tbuckley/cabot-search huggingface dataset:
A Distinct p53 Protein Isoform Signature Reflects the Onset of Induction Chemotherapy for Acute Myeloid Leukemia
Authors: Nina Anensen, Anne Margrete Oyan, Jean-Christophe Bourdon, Karl Henning Kalland, Oystein Bruserud, Bjorn Tore Gjertsen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The antioncogene protein product p53 has not been studied previously in cancer patients during in vivo chemotherapy. This study examined the early p53 protein and gene expression during induction chemotherapy in acute myeloid leukemia (AML). Experimental Design: Leukemic cells were collected from five AML patients during their first 18 hours of induction chemotherapy and examined for p53 protein and gene expression by one- and two-dimensional gel immunoblot and high-density gene expression arrays. Results: Up-regulation of p53 protein expression was detected in AML patients posttreatment in vivo. One- and two-dimensional gel immunoblots showed two main forms of p53, denominated αp53 and Δp53, both recognized by various NH2-terminal directed antibodies. As a response to treatment, we detected rapid accumulation of αp53, with significantly altered protein expression levels already after 2 hours. The accumulation of αp53 was accompanied by increased transcription of putative p53 target genes and subsequent cytopenia in the patients. Conclusion: Up-regulation of the p53 protein and target genes seems to be a prominent feature in induction chemotherapy of AML. The rapid shift from a shorter p53 protein form (Δ) toward the full-length protein (α) underscores the complexity of p53 protein modulation in patients undergoing chemotherapy.
Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice.
Authors: R Bruck, H Shirin, R Hershkoviz, O Lider, G Kenet, H Aeed, Z Matas, L Zaidel, Z Halpern
Journal: Gut (1997)

BACKGROUND/AIMS: It has been shown that synthetic non-peptidic analogues of Arg-Gly-Asp, a major cell adhesive ligand of extracellular matrix, prevented an increase in serum aminotransferase activity, as a manifestation of concanavalin A induced liver damage in mice. This study examined the effects of an Arg-Gly-Asp mimetic on liver histology and cytokine release in response to concanavalin A administration, and the efficacy of soluble receptor of tumour necrosis factor (TNF) alpha in preventing hepatitis in this model of liver injury. METHODS: Mice were pretreated with either the Arg-Gly-Asp mimetic SF-6,5 or recombinant soluble receptor of TNF alpha before their inoculation with 10 mg/kg concanavalin A. Liver enzymes, histology, and the serum values of TNF alpha and interleukin (IL)6 were examined. RESULTS: The histopathological damage in the liver, and the concanavalin A induced release of TNF alpha and IL6 were significantly inhibited by the synthetic Arg-Gly-Asp mimetic (p &lt; 0.001). Liver injury, manifested by the increase in serum aminotransferase and cytokines, as well as by histological manifestations of hepatic damage, was effectively prevented by pretreatment of the mice with the soluble TNF receptor (p &lt; 0.001). CONCLUSIONS: This study confirms the efficacy of a synthetic Arg-Gly-Asp mimetic and soluble TNF receptor in the prevention of immune mediated liver damage in mice.
Antibody-specific immunoregulation
Authors: SK Pierce, NR Klinman
Journal: The Journal of Experimental Medicine (1977)

In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.
What about IgA rheumatoid factor in rheumatoid arthritis?
Authors: T. JONSSON, H. VALDIMARSSON;, J. AXFORD, A. SOLTYS
Journal: Annals of the Rheumatic Diseases (1998)

We read with interest the editorial by Soltys and colleagues about rheumatoid factors (RFs).1 They correctly stated that most naturally occurring RFs were of the IgM isotype while IgG RFs were thought to be associated with rhematoid arthritis (RA). It should be pointed out in this context that it is very difficult to measure IgG RF and this RF isotype can only be detected in approximately 50% of RA patients whereas IgA RF, usually in combination with IgM RF, can be detected in most patients with seropositive RA.2-4 It should also be noted that increased IgA RF is associated with severe manifestations in RA and this has been extensively reported by several different groups in the last 15 years.5-10 

Furthermore, several reports have shown that RFs may be increased in serum many months or even years before clinical symptoms …
What is the evidence for our standards of care?
Authors: Laurence A. Turka, Arthur Caplan
Journal: Journal of Clinical Investigation (2011)

The term evidence-based medicine is overused, abused, and is beginning to ring hollow. It is not that evidence (or at least of what most people in biomedicine think evidence-based medicine should strive to be) is a bad thing. Rather, there is more rhetoric about evidence than there is actual evidence to support the degree of talk.
US medical schools should consider race in admitting students
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Medical schools should continue to consider race when admitting students despite recent US court decisions against “affirmative action” (positive discrimination), said Dr Jordan Cohen, president of the Association of American Medical Colleges, which represents all 125 medical schools in the United States.

Affirmative action benefits the profession and patients and is particularly timely because of efforts to make it unlawful to consider race when making admissions decisions, he wrote in an article in Health Affairs (2002;21:90-102)

A more diverse medical profession would improve cultural competency (understanding the beliefs and language of patients), increase patients' access …
Psychometric Properties, Norms, and Factor Structure of the Diabetes Eating Problem Survey–Revised in a Large Sample of Children and Adolescents With Type 1 Diabetes
Authors: Line Wisting, Dag Helge Frøisland, Torild Skrivarhaug, Knut Dahl-Jørgensen, Øyvind Rø
Journal: Diabetes Care (2013)

OBJECTIVE The purpose of this study was to examine the psychometric properties of the Diabetes Eating Problem Survey–Revised (DEPS-R) in a large sample of young patients with type 1 diabetes, to establish norms, and to validate it against the Eating Attitudes Test–12 (EAT-12). RESEARCH DESIGN AND METHODS A total of 770 children and adolescents aged 11–19 years with type 1 diabetes completed the DEPS-R and the EAT-12. In addition, age- and sex-standardized BMI and HbA1c data were obtained from the Norwegian Childhood Diabetes Registry. In addition to tests of validity, principal axis factoring was conducted to investigate the factor structure of the 16-item DEPS-R. RESULTS The DEPS-R demonstrated satisfactory Cronbach α (0.89) and was significantly correlated with the EAT-12 (0.65; P &amp;lt; 0.01), indicating convergent validity. The mean (SD) DEPS-R scores were 11.0 (10.7) for the total sample and 7.7 (7.4) and 14.2 (2.4) for males and females, respectively. CONCLUSIONS This study replicates and extends previous research demonstrating the psychometric properties of the abbreviated 16-item DEPS-R. Findings support the utility of this important screening tool to identify disturbed eating in young patients with type 1 diabetes.
The cytotoxic effect of neonatal lupus erythematosus and maternal sera on keratinocyte cultures is complement-dependent and can be augmented by ultraviolet irradiation
Authors: H.-S. YU, L.-C. CHIANG, C.-H. CHANG, J.-W. KANG, C.-L. YU
Journal: British Journal of Dermatology (1996)

To elucidate the role of autoantibodies and ultraviolet (UV) exposure in the pathogenesis of the skin lesions in neonatal lupus erythematosus (NLE), keratinocytes were cultured, as the target cells, from a patient with NLE and from a normal neonate. We demonstrated that the expression of nuclear/cytoplasmic Ro/SSA and La/SSB molecules on to the surface of NLE keratinocytes occurred to a much greater extent than that on normal keratinocytes. A dose of 200 mJ/cm2 UVB irradiation on NLE keratinocytes induced a 2.5-3-fold increase in Ro/SSA and La/SSB expression compared to non-irradiated cells. Sera derived from both the NLE patient and from his mother exhibited a cytotoxic effect on NLE keratinocytes, but not on control cells, in the presence of complement. Furthermore, the cytotoxicity of the sera was enhanced on UVB-irradiated NLE keratinocytes, whereas it had no cytotoxic effects on UVB-irradiated control cells. This suggests that the abnormal expression of both Ro/SSA and La/SSB on the surface membrane of NLE keratinocytes induces the autoantibodies and complements to injure the cells. This complement-mediated cytotoxic effect can be augmented by UV irradiation, a concept not incompatible with the exacerbation of the skin eruption in sun-exposed skin sites.
Introduction to the 5th World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy)
Authors: Itamar Raz, William T. Cefalu, Hasan Ilkova, Stefano Del Prato
Journal: Diabetes Care (2016)

The recent increase in the number and variety of pharmacological agents for the treatment of diabetes and hypertension has created enormous challenges that in the past were unknown in clinical practice. These therapies aim to modify complex underlying pathologies, but do they ultimately promote health and prolong lives? The practicing clinician faces the daunting task of balancing the benefits of such therapies against their potential risks in the short and long term.

It is well known that along with reaching therapeutic targets and modifying pathologies, each therapy has side effects. One typical example is that of antidiabetes medications, which can lead to weight gain and hypoglycemia while requiring close monitoring that affects the patient’s quality of life and raises the cost of treatment. Lately, the “art” of treating diabetes has presented physicians with particularly complex decisions concerning side effects. Studies published in the years 2007–2010 have shown that drugs can positively affect surrogate markers in the short term but prove to be damaging in the long term because of known as well as still unrecognized side effects (1,2). In other words, a short-term positive response to therapy does not necessarily entail a positive outcome in the long term. As for new drugs, such as those from the incretin family, the risk of acute pancreatitis has not yet definitively been ruled out and these drugs have yet to be evaluated for other risks as well as cardiovascular safety.

Challenging decisions also concern the appropriate degree of modification for pathologies commonly associated with diabetes. Epidemiological studies have clearly demonstrated that obesity and hypertension, as well as fasting and, particularly, postprandial hyperglycemia, are associated with late micro- and macrovascular complications, hence the pursuit of near-normalization of these parameters. This indication may, however, not be valid for every diabetic patient, as recent …
The Two Components of the Human Atrial Action Potential
Authors: Alexandre Fabiato, Fran$$$oise Fabiato
Journal: Circulation Research (1971)

Action potentials studied in 36 human atrial strips at 27°C were found to be separated into two components. Simultaneous recordings with two microelectrodes demonstrated an independent conduction of the second component through selective and variable pathways. Increased separation of the two components was elicited by higher rate and lower intensity of stimulation, high K + , low Ca 2+ hypertonic solutions as well as by low temperature. Opposite procedures resulted in a more homogeneous and less variable excitation. Consequently, low rate and high intensity of stimulation allowed the study of the membrane permeabilities related to the two successive depolarizations. The first was suppressed by tetrodotoxin, the second by MnCl 2 and both by low Na + solutions. Hence, it was concluded that the separation was related to a nonhomogeneous excitation of the preparation and that the two components are triggered by two relatively independent depolarizations using different channels. Furthermore, the small amplitude of the first depolarization, without overshoot, and its modifications with stimulation intensity suggest that it might be due to an electrotonic spread or to a junctional mechanism.
Scambio, a novel guanine nucleotide exchange factor for Rho.
Authors: Christina Curtis, Bianca Hemmeryckx, Leena Haataja, Dinithi Senadheera, John Groffen, Nora Heisterkamp
Journal: Molecular Cancer (2004)

Small GTPases of the Rho family are critical regulators of various cellular functions including actin cytoskeleton organization, activation of kinase cascades and mitogenesis. For this reason, a major objective has been to understand the mechanisms of Rho GTPase regulation. Here, we examine the function of a novel protein, Scambio, which shares homology with the DH-PH domains of several known guanine nucleotide exchange factors for Rho family members. Scambio is located on human chromosome 14q11.1, encodes a protein of around 181 kDa, and is highly expressed in both heart and skeletal muscle. In contrast to most DH-PH-domain containing proteins, it binds the activated, GTP-bound forms of Rac and Cdc42. However, it fails to associate with V14RhoA. Immunofluorescence studies indicate that Scambio and activated Rac3 colocalize in membrane ruffles at the cell periphery. In accordance with these findings, Scambio does not activate either Rac or Cdc42 but rather, stimulates guanine nucleotide exchange on RhoA and its close relative, RhoC. Scambio associates with Rac in its activated conformation and functions as a guanine nucleotide exchange factor for Rho.
Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy?
Authors: Ivo P. Touw, Marijke Bontenbal
Journal: JNCI Journal of the National Cancer Institute (2007)

Granulocyte colony-stimulating factor (G-CSF), the major cytokine involved in the control of neutrophil production, is used in the clinic for treatment of congenital and acquired neutropenias and to reduce febrile neutropenia before or during courses of intensive cytoreductive therapy. In addition, healthy stem cell donors are treated with G-CSF for mobilization of hematopoietic stem cells in the peripheral blood. Recent studies have uncovered novel roles for G-CSF in myocardial regeneration following cardiac infarction ( 1 – 3 ) and in ameliorating programmed cell death in neuronal cells caused by acute ischemic stroke, thereby reducing the volume of the brain infarct ( 4 ). Thus, it may be anticipated that the therapeutic application of G-CSF will increase considerably in the near future, making careful and timely risk assessment of vital importance. In this issue of the Journal, Hershman et al. ( 5 ) report a two fold increased risk of secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients who received G-CSF (or granulocyte-macrophage CSF) during adjuvant chemotherapy, compared with patients who did not receive growth factor treatment. This and other recent studies raise questions concerning the underlying molecular and cellular mechanisms whereby myeloid growth factors would initiate or accelerate the development of MDS/AML and how to deal with the potential
Diabetes, Hyperglycemia, and Inflammation in Older Individuals
Authors: Nathalie de Rekeneire, Rita Peila, Jingzhong Ding, Lisa H. Colbert, Marjolein Visser, Ronald I. Shorr, Stephen B. Kritchevsky, Lewis H. Kuller, Elsa S. Strotmeyer, Ann V. Schwartz, Bruno Vellas, Tamara B. Harris
Journal: Diabetes Care (2006)

The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT]) and diabetes in older individuals.Baseline data from the Health, Aging and Body Composition study included 3,075 well-functioning black and white participants, aged 70-79 years.Of the participants, 24% had diabetes and 29% had IFG/IGT at baseline. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels (P < 0.001) were significantly higher among diabetic participants and those with IFG/IGT. Odds of elevated IL-6 and TNF-alpha (>75th percentile) were, respectively, 1.95 (95% CI 1.56-2.44) and 1.88 (1.51-2.35) for diabetic participants and 1.51 (1.21-1.87) and 1.14 (0.92-1.42) for those with IFG/IGT after adjustment for age, sex, race, smoking, alcohol intake, education, and study site. Odds ratios for elevated CRP were 2.90 (2.13-3.95) and 1.45 (1.03-2.04) for diabetic women and men and 1.33 (1.07-1.69) for those with IFG/IGT regardless of sex. After adjustment for obesity, fat distribution, and inflammation-related conditions, IL-6 remained significantly related to both diabetes and IFG/IGT. CRP in women and TNF-alpha in both sexes were significantly related to diabetes, respectively, whereas risk estimates for IFG/IGT were decreased by adjustment for adiposity. Among diabetic participants, higher levels of HbA(1c) were associated with higher levels of all three markers of inflammation, but only CRP remained significant after full adjustment.Our findings show that dysglycemia is associated with inflammation, and this relationship, although consistent in diabetic individuals, also extends to those with IFG/IGT.
Molecular Classification and Prognostication of Adrenocortical Tumors by Transcriptome Profiling
Authors: Thomas J. Giordano, Rork Kuick, Tobias Else, Paul G. Gauger, Michelle Vinco, Juliane Bauersfeld, Donita Sanders, Dafydd G. Thomas, Gerard Doherty, Gary Hammer
Journal: Clinical Cancer Research (2009)

Our understanding of adrenocortical carcinoma (ACC) has improved considerably, yet many unanswered questions remain. For instance, can molecular subtypes of ACC be identified? If so, what is their underlying pathogenetic basis and do they possess clinical significance?We did a whole genome gene expression study of a large cohort of adrenocortical tissues annotated with clinicopathologic data. Using Affymetrix Human Genome U133 Plus 2.0 oligonucleotide arrays, transcriptional profiles were generated for 10 normal adrenal cortices (NC), 22 adrenocortical adenomas (ACA), and 33 ACCs.The overall classification of adrenocortical tumors was recapitulated using principal component analysis of the entire data set. The NC and ACA cohorts showed little intragroup variation, whereas the ACC cohort revealed much greater variation in gene expression. A robust list of 2,875 differentially expressed genes in ACC compared with both NC and ACA was generated and used in functional enrichment analysis to find pathways and attributes of biological significance. Cluster analysis of the ACCs revealed two subtypes that reflected tumor proliferation, as measured by mitotic counts and cell cycle genes. Kaplan-Meier analysis of these ACC clusters showed a significant difference in survival (P < 0.020). Multivariate Cox modeling using stage, mitotic rate, and gene expression data as measured by the first principal component for ACC samples showed that gene expression data contains significant independent prognostic information (P < 0.017).This study lays the foundation for the molecular classification and prognostication of adrenocortical tumors and also provides a rich source of potential diagnostic and prognostic markers.
Ranitidine--a new H2-receptor antagonist.
Authors: E P Woodings, G T Dixon, C Harrison, P Carey, D A Richards
Journal: Gut (1980)

The pharmacokinetics and gastric antisecretory effects of a new histamine H2-receptor antagonist, ranitidine hydrochloride, have been investigated in healthy subjects. In the pharmacokinetic study six subjects received 20 mg, 40 mg, and 80 mg ranitidine, both orally and intravenously. Plasma levels of ranitidine were dose-related and in most subjects after oral drug the concentration time curve was bimodal. The estimated elimination half-life was 140 minutes and the bioavailability of the oral drug was about 50%. Five subjects received bolus intravenous injections of ranitidine 20 mg, 40 mg, and 80 mg during continuous gastric stimulation with pentagastrin. There was a dose-related reduction in acid output (P less than 0.05).