forced expression of mda-7/IL-24 (Ad.mda-7) or SARI (Ad.SARI) promotes cancer-specific cell death. Ectopic expression of mda-7/IL-24 induces SARI mRNA and protein in a panel of different cancer cells, leading to cell death, without harming corresponding normal cells. Simultaneous inhibition of K-ras downstream extracellular signal-regulated kinase 1/2 signaling in pancreatic cancer cells reverses the translational block of MDA-7/IL-24 and induces SARI expression and cell death. Using SARI-antisense-based approaches, we demonstrate that SARI expression is necessary for mda-7/IL-24 antitumor effects. Secreted MDA-7/IL-24 protein induces antitumor “bystander” effects by promoting its own expression. Recombinant MDA-7/IL-24 (His-MDA-7) induces SARI expression, supporting the involvement of SARI in the MDA-7/IL-24-driven autocrine loop, culminating in antitumor effects. Moreover, His-MDA-7, after binding to its cognate receptors (IL-20R1/IL-20R2 or IL-22R/IL-20R2), induces intracellular signaling by phosphorylation of p38 MAPK, leading to transcription of a family of growth arrest and DNA damage inducible (GADD) genes, culminating in apoptosis. Inhibition of p38 MAPK fails to induce SARI following Ad.mda-7 infection. These findings reveal the significance of the mda-7/IL-24-SARI axis in cancer-specific killing and provide a potential strategy for treating both local and metastatic disease. Cancer Res; 74(2); 563–74. ©2013 AACR.
Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines
Authors: Tewarit Sarachana, Rulun Zhou, Guang Chen, Husseini K Manji, Valerie W Hu
Journal: Genome Medicine (2010)

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by abnormalities in reciprocal social interactions and language development and/or usage, and by restricted interests and repetitive behaviors. Differential gene expression of neurologically relevant genes in lymphoblastoid cell lines from monozygotic twins discordant in diagnosis or severity of autism suggested that epigenetic factors such as DNA methylation or microRNAs (miRNAs) may be involved in ASD.Global miRNA expression profiling using lymphoblasts derived from these autistic twins and unaffected sibling controls was therefore performed using high-throughput miRNA microarray analysis. Selected differentially expressed miRNAs were confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, and the putative target genes of two of the confirmed miRNA were validated by knockdown and overexpression of the respective miRNAs.Differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases, circadian rhythm signaling, as well as steroid hormone metabolism and receptor signaling. Novel network analyses of the putative target genes that were inversely expressed relative to the relevant miRNA in these same samples further revealed an association with ASD and other co-morbid disorders, including muscle and gastrointestinal diseases, as well as with biological functions implicated in ASD, such as memory and synaptic plasticity. Putative gene targets (ID3 and PLK2) of two RT-PCR-confirmed brain-specific miRNAs (hsa-miR-29b and hsa-miR-219-5p) were validated by miRNA overexpression or knockdown assays, respectively. Comparisons of these mRNA and miRNA expression levels between discordant twins and between case-control sib pairs show an inverse relationship, further suggesting that ID3 and PLK2 are in vivo targets of the respective miRNA. Interestingly, the up-regulation of miR-23a and down-regulation of miR-106b in this study reflected miRNA changes previously reported in post-mortem autistic cerebellum by Abu-Elneel et al. in 2008. This finding validates these differentially expressed miRNAs in neurological tissue from a different cohort as well as supports the use of the lymphoblasts as a surrogate to study miRNA expression in ASD.Findings from this study strongly suggest that dysregulation of miRNA expression contributes to the observed alterations in gene expression and, in turn, may lead to the pathophysiological conditions underlying autism.
Polymorphism in the β <sub>1</sub> -Adrenergic Receptor Gene and Hypertension
Authors: Kristina Bengtsson, Olle Melander, Marju Orho-Melander, Ulf Lindblad, Jonas Ranstam, Lennart Råstam, Leif Groop
Journal: Circulation (2001)

Background — The Arg389 variant of the β 1 -adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results — A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele was 1.9 (95% confidence interval, 1.3 to 2.7; P =0.0005) when compared with carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling pair analysis revealed that siblings homozygous for the Arg389 allele had significantly higher diastolic blood pressures (79.4±9.9 versus 76.0±10.1 mm Hg; P =0.003) and higher heart rates (68.3±11.0 versus 65.1±9.4 bpm; P =0.02) than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly polymorphism was not associated with hypertension. Conclusion — Our data suggest that individuals homozygous for the Arg389 allele of the β 1 -adrenergic receptor gene are at increased risk to develop hypertension.
Jaundice From Diabetes Therapy
Authors: Anja Hieronimus, Reinhild Klein, Hans-Ulrich Häring, Andreas Fritsche, Robert Wagner
Journal: Diabetes Care (2014)

In January 2013, a 41-year-old man presented for follow-up to our diabetes unit with jaundice, fatigue, dark urine, and stool discoloration. Four weeks earlier, he had suffered a sudden sensorineural hearing loss and was treated with a prednisolone taper scheme starting with 250 mg q.i.d. in addition to α-lipoic acid. Fasting hyperglycemia (274 mg/dL) was detected after initiation of the therapy. Further laboratory workup revealed a preexisting type 2 diabetes (HbA1c 11.8% [105 mmol/mol], no GAD2 antibodies). Transaminases were normal. Insulin glargine and metformin 500 mg t.i.d. were initiated.

Upon follow-up, the patient reported that fatigue and yellow sclera manifested 4 days before. Thereafter, he stopped taking his medication. Physical examination was unremarkable except for jaundice. Total bilirubin was 18.1 mg/dL, aspartate aminotransferase 419 units/L, alanine aminotransferase 863 units/L, alkaline phosphatase 479 units/L, and γ-glutamyl transferase 2,181 units/L. Differential blood count was normal apart from mild eosinophilia (5.7%). The patient had no history of gastrointestinal …
Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes
Authors: M J Rood, V Keijsers, M W van der Linden, T Q T Tong, S E Borggreve, C L Verweij, F C Breedveld, T W J Huizinga
Journal: Annals of the Rheumatic Diseases (1999)

To investigate the association of interleukin 10 (IL10) promoter polymorphisms and neuropsychiatric manifestations of systemic lupus erythematosus (SLE).IL10 haplotypes of 11 healthy volunteers were cloned to confirm that in the Dutch population, only the three common haplotypes (-1082/-819/-592) GCC, ACC and ATA exist. The IL10 promoter polymorphisms of 92 SLE patients and 162 healthy controls were determined. The medical records of the SLE patients were screened for the presence of neuropsychiatric involvement.All cloned haplotypes were either GCC, ACC or ATA. Forty two SLE patients had suffered from neuropsychiatric manifestations (NP-SLE). In NP-SLE patients, the frequency of the ATA haplotype is 30% versus 18% in the controls and 17% in the non-NP-SLE group (odds ratios 1.9, p = 0.02, and 2.1, p = 0.04, respectively), whereas the GCC haplotype frequency is lower in the NP-SLE group compared with controls and non-NP-SLE patients (40% versus 55% and 61%, odds ratios 0.6, p = 0.02 and 0.4 p = 0.006). The odds ratio for the presence of NP-SLE is inversely proportional to the number of GCC haplotypes per genotype when the NP-SLE group is compared with non-NP-SLE patients.The IL10 locus is associated with neuropsychiatric manifestations in SLE. This suggests that IL10 is implicated in the immunopathogenesis of neuropsychiatric manifestations in SLE.
THE INFLUENCE OF OVARIECTOMY ON THE SPONTANEOUS OCCURRENCE OF MAMMARY CARCINOMAS IN MICE
Authors: Carl F. Cori
Journal: The Journal of Experimental Medicine (1927)

1. Castration of female mice between 15 and 22 days of age entirely prevented the occurrence of spontaneous adenocarcinoma of the breast, while the non-breeding control mice of the same strain showed a tumor incidence of 78.5 per cent. 3 of the spayed animals developed a spontaneous spindle cell sarcoma. This indicates that the influence of the ovary on the development of breast carcinomas is a specific one, since ovariectomy does not lead to a resistance against other types of spontaneous tumors. 2. Castration between 2 and 6 months of age led to a marked reduction of the tumor incidence, but did not entirely prevent the occurrence of mammary tumors. 3. It is concluded that the spontaneous mammary carcinoma of the mouse is due to a hereditary organ disposition, which remains latent in the absence of ovarian function, but which becomes manifest when a certain amount of ovarian hormone, corresponding to 5 to 30 estrus cycles, has acted on the breast tissue.
Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies
Authors: Achim J. Kaasch, Gavin Barlow, Jonathan D. Edgeworth, Vance G. Fowler, Martin Hellmich, Susan Hopkins, Winfried V. Kern, Martin J. Llewelyn, Siegbert Rieg, Jesús Rodriguez-Baño, Matthew Scarborough, Harald Seifert, Alex Soriano, Robert Tilley, M. Estée Tőrők, Verena Weiß, A.Peter R. Wilson, Guy E. Thwaites
Journal: Journal of Infection (2013)
Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor expression via activation of nuclear factor- B
Authors: Y Sato, J Kato, R Takimoto, K Takada, Y Kawano, K Miyanishi, M Kobune, Y Sato, T Takayama, T Matunaga, Y Niitsu
Journal: Gut (2006)

Hepatitis C virus (HCV) infection is a major cause of human hepatocellular carcinoma (HCC). The precise mechanism of hepatocarcinogenesis in humans by HCV is currently unclear. It was recently shown, however, that transgenic mice with the HCV core gene often develop HCC, suggesting tumorigenic activity of the HCV core protein. Further, the HCV core protein expressed in HepG2 cells transfected with the core gene was shown to stimulate proliferation of transfectants through activation of nuclear factor-kappaB (NF-kappaB). The downstream target molecule(s) of NF-kappaB activated by the HCV core protein to evoke cell proliferation is not yet identified. Transforming growth factor (TGF) alpha, which is often overexpressed in various tumour tissues such as HCC, has been shown to stimulate hepatocyte proliferation through activation of the mitogen-activated protein kinase or extracellular signal-related protein kinase (MAPK/ERK) cascade.To explore the possibility that TGFalpha might be a target molecule for NF-kappaB activated by the HCV core, and that TGFalpha participates in the growth promotion of the core transfectants in an autocrine manner, activating the MAPK/ERK pathway.A HCV core expression vector was transfected into human hepatoma Huh-7, HepG2 and Hep3B cells. NF-kappaB activity was examined by an electrophoretic mobility shift assay. TGFalpha transcription was assessed by a luciferase reporter assay. TGFalpha protein was determined by immunoblot and ELISA. MAPK/ERK activity was examined by an in vitro kinase assay. Cell proliferation was assessed by a water-soluble tetrazolium salt-1 assay.In the HCV core transfectants, NF-kappaB bound to the kappaB site in the TGFalpha proximal promoter region, resulting in an increase in TGFalpha transcription. Immunoblot as well as ELISA showed increased TGFalpha expression in the HCV core transfectants. SN50, a specific inhibitory peptide for NF-kappaB, cancelled HCV core-induced TGFalpha expression. HCV core protein increased cell proliferation as well as ERK activity of the HCV core transfectants as compared with the mock transfectants. The growth-promoting activity and activation of ERK by the HCV core protein were negated by treatment with anti-TGFalpha antibodies.These results suggest that the HCV core protein promotes proliferation of human hepatoma cells by activation of the MAPK/ERK pathway through up regulation of TGFalpha transcription via activation of NF-kappaB. Our finding provides a new insight into the mechanism of hepatocarcinogenesis by HCV infection.