tbuckley/cabot-search huggingface dataset:
Widespread Occurrence of N-Terminal Acylation in Animal Globins and Possible Origin of Respiratory Globins from a Membrane-Bound Ancestor
Authors: Miriam Blank, Thorsten Burmester
Journal: Molecular Biology and Evolution (2012)

Proteins of the (hemo-)globin superfamily have been identified in many different animals but also occur in plants, fungi, and bacteria. Globins are renowned for their ability to store and to transport oxygen, but additional globin functions such as sensing, signaling, and detoxification have been proposed. Recently, we found that the zebrafish globin X protein is myristoylated and palmitoylated at its N-terminus. The addition of fatty acids results in an association with the cellular membranes, suggesting a previously unrecognized globin function. In this study, we show that N-terminal acylation likely occurs in globin proteins from a broad range of phyla. An N-terminal myristoylation site was identified in 90 nonredundant globins from Chlorophyta, Heterokontophyta, Cnidaria, Mollusca, Arthropoda, Nematoda, Echinodermata, Hemichordata, and Chordata (including Cephalochordata), of which 66 proteins carry an additional palmitoylation site. Bayesian phylogenetic analyses identified five major globin families, which may mirror the ancient globin diversity of the Metazoa. Globin X-like proteins form two related clades, which diverged before the radiation of the Eumetazoa. Vertebrate hemoglobin (Hb), myoglobin, cytoglobin, globin E, and globin Y form a strongly supported common clade, which is the sister group of a clade consisting of invertebrate Hbs and relatives. The N-terminally acylated globins do not form a single monophyletic group but are distributed to four distinct clades. This pattern may be either explained by multiple introduction of an N-terminal acylation site into distinct globin lineages or by the origin of animal respiratory globins from a membrane-bound ancestor. Similarly, respiratory globins were not monophyletic. This suggests that respiratory globins might have emerged independently several times and that the early metazoan globins might have been associated with a membrane and carried out a function that was related to lipid protection or signaling.
CHARACTERISTICS OF A NON-COMPLEMENT-DEPENDENT C3-REACTIVE COMPLEX FORMED FROM FACTORS IN NEPHRITIC AND NORMAL SERUM
Authors: Enrique H. Vallota, Judith Forristal, Roger E. Spitzer, Neil C. Davis, Clark D. West
Journal: The Journal of Experimental Medicine (1970)

When serum from a patient with membrano-proliferative glomerulonephritis and normal serum are mixed at 37 degrees C, C3 is rapidly broken down to two more rapidly migrating components. In the mixture, a heat-labile pseudoglobulin, designated as the C3 nephritic factor or C3NeF, reacts with a pseudogolbulin in the normal serum, designated as cofactor, to form a C3 inactivator. By analogy with the cobra venom factor, the C3 inactivator is most likely a complex of the nephritic factor and cofactor. The complex has been designated as the C3 lytic nephritic factor or C3LyNeF. The reaction which results in the Formation of C3LyNeF requires the presence of Mg(++), is highly temperature sensitive but occurs very rapidly at 37 degrees C. In 20 min at 37 degrees C, C3LyNeF can break down over 80% of the C3 in a mixture of normal and nephritic serum. The two-step reaction which leads to C3 breakdown has an optimum pH ranging from 6.0 to 9.0. Experiments employing serum depleted of C4 and C2, as well as certain characteristics of the C3NeF system provide evidence that C3 breakdown with nephritic serum is not dependent on complement-inactivating immune complexes or on the action of convertase (C4, 2). Data relating rate of C3 breakdown to the concentrations of C3NeF, C3, and C3LyNeF in the reaction mixture are similar to those for the reaction of enzyme with substrate. The biological significance of C3LyNeF in the production of glomerular inflammation has not been established.
Risk Imparted by Various Parameters of Smoking in Japanese Men With Type 2 Diabetes on Their Development of Microalbuminuria
Authors: Kazumi Saito, Hirohito Sone, Koichi Kawai, Shiro Tanaka, Satoru Kodama, Miao Shu, Emiko Suzuki, Kazuo Kondo, Shigeru Yamamoto, Hitoshi Shimano, Yasuo Ohashi, Nobuhiro Yamada
Journal: Diabetes Care (2007)

Whether smoking is an independent risk factor for the development of microalbuminuria has yet to be established. Inconsistencies in previous studies (1–12) might have been due to inadequacies in assessing smoking status of patients (i.e., current, ex-, or never) (13). Moreover, although detailed quantitative assessment is critical for evaluating smoking risks (14), the dose effect of smoking on the development of nephropathy is not known (13). Therefore, we examined a wide variety of smoking parameters to clarify their relationship to microalbuminuria in a cohort of Japanese patients with type 2 diabetes.

Data were derived from the ongoing Tsukuba Kawai Diabetes Registry database of the Kawai Clinic, which began collecting patient information in 1995. The Kawai Clinic is a typical diabetes clinic located in a suburb of Tokyo. All type 2 diabetic patients were consecutively registered for this study at their first visit. Study protocol was consistent with the Japanese Government's Ethical Guidelines Regarding Epidemiological Studies in accordance with the Declaration of Helsinki. Data from 357 normoalbuminuric male patients with type 2 diabetes (diagnosed according to the World Health Organization criteria [14]) who had been followed for at least 3 years were analyzed. No data from female patients were included because their smoking frequency was quite low (9.4%). Patients were said to be normoalbuminuric if …
A History of the Concept of Neurosis, with a Memoir of William Cullen
Authors: WILLIAM F. KNOFF
Journal: American Journal of Psychiatry (1970)

In the continuing effort to translate clinical observations into more accurate nosological metaphors, the term "neurosis" has been remarkably long-lived. The author seeks an explanation for its durability in tracing the historical vicissitudes of its use, from William Cullen, who introduced it, to Freud and the 20th century.
Anticytokine Autoantibody–Associated Immunodeficiency
Authors: Sarah K. Browne
Journal: Annual Review of Immunology (2014)

Anticytokine autoantibodies are an emerging mechanism of disease in previously healthy adults. Patients with these syndromes demonstrate a unique infectious phenotype associated with neutralizing autoantibodies that target a specific cytokine. Examples include anti-interferon (IFN)-γ autoantibodies and disseminated nontuberculous mycobacteria; anti-granulocyte macrophage colony-stimulating factor autoantibodies and cryptococcal meningitis; anti-interleukin (IL)-6 autoantibodies and staphylococcal skin infection; and anti-IL-17A, anti-IL-17F, or anti-IL-22 autoantibodies and mucocutaneous candidiasis in the setting of either APECED (autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy syndrome) or thymoma. Other anticytokine autoantibodies may contribute to an infectious phenotype such as anti-granulocyte colony stimulating factor and anti-IFN-α autoantibodies, although the strength of the association is less clear. Their identification not only affects disease management but also may uncover key mechanisms of host defense against specific organisms. Furthermore, it raises the possibility that currently idiopathic diseases will someday be explained by a yet unidentified anticytokine autoantibody. This review focuses on the current understanding, both clinical and mechanistic, of anticytokine autoantibody-associated immunodeficiency.
Prognostic Factors for the Outcome of Chemotherapy in Advanced Soft Tissue Sarcoma: An Analysis of 2,185 Patients Treated With Anthracycline-Containing First-Line Regimens—A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study
Authors: M. Van Glabbeke, A.T. van Oosterom, J.W. Oosterhuis, H. Mouridsen, D. Crowther, R. Somers, J. Verweij, A. Santoro, J. Buesa, T. Tursz
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. PATIENTS AND METHODS: Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. RESULTS: Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P &lt; .05 for all log-rank and χ 2 tests). The Cox model selected good performance status (P &lt; .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P &lt; .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. CONCLUSION: This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.
Racial Composition of Hospitals: Effects on Surgery for Early-Stage Non–Small-Cell Lung Cancer
Authors: Christopher S. Lathan, Bridget A. Neville, Craig C. Earle
Journal: Journal of Clinical Oncology (2008)

Purpose Black patients undergo potentially curative surgery for early-stage lung cancer at a lower rate when compared with white patients. Our study examines the relationship between the percentage of black patients treated at a hospital to determine whether it affects the likelihood of obtaining cancer-directed surgery for patients with non–small-cell lung cancer (NSCLC). Patients and Methods We examined claims data of Medicare-eligible patients with nonmetastatic NSCLC living in areas monitored by the Surveillance, Epidemiology, and End Results program between 1991 and 2001. Hospitals were categorized by the percentage of black patients seen: ≤ 8%, more than 8% to 29%, and ≥ 30%. Logistic regression with clustering analysis was used to calculate the odds of undergoing surgical resection. Results Among 9,688 patients with NSCLC, 59% of white patients were seen at a hospital that had ≤ 8% black patients, whereas 60% of black patients were seen in hospitals that had ≥ 30% black patients. Regression analysis revealed that hospital racial composition of 30% or greater black patients had a significant negative effect on the likelihood of undergoing surgery for all patients (odds ratio [OR] = 0.71; 95% CI, 0.57 to 0.87), with black race (OR = 0.69; 95% CI, 0.56 to 0.85) and being seen at a low-volume hospital (OR = 0.64; 95% CI, 0.0.49 to 0.83) having a significant negative impact on likelihood of undergoing surgery. Conclusion Our study results indicate that patient and hospital characteristics are significant predictors of undergoing surgery for Medicare beneficiaries with localized lung cancer. Further examination of the role of the patient-, provider-, and hospital-level factors, in association with the decision to pursue surgical treatment of localized lung cancers, is needed.
Features of Alagille Syndrome in 92 Patients: Frequency and Relation to Prognosis
Authors: Karan M. Emerick, Elizabeth B. Rand, Elizabeth Goldmuntz, Ian D. Krantz, Nancy B. Spinner, David A. Piccoli
Journal: Hepatology (1999)

We have studied 92 patients with Alagille syndrome (AGS) to determine the frequency of clinical manifestations and to correlate the clinical findings with outcome. Liver biopsy specimens showed paucity of the interlobular ducts in 85% of patients. Cholestasis was seen in 96%, cardiac murmur in 97%, butterfly vertebrae in 51%, posterior embryotoxon in 78%, and characteristic facies in 96% of patients. Renal disease was present in 40% and intracranial bleeding or stroke occurred in 14% of patients. The presence of intracardiac congenital heart disease was the only clinical feature statistically associated with increased mortality ( P &lt; .001). Initial measures of hepatic function in infancy including absence of scintiscan excretion were not predictive of risk for transplantation or increased mortality. The hepatic histology of these AGS patients showed a significant increase in the prevalence of bile duct paucity ( P = .002) and fibrosis ( P &lt; .001) with increasing age. Liver transplantation for hepatic decompensation was necessary in 21% (19 of 92) of patients with 79% survival 1–year posttransplantation. Current mortality is 17% (16 of 92). The factors that contributed significantly to mortality were complex congenital heart disease (15%), intracranial bleeding (25%), and hepatic disease or hepatic transplantation (25%). The 20–year predicted life expectancy is 75% for all patients, 80% for those not requiring liver transplantation, and 60% for those who required liver transplantation.
Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice
Authors: Tahar Hajri, Xiao Xia Han, Arend Bonen, Nada A. Abumrad
Journal: Journal of Clinical Investigation (2002)

Deficiency of the membrane protein FAT/CD36 causes a marked defect in fatty acid uptake by various tissues and is genetically linked to insulin resistance in rats and humans. Here, we examined insulin responsiveness of CD36–/– mice. When fed a diet high in complex carbohydrates and low (5%) in fat, these animals cleared glucose faster than the wild-type. In vivo, uptake of 2-fluorodeoxyglucose by muscle was increased severalfold, and in vitro, insulin responsiveness of glycogenesis by the soleus was enhanced. Null mice had lower glycogen levels in muscle and liver, lower muscle triglyceride levels, and increased liver triglyceride content—all findings consistent with increased insulin-sensitivity. However, when the chow diet was switched to one high in fructose, CD36–/– mice but not wild-type mice developed marked glucose intolerance, hyperinsulinemia, and decreased muscle glucose uptake. High-fat diets impaired glucose tolerance equally in both groups, although CD36 deficiency helped moderate insulin-responsive muscle glucose oxidation. In conclusion, CD36 deficiency enhances insulin responsiveness on a high-starch, low-fat diet. It predisposes to insulin resistance induced by high fructose and partially protects from that induced by high-fat diets. In humans, CD36 deficiency may be an important factor in the metabolic adaptation to diet and in susceptibility to some forms of diet-induced pathology.
The Human Proteome Organization (HUPO) and Environmental Health
Authors: BA Merrick
Journal: Environmental Health Perspectives (2003)

The Human Proteome Organization, or HUPO, was formed to promote research and large-scale analysis of the human proteome. By consolidating national proteome organizations into an international body, HUPO will coordinate international initiatives, biological resources, protocols, standards and data for studying the human proteome. HUPO has identified five key areas to advance study of the human proteome, specifically in bioinformatics, new technologies, the plasma proteome, cell models, and a public antibody initiative. Consideration of three major issue areas may help develop HUPO's strategy for human proteome study. First is the need to distinguish the value of high throughput platforms from discovery platforms in proteomics. Second is the importance for international planning on integrating both transcriptome and proteome data and databases. Last is that effects of the environment from chemical, physical, and biological exposures alter the expression and structure of the proteome, which become manifest in long-term adverse health effects and disease. Environmental health research stands to greatly benefit from the shared resources, data, and vision of the HUPO organization as a valuable resource in exploiting knowledge of the human proteome toward improving public health.
Antibody recognition of the tumor-specific bcr-abl joining region in chronic myeloid leukemia.
Authors: J van Denderen, A Hermans, T Meeuwsen, C Troelstra, N Zegers, W Boersma, G Grosveld, W van Ewijk
Journal: The Journal of Experimental Medicine (1989)

Chronic myeloid leukemia (CML) is characterized by the presence of a 210-kD protein (P210bcr-abl) in the cytoplasm of leukemic cells, generated by the reciprocal translocation between chromosome 9 and chromosome 22. Due to this translocation, the abl oncogene is coupled to the bcr gene, forming a new determinant in this protein encoded by the bcr-abl joining region. In the joining region itself, either the bcr exon 2 is coupled to the abl exon 2 (b2-a2), or the bcr exon 3 is coupled to the abl exon 2 (b3-a2). Thus, these joining regions form by definition new tumor-specific determinants in the respective chimeric P210-bcr-abl molecules. This paper addresses the question as to whether these tumor-specific joining regions are exposed on the P210bcr-abl molecule in such a way that antibodies can be generated to detect these sites. To test this possibility a polyclonal antiserum, termed BP-1, was raised against a synthetic peptide representative for the b2-a2 joining region. The reactivity of BP-1 was analyzed in an ELISA system on various synthetic peptides. Peptide inhibition studies showed the presence of antibodies to different parts of the b2-a2 peptide in the polyvalent antiserum. The reactivity of BP-1 was then tested with native P210bcr-abl molecules in various CML cell lines (K562, LAMA-84, and BV173) using a protein kinase assay. In this context, the bcr-abl junctions were first analyzed at the DNA and RNA level. The present study indicates that BP-1 specifically recognizes the b2-a2 junction in native P210bcr-abl. Furthermore, BP-1 clearly discriminates between b2-a2 P210bcr-abl and b3-a2 P210bcr-abl. We conclude that the tumor-specific b2-a2 joining region is antigenically exposed on the native P210bcr-abl molecule.
Adrenomedullin Reduces Endothelial Hyperpermeability
Authors: Stefan Hippenstiel, Martin Witzenrath, Bernd Schmeck, Andreas Hocke, Mathias Krisp, Matthias Krüll, Joachim Seybold, Werner Seeger, Wolfgang Rascher, Hartwig Schütte, Norbert Suttorp
Journal: Circulation Research (2002)

Endothelial hyperpermeability induced by inflammatory mediators is a hallmark of sepsis and adult respiratory distress syndrome. Increased levels of the regulatory peptide adrenomedullin (ADM) have been found in patients with systemic inflammatory response. We analyzed the effect of ADM on the permeability of cultured human umbilical vein endothelial cell (HUVEC) and porcine pulmonary artery endothelial cell monolayers. ADM dose-dependently reduced endothelial hyperpermeability induced by hydrogen peroxide (H 2 O 2 ), thrombin, and Escherichia coli hemolysin. Moreover, ADM pretreatment blocked H 2 O 2 -related edema formation in isolated perfused rabbit lungs and increased cAMP levels in lung perfusate. ADM bound specifically to HUVECs and porcine pulmonary artery endothelial cells and increased cellular cAMP levels. Simultaneous inhibition of cAMP-degrading phosphodiesterase isoenzymes 3 and 4 potentiated ADM-dependent cAMP accumulation and synergistically enhanced ADM-dependent reduction of thrombin-induced hyperpermeability. However, ADM showed no effect on endothelial cGMP content, basal intracellular Ca 2+ levels, or the H 2 O 2 -stimulated, thrombin-stimulated, or Escherichia coli hemolysin–stimulated Ca 2+ increase. ADM diminished thrombin- and H 2 O 2 -related myosin light chain phosphorylation as well as stimulus-dependent stress fiber formation and gap formation in HUVECs, suggesting that ADM may stabilize the barrier function by cAMP-dependent relaxation of the microfilament system. These findings identify a new function of ADM and point to ADM as a potential interventional agent for the reduction of vascular leakage in sepsis and adult respiratory distress syndrome.
A New Antigen System Expressed in Human Endothelial Cells
Authors: J. Roberto Moraes, Peter Stastny
Journal: Journal of Clinical Investigation (1977)

Kidney transplant recipients were previously found to have antibodies that reacted with cells isolated from the endothelium of umbilical cord veins and which were not cytotoxic for lymphocytes from the same donors. Results of the present experiments indicate that endothelial (E) antigens are different from previously known HLA antigens and also from Ia-like antigens of bone marrow-derived (B) lymphocytes. Attempts to absorb E antibodies with lymphocytes from E-positive donors failed in most cases. Antigen redistribution experiments showed that E antigens were located in separate molecules from the products of HLA-A, B, and C. Thus, E cells treated with E antibody became resistant to lysis by the antibody used, but remained susceptible to the effects of typing sera for alleles of HLA-A, B, and C. Antibodies to E cells were also cytotoxic for blood monocytes. Moreover, monocytes were able to absorb E-antibody reactions, indicating that similar antigens were expressed in both cells. E antibodies did not react with B lymphocytes isolated from peripheral blood. In that regard E antibodies were different from antibodies to human Ia-like antigens which reacted with E cells, monocytes, and isolated B lymphocytes. Thus it appears that E antigens constitute a system of human alloantigens which has not been previously identified. The possibility that these antigens play a role in kidney allograft rejection should now be investigated since matching can be performed using monocytes isolated from the blood of recipients and donors.
Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells
Authors: Helga Ellingsgaard, Irina Hauselmann, Beat Schuler, Abdella M Habib, Laurie L Baggio, Daniel T Meier, Elisabeth Eppler, Karim Bouzakri, Stephan Wueest, Yannick D Muller, Ann Maria Kruse Hansen, Manfred Reinecke, Daniel Konrad, Max Gassmann, Frank Reimann, Philippe A Halban, Jesper Gromada, Daniel J Drucker, Fiona M Gribble, Jan A Ehses, Marc Y Donath
Journal: Nature Medicine (2011)